Patent Publication Number: US-10329256-B2

Title: (Hetero)aryl cyclopropylamine compounds as LSD1 inhibitors

Description:
This application is a continuation of application Ser. No. 15/271,772, filed on Sep. 21, 2016, which is a divisional application of application Ser. No. 14/352,711, filed on Apr. 18, 2014 (now U.S. Pat. No. 9,487,512, issued Nov. 8, 2016), which is a national stage filing under 35 U.S.C. § 371 of International Patent Application No. PCT/EP2012/070898, filed on Oct. 22, 2012, which was published in English as WO 2013/057320 A1 on Apr. 25, 2013, and which is a non-provisional of U.S. Provisional Patent Applications Nos. 61/558,367, filed Nov. 10, 2011, and 61/558,365, filed Nov. 10, 2011, all of which are incorporated herein by reference. International Patent Application No. PCT/EP2012/070898 claims the benefit of the filing date of European Patent Application Nos. 11382325.6, filed on Oct. 20, 2011, and 11382331.4, filed on Oct. 27, 2011, all of which are incorporated herein by reference. 
    
    
     The invention relates to (hetero)aryl cyclopropylamine compounds, particularly compounds of formula I, Ia, Ia-1, Ib and Ic, more particularly compounds of formula I and Ia, as described and defined herein, and their use in therapy, including e.g., in the treatment or prevention of cancer, a neurological disease, or a viral infection. 
     Aberrant gene expression in affected tissue as compared to normal tissue is a common characteristic of many human diseases. This is true for cancer and many neurological diseases which are characterized by changes in gene expression patterns. Gene expression patterns are controlled at multiple levels in the cell. Control of gene expression can occur through modifications of DNA: DNA promoter methylation is associated with suppression of gene expression. Several inhibitors of DNA methylation are approved for clinical use including the blockbuster Vidaza™. Another class of modifications involve histones which form the protein scaffold that DNA is normally associated with (coiled around) in eukaryotic cells. Histones play a crucial role in organizing DNA and the regulated coiling and uncoiling of DNA around the histones is critical in controlling gene expression—coiled DNA is typically not accessible for gene transcription. A number of histone modifications have been discovered including histone acetylation, histone lysine methylation, histone arginine methylation, histone ubiquinylation, and histone sumoyiation, many of which modify accessibility to the associated DNA by the cells transcriptional machinery. These histone marks serve to recruit various protein complexes involved in transcription and repression. An increasing number of studies are painting an intricate picture of how various combinations of histone marks control gene expression in cell-type specific manner and a new term has been coined to capture this concept: the histone code. 
     The prototypical histone mark is histone acetylation. Histone acetyl transferase and histone deacetylases are the catalytic machines involved in modulation of this histone mark although typically these enzymes are parts of multiprotein complexes containing other proteins involved in reading and modifying histone marks. The components of these protein complexes are typically cell-type specific and typically comprise transcriptional regulators, repressors, co-repressors, receptors associated with gene expression modulation (e.g., estrogen or androgen receptor). Histone deacetylase inhibitors alter the histone acetylation profile of chromatin. Accordingly, histone deacetylase inhibitors like Vorinostat (SAHA), Trichostatin A (TSA), and many others have been shown to alter gene expression in various in vitro and in vivo animal models. Clinically, histone deacetylase inhibitors have demonstrated activity in the cancer setting and are being investigated for oncology indications as well as for neurological conditions and other diseases. 
     Another modification that is involved in regulating gene expression is histone methylation including lysine and arginine methylation. The methylation status of histone lysines has recently been shown to be important in dynamically regulating gene expression. 
     A group of enzymes known as histone lysine methyl transferases and histone lysine demethylases are involved in histone lysine modifications. One particular human histone lysine demethylase enzyme called Lysine Specific Demethylase-1 (LSD1) was recently discovered (Shi et al. (2004)  Cell  119:941) to be involved in this crucial histone modification. LSD1 has a fair degree of structural similarity, and amino acid identity/homology to polyamine oxidases and monoamine oxidases, all of which (i.e., MAO-A, MAO-B and LSD1) are flavin dependent amine oxidases which catalyze the oxidation of nitrogen-hydrogen bonds and/or nitrogen carbon bonds. LSD1 has been recognized as an interesting target for the development of new drugs to treat cancer, neurological diseases and other conditions. 
     Cyclopropylamine containing compounds are known to inhibit a number of medically important targets including amine oxidases like Monoamine Oxidase A (MAO-A; or MAOA), Monoamine Oxidase B (MAO-B; or MAOB), and Lysine Specific Demethylase-1 (LSD1). Tranylcypromine (also known as 2-phenylcyclopropylamine), which is the active ingredient of Parnate® and one of the best known examples of a cyclopropylamine, is known to inhibit all of these enzymes. Since MAO-A inhibition may cause undesired side effects, it would be desirable to identify cyclopropylamine derivatives that exhibit potent LSD1 inhibitory activity while being devoid of or having substantially reduced MAO-A inhibitory activity. 
     In view of the lack of adequate treatments for conditions such as cancer and neurodegeneration, there is a desperate need for disease modifying drugs and drugs that work by inhibiting novel targets. There is thus a need for the development of LSD1 inhibitors, particularly those which selectively inhibit LSD1. 
     SUMMARY OF THE INVENTION 
     The present invention relates to the identification of compounds and their use in treating or preventing diseases. The invention provides (hetero)aryl cyclopropylamine compounds, including the compounds of Formula I, Ia, Ia-1, Ib and Ic, and particularly the compounds I, Ia and Ia-1, as described and defined herein. The present invention particularly provides a compound of Formula I, Ia, Ia-1, Ib and Ic, and particularly a compound of Formula I, Ia and Ia-1, pharmaceutical compositions comprising a compound of Formula I, Ia, Ia-1, Ib or Ic, and particularly a compound of Formula I, Ia or Ia-1, and a pharmaceutically acceptable carrier, and their uses for treating diseases. One use of the compound of Formula I, Ia, Ia-1, Ib and Ic is for treating or preventing cancer. Another use for the compound of Formula I, Ia, Ia-1, Ib and Ic is to inhibit LSD1. The invention thus relates to a compound of Formula I, Ia, Ia-1, Ib or Ic, and particularly a compound of Formula I, Ia or Ia-1, for use in treating or preventing human disease. The present invention further relates to a compound of Formula I, Ia, Ia-1, Ib and Ic, and particularly a compound of Formula I, Ia or Ia-1, for use in treating or preventing cancer. The present invention further relates to a compound of Formula I, Ia, Ia-1, Ib and Ic, and particularly a compound of Formula I, Ia or Ia-1, for use in treating or preventing a neurological disease. The present invention further relates to a compound of Formula I, Ia, Ia-1, Ib and Ic, and particularly a compound of Formula I, Ia or Ia-1, for use in treating or preventing a viral infection. 
     Accordingly, the present invention provides a compound of Formula I and relates, in particular, to the compound of Formula I for use as a medicament: 
                         
wherein:
 
A is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R 1 ;
 
B is H, R 1  or -L 1 -E;
 
E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ;
 
L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene;
 
L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,   wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,   wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,   wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and   wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
   (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,   wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,   wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,   wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and   wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ;
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea; and
 
each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl.
       

     In another embodiment, the present invention provides a compound of Formula I wherein R w , R x , R y  and R z  are each hydrogen, i.e. a compound of formula Ia, and relates, in particular, to the compound of Formula Ia for use as a medicament: 
                         
wherein:
 
A is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R 1 ;
 
B is H, R 1  or -L 1 -E;
 
E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ;
 
L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene;
 
L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,   wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula Ia through a ring C atom,   wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,   wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and   wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
   (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,   wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula Ia through a ring C atom,   wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,   wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and   wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ;
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea; and
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea.
       

     In another embodiment, the invention provides a compound of formula Ia as defined above wherein the substituents of the cyclopropyl moiety -A-B and —NH-L 2 -D are in the trans-configuration, i.e. a compound of formula Ia-1: 
                         
wherein the groups and variables of formula Ia-1, including A, B, D, E, L 1 , L 2 , R 1 , R 2  and R 3 , are as defined above in relation to a compound of formula Ia. The above chemical representation for a compound of formula Ia-1 does not intend to indicate absolute stereochemistry of the two chiral centers on the cyclopropyl ring, but only their relative stereochemistry (which is trans). Thus a compound of formula Ia-1 could likewise be represented as
 
     
       
         
         
             
             
         
       
     
     A compound of formula Ia-1 therefore relates to the individual optically active trans isomers as well as any mixtures thereof. 
     In another embodiment, the invention provides a compound of formula I as defined above wherein each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl with the proviso that at least one of R w , R x , R y  and R z  is not hydrogen; that compound is referred to as a compound of formula Ib in the following. In a more preferred embodiment, R w  is selected from halo and C 1-4  alkyl, preferably from fluoro and methyl, and each R x , R y  and R z  is hydrogen. A compound of formula I wherein R w  is selected from halo and C 1-4  alkyl, preferably from fluoro and methyl, and each R x , R y  and R z  is hydrogen is referred to as a compound of formula Ic in the following. 
     Also included within the scope of the invention are all isomers, including all stereoisomers and mixtures thereof, of the compounds of formula I, Ia, Ia-1, Ib and Ic. All salts and all solvates, preferably pharmaceutically acceptable salts and solvates, of the compounds of formula I, Ia, Ia-1, Ib and Ic are also encompassed within the scope of the invention. Furthermore, all physical forms (including amorphous and crystalline forms) of any such compounds are also encompassed within the scope of the invention. Any reference to a compound of formula I, Ia, Ia-1, Ib or Ic should be construed, unless otherwise indicated, as a reference to a compound of formula I, Ia, Ia-1, Ib or Ic (respectively), any isomer thereof (including any stereoisomer thereof or any mixtures thereof), any salt thereof (including any pharmaceutically acceptable salt thereof), any solvate thereof (including any pharmaceutically acceptable solvate thereof), and any physical form thereof. 
     The compounds of formula Ia, including also the compounds of formula Ia-1, are particularly preferred compounds according to the present invention. The most preferred compounds of the invention are the compounds of formula Ia-1. 
     Any chemical drawing or formula given herein is intended to represent unlabeled forms as well as isotopically labeled forms of the compounds of the invention. Isotopically labeled compounds have structures depicted by the formulas given herein except that one or more atoms are replaced by an atom having a selected atomic mass or mass number. Examples of isotopes that can be incorporated into compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine, and iodine, such as  2 H,  3 H,  11 C,  13 C  14 C,  15 N,  18 O,  17 O,  31 P,  32 P,  35 S,  18 F, 36Cl, and  125 I, respectively. Such isotopically labelled compounds are useful in metabolic studies (preferably with  14 C), reaction kinetic studies (with, for example  2 H or  3 H), detection or imaging techniques [such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT)] including drug or substrate tissue distribution assays, or in radioactive treatment of patients. In particular, an  18 F or  11 C labeled compound may be particularly preferred for PET or SPECT studies. Further, substitution with heavier isotopes such as deuterium (i.e.,  2 H) may afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements. Particularly preferred are the deuterated forms of the compounds of the invention, i.e. a compound of formula I, Ia, Ia-1, Ib and Ic above wherein one or more hydrogen atoms has been replaced with deuterium. Isotopically labeled compounds of the invention can generally be prepared by carrying out the procedures disclosed in the schemes or in the examples and preparations described below by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. In addition to the unlabeled form, all isotopically labeled forms of the compounds of formula I, Ia, Ia-1, Ib and Ic are included within the scope of the invention. 
     In a compound of formula I, Ia, Ib or Ic the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are preferably in the trans-configuration. 
     The compounds of formula I, Ia, Ia-1, Ib and Ic are potent inhibitors of LSD1 and therefore can be useful for the treatment or prevention of any disease associated with LSD1. 
     The invention thus provides a pharmaceutical composition comprising a compound of Formula I, Ia, Ia-1, Ib or Ic and a pharmaceutically acceptable carrier. Preferred embodiments of the compound of Formula I, Ia, Ia-1, Ib and Ic, e.g. for use in the compositions of the invention, are defined and described herein below in more detail. 
     In another aspect, the invention provides a method of treating or preventing a disease comprising administering, to a patient (preferably a human) in need of such treatment or prevention, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as described above or as defined in the embodiments thereof described below) effective to treat or prevent said disease. In one embodiment, such disease is a disease associated with LSD1. 
     In a related aspect, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (as described above or as defined in the embodiments thereof as described below) for use as a medicament. In a more specific embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic for use in the treatment or prevention of a disease associated with LSD1. 
     In yet another aspect, the invention provides a method of inhibiting LSD1 activity comprising administering, to a patient in need of treatment, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic sufficient to inhibit LSD1 activity. Preferably the patient is a human. In a related aspect, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic as herein defined for use as a LSD1 inhibitor. Preferred embodiments of the compounds of Formula I, Ia, Ia-1, Ib or Ic for use herein are as described in more detail below. 
     In another aspect, the invention provides a method of treating or preventing cancer comprising administering, to a patient (preferably a human) in need of such treatment or prevention, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or as defined in the embodiments described in more detail herein) sufficient to treat or prevent such cancer. In a related aspect, the invention provides a method of treating or preventing a cancer wherein said cancer is chosen from breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, skin cancer, blood cancer (e.g., leukemia, including, for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia), lymphoma and myeloma, comprising administering to a patient (preferably a human) in need of such treatment or prevention, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or as defined in the embodiments described in more detail herein) sufficient to treat or prevent such cancer. In an even more specific aspect, said cancer is chosen from prostate, brain, colorectal, lung, breast, skin, and blood cancer. In one specific aspect, the cancer is prostate cancer. In one specific aspect, the cancer is lung cancer. In one specific aspect, the cancer is brain cancer. In one specific aspect, the cancer is blood cancer (e.g., leukemia, including, for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia). In one specific aspect, the cancer is breast cancer. In one specific aspect, the cancer is colorectal cancer. In one specific aspect, the cancer is lymphoma. In one specific aspect, the cancer is myeloma. In a preferred embodiment, the method comprises administering a therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic sufficient for treating or preventing said cancer. In a preferred aspect, the therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic is an amount sufficient to inhibit LSD1. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-4 methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-9 methylation levels. While the present invention relates to both the treatment and the prevention of cancer, the treatment of cancer is particularly preferred. 
     In a related aspect, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or as defined in the embodiments described in more detail herein), for use in the treatment or prevention of cancer. In another related aspect, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic for use in the treatment or prevention of a cancer wherein said cancer is chosen from breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, skin cancer, blood cancer (e.g., leukemia, including, for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia), lymphoma and myeloma. In a more specific aspect, said cancer is chosen from prostate, brain, colorectal, lung, breast, skin, and blood cancer. In one specific aspect, the cancer is prostate cancer. In one specific aspect, the cancer is lung cancer. In one specific aspect, the cancer is brain cancer. In one specific aspect, the cancer is blood cancer (e.g., leukemia, including, for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia). In one specific aspect, the cancer is breast cancer. In one specific aspect, the cancer is colorectal cancer. In one specific aspect, the cancer is lymphoma. In one specific aspect, the cancer is myeloma. In preferred embodiment, a therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic sufficient for treating or preventing said cancer is administered. In a preferred aspect, the therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic is an amount sufficient to inhibit LSD1. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-4 methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-9 methylation levels. 
     In another aspect, the invention provides a method of treating or preventing a neurological disease (e.g., a neurodegenerative disease) comprising administering, to a patient in need of such treatment or prevention, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) sufficient to treat or prevent said neurological disease. In a related aspect, the invention provides a method of treating or preventing a neurological disease wherein said neurological disease is selected from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease, Amyotrophic Lateral Sclerosis, Dementia with Lewy Bodies, or Frontotemporal Dementia, particularly from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease, or Dementia with Lewy Bodies, comprising administering to a patient (preferably a human) in need of such treatment or prevention, an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or as defined in the embodiments described in more detail herein) sufficient to treat or prevent such neurological disease. In a preferred embodiment, the method comprises administering a therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic sufficient for treating or preventing said neurological disease. In a preferred aspect, the therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic is an amount sufficient to inhibit LSD1. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-4 methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-9 methylation levels. 
     In another related aspect, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for use in the treatment or prevention of a neurological disease (e.g., a neurodegenerative disease). In one embodiment, said neurological disease is selected from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease, Amyotrophic Lateral Sclerosis, Dementia with Lewy Bodies and Frontotemporal Dementia, particularly from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease and Dementia with Lewy Bodies. In a preferred embodiment, a therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic sufficient for treating or preventing said neurological disease is administered. In a preferred aspect, the therapeutically effective amount of a compound of Formula I, Ia, Ia-1, Ib or Ic is an amount sufficient to inhibit LSD1. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-4 methylation levels. In another preferred aspect, the therapeutically effective amount is an amount sufficient to modulate histone-3 lysine-9 methylation levels. 
     In another aspect, the invention provides a method of treating or preventing a viral infection comprising administering to a patient in need thereof (preferably a human) an amount of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) sufficient to treat or prevent said viral infection In a related aspect, the invention also provides a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for use in treating or preventing a viral infection. In one specific embodiment, the viral infection is a herpesvirus infection. In a more specific embodiment, the herpesvirus infection is caused by and/or associated with a herpesvirus chosen from HSV-1, HSV-2, and Epstein-Barr virus. In another embodiment, the viral infection is caused by and/or associated with HIV. In another embodiment, the viral infection is caused by and/or associated with a Hepadnavirus (i.e., a virus of the Hepadnaviridae family), particularly Hepatitis B virus (HBV). In another embodiment, the viral infection is caused by and/or associated with a Flavivirus (i.e., a virus of the Flaviviridae family), particularly Hepatitis C virus (HCV), yellow fever virus, West Nile virus, Dengue virus or Japanese encephalitis virus, and more preferably HCV. In an even more specific embodiment, the invention provides a method for treating or preventing viral reactivation after latency, the method comprising administering to an individual (preferably a human) a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein). Accordingly, the invention also provides a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for use in treating or preventing viral reactivation after latency. In a specific embodiment, the virus that is reactivating is a herpesvirus. In a more specific embodiment, the herpesvirus that is reactivating is chosen from HSV-1, HSV-2, and Epstein-Barr virus. In an even more specific embodiment, the virus that is reactivating is HSV. In a further specific embodiment, the virus that is reactivating is HIV. 
     In still another aspect, the invention provides the use of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for the manufacture of a medicament for the treatment or prevention of cancer. In a preferred embodiment, said cancer is chosen from breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, skin cancer, blood cancer (e.g., leukemia, including, for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia), lymphoma and myeloma. 
     In still another aspect, the invention provides the use of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for the manufacture of a medicament for the treatment or prevention of a neurological disease (e.g., a neurodegenerative disease). In a preferred embodiment said neurological disease is selected from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease, Amyotrophic Lateral Sclerosis, Dementia with Lewy Bodies, or Frontotemporal Dementia, particularly from depression, Alzheimer&#39;s disease, Huntington disease, Parkinson&#39;s disease, and Dementia with Lewy Bodies. 
     In still another aspect, the invention provides the use of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for the manufacture of a medicament for the treatment or prevention of a viral infection. In a preferred embodiment, said viral infection is a herpesvirus infection (e.g., a herpesvirus infection caused by and/or associated with a herpesvirus chosen from HSV-1, HSV-2, and Epstein-Barr virus) or a viral infection caused by and/or associated with HIV. In another preferred embodiment, said viral infection is caused by and/or associated with a Hepadnavirus, particularly Hepatitis B virus (HBV). In another embodiment, said viral infection is caused by and/or associated with a Flavivirus, particularly Hepatitis C virus (HCV), yellow fever virus, West Nile virus, Dengue virus or Japanese encephalitis virus, and more preferably HCV. 
     In still another aspect, the invention provides the use of a compound of Formula I, Ia, Ia-1, Ib or Ic (as defined above or in the embodiments described in more detail herein) for the manufacture of a medicament for the treatment or prevention of viral reactivation after latency. In a preferred embodiment, the virus that is reactivating is a herpesvirus (e.g., HSV-1, HSV-2, or Epstein-Barr virus), HSV, or HIV. 
     In still another aspect, the invention provides a method for identifying a compound which is a selective inhibitor of LSD1, the method comprising selecting or providing a compound of Formula I, Ia, Ia-1, Ib or Ic as defined herein, and determining the ability of the compound to inhibit LSD1 and MAO-A and/or MAO-B, wherein a compound that inhibits LSD1 to a greater extent than MAO-A and/or MAO-B is identified as a LSD1 selective inhibitor. The compound of this aspect that is an LSD1 inhibitor can be used to treat disease, particularly human disease. 
     In another aspect, the invention provides a process for the preparation of a compound of formula I, or a salt thereof, which comprises reacting a compound of formula II 
                         
wherein A, B, R w , R x , R y , R z  have the meaning disclosed above in relation to a compound of formula I, with a compound of formula IIIa, IIIb or IIIc
 
                         
wherein D has the meaning disclosed above in relation to a compound of formula I, and wherein any amino group that may be present in D is optionally protected with a protecting group,
 
in the presence of a reducing agent, followed by the removal of any protecting group that may be present. The reducing agent may be, e.g., a borohydride, such as sodium borohydride or sodium triacetoxyborohydride.
 
     Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. 
     Other features and advantages of the invention will be apparent from the following detailed description, and from the claims. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention relates to the identification of compounds and their use in treating and preventing diseases. The present invention provides compounds of Formula I, Ia, Ia-1, Ib and Ic, pharmaceutical compositions comprising a compound of Formula I, Ia Ia-1, Ib or Ic and a pharmaceutically acceptable carrier, and their use for treating diseases. One use of the compounds of Formula I, Ia, Ia-1, Ib and Ic is for treating cancer. 
     The present invention provides a compound of Formula I and relates, in particular, to the compound of Formula I for use as a medicament. 
     
       
         
         
             
             
         
       
     
     In a compound of formula I, each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl. In one embodiment, each R w , R x , R y  and R z  is independently selected from hydrogen, fluoro and C 1-4  alkyl, preferably from hydrogen, fluoro and methyl. In another embodiment, each R w , R x , R y  and R z  is independently selected from hydrogen and fluoro. In another embodiment, R w  is fluoro and each R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R w  is fluoro and each R x , R y  and R z  is hydrogen. In another embodiment, R z  is fluoro and each R w , R x  and R y  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R z  is fluoro and each R w , R x  and R y  is hydrogen. In another embodiment, R w  and R z  are fluoro and each R x  and R y  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R w  and R z  are fluoro and each R x  and R y  is hydrogen. In a preferred embodiment, R w  is selected from hydrogen, halo and C 1-4  alkyl, preferably from hydrogen, fluoro and methyl, and each R x , R y  and R z  is hydrogen. In a more preferred embodiment, each R w , R x , R y  and R z  is hydrogen. A compound of formula I wherein each R w , R x , R y  and R z  is hydrogen is a compound of formula Ia, which can be depicted as follows: 
     
       
         
         
             
             
         
       
     
     In another embodiment, in a compound of formula I each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl with the proviso that at least one of R w , R x , R y  and R z  is not hydrogen, this is a compound of formula Ib. In a more preferred embodiment, R w  is selected from halo and C 1-4  alkyl, preferably fluoro and methyl, and each R x , R y  and R z  is hydrogen. A compound of formula I wherein R w  is selected from halo and C 1-4  alkyl, preferably fluoro and methyl, and each R x , R y  and R z  is hydrogen is a compound of formula Ic. Preferably, in a compound of formula Ic R w  is methyl. 
     The invention also relates to a compound of formula Ia, Ia-1, Ib and Ic as defined above, and in particular to a compound of formula Ia, Ia-1, Ib and Ic for use as a medicament. 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, the group A is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 1 . In one embodiment, A is aryl (preferably phenyl or naphthyl) optionally substituted with one or more R 1 . In a specific embodiment, A is phenyl optionally substituted with one or more R 1 . In another specific embodiment, A is naphthyl (preferably 2-naphthyl) optionally substituted with one or more R 1 . In another embodiment, A is heteroaryl optionally substituted with one or more R 1 . In a more specific embodiment, A is monocyclic heteroaryl optionally substituted with one or more R 1 . In a preferred embodiment, A is phenyl, naphthyl or monocyclic heteroaryl, wherein said phenyl, said naphthyl or said monocyclic heteroaryl is optionally substituted with one or more R 1 . Preferably, A is monocyclic aryl (i.e. phenyl) or monocyclic heteroaryl, wherein said monocyclic aryl or said monocyclic heteroaryl is optionally substituted with one or more R 1 . More preferably, A is phenyl, pyridyl, thiophenyl, pyrrolyl, furanyl, or thiazolyl, wherein A (i.e. said phenyl, said pyridyl, said thiophenyl, said pyrrolyl, said furanyl, or said thiazolyl) is optionally substituted with one or more R 1 . Still more preferably, A is phenyl, pyridyl or thiazolyl, wherein A is optionally substituted with one or more R 1 . Even more preferably, A is phenyl, 3-pyridyl or 5-thiazolyl, as shown below: 
                         
wherein A is optionally substituted with one or more R 1 . In one embodiment, A is phenyl or pyridyl, preferably phenyl or 3-pyridyl. In another embodiment, A is phenyl. In another embodiment, A is pyridyl, preferably 3-pyridyl. In another embodiment, A is thiazolyl, preferably 5-thiazolyl. In one embodiment, A has 0, 1 or 2 substituents R 1 . In a further embodiment, A has 0 or 1 substituent R 1 . In a further embodiment, A has 0 substituent R 1 . In a further embodiment, A has 1 or 2 substituents R 1 . In a further embodiment, A has 1 substituent R 1 . In the aforementioned embodiments, in which A has 0, 1 or 2 substituents R 1 , the total number of substituents R 1  is defined, including the possibility that B may be R 1 . Accordingly, if A has 0 substituents R 1 , then B is not R 1 .
 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, B is hydrogen, R 1  or -L 1 -E. In one embodiment, B is -L 1 -E. In another embodiment, B is hydrogen or R 1 . In a further embodiment, B is hydrogen. In another embodiment, B is R 1 . 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . In one embodiment, E is an aryl group (e.g., phenyl, naphthyl or anthracenyl) optionally substituted with one or more R 2 . In another embodiment, E is a heteroaryl group (e.g., pyridinyl, thiophenyl, pyrrolyl, furanyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolyl, indolyl, pyrazolyl, indazolyl, imidazolyl or benzimidazolyl) optionally substituted with one or more R 2 . In another embodiment, E is pyridinyl, thiophenyl, pyrrolyl, furanyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolyl, indolyl, indazolyl, imidazolyl or benzimidazolyl, wherein said pyridinyl, said thiophenyl, said pyrrolyl, said furanyl, said thiazolyl, said oxazolyl, said isoxazolyl, said oxadiazolyl, said thiadiazolyl, said triazinyl, said pyridazinyl, said pyrazinyl, said pyrimidinyl, said quinolyl, said indolyl, said indazolyl, said imidazolyl or said benzimidazolyl is optionally substituted with one or more R 2 . Preferably, E is monocyclic aryl (i.e. phenyl) or monocyclic heteroaryl, wherein said monocyclic aryl or said monocyclic heteroaryl is optionally substituted with one or more R 2 . In one preferred embodiment, E is phenyl or pyridinyl, wherein said phenyl or said pyridinyl is optionally substituted with one or more R 2 . In one embodiment, E has 0, 1, 2 or 3 substituents R 2 . In another embodiment, E has 0, 1 or 2 substituents R 2 . In another embodiment, E has 0 or 1 substituents R 2 . In another embodiment, E has 0 substituents R 2 . In another embodiment, E has 1 substituent R 2 . Preferably, E is phenyl optionally substituted with one or more R 2 . In one embodiment, E is phenyl optionally substituted with one, two or three R 2 . In another embodiment, E is phenyl optionally substituted with one or two R 2 . In a further embodiment, E is phenyl optionally substituted with one R 2 . In another embodiment, E is phenyl. In another embodiment, E is phenyl substituted with one, two or three, preferably one or two, R 2 . In another preferred embodiment, E is heteroaryl, preferably monocyclic heteroaryl, optionally substituted with one or more (preferably one, two or three) R 2 . In one embodiment, E is heteroaryl, preferably monocyclic heteroaryl. In another embodiment, E is heteroaryl (preferably monocyclic heteroaryl) substituted with one, two or three, preferably one or two, R 2 . 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4  alkylene. Preferably said heteroC 1-4  alkylene is —(CH 2 ) x —NH—, or —(CH 2 ) x —O—, wherein x is 1, 2, 3 or 4; still more preferably, said —(CH 2 ) x —NH— or —(CH 2 ) x —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —(CH 2 ) x — group. More preferably, said heteroC 1-4  alkylene is —CH 2 —NH— or —CH 2 —O—, wherein said —CH 2 —NH— and —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. 
     In one embodiment, L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, —CH 2 —, CH 2 —CH 2 —, —CH 2 —NH—, or —CH 2 —O—. In another embodiment, L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, —CH 2 —NH—, or —CH 2 —O—. In another embodiment, L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—. In another embodiment, L 1  is a bond, —O—, —NH—, or —CH 2 —NH—. In another embodiment, L 1  is a bond or —CH 2 —O—. In another embodiment, L 1  is —NH— or —CH 2 —NH—. In a further embodiment, L 1  is a bond. In another embodiment, L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4  alkylene; preferably, L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, —CH 2 —, CH 2 —CH 2 —, —CH 2 —NH—, or —CH 2 —O—; more preferably L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, —CH 2 —NH—, or —CH 2 —O—; even more preferably L 1 -O—, —NH—, —CH 2 —NH—, or —CH 2 —O—; and particularly preferably L 1  is —CH 2 —O—. In another embodiment, L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene, —(CH 2 ) x —NH—, —SO 2 NH— or —SO 2 N(CH 3 )—, wherein x is 1, 2, 3 or 4; preferably L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene, or —CH 2 —NH—, and more preferably L 1  is —O—, —NH— or —CH 2 —NH—. Preferably, in all these embodiments, said —(CH 2 )—NH—, —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. 
     In one embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein the groups —CH 2 —NH— and —CH 2 —O— are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is phenyl, pyridinyl, thiophenyl, pyrrolyl, furanyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolyl, indolyl, indazolyl, imidazolyl or benzimidazolyl, wherein said phenyl, said pyridinyl, said thiophenyl, said pyrrolyl, said furanyl, said thiazolyl, said oxazolyl, said isoxazolyl, said oxadiazolyl, said thiadiazolyl, said triazinyl, said pyridazinyl, said pyrazinyl, said pyrimidinyl, said quinolyl, said indolyl, said indazolyl, said imidazolyl or said benzimidazolyl is optionally substituted with one or more R 2 ; and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein the groups —CH 2 —NH— and —CH 2 —O— are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is phenyl optionally substituted with one or more R 2 ; and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein the groups —CH 2 —NH— and —CH 2 —O— are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is a bond or —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is phenyl optionally substituted with one or more R 2 ; and L 1  is a bond or —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is a bond. In another embodiment, B is -L 1 -E; E is aryl, pyridinyl, thiophenyl, pyrrolyl, furanyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolyl, indolyl, indazolyl, imidazolyl or benzimidazolyl, wherein said aryl, said pyridinyl, said thiophenyl, said pyrrolyl, said furanyl, said thiazolyl, said oxazolyl, said isoxazolyl, said oxadiazolyl, said thiadiazolyl, said triazinyl, said pyridazinyl, said pyrazinyl, said pyrimidinyl, said quinolyl, said indolyl, said indazolyl, said imidazolyl or said benzimidazolyl is optionally substituted with one or more R 2 ; and L 1  is a bond. In another embodiment, B is -L-E; E is aryl, wherein said aryl is optionally substituted with one or more R 2 ; and L 1  is a bond. In another embodiment, B is -L 1 -E; E is phenyl optionally substituted with one or more R 2 ; and L 1  is a bond. In another embodiment, B is -L 1 -E; E is pyridinyl optionally substituted with one or more R 2 ; and L 1  is a bond. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl; and L 1  is a bond. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is heteroaryl (preferably monocyclic heteroaryl, more preferably pyridinyl), wherein said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is phenyl optionally substituted with one or more R 2 ; and L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene, —(CH 2 ) x —NH—, —SO 2 NH— or —SO 2 N(CH 3 )—, wherein x is 1, 2, 3 or 4, preferably L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene, or —CH 2 —NH—, and more preferably L 1  is —O—, —NH— or —CH 2 —NH— wherein the group —CH 2 —NH— is linked to ring A through the N atom and to ring E through the —CH 2 — group. In another embodiment, B is -L 1 -E; E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and L 1  is —NH— or —CH 2 —NH—, wherein the group —CH 2 —NH— is linked to ring A through the N atom and to ring E through the —CH 2 — group. 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea. When there is more than one R 1  as a substituent on ring A, they can be the same or different. In one embodiment, each R 1  is independently selected from C 1-8  alkyl, cyclyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 4-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another embodiment, each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another embodiment, each R 1  is independently selected from C 1-8  alkyl, amino, amido, halo, haloC 1 -8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea. When there is more than one R 2  as a substituent on ring E, they can be the same or different. In one embodiment, each R 2  is independently selected from C 1-8  alkyl, cyclyl, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide and C 1-8  alkoxy. In another embodiment, each R 2  is independently selected from C 1-8  alkyl, cyclyl, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, N-sulfonamido and C 1-8  alkoxy. In another embodiment, each R 2  is independently selected from hydroxyl, halo (for example fluoro or chloro), haloC 1-8  alkyl (for example trifluoromethyl) and sulfonamide (preferably N-sulfonamido). In another embodiment, each R 2  is independently selected from hydroxyl, halo, haloC 1-8  alkyl and N-sulfonamido. In another embodiment, each R 2  is independently selected from hydroxyl, halo, haloC 1-8  alkyl and —NR′SO 2 R (wherein R and R′ are as defined herein below; preferably R′ is H and R is C-s alkyl (for example, methyl, ethyl or isopropyl) or R′ is H and R is optionally substituted phenyl). In another embodiment, each R 2  is independently selected from hydroxyl, halo and haloC 1-8  alkyl. In another embodiment, each R 2  is independently selected from hydroxyl, halo and haloC 1-4  alkyl. In another embodiment, each R 2  is independently selected from hydroxyl, chloro, fluoro or trifluoromethyl. In a further embodiment, ring E is substituted with one R 2  and said R 2  is N-sulfonamido, i.e. —NR′SO 2 R (wherein R and R′ are as defined herein below; preferably R′ is H and R is C 1-8  alkyl (for example, methyl, ethyl or isopropyl) or R′ is H and R is optionally substituted phenyl). 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, L 2  and D have the following meanings: 
     L 2  is a bond and D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I (i.e., of formula I, Ia, Ia-1, Ib or Ic, respectively) through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
 
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered poly cyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I (i.e., of formula I, Ia, Ia-1, Ib or Ic, respectively) through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ; 
           
         
       
    
     In one embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I, Ia, Ia-1, Ib or Ic through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     D can thus be a monocyclic ring (group i) or polycyclic ring (group ii). “Polycyclic ring system” as used herein means a ring system containing 2 or more rings, preferably containing two (i.e. bicyclic) or three (i.e. tricyclic) rings, which rings can be fused, bridged or spiro rings, or any combination thereof. Thus, tricyclic rings include for example three fused rings, or two rings fused together, one of which is a spiro bicyclic ring. A fused ring as used herein means that two rings are linked to each other through two adjacent ring atoms common to both rings. A bridged ring as used herein means that a ring comprises a linker group —(C(R a ) 2 ) p — linking together any two non-adjacent carbon or nitrogen atoms of the ring, wherein p is 1 or 2 and each R a  independently is hydrogen or C 1-4  alkyl. A spiro ring as used herein means two rings linked together via a single carbon atom common to both rings. 
     Ring D can contain 1 or 2 heteroatoms independently selected from N, O and S in case of cyclic group (i) or from 1 to 4 heteroatoms independently selected from N, O and S in case of cyclic group (ii). In one embodiment, D contains 1 or 2 heteroatoms independently selected from N, O and S in case of cyclic group (i) or from 1 to 4 heteroatoms independently selected from N, O and S in case of cyclic group (ii), wherein ring D contains at least 1 N atom. In another embodiment, cyclic group (i) contains 1 heteroatom selected from N, O and S. In another embodiment, cyclic group (i) contains 1 N atom. In another embodiment, cyclic group (ii) contains 1 or 2 heteroatoms independently selected from N, O and S. In another embodiment, cyclic group (ii) contains 1 or 2 N atoms. 
     Cyclic group (ii) as defined above refers to a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring. One ring forming part of cyclic group (ii) must thus be a saturated heterocyclic ring, while the other ring(s) can be saturated, partially unsaturated or aromatic carbocyclic or heterocyclic rings. It is to be understood that, in the polycyclic ring group (ii), a saturated heterocyclic ring which is fused to an aromatic ring is still to be considered as a saturated heterocyclic ring, even if the two adjacent ring atoms common to both rings (i.e., common to the saturated heterocyclic ring and to the aromatic ring) are connected by a double bond. Accordingly, the cyclic group (ii) may also be, e.g., a saturated heterocyclic ring which is fused to an aromatic carbocyclic or heterocyclic ring. In one embodiment, cyclic group (ii) is a saturated polycyclic ring system, i.e. all rings forming cyclic group (ii) are saturated. 
     D (i.e. groups (i) or (ii)) is linked to the remainder of the compound of Formula I through a ring C atom. In the case of cyclic group (ii), the C atom linking D to the remainder of the compound of formula I can be in any of the rings and thus can be in the saturated heterocyclic ring or any other ring forming part of cyclic group (ii). 
     D, i.e. cyclic group (i) or (ii), may be optionally substituted with one or more R 3 , which can be the same or different and may be placed at any available carbon or nitrogen atom of cyclic group (i) or of any of the rings of cyclic group (ii). In one embodiment, the substituent(s) R 3 , if present, are placed on ring C atom(s). In another embodiment, D is not substituted with any R 3 . 
     In one embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I (i.e., the remainder of the compound of Formula I, Ia, Ia-1, Ib or Ic, respectively) through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) contains at least one N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) contains at least one N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and   (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) contains at least one N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and   (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, and   (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, wherein the polycyclic ring system contains 1 N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is a bond and D is a cyclic group selected from:
         (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) contains at least one N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 , wherein said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
       

     In another embodiment, L 2  is a bond and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 heteroatom selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one S atom in ring D, if present, is optionally oxidized to form independently SO group or SO 2  group, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is a 6-membered monocyclic saturated heterocyclic ring containing 1 heteroatom selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one S atom in ring D, if present, is optionally oxidized to form independently SO group or SO 2  group, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is piperidinyl, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 , wherein said substituent(s) R 3 , if present, are placed on C atom(s) of said piperidine ring. 
     In another embodiment, L 2  is a bond and D is 4-piperidinyl optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is 4-piperidinyl optionally substituted with one or more R 3 , wherein said substituent(s) R 3 , if present, are placed on C atom(s) of said piperidine ring. 
     In a specific embodiment, L 2  is a bond and D is 4-piperidinyl. 
     In another specific embodiment, L 2  is a bond and D is a group of the following formula: 
     
       
         
         
             
             
         
       
     
     In another embodiment, L 2  is a bond and D is a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is a bond and D is a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In a preferred embodiment, L 2  is a bond and D is a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, wherein the polycyclic ring system contains 1 or 2 N atoms, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In a specific embodiment, L 2  is a bond and D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b), (c) and (d) 
                         
wherein D is optionally substituted with one or more R 3 . Said substituent(s) R 3 , if present, can be placed on any available position, including on the N atom.
 
     In another specific embodiment, L 2  is a bond and D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b) and (c) 
                         
wherein D is optionally substituted with one or more R 3 . Said substituent(s) R 3 , if present, can be placed on any available position, including on the N atom.
 
     In a further embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I, Ia, Ia-1, Ib or Ic through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 .
       

     D can thus be a monocyclic saturated ring (group iii) or polycyclic saturated ring (group iv). “Polycyclic saturated ring system” as used herein means a ring system containing 2 or more saturated rings, preferably containing two (i.e. bicyclic) or three (i.e. tricyclic) saturated rings, which rings can be fused, bridged or spiro rings, or any combination thereof. Thus, tricyclic rings include for example three fused rings, or two rings fused together, one of which is a spiro bicyclic ring. A fused ring as used herein means that two rings are linked to each other through two adjacent ring atoms common to both rings. A bridged ring as used herein means that a ring comprises a linker group —(C(R a ) 2 ) p — linking together any two non-adjacent carbon or nitrogen atoms of the ring, wherein p is 1 or 2 and each R a  independently is hydrogen or C 1-4  alkyl. A spiro ring as used herein means two rings linked together via a single carbon atom common to both rings. 
     Ring D can contain 1 or 2 heteroatoms independently selected from N, O and S in case of cyclic group (iii) or from 1 to 4 heteroatoms independently selected from N, O and S in case of cyclic group (iv). In one embodiment, D contains 1 or 2 heteroatoms independently selected from N, O and S in case of cyclic group (iii) or from 1 to 4 heteroatoms independently selected from N, O and S in case of cyclic group (iv), wherein ring D contains at least 1 N atom. In another embodiment, cyclic group (iii) contains 1 heteroatom selected from N, O and S. In another embodiment, cyclic group (iv) contains 1 N atom. In another embodiment, cyclic group (iii) contains 1 or 2 heteroatoms independently selected from N, O and S. In another embodiment, cyclic group (iv) contains 1 or 2 N atoms. 
     Cyclic group (iv) as defined above refers to a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring. One ring forming part of cyclic group (iv) must thus be a saturated heterocyclic ring, while the other ring(s) can be saturated carbocyclic or heterocyclic rings. 
     D (i.e. groups (iii) or (iv)) is linked to the remainder of the compound of Formula I through a ring C atom. In the case of cyclic group (iv), the C atom linking D to the remainder of the compound of formula I can be in any of the rings and thus can be in the saturated heterocyclic ring or any other (carbocyclic or heterocyclic) saturated ring forming part of cyclic group (iv). 
     D, i.e. cyclic group (iii) or (iv), may be optionally substituted with one or more R 3 , which can be the same or different and may be placed at any available carbon or nitrogen atom of cyclic group (iii) or of any of the rings of cyclic group (iv). In one embodiment, the substituent(s) R 3 , if present, are placed on ring C atom(s). In another embodiment, D is not substituted with any R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (iii) or (iv) contains at least one N atom,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I (i.e., the remainder of the compound of Formula I, Ia, Ia-1, Ib or Ic, respectively) through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 2 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (iii) or (iv) contains at least one N atom,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, and   (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains 1 N atom,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 .
       

     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a cyclic group selected from:
         (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and   (iv) a 7- to 15-membered saturated polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (iii) or (iv) contains at least one N atom,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 , wherein said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
       

     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 heteroatom selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one S atom in ring D, if present, is optionally oxidized to form independently SO group or SO 2  group, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 6-membered monocyclic saturated heterocyclic ring containing 1 heteroatom selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one S atom in ring D, if present, is optionally oxidized to form independently SO group or SO 2  group, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is piperidinyl, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 , wherein said substituent(s) R 3 , if present, are placed on C atom(s) of said piperidine ring. 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is 4-piperidinyl optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is 4-piperidinyl optionally substituted with one or more R 3 , wherein said substituent(s) R 3  if present, are placed on C atom(s) of said piperidine ring. 
     In a specific embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is 4-piperidinyl. 
     In another specific embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a group of the following formula: 
     
       
         
         
             
             
         
       
     
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is azetidinyl, wherein said azetidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said azetidinyl is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is 3-azetidinyl optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, 
     wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, 
     wherein the polycyclic saturated ring system contains 1 or 2 N atoms, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b), (c) and (d) 
                         
wherein D is optionally substituted with one or more R 3 . Said substituent(s) R 3 , if present, can be placed on any available position, including on the N atom.
 
     In another embodiment, L 2  is C 1-4  alkylene (preferably linear C 1-4  alkylene, more preferably —CH 2 — or —CH 2 CH 2 —) and D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b), (c) 
                         
wherein D is optionally substituted with one or more R 3 . Said substituent(s) R 3 , if present, can be placed on any available position, including on the N atom.
 
     In a compound of formula I, Ia, Ia-1, Ib or Ic, each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea. In one embodiment, each R 3  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea. In another embodiment, each R 3  is independently selected from C 1-8  alkyl, halo, C 1-8  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, each R 3  is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     The substituents of the cyclopropyl moiety -A-B and —NH-L 2 -D in a compound of formula I, Ia, Ib or Ic are preferably in the trans-configuration. Thus, in one embodiment, the invention provides a compound of formula I (including a compound Ia, Ib or Ic) wherein the groups -A-B and —NH-L 2 -D are in trans configuration. In a preferred embodiment, the invention provides a compound of formula Ia wherein the groups -A-B and —NH-L 2 -D are in trans configuration, which is a compound of formula Ia-1: 
                         
wherein the groups and variables of formula Ia-1, including A, B, D, E, L 1 , L 2 , R 1 , R 2  and R 3 , are as defined above in relation to a compound of formula I and Ia and in the various preferred embodiments for a compound of formula I and Ia described above. The above chemical representation for a compound of formula Ia-1 does not intend to indicate absolute stereochemistry of the two chiral centers on the cyclopropyl ring, but only their relative stereochemistry (which is trans). Thus a compound of formula Ia-1 therefore relates to individual optically active trans isomers as well as mixtures of trans-isomers.
 
     In one embodiment, the invention provides a compound of formula I wherein each R w , R x , R y  and R z  is independently selected from hydrogen, fluoro and C 1-4  alkyl, preferably from hydrogen, fluoro and methyl. 
     In another embodiment, the invention provides a compound of formula I wherein each R w , R x , R y  and R z  is independently selected from hydrogen and fluoro. 
     In another embodiment, the invention provides a compound of formula I wherein R w  is fluoro and each R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R w  is fluoro and each R x , R y  and R z  is hydrogen. 
     In another embodiment, the invention provides a compound of formula I wherein R z  is fluoro and each R w , R x  and R y  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R z  is fluoro and each R w , R x  and R y  is hydrogen. 
     In another embodiment, the invention provides a compound of formula I wherein R w  and R z  are fluoro and each R x  and R y  is independently selected from hydrogen, halo and C 1-4  alkyl; preferably, R w  and R z  are fluoro and each R x  and R y  is hydrogen. 
     In a preferred embodiment, the invention provides a compound of formula I wherein R w  is selected from hydrogen, halo and C 1-4  alkyl, preferably from hydrogen, fluoro and methyl, and each R x , R y  and R z  is hydrogen. 
     In a more preferred embodiment, the invention provides a compound of formula I wherein each R w , R x , R y  and R z  is hydrogen, i.e. a compound of formula Ia: 
     
       
         
         
             
             
         
       
     
     In another embodiment, the invention provides a compound of formula I wherein each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl with the proviso that at least one is not hydrogen, i.e. a compound of formula Ib. 
     In another embodiment, the invention provides a compound of formula I wherein R w  is selected from halo and C 1-4  alkyl, preferably from fluoro and methyl, and each R x , R y  and R z  is hydrogen, i.e. a compound of formula Ic. Preferably, in a compound of formula Ic R w  is methyl. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein L 2  is a bond or linear C 1-4  alkylene, preferably L 2  is a bond or linear C 1-2  alkylene. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein L 2  is a bond. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein L 2  is CH 2 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein L 2  is CH 2 CH 2 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) contains at least one N atom,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and 
             (ii) a 7- to 15-membered saturated polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1 -4 alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, 
     wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, 
     wherein the polycyclic ring system contains 1 or 2 N atoms, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, the invention provides a compound of formula I. Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; and 
     D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b), (c) and (d) 
                         
wherein D is optionally substituted with one or more R 3 .
 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a cyclic group selected from: 
     
         
         
           
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (iii) or (iv) contains at least one N atom,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula i through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (iii) or (iv).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a cyclic group selected from: 
     
         
         
           
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 N atoms, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 2 N atoms,
 
wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, and
 
wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (iii) or (iv).
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula i through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein ring D is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 N atom, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, and 
     wherein ring D is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is CH 2 ; and 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is CH 2 CH 2 ; and 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 . In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is 4-piperidinyl. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a group of formula: 
     
       
         
         
             
             
         
       
     
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is 3-azetidinyl optionally substituted with one or more R 3 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, 
     wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, 
     wherein one or more S atoms in D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a 7- to 15-membered saturated polycyclic ring system which comprises at least one heterocyclic ring, 
     wherein the polycyclic saturated ring system contains 1 or 2 N atoms, 
     wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
     wherein one or more ring C atoms in D are optionally oxidized to form CO groups, and 
     wherein D is optionally substituted with one or more R 3 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; and 
     D is a 7- to 15-membered saturated polycyclic ring system selected from a group of formula (a), (b), (c) and (d), preferably from a group of formula (a), (b) and (c): 
                         
wherein D is optionally substituted with one or more R 3 .
 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein A is phenyl, naphthyl or monocyclic heteroaryl, wherein said phenyl, naphthyl or monocyclic heteroaryl is optionally substituted with one or more (e.g., one or two) R 1 . In a more preferred embodiment, A is phenyl, naphthyl, pyridyl, thiophenyl, pyrrolyl, furanyl, or thiazolyl, wherein A is optionally substituted with one or more R 1 . More preferably, A is phenyl, naphthyl, pyridyl or thiazolyl, wherein A is optionally substituted with one or more R 1 . Still more preferably, A is phenyl, 2-naphthyl, 3-pyridyl or 5-thiazolyl, wherein A is optionally substituted with one or more R 1 . In one embodiment, A is phenyl optionally substituted with one or more R 1 . In another embodiment, A is naphthyl, preferably 2-naphthyl, optionally substituted with one or more R 1 . In another embodiment, A is pyridyl, preferably 3-pyridyl, optionally substituted with one or more R 1 . In another embodiment, A is thiazolyl, preferably 5-thiazolyl, optionally substituted with one or more R 1 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein A is phenyl or monocyclic heteroaryl, wherein said phenyl or said monocyclic heteroaryl is optionally substituted with one or more R 1 . In a more preferred embodiment, A is phenyl, pyridyl, thiophenyl, pyrrolyl, furanyl, or thiazolyl, wherein A is optionally substituted with one or more R 1 . More preferably, A is phenyl, pyridyl or thiazolyl, wherein A is optionally substituted with one or more R 1 . In one embodiment, A is phenyl. In another embodiment, A is monocyclic heteroaryl. In another embodiment, A is pyridyl, thiophenyl, pyrrolyl, furanyl, or thiazolyl. In another embodiment, A is 3-pyridyl. In another embodiment, A is 5-thiazolyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein A is phenyl optionally substituted with one or more R 1 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein A is naphthyl (e.g. 2-naphthyl) optionally substituted with one or more R 1 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein A is heteroaryl optionally substituted with one or more R 1 . Preferably, A is monocyclic heteroaryl optionally substituted with one or more R 1 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; 
     B is hydrogen, R 1  or -L 1 -E; 
     E is phenyl optionally substituted with one or more R 2 ; and 
     L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl, naphthyl or monocyclic heteroaryl, wherein said phenyl, said naphthyl or said monocyclic heteroaryl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl or monocyclic heteroaryl, wherein said phenyl or said monocyclic heteroaryl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is heteroaryl, wherein said heteroaryl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is monocyclic heteroaryl, wherein said monocyclic heteroaryl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloakyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl, pyridyl or thiazolyl (preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6  cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is naphthyl, wherein said naphthyl is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In the above embodiment, preferably each R 1  is independently selected from C 1-8  alkyl, amino, amido, hydroxyl, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, carbamate, and urea. In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl (e.g. methyl), haloC 1-4  alkyl (e.g. trifluoromethyl), C 1-4  alkoxy (e.g. methoxy) and C 3-6  cycloalkyl (e.g. cyclopropyl). In another preferred embodiment, each R 1  is independently selected from halo, C 1-4  alkyl and C 3-6 cycloalkyl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl, naphthyl or monocyclic heteroaryl; and 
     B is hydrogen. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl, pyridyl or thiazolyl (preferably phenyl, 3-pyridyl or 5-thiazolyl); and 
     B is hydrogen. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl; and 
     B is hydrogen. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is naphthyl, preferably 2-naphthyl; and 
     B is hydrogen. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is heteroaryl, preferably monocyclic heteroaryl; and 
     B is hydrogen. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, and more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein said phenyl or said monocyclic heteroaryl is optionally substituted with one or more R 1 ; and 
     B is -L 1 -E. 
     In the above embodiment preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is -L 1 -E. 
     In the above embodiment preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is phenyl; and 
     B is -L 1 -E. 
     In the above embodiment preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     A is 3-pyridyl; and 
     B is -L 1 -E. 
     In the above embodiment preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1 -4 alkylene, —(CH 2 ) x —NH—, —SO 2 NH— or —SO 2 N(CH 3 )—, wherein x is 1, 2, 3 or 4; 
     preferably L 1  is —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene, or —CH 2 —NH, and more preferably L 1  is —O—, —NH— or —CH 2 —NH—; and 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein the groups —CH 2 —NH— and —CH 2 —O— are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group; and 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein the groups —CH 2 —NH— and —CH 2 —O— are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group; and 
     E is phenyl optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond or —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group; and 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein:
 
B is -L-E;
 
L 1  is a bond; and
 
E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 .
 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond; and 
     E is aryl, pyridinyl, thiophenyl, pyrrolyl, furanyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolyl, indolyl, indazolyl, imidazolyl or benzimidazolyl, wherein said aryl, said pyridinyl, said thiophenyl, said pyrrolyl, said furanyl, said thiazoyl, said oxazolyl, said isoxazolyl, said oxadiazolyl, said thiadiazolyl, said triazinyl, said pyridazinyl, said pyrazinyl, said pyrimidinyl, said quinolyl, said indolyl, said indazolyl, said imidazolyl or said benzimidazolyl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond, and 
     E is aryl (preferably phenyl), wherein said aryl is optionally substituted with one or more R 2    
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond; and 
     E is pyridinyl optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 1  is a bond; and 
     E is aryl or heteroaryl. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is a bond; 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; and 
     each R 2  is independently selected from hydroxyl, halo, haloC 1-8  alkyl and N-sulfonamido. 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group; and 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group; and 
     E is heteroaryl (preferably monocyclic heteroaryl, more preferably pyridinyl), wherein said heteroaryl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is —CH 2 —O—, wherein the group —CH 2 —O— is linked to ring A through the O atom and to ring E through the —CH 2 — group; and 
     E is phenyl optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     B is -L 1 -E; 
     L 1  is —NH— or —CH 2 —NH—, wherein the group —CH 2 —NH— is linked to ring A through the N atom and to ring E through the —CH 2 — group; and 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 . 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is phenyl, pyridyl or thiazolyl (preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ;
 
B is hydrogen, R 1  or -L 1 -E;
 
E is phenyl optionally substituted with one or more R 2 ; and
 
L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is aryl or heteroaryl, wherein A is optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In another embodiment, the invention provides a compound of formula I, ala-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) s optionally substituted with one or more R 3 ;
 
A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, and more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is phenyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is naphthyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is phenyl; and
 
B is hydrogen.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula i through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 1 ; and
 
B is -L 1 -E.
 
           
         
       
    
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S,
 
wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom,
 
wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups,
 
wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and
 
wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is -L 1 -E.
 
           
         
       
    
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —C 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of cyclic group (i) or (ii). 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ;
 
B is hydrogen, R 1  or -L 1 -E;
 
E is phenyl optionally substituted with one or more R 2 ; and
 
L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the 0 atom and to ring E through the —CH 2 — group.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , i present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is naphthyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl; and
 
B is hydrogen.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, heteroatoms independently selected from N, O and S, preferably containing 1 heteroatom selected from N, O and S, and more preferably containing 1 N atom, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is -L 1 -E.
 
           
         
       
    
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment of the above embodiments, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; 
     B is hydrogen, R 1  or -L 1 -E; 
     E is phenyl optionally substituted with one or more R 2 ; and 
     L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond, 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is naphthyl optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl; and 
     B is hydrogen. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is naphthyl; and 
     B is hydrogen. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is aryl or heteroaryl, wherein said aryl o said heteroaryl is optionally substituted with one or more R 1 ; and 
     B is -L 1 -E. 
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment of the above embodiments, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is a bond; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is -L 1 -E. 
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment of the above embodiments, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ;
 
B is hydrogen, R 1  or -L 1 -E;
 
E is phenyl optionally substituted with one or more R 2 ;
 
L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the 0 atom and to ring E through the —CH 2 — group.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, ala-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is naphthyl optionally substituted with one or more R 1 ; and
 
B is hydrogen or R 1 .
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R, if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl; and
 
B is hydrogen.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is naphthyl; and
 
B is hydrogen.
 
           
         
       
    
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2, preferably 1, heteroatoms independently selected from N, O and S, 
     
         
         
           
             wherein D is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in ring D are optionally oxidized to form CO groups, 
             wherein one or more S atoms in ring D, if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein ring D is optionally substituted with one or more R 3 ;
 
A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and
 
B is -L 1 -E.
 
           
         
       
    
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment of the above embodiments, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; 
     B is hydrogen, R 1  or -L 1 -E; 
     E is phenyl optionally substituted with one or more R 2 ; 
     L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or monocyclic heteroaryl (preferably phenyl, pyridyl or thiazolyl, more preferably phenyl, 3-pyridyl or 5-thiazolyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is naphthyl optionally substituted with one or more R 1 ; and 
     B is hydrogen or R 1 . 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl; and 
     B is hydrogen. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is naphthyl; and 
     B is hydrogen. 
     In a more specific embodiment, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In another embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) wherein: 
     L 2  is C 1-4  alkylene, preferably linear C 1-4  alkylene, more preferably linear C 1-2  alkylene; 
     D is piperidinyl, preferably 4-piperidinyl, wherein said piperidinyl is linked to the remainder of the compound of Formula I through a ring C atom, and 
     wherein said piperidinyl is optionally substituted with one or more R 3 ; 
     A is phenyl or pyridyl (preferably phenyl or 3-pyridyl), wherein A is optionally substituted with one or more R 1 ; and 
     B is -L 1 -E. 
     In the above embodiment, preferably L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. In a more specific embodiment, E is phenyl optionally substituted with one or more R 2  and L 1  is a bond, —O—, —NH—, —CH 2 —NH—, or —CH 2 —O—, wherein said —CH 2 —NH— or —CH 2 —O— groups are linked to ring A through the N or O atom, respectively, and are linked to ring E through the —CH 2 — group. Preferably, L 1  is a bond or —CH 2 —O—, wherein said —CH 2 —O— group is linked to ring A through the O atom and to ring E through the —CH 2 — group. 
     In a more specific embodiment of the above embodiments, said substituent(s) R 3 , if present, are placed on ring C atom(s) of ring D. In a further specific embodiment, each R 3 , if present, is independently selected from C 1-4  alkyl, halo, C 1-4  alkoxy, hydroxyl, amino, and amido. 
     In a further embodiment, the invention provides a compound of formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) selected from:
     N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   (Trans)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   N-((trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   (Trans)-2-phenyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine;   (Trans)-2-(4′-chloro-[1,1′-biphenyl]-4-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine;   N-((trans)-2-(pyridin -3-y)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(3-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (Trans)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-y)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(3-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (Trans)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   N-((trans)-2-phenylcyclopropyl)piperidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)piperidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-3-amine;   N-((trans)-2-phenylcyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-phenylcyclopropyl)azetidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)azetidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)azetidin-3-amine;   N-((trans)-2-phenylcyclopropyl)azepan-3-amine;   N-((trans)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine;   N-((trans)-2-phenylcyclopropyl)-3-azabicyclo[3.2.1]octan-8-amine;   N-((trans)-2-phenylcyclopropyl)decahydroquinolin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1,2,3,4-tetrahydroquinolin-4-amine;   N-((trans)-2-phenylcyclopropyl)-3-azaspiro[5.5]undecan-9-amine;   N-((trans)-2-phenylcyclopropyl)-2-azaspiro[4.5]decan-8-amine;   N-((trans)-2-phenylcyclopropyl)-2,3-dihydrospiro[indene-1,4′-piperidin]-3-amine;   N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1S,2S)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-(thiazol-5-yl)cyclopropyl)piperid in-4-amine;   N-((1S,2R)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   (1S,2R)-2-phenyl-N-(piperid in-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(piperid in-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1S,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-y)ethyl)-2-(3-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   N-((trans)-2-phenylcyclopropyl)-7-azaspiro[3.5]nonan-2-amine;   N-(2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-(2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-(2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-(2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine;   N-(2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-(2-methyl-2-phenylcyclopropyl)piperidin-4-amine;   N-(6-methoxy-4′-((trans)-2-(piperid in-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)methanesulfonamide;   N-(4′-((trans)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide;   1-(methylsulfonyl)-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-(4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)piperidin-1-yl)ethanone;   4-(((trans)-2-(4 bromophenyl)cyclopropyl)amino)piperidine-1-carboxamide;   N-((trans)-2-(4-bromophenyl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   2,2,6,6-tetramethyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-methyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-isopropyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)piperidin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1-(pyridin-4-yl)piperidin-4-amine;   4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide;   N-((trans)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1S,2S)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-fluoro-2-phenylcyclopropyl) piperidin-4-amine;   N-((trans)-2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-methyl-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine;   (Trans)-2-phenyl-N-(pyrrolidin-3-ylmethyl)cyclopropanamine;   (Trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(azetidin-3-ylmethyl)-2-phenylcyclopropanamine;   (Trans)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(4-(pyridin-3-yl)phenyl)cyclopropanamine;   (Trans)-2-(4-(1H-pyrazol-5-yl)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-2-(naphthalen-2-yl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (trans)-2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (trans)-2-(4-(benzyloxy)phenyl)-N-((1-methyl piperidin-4-yl)methyl)cyclopropanamine; as well as salts and solvates thereof (including also pharmaceutically acceptable salts and solvates thereof).   

     Moreover, the invention provides the following compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1), in which L 2  is a bond:
     N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   N-((trans)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperid in-4-amine;   N-((trans)-2-phenylcyclopropyl)piperidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-3-amine;   N-((trans)-2-phenylcyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)pyrrolidin-3-amine;   N-((trans)-2-phenylcyclopropyl)azetidin-3-amine;   N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)azetidin-3-amine;   N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)azetidin-3-amine;   N-((trans)-2-phenylcyclopropyl)azepan-3-amine;   N-((trans)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine;   N-((trans)-2-phenylcyclopropyl)-3-azabicyclo[3.2.1]octan-8-amine;   N-((trans)-2-phenylcyclopropyl)decahydroquinolin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1,2,3,4-tetrahydroquinolin-4-amine;   N-((trans)-2-phenylcyclopropyl)-3-azaspiro[5.5]undecan-9-amine;   N-((trans)-2-phenylcyclopropyl)-2-azaspiro[4.5]decan-8-amine;   N-((trans)-2-phenylcyclopropyl)-2,3-dihydrospiro[indene-1,4′-piperidin]-3-amine;   N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1S,2S)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   N-(1R,2S)-2-(3′-(trifluoromethyl) -[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-phenylcyclopropyl)-7-azaspiro[3.5]nonan-2-amine;   N-(2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-(2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-(2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-(2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine;   N-(2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-(2-methyl-2-phenylcyclopropyl)piperidin-4-amine;   N-(6-methoxy -4′-((trans)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)methanesulfonamide;   N-(4′-((trans)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide;   1-(methylsulfonyl)-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-(4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)piperidin-1-yl)ethanone;   4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)piperidine-1-carboxamide;   N-((trans)-2-(4-bromophenyl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   2,2,6,6-tetramethyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-methyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   1-isopropyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)piperidin-4-amine;   N-((trans)-2-phenylcyclopropyl)-1-(pyridin-4-yl)piperidin-4-amine;   4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide;   N-((trans)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1S,2S)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-methyl-2-phenylcyclopropyl)piperidin-4-amine;   N-((trans)-2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-((trans)-2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine; as well as salts and solvates thereof (including also pharmaceutically acceptable salts and solvates).   

     The invention further provides the following compounds of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1), in which L 2  is C 1-4  alkylene:
     (Trans)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (Trans)-2-phenyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine;   (Trans)-2-(4′-chloro-[1,1′-biphenyl]-4-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (Trans)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (Trans)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1S,2S)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1S,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (Trans)-2-phenyl-N-(pyrrolidin-3-ylmethyl)cyclopropanamine;   (Trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(azetidin-3-ylmethyl)-2-phenylcyclopropanamine;   (Trans)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-N-(piperidin-4-ylmethyl)-2-(4-(pyridin-3-yl)phenyl)cyclopropanamine;   (Trans)-2-(4-(1H-pyrazol-5-yl)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (Trans)-2-(naphthalen-2-yl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (trans)-2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (trans)-2-(4-(benzyloxy)phenyl)-N-((1-methyl piperidin-4-yl)methyl)cyclopropanamine; as well as salts and solvates thereof (including also pharmaceutically acceptable salts and solvates).   

     In a further embodiment, the invention provides a compound of formula I selected from:
     N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   N-((i R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine;   (S)—N-((1S,2R)-2-phenylcyclopropyl)piperidin-3-amine;   (R)—N-((1S,2R)-2-phenylcyclopropyl)piperidin-3-amine;   (S)—N-((1R,2S)-2-phenylcyclopropyl)piperidin-3-amine;   (R)—N-((1R,2S)-2-phenylcyclopropyl)piperidin-3-amine;   (S)—N-((1S,2R)-2-phenylcyclopropyl)pyrrolidin-3-amine;   (R)—N-((1S,2R)-2-phenylcyclopropyl)pyrrolidin-3-amine;   (S)—N-((1R,2S)-2-phenylcyclopropyl)pyrrolidin-3-amine;   (R)—N-((1R,2S)-2-phenylcyclopropyl)pyrrolidin-3-amine;   N-((1S,2R)-2-phenylcyclopropyl)azetidin-3-amine;   N-(1R,1S)-2-phenylcyclopropyl)azetidin-3-amine;   N-((1S,2R)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)azetidin-3-amine;   N-((1R,2S)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)azetidin-3-amine;   N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)azetidin-3-amine;   N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)azetidin-3-amine;   N-((1R,2S)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine;   N-((1S,2R)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine;   N-((1R,2S)-2-phenylcyclopropyl)-3-azabicyclo[3.2.1]octan-8-amine;   N-((1S,2R)-2-phenylcyclopropyl)-3-azabicyclo[3.2.1]octan-8-amine;   N-(1R,2S)-2-phenylcyclopropyl)-3-azaspiro[5.5]undecan-9-anine;   N-((1S,2R)-2-phenylcyclopropyl)-3-azaspiro[5.5]undecan-9-amine;   N-((1S,2R)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine;   N-((1S,2S)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-(thiazol-5-yl)cyclopropyl)piperid in-4-amine;   N-((1S,2R)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine;   N-((18S,2R)-2-phenylcyclopropyl)-7-azaspiro[3.5]nonan-2-amine;   N-((1R,2S)-2-phenylcyclopropyl)-7-azaspiro[3.5]nonan-2-amine;   N-(6-methoxy-4′-((1R,2S)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-y)methanesulfonamide;   N-(6-methoxy-4′-((1S,2R)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)methanesulfonamide;   N-(4′-((1R,2S)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide;   N-(4′-((1S,2R)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1-biphenyl]-3-yl)propane-2-sulfonamide;   1-(4-(((1R,2S)-2-(4-bromophenyl)cyclopropyl)amino)piperidin-1-yl)ethanone;   1-(4-(((1S,2R)-2-(4-bromophenyl)cyclopropyl)amino)piperidin-1-yl)ethanone;   4-(((1R,2S)-2-(4-bromophenyl)cyclopropyl)amino)piperidine-1-carboxamide;   4-(((1S,2R)-2-(4-bromophenyl)cyclopropyl)amino)piperidine-1-carboxamide;   N-((1R,2S)-2-(4-bromophenyl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   N-((1S,2R)-2-(4-bromophenyl)cyclopropyl)tetrahydro-2H-pyran-4-amine;   2,2,6,6-tetramethyl-N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   2,2,6,6-tetramethyl-N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   1-methyl-N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   1-methyl-N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   1-isopropyl-N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine;   1-isopropyl-N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-phenylcyclopropyl)-1-(pyridin-4-yl)piperidin-4-amine;   N-((1S,2R)-2-phenylcyclopropyl)-1-(pyridin-4-yl)piperidin-4-amine;   4-(((1R,2S)-2-(4-bromophenyl)cyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide;   4-(((1S,2R)-2-(4-bromophenyl)cyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide;   N-((1S,2S)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2R)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(o-tolyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine;   N-((1R,2S)-2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine;   N-((1S,2R)-2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine;
 
as well as salts and solvates thereof (including also pharmaceutically acceptable salts and solvates).
   

     The present invention furthermore provides a compound of formula I selected from:
     (1S,2R)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1S,2S)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine;   (1S,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1R,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine;   (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N—((S)-pyrrolidin-3-ylmethyl)cyclopropanamine;   (1S,2R)-2-phenyl-N—((R)-pyrrolidin-3-ylmethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N—((S)-pyrrolidin-3-ylmethyl)cyclopropanamine;   (1R,2S)-2-phenyl-N—((R)-pyrrolidin-3-ylmethyl)cyclopropanamine;   (1R,2S)-2-(4-((2-fluorobenzyl)oxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-(4-((2-fluorobenzyl)oxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)—N-(azetidin-3-ylmethyl)-2-phenylcyclopropanamine;   (1S,2R)—N-(azetidin-3-ylmethyl)-2-phenylcyclopropanamine;   (1R,2S)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)—N-(piperidin-4-ylmethyl)-2-(4-(pyridin-3-yl)phenyl)cyclopropanamine;   (1S,2R)—N-(piperidin-4-ylmethyl)-2-(4-(pyridin-3-yl)phenyl)cyclopropanamine;   (1R,2S)-2-(4-(1H-pyrazol-5-yl)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-(4-(1H-pyrazol-5-yl)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-(naphthalen-2-yl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1S,2R)-2-(naphthalen-2-yl)-N-(piperidin-4-ylmethyl)cyclopropanamine;   (1R,2S)-2-(4-(benzyloxy)phenyl)-N-((1-methylpiperidin-4-yl)methyl)cyclopropanamine;   (1S,2R)-2-(4-(benzyloxy)phenyl)-N-((1-methylpiperidin-4-yl)methyl)cyclopropanamine;
 
as well as salts and solvates thereof (including also pharmaceutically acceptable salts and solvates).
   

     The invention also relates to any one or any subgroup of the compounds listed above. The invention likewise relates to a pharmaceutically acceptable salt, preferably a hydrochloride salt (such as, e.g., a monohydrochloride salt, a dihydrochloride salt or, where applicable, a trihydrochloride salt), of any of the compounds listed above. 
     It is preferred that the compound of Formula I, Ia or Ia-1 is not 1-methyl-N-(2-phenylcyclopropyl)-4-piperidinamine or a salt or solvate thereof. Accordingly, in all of the embodiments described herein, the compound Formula I, Ia or Ia-1 for use as a medicament as well as for use in the treatment or prevention of cancer, a neurological disease or a viral infection is preferably not 1-methyl-N-(2-phenylcyclopropyl)-4-piperidinamine or a salt or solvate thereof. 
     Preferred embodiments of the compounds of Formula I, Ia, Ia-1, Ib and Ic for use in the compositions and methods of the invention are as defined herein above. 
     The present invention also provides compounds of Formula I, Ia or Ia-1, as defined and described herein above, including also compounds as defined in any of the preferred embodiments of Formula I, Ia or Ia-1 described herein, with the proviso that the following compounds are excluded:
     1-(1-methylethyl)-N-(2-phenylcyclopropyl)-3-Pyrrolidinamine;   4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran-4-carboxylic acid 1,1-dioxide;   N-(2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)-4-Piperidinamine;   1-(3-methyl-2-buten-1-yl)-N-(2-phenylcyclopropyl)-4-Piperidinamine;   4-[(2-phenylcyclopropyl)amino]-1-Piperidinecarboxylic acid ethyl ester;   1-[4-[(2-phenylcyclopropyl)amino]-1-piperidinyl]-ethanone;   hexahydro-3-[(2-phenylcyclopropyl)amino]-2H-azepin-2-one;   1-cyclopropyl-3-[(2-phenylcyclopropyl)amino]-2,5-pyrrolidinedione;   3-[(2-phenylcyclopropyl)amino]-1-propyl-2,5-pyrrolidinedione;   1-(1-methylethyl)-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione;   1-(1-methylpropyl)-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione;   1,2,5-trimethyl-N-(2-phenylcyclopropyl)-4-Piperidinamine;   3-((2-phenylcyclopropyl)amino)tetrahydrothiophene 1,1-dioxide;   4-[(2-phenylcyclopropyl)amino]-1-piperidinecarboxamide;   3-hydroxy-4-((2-phenylcyclopropyl)amino)tetrahydrothiophene 1,1-dioxide;   tetrahydro-4-[(2-phenylcyclopropyl)amino]-2H-pyran-4-carboxylic acid;   4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide;   N-(2-phenylcyclopropyl)-1-(2-propyn-1-yl)-4-piperidinamine;   1-ethyl-N-(2-phenylcyclopropyl)-4-piperidinamine;   1-ethyl-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione;   4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran-4-carboxylic acid;   N-(2-phenylcyclopropyl)-1-propyl-4-piperidinamine;   3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione;   tetrahydro-3-[(2-phenylcyclopropyl)amino]-3-Thiophenecarboxylic acid;   tetrahydro-N-(2-phenylcyclopropyl)-2H-Thiopyran-4-amine 1-oxide;   1-(1-methylethyl)-N-(2-phenylcyclopropyl)-4-piperidinamine;   1-methyl-3-[(2-phenylcyclopropyl)amino]-2,5-pyrrolidinedione;   tetrahydro-3-[(2-phenylcyclopropyl)amino]-2H-thiopyran-3-carboxylic acid;   tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-4-amine;   N-(2-phenylcyclopropyl)-3-piperidinamine;   tetrahydro-4-[(2-phenylcyclopropyl)amino]-3-furanol;   N-(2-phenylcyclopropyl)-4-piperidinamine;   tetrahydro-N-(2-phenylcyclopropyl)-2H-thiopyran-4-amine;   tetrahydro-N-(2-phenylcyclopropyl)-3-thiophenamine;   1-methyl-N-(2-phenylcyclopropyl)-4-piperidinamine;   3-methoxy-N-[[5-[[4-[[(1S,2R)-2-phenylcyclopropyl]amino]-1-piperidinyl]sulfonyl]-2-thienyl]methyl]-benzamide;   N-(2-phenylcyclopropyl)-1,4-dioxaspiro[4.5]decan-8-amine;   8-methyl-N-(2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine;   N-(2-phenylcyclopropyl)-1-azabicyclo[2.2.2]octan-3-amine;   6-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine;   8-fluoro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine;   3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine;   5-amino-1,3-dihydro-6-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzopyran-4-amine;   6-bromo-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzopyran-4-amine;   2,3-dihydro-3-[(2-phenylcyclopropyl)amino]-6-benzofuranol;   2,3-dihydro-N-(2-phenylcyclopropyl)-benzo[b]thiophen-3-amine 1,1-dioxide;   2,3-dihydro-N6-(2-phenylcyclopropyl)-1,4-benzodioxin-6,7-diamine;   3,4-dihydro-N-(2-phenylcyclopropyl)-1H-2-benzothiopyran-4-amine;   7-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   1,3-dihydro-1-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   1,3-dihydro-7-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   6-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   5-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   7-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   6-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   4-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   4-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   5-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   1,3-dihydro-5-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   5-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   6-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one;   3-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-thieno[3,2-b]pyrrol-5-amine;   8-methoxy-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   8-methyl-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   8-ethoxy-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   8-fluoro-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   8-chloro-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine;   5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(2-phenylcyclopropyl)amino]-benzo[g]pteridine-2,4(3H,4aH)-dione;   1-ethyl-a-methyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine;   1-ethyl-a-methyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   a-methyl-N-(2-phenylcyclopropyl)-1-propyl-3-piperidinemethanamine;   tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-2-methanamine;   octahydro-N-(2-phenylcyclopropyl)-1H-indole-2-methanamine;   a-methyl-N-(2-phenylcyclopropyl)-1-propyl-4-piperidinemethanamine;   3-methyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine;   N-(2-phenylcyclopropyl)-2-piperidinemethanamine;   N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   a,1-dimethyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine;   N-(2-phenylcyclopropyl)-3-piperidinemethanamine;   4-methoxy-N-(2-phenylcyclopropyl)-2-pyrrolidinemethanamine;   N-(2-phenylcyclopropyl)-3-propy-3-pyrrolidinemethanamine;   N-(2-phenylcyclopropyl)-2-morpholinemethanamine;   4-ethyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   4-methyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   a,1-dimethyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   1-methyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine;   tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-4-methanamine;   3-methyl-N-(2-phenylcyclopropyl)-3-pyrrolidinemethanamine;   N-(2-phenylcyclopropyl)-2-pyrrolidinemethanamine;   tetrahydro-N-(2-phenylcyclopropyl)-3-furanmethanamine;   tetrahydro-N-(2-phenylcyclopropyl)-2-furanmethanamine;   N-(2-phenylcyclopropyl)-4-piperidineethanamine;   N-(2-phenylcyclopropyl)-2-pyrrolidineethanamine;   1-methyl-N-(2-phenylcyclopropyl)-2-piperidineethanamine; and   N-(2-phenylcyclopropyl)-3-piperidinepropanamine.   

     Accordingly, the invention relates to a compound of Formula I wherein: 
     A is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R 1 ; 
     B is H, R 1  or -L 1 -E; 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; 
     L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene; 
     L 2  is a bond and D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
 
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ;
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea; and
 
each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl;
 
or a salt or solvate thereof;
 
with the proviso that the following compounds are excluded:
 
           
         
         1-(1-methylethyl)-N-(2-phenylcyclopropyl)-3-Pyrrolidinamine; 
         4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran-4-carboxylic acid 1,1-dioxide; 
         N-(2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)-4-Piperidinamine; 
         1-(3-methyl-2-buten-1-yl)-N-(2-phenylcyclopropyl)-4-Piperidinamine; 
         4-[(2-phenylcyclopropyl)amino]-1-Piperidinecarboxylic acid ethyl ester; 
         1-[4-[(2-phenylcyclopropyl)amino]-1-piperidinyl]-ethanone; 
         hexahydro-3-[(2-phenylcyclopropyl)amino]-2H-azepin-2-one; 
         1-cyclopropyl-3-[(2-phenylcyclopropyl)amino]-2,5-pyrrolidinedione; 
         3-[(2-phenylcyclopropyl)amino]-1-propyl-2,5-pyrrolidinedione; 
         1-(1-methylethyl)-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione; 
         1-(1-methylpropyl)-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione; 
         1,2,5-trimethyl-N-(2-phenylcyclopropyl)-4-Piperidinamine; 
         3-((2-phenylcyclopropyl)amino)tetrahydrothiophene 1,1-dioxide; 
         4-[(2-phenylcyclopropyl)amino]-1-piperidinecarboxamide; 
         3-hydroxy-4-((2-phenylcyclopropyl)amino)tetrahydrothiophene 1,1-dioxide; 
         tetrahydro-4-[(2-phenylcyclopropyl)amino]-2H-pyran-4-carboxylic acid; 
         4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide; 
         N-(2-phenylcyclopropyl)-1-(2-propyn-1-yl)-4-piperidinamine; 
         1-ethyl-N-(2-phenylcyclopropyl)-4-piperidinamine; 
         1-ethyl-3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione; 
         4-((2-phenylcyclopropyl)amino)tetrahydro-2H-thiopyran-4-carboxylic acid; 
         N-(2-phenylcyclopropyl)-1-propyl-4-piperidinamine; 
         3-[(2-phenylcyclopropyl)amino]-2,5-Pyrrolidinedione; 
         tetrahydro-3-[(2-phenylcyclopropyl)amino]-3-Thiophenecarboxylic acid; 
         tetrahydro-N-(2-phenylcyclopropyl)-2H-Thiopyran-4-amine 1-oxide; 
         1-(1-methylethyl)-N-(2-phenylcyclopropyl)-4-piperidinamine; 
         1-methyl-3-[(2-phenylcyclopropyl)amino]-2,5-pyrrolidinedione; 
         tetrahydro-3-[(2-phenylcyclopropyl)amino]-2H-thiopyran-3-carboxylic acid; 
         tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-4-amine; 
         N-(2-phenylcyclopropyl)-3-piperidinamine; 
         tetrahydro-4-[(2-phenylcyclopropyl)amino]-3-furanol; 
         N-(2-phenylcyclopropyl)-4-piperidinamine; 
         tetrahydro-N-(2-phenylcyclopropyl)-2H-thiopyran-4-amine; 
         tetrahydro-N-(2-phenylcyclopropyl)-3-thiophenamine; 
         1-methyl-N-(2-phenylcyclopropyl)-4-piperidinamine; 
         3-methoxy-N-[[5-[[4-[[(1S,2R)-2-phenylcyclopropyl]amino]-1-piperidinyl]sulfonyl]-2-thienyl]methyl]-benzamide; 
         N-(2-phenylcyclopropyl)-1,4-dioxaspiro[4.5]decan-8-amine; 
         8-methyl-N-(2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine; 
         N-(2-phenylcyclopropyl)-1-azabicyclo[2.2.2]octan-3-amine; 
         6-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine; 
         8-fluoro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine; 
         3,4-dihydro-N-2-phenylcyclopropyl)-2H-1-benzothiopyran-4-amine; 
         5-amino-1,3-dihydro-6-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzopyran-4-amine; 
         6-bromo-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-1-benzopyran-4-amine; 
         2,3-dihydro-3-[(2-phenylcyclopropyl)amino]-6-benzofuranol; 
         2,3-dihydro-N-(2-phenylcyclopropyl)-benzo[b]thiophen-3-amine 1,1-dioxide; 
         2,3-dihydro-N6-(2-phenylcyclopropyl)-1,4-benzodioxin-6,7-diamine; 
         3,4-dihydro-N-(2-phenylcyclopropyl)-1H-2-benzothiopyran-4-amine; 
         7-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         1,3-dihydro-1-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         1,3-dihydro-7-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         6-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         5-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         7-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         6-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         4-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         4-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         5-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         1,3-dihydro-5-methyl-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         5-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         6-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-2H-indol-2-one; 
         3-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-2H-thieno[3,2-b]pyrrol-5-amine; 
         8-methoxy-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         8-methyl-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         8-ethoxy-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         8-fluoro-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         8-chloro-N-(2-phenylcyclopropyl)-5H-pyrimido[5,4-b]indol-4-amine; 
         5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(2-phenylcyclopropyl)amino]-benzo[g]pteridine-2,4(3H,4aH)-dione; 
         1-ethyl-a-methyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine; 
         1-ethyl-a-methy-N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         a-methyl-N-(2-phenylcyclopropyl)-1-propyl-3-piperidinemethanamine; 
         tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-2-methanamine; 
         octahydro-N-(2-phenylcyclopropyl)-1H-indole-2-methanamine; 
         a-methyl-N-(2-phenylcyclopropyl)-1-propyl-4-piperidinemethanamine; 
         3-methyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine; 
         N-(2-phenylcyclopropyl)-2-piperidinemethanamine; 
         N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         a, 1-dimethyl-N-(2-phenylcyclopropyl)-3-piperidinemethanamine; 
         N-(2-phenylcyclopropyl)-3-piperidinemethanamine; 
         4-methoxy-N-(2-phenylcyclopropyl)-2-pyrrolidinemethanamine; 
         N-(2-phenylcyclopropyl)-3-propyl-3-pyrrolidinemethanamine; 
         N-(2-phenylcyclopropyl)-2-morpholinemethanamine; 
         4-ethyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         4-methyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         a,1-dimethyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         1-methyl-N-(2-phenylcyclopropyl)-4-piperidinemethanamine; 
         tetrahydro-N-(2-phenylcyclopropyl)-2H-pyran-4-methanamine; 
         3-methyl-N-(2-phenylcyclopropyl)-3-pyrrolidinemethanamine; 
         N-(2-phenylcyclopropyl)-2-pyrrolidinemethanamine; 
         tetrahydro-N-(2-phenylcyclopropyl)-3-furanmethanamine; 
         tetrahydro-N-(2-phenylcyclopropyl)-2-furanmethanamine; 
         N-(2-phenylcyclopropyl)-4-piperidineethanamine; 
         N-(2-phenylcyclopropyl)-2-pyrrolidineethanamine; 
         1-methyl-N-(2-phenylcyclopropyl)-2-piperidineethanamine; and 
         N-(2-phenylcyclopropyl)-3-piperidinepropanamine. 
       
    
     Accordingly, the invention relates to a compound of Formula I, Ia or Ia-1, as defined and described herein above, including also compounds as defined in any of the preferred embodiments of Formula I, Ia or Ia-1 described herein, with the proviso that the following compounds are excluded:
     3-Pyrrolidinamine, 1-(1-methylethyl)-N-(2-phenylcyclopropyl)-;   2H-Thiopyran-4-carboxylic acid, tetrahydro-4-[(2-phenylcyclopropyl)amino]-, 1,1-dioxide;   4-Piperidinamine, N-(2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)-;   4-Piperidinamine, 1-(3-methyl-2-buten-1-yl)-N-(2-phenylcyclopropyl)-;   1-Piperidinecarboxylic acid, 4-[(2-phenylcyclopropyl)amino]-, ethyl ester;   Ethanone, 1-[4-[(2-phenylcyclopropyl)amino]-1-piperidinyl]-;   2H-Azepin-2-one, hexahydro-3-[(2-phenylcyclopropyl)amino]-;   2,5-Pyrrolidinedione, 1-cyclopropyl-3-[(2-phenylcyclopropyl)amino]-;   2,5-Pyrrolidinedione, 3-[(2-phenylcyclopropyl)amino]-1-propyl-;   2,5-Pyrrolidinedione, 1-(1-methylethyl)-3-[(2-phenylcyclopropyl)amino]-;   2,5-Pyrrolidinedione, 1-(1-methylpropyl)-3-[(2-phenylcyclopropyl)amino]-;   4-Piperidinamine, 1,2,5-trimethyl-N-(2-phenylcyclopropyl)-;   3-Thiophenamine, tetrahydro-N-(2-phenylcyclopropyl)-, 1,1-dioxide;   1-Piperidinecarboxamide, 4-[(2-phenylcyclopropyl)amino]-;   Thiophene-3-ol, tetrahydro-4-[(2-phenylcyclopropyl)amino]-, 1,1-dioxide; 2H-Pyran-4-carboxylic acid,   tetrahydro-4-[(2-phenylcyclopropyl)amino]-;   2H-Thiopyran-4-amine, tetrahydro-N-(2-phenylcyclopropyl)-, 1,1-dioxide;   4-Piperidinamine, N-(2-phenylcyclopropyl)-1-(2-propyn-1-yl)-;   4-Piperidinamine, 1-ethyl-N-(2-phenylcyclopropyl)-;   2,5-Pyrrolidinedione, 1-ethyl-3-[(2-phenylcyclopropyl)amino]-;   2H-Thiopyran-4-carboxylic acid, tetrahydro-4-[(2-phenylcyclopropyl)amino]-;   4-Piperidinamine, N-(2-phenylcyclopropyl)-1-propyl-;   2,5-Pyrrolidinedione, 3-[(2-phenylcyclopropyl)amino]-;   3-Thiophenecarboxylic acid, tetrahydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Thiopyran-4-amine, tetrahydro-N-(2-phenylcyclopropyl)-, 1-oxide;   4-Piperidinamine, 1-(1-methylethyl)-N-(2-phenylcyclopropyl)-;   2,5-Pyrrolidinedione, 1-methyl-3-[(2-phenylcyclopropyl)amino]-;   2H-Thiopyran-3-carboxylic acid, tetrahydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Pyran-4-amine, tetrahydro-N-(2-phenylcyclopropyl)-;   3-Piperidinamine, N-(2-phenylcyclopropyl)-;   3-Furanol, tetrahydro-4-[(2-phenylcyclopropyl)amino]-;   4-Piperidinamine, N-(2-phenylcyclopropyl)-;   2H-Thiopyran-4-amine, tetrahydro-N-(2-phenylcyclopropyl)-;   3-Thiophenamine, tetrahydro-N-(2-phenylcyclopropyl)-;   4-Piperidinamine, 1-methyl-N-(2-phenylcyclopropyl)-;   Benzamide, 3-methoxy-N-[[5-[[4-[[(1S,2R)-2-phenylcyclopropyl]amino]-1-piperidinyl]sulfonyl]-2-thienyl]methyl]-;   1,4-Dioxaspiro[4.5]decan-8-amine, N-(2-phenylcyclopropyl)-;   8-Azabicyclo[3.2.1]octan-3-amine, 8-methyl-N-(2-phenylcyclopropyl)-;   1-Azabicyclo[2.2.2]octan-3-amine, N-(2-phenylcyclopropyl)-;   2H-1-Benzothiopyran-4-amine, 6-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-;   2H-1-Benzothiopyran-4-amine, 8-fluoro-3,4-dihydro-N-(2-phenylcyclopropyl)-;   2H-1-Benzothiopyran-4-amine, 3,4-dihydro-N-(2-phenylcyclopropyl)-;   2H-Indol-2-one, 5-amino-1,3-dihydro-6-[(2-phenylcyclopropyl)amino]-;   2H-1-Benzopyran-4-amine, 3,4-dihydro-N-(2-phenylcyclopropyl)-;   2H-1-Benzopyran-4-amine, 6-bromo-3,4-dihydro-N-(2-phenylcyclopropyl)-;   -Benzofuranol, 2,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   Benzo[b]thiophen-3-amine, 2,3-dihydro-N-(2-phenylcyclopropyl)-, 1,1-dioxide;   1,4-Benzodioxin-6,7-diamine, 2,3-dihydro-N6-(2-phenylcyclopropyl)-;   1H-2-Benzothiopyran-4-amine, 3,4-dihydro-N-(2-phenylcyclopropyl)-;   2H-Indol-2-one, 7-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 1,3-dihydro-1-methyl-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 1,3-dihydro-7-methyl-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 6-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 5-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 7-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 6-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 4-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 4-bromo-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 5-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 1,3-dihydro-5-methyl-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 5-fluoro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Indol-2-one, 6-chloro-1,3-dihydro-3-[(2-phenylcyclopropyl)amino]-;   2H-Thieno[3,2-b]pyrrol-5-amine, 3-chloro-3,4-dihydro-N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, 8-methoxy-N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, 8-methyl-N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, 8-ethoxy-N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, 8-fluoro-N-(2-phenylcyclopropyl)-;   5H-Pyrimido[5,4-b]indol-4-amine, 8-chloro-N-(2-phenylcyclopropyl)-;   Benzo[g]pteridine-2,4(3H,4aH)-dione, 5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(2-phenylcyclopropyl)amino]-;   3-Piperidinemethanamine, 1-ethyl-a-methyl-N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, 1-ethyl-a-methyl-N-(2-phenylcyclopropyl)-;   3-Piperidinemethanamine, a-methyl-N-(2-phenylcyclopropyl)-1-propyl-;   2H-Pyran-2-methanamine, tetrahydro-N-(2-phenylcyclopropyl)-;   1H-indole-2-methanamine, octahydro-N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, a-methyl-N-(2-phenylcyclopropyl)-1-propyl-;   3-Piperidinemethanamine, 3-methyl-N-(2-phenylcyclopropyl)-;   2-Piperidinemethanamine, N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, N-(2-phenylcyclopropyl)-;   3-Piperidinemethanamine, a,1-dimethyl-N-(2-phenylcyclopropyl)-;   3-Piperidinemethanamine, N-(2-phenylcyclopropyl)-;   2-Pyrrolidinemethanamine, 4-methoxy-N-(2-phenylcyclopropyl)-;   3-Pyrrolidinemethanamine, N-(2-phenylcyclopropyl)-3-propyl-;   2-Morpholinemethanamine, N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, 4-ethyl-N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, 4-methyl-N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, a,1-dimethyl-N-(2-phenylcyclopropyl)-;   4-Piperidinemethanamine, 1-methyl-N-(2-phenylcyclopropyl)-;   2H-Pyran-4-methanamine, tetrahydro-N-(2-phenylcyclopropyl)-;   3-Pyrrolidinemethanamine, 3-methyl-N-(2-phenylcyclopropyl)-;   2-Pyrrolidinemethanamine, N-(2-phenylcyclopropyl)-;   3-Furanmethanamine, tetrahydro-N-(2-phenylcyclopropyl)-;   2-Furanmethanamine, tetrahydro-N-(2-phenylcyclopropyl)-;   4-Piperidineethanamine, N-(2-phenylcyclopropyl)-;   2-Pyrrolidineethanamine, N-(2-phenylcyclopropyl)-;   2-Piperidineethanamine, 1-methyl-N-(2-phenylcyclopropyl)-; and   3-Piperidinepropanamine, N-(2-phenylcyclopropyl)-.   

     The present invention further provides compounds of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1), as defined and described herein above, including also compounds as defined in any of the preferred embodiments of Formula I, Ia, Ia-1, Ib or Ic described herein, in which (i) A is aryl optionally substituted with one or more R 1  and B is -L 1 -E, or (ii) A is heteroaryl optionally substituted with one or more R 1  and B is H, R 1  or -L 1 -E. 
     Accordingly, the invention provides a compound of Formula I wherein: 
     A is aryl optionally substituted with one or more R 1 , and B is -L 1 -E, or 
     A is heteroaryl optionally substituted with one or more R 1 , and B is H, R 1  or -L 1 -E; 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; 
     L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene; 
     L 2  is a bond and D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
 
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ;
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea; and
 
each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl;
 
or a salt or solvate thereof.
 
           
         
       
    
     The present invention furthermore provides compounds of Formula I, Ia, Ib or Ic (preferably a compound of formula I or Ia, more preferably a compound of formula Ia), as defined and described herein above, including also compounds as defined in any of the preferred embodiments of Formula I, Ia, Ia-1, Ib or Ic described herein, in which the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration. For these compounds, it is preferred that the compound 5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(2-phenylcyclopropyl)amino]-benzo[g]pteridine-2,4(3H,4aH)-dione is excluded. 
     Accordingly, the invention provides a compound of Formula I wherein: 
     A is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R 1 ; 
     B is H, R 1  or -L 1 -E; 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; 
     L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene; 
     L 2  is a bond and D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
 
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3  
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl;
 
or a salt or solvate thereof;
 
wherein the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration,
 
and further wherein it is preferred that the compound 5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(2-phenylcyclopropyl)amino]-benzo[g]pteridine-2,4(3H,4aH)-dione is excluded.
 
           
         
       
    
     Accordingly, for the compounds of Formula I, Ia and Ia-1, in which the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration, it is preferred that the compound 5-ethyl-5,10-dihydro-3,7,8,10-tetramethyl-4a-[(trans-2-phenylcyclopropyl)amino]-benzo[g]pteridine-2,4(3H,4aH)-dione is excluded. 
     The present invention also provides compounds of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1), as defined and described herein above, including also compounds as defined in any of the preferred embodiments of Formula I, Ia, Ia-1, Ib or Ic described herein, in which the compound of formula I, la, Ia-1, Ib or Ic is an optically active stereoisomer. 
     Accordingly, the invention provides a compound of Formula I wherein: 
     A is aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R 1 ; 
     B is H, R 1  or -L 1 -E; 
     E is aryl or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with one or more R 2 ; 
     L 1  is a bond, —O—, —NH—, —N(C 1-4  alkyl)-, C 1-4  alkylene or heteroC 1-4 alkylene; 
     L 2  is a bond and D is a cyclic group selected from: 
     
         
         
           
             (i) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (ii) a 7- to 15-membered polycyclic ring system which comprises at least one saturated heterocyclic ring, wherein the polycyclic ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (i) or (ii) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (i) or (ii) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (i) or (ii), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (i) or (ii) is optionally substituted with one or more R 3 ;
 
or L 2  is C 1-4  alkylene and D is a cyclic group selected from:
 
             (iii) a 3- to 7-membered monocyclic saturated heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O and S, and 
             (iv) a 7- to 15-membered polycyclic saturated ring system which comprises at least one heterocyclic ring, wherein the polycyclic saturated ring system contains from 1 to 4 heteroatoms independently selected from N, O and S, 
             wherein the cyclic group (iii) or (iv) is linked to the remainder of the compound of Formula I through a ring C atom, 
             wherein one or more ring C atoms in the cyclic group (iii) or (iv) are optionally oxidized to form CO groups, 
             wherein one or more S atoms in the cyclic group (iii) or (iv), if present, are optionally oxidized to form independently SO groups or SO 2  groups, and 
             wherein the cyclic group (iii) or (iv) is optionally substituted with one or more R 3 ;
 
each R 1  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 2  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea;
 
each R 3  is independently selected from C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, cyclyl, amino, amido, hydroxyl, nitro, halo, haloC 1-8  alkyl, haloC 1-8  alkoxy, cyano, sulfinyl, sulfonyl, sulfonamide, C 1-8  alkoxy, acyl, carboxyl, O-carboxy, C-carboxy, carbamate and urea; and
 
each R w , R x , R y  and R z  is independently selected from hydrogen, halo and C 1-4  alkyl;
 
or a salt or solvate thereof;
 
wherein the compound of formula I is an optically active stereoisomer.
 
           
         
       
    
     The invention relates to compounds which are cyclopropylamino derivatives, so that cyclopropylimino compounds are not covered. Accordingly, compounds such as, e.g., (S,Z)—N-(2,3-dichlorophenyl)-3-oxo-1-(((1S,2R)-2-phenylcyclopropyl)imino)tetrahydro-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxamide, (S,Z)-tert-butyl 3-oxo-1-(((1S,2R)-2-phenylcyclopropyl)imino)tetrahydro-1H-oxazolo[3,4-a]pyrazine-7(3H)-carboxylate or 3H-Oxazolo[3,4-a]pyrazin-3-one, hexahydro-1-[[(1S,2R)-2-phenylcyclopropyl]imino]-, (8aS)-are not covered by the definition of a compound of formula I, Ia, Ia-1, Ib or Ic. 
     In a further aspect, the invention provides a method for identifying a compound which is a selective inhibitor of LSD1, the method comprising selecting or providing a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) and determining the ability of the said compound to inhibit LSD1 and MAO-A and/or MAO-B using assays such as the ones disclosed in more detail later on, wherein a compound that inhibits LSD1 to a greater extent than MAO-A and/or MAO-B is identified as a LSD1 selective inhibitor. LSD1 selective inhibitors have IC50 values for LSD1 which are lower than the IC50 value for MAO-A and/or MAO-B. Preferably, the IC50 values for LSD1 are two-fold lower than for MAO-A and/or MAO-B. In one aspect of this embodiment, the LSD1 IC50 value is at least 5-fold lower than the IC50 value for MAO-A and/or MAO-B. In one aspect of this embodiment, the LSD1 IC50 value is at least 10-fold lower than the IC50 value for MAO-A and/or MAO-B. Preferably, a selective LSD1 inhibitor exhibits an IC50 value for LSD1 that is &gt;50-fold, preferably &gt;100-fold lower than the IC50 value for MAO-A and/or MAO-B. 
     Asymmetric centers exist in the compounds of formula I, Ia, Ia-1, Ib and Ic disclosed herein. It should be understood that the invention encompasses all individual stereochemical isomeric forms of a compound of formula I, Ia, Ia-1, Ib and Ic, including diastereomeric, enantiomeric, and epimeric forms, as well as d-isomers and l-isomers ((+)-isomers and (−)-isomers)), and any mixtures thereof, including wholly or partially equilibrated mixtures. Individual stereoisomers of compounds of the invention can be prepared synthetically from commercially available chiral starting materials or by separation from mixtures of stereoisomers, as also shown in the Examples. Methods of separation of enantiomeric and diastereomeric mixtures are well known to one skilled in the art. For example, mixtures of diastereomers can be separated by conventional separation techniques such as recrystallization or chromatography. Mixtures of enantiomeric products can be separated by conversion to a mixture of diastereomers followed by separation using recrystallization or chromatographic techniques, direct separation of enantiomers on chiral chromatographic columns, or any other appropriate method of chiral resolution known in the art. Starting compounds of particular stereochemistry are either commercially available or can be made and resolved by techniques known in the art. 
     Additionally, the compounds disclosed herein may exist as geometric isomers. The present invention includes all cis, trans, syn, anti, entgegen (E), and zusammen (Z) isomers as well as the mixtures thereof. 
     Additionally, compounds may exist as tautomers; all tautomeric isomers are provided by this invention. 
     The compounds of the invention contain one or more basic nitrogen atoms and may therefore form salts with organic or inorganic acids. The compounds of the invention may also contain one or more acidic protons and therefore they may also form salts with bases. There is no limitation on the type of salt that can be used provided that these are pharmaceutically acceptable when used for therapeutic purposes. The salts of a compound of the invention can be obtained during the final isolation and purification of the compounds of the invention or can be obtained by treating a compound of formula I, Ia, Ia-1, Ib or Ic with a sufficient amount of the desired acid or base to give the corresponding salt in a conventional manner. All salts of the compounds of formula I, Ia, Ia-1, Ib or Ic, including pharmaceutically acceptable salts, are included within the scope of the invention. In one embodiment, a compound of formula I, Ia, Ia-1, Ib or Ic is provided in the form of a salt. In a more preferred embodiment, a compound of formula I, Ia, Ia-1, Ib or Ic is provided in the form of a pharmaceutically acceptable salt. In one embodiment, such pharmaceutically acceptable salt is a hydrochloride, for example a monohydrochloride, a dihydrochloride or a trihydrochloride. 
     Additionally, the compounds disclosed herein can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. Solvated forms with water are known as hydrates. In general, the solvated forms are considered equivalent to the unsolvated forms. The invention thus relates to the unsolvated and solvated forms of the compounds of formula I, Ia, Ia-1, Ib or Ic (or of any salt thereof). 
     The compounds of formula I, Ia, Ia-1, Ib and Ic may exist in different physical forms, i.e. amorphous and crystalline forms. Moreover, the compounds of the invention may have the ability to crystallize in more than one form, a characteristic which is known as polymorphism. Polymorphs can be distinguished by various physical properties well known in the art such as X-ray diffraction pattern, melting point or solubility. All physical forms of the compounds of the invention, including all polymorphic forms (also known as polymorphs) thereof, are included within the scope of the invention. 
     The present invention further covers all unlabeled and isotopically labeled forms of the compounds of formula I, Ia, Ia-1, Ib and Ic. In one embodiment, the invention relates to deuterated forms of the compounds of formula I, Ia and Ia-1. 
     The invention also relates to a compound of Formula I, Ia, Ia-1, Ib or Ic (preferably a compound of formula I, Ia, or Ia-1, more preferably a compound of formula Ia or Ia-1, and most preferably a compound of formula Ia-1) as described and defined herein, wherein the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration and further wherein the compound is optically active. As used herein, the term “optically active,” refers to the ability of a compound to rotate plane polarized light. 
     The invention, in another aspect, relates to a substantially pure, optically active stereoisomer of a compound of Formula I, Ia, Ia-1 Ib or Ic as described and defined herein, wherein the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration, or a pharmaceutically acceptable salt or solvate thereof, as well as its use as a medicament. As used herein, “substantially pure” means that there is 90 mole-% or greater of the desired stereoisomer and 10 mole-% or less of any other stereoisomer, preferably that there is 95 mole-% or greater of the desired stereoisomer and 5 mole-% or less of any other stereoisomer, more preferably, that there is 98 mole-% or greater of the desired stereoisomer and 2 mole-% or less of any other stereoisomer, still more preferably, that there is 99 mole-% or greater of the desired stereoisomer and 1 mole-% or less of any other stereoisomer, and even more preferably that there is 99.5 mole-% or greater of the desired stereoisomer and 0.5 mole-% or less of any other stereoisomer. The substantially pure, optically active stereoisomer of a compound of Formula I, Ia, Ia-1, Ib or Ic as described and defined herein, wherein the substituents -A-B and —NH-L 2 -D on the cyclopropyl moiety are in trans-configuration, is useful in treating or preventing a disease or disorder, particularly cancer, a neurological disease, or a viral infection. 
     Definitions 
     Any definition herein may be used in combination with any other definition to describe a composite structural group. By convention, the trailing element of any such definition is that which attaches to the parent moiety. 
     As used herein, the term “acyl” refers to a carbonyl attached to an alkenyl, alkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, or any other moiety where the atom attached to the carbonyl is carbon. Preferably, the term “acyl” refers to a group of formula —C(═O)R″, wherein R″ represents alkenyl, alkyl, aryl, cycloalkyl, heteroaryl or heterocyclyl. An “acetyl” group refers to a —C(═O)CH 3  group. An “alkylcarbonyl” or “alkanoyl” group refers to an alkyl group attached to the parent molecular moiety through a carbonyl group. Examples of such groups include, but are not limited to, methylcarbonyl or ethylcarbonyl. Examples of acyl groups include, but are not limited to, formyl, alkanoyl or aroyl. 
     As used herein, the term “alkenyl” refers to a straight-chain or branched-chain hydrocarbon group having one or more double bonds and containing from 2 to 20 carbon atoms. A C 2-8  alkenyl is an alkenyl group having from 2 to 8 carbon atoms. 
     As used herein, the term “alkoxy” refers to an alkyl ether group (ie a group of formula alkyl-O—), wherein the term alkyl is as defined below. Examples of suitable alkyl ether groups include, but are not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, or n-pentoxy. The term C 1-z  alkoxy refers to an alkoxy group wherein the alkyl moiety has from 1 to z carbon atoms; for example a C 1-8  alkoxy is an alkoxy group wherein the alkyl moiety is C 1-8  alkyl, i.e. a group of formula C 1-8  alkyl-O—. 
     As used herein, the term “alkyl” refers to a straight-chain or branched-chain alkyl group containing from 1 to 20 carbon atoms. A C 1-z  alkyl is an alkyl from 1 to z carbon atoms; thus, a C 1-8  alkyl has from 1 to 8 carbon atoms, a C 1-4  alkyl has from 1 to 4 carbon atoms and a C 1-2  alkyl has from 1 to 2 carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neo-pentyl, iso-amyl, hexyl, heptyl, octyl, or nonyl. 
     As used herein, the term “C 1-4  alkylene” refers to an C 1-4  alkyl group attached at two positions, i.e. an alkanediyl group. Examples include, but are not limited to, methylene, ethylene, propylene and butylene. Accordingly, the term “C 1-4  alkylene” may refer to a straight-chain or branched-chain alkylene group having from 1 to 4 carbon atoms. A “linear C 1-4  alkylene” refers to a straight chain alkylene group having from 1 to 4 carbon atoms, i.e. a —(CH 2 ) y — group wherein y is 1, 2, 3 or 4. 
     As used herein, the term “alkynyl” refers to a straight-chain or branched-chain hydrocarbon group having one or more triple bonds and containing from 2 to 20 carbon atoms. A C 2-8  alkynyl has from 2 to 8 carbon atoms. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl, 3-methylbutyn-1-yl, or hexyn-2-yl. 
     As used herein, the term “amido” refers to an amino group as described below attached to the parent molecular moiety through a carbonyl group (e.g., —C(═O)NRR′), or vice versa (—N(R)C(═O)R′). “Amido” encompasses “C-amido” and “N-amido” as defined herein. R and R′ are as defined herein. 
     As used herein, the term “C-amido” refers to a —C(═O)NRR′ group with R and R′ as defined herein. 
     As used herein, the term “N-amido” refers to a —N(R)C(═O)R′ group with R and R′ as defined herein. 
     As used herein, the term “amino” refers to —NRR′, wherein R and R′ are independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl, carbocyclyl, and heterocyclyl. Additionally, R and R′ may be combined to form a heterocyclyl. Exemplary “amino” groups include, without being limited thereto, —NH 2 , —NH(C 1-4  alkyl) and —N(C 1-4  alkyl)(C 1-4  alkyl). 
     As used herein, the term “aryl” refers to a carbocyclic aromatic system containing one ring, or two or three rings fused together where in the ring atoms are all carbon. The term “aryl” groups includes, but is not limited to groups such as phenyl, naphthyl, or anthracenyl. The term “monocyclic aryl” refers to phenyl. 
     As used herein, the term “aryloxy” refers to an aryl group attached to the parent molecular moiety through an oxy (—O—). 
     As used herein, the term “carbamate” refers to an O-carbamyl or N-carbamyl group as defined herein. An N-carbamyl group refers to —NR—COOR′, wherein R and R′ are as defined herein. An O-carbamyl group refers to —OCO—NRR′, wherein R and R′ are as defined herein. 
     As used herein, the term “carbonyl” when alone includes formyl —C(═O)H and in combination is a —C(═O)— group. 
     As used herein, the term “carboxyl” or “carboxy” refers to —C(═O)OH or the corresponding “carboxylate” anion, such as is in a carboxylic acid salt. 
     An “O-carboxy” group refers to a RC(═O)O— group, where R is as defined herein. 
     A “C-carboxy” group refers to a —C(═O)OR groups where R is as defined herein. 
     As used herein, the term “cyano” refers to —CN. 
     As used herein, the term “carbocyclyl” refers to a saturated or partially saturated monocyclic or a fused bicyclic or tricyclic group wherein the ring atoms of the cyclic system are all carbon and wherein each cyclic moiety contains from 3 to 12 carbon atom ring members. “Carbocyclyl” encompasses benzo fused to a carbocyclyl ring system. One group of carbocyclyls have from 5 to 7 carbon atoms. Examples of carbocyclyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, tetrahydronaphthyl, indanyl, octahydronaphthyl, 2,3-dihydro-1H-indenyl, or adamantyl. 
     As used herein, the term “cycloalkyl” refers to a saturated monocyclic, bicyclic or tricyclic group wherein the ring atoms of the cyclic system are all carbon and wherein each cyclic moiety contains from 3 to 12 carbon atom ring members. A C 3-6  cycloalkyl is a cycloalkyl that has from 3 to 6 carbon atoms, i.e. cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or adamantyl. 
     As used herein, the term “cyclyl” refers to an aryl, heterocyclyl, or carbocyclyl group as defined herein. 
     As used herein, the term “halo” or “halogen” refers to fluorine, chlorine, bromine, or iodine. 
     As used herein, the term “haloalkoxy” refers to a haloalkyl group (as defined below) attached to the parent molecular moiety through an oxygen atom. A haloC 1-8  alkoxy group refers to a haloalkoxy group wherein the haloalkyl moiety has from 1 to 8 C atoms. Examples of haloalkoxy groups include, but are not limited to, trifluoromethoxy, 2-fluoroethoxy, pentafluoroethoxy, or 3-chloropropoxy. 
     As used herein, the term “haloalkyl” refers to an alkyl group having the meaning as defined above wherein one or more hydrogens are replaced with a halogen. A haloC 1-8  alkyl group refers to a haloalkyl group wherein the alkyl moiety has from 1 to 8 C atoms. Specifically embraced are monohaloalkyl, dihaloalkyl or polyhaloalkyl groups. A monohaloalkyl group, for one example, may have an iodo, bromo, chloro or fluoro atom within the group. Dihalo or polyhaloalkyl groups may have two or more of the same halo atoms or a combination of different halo groups. Examples of haloalkyl groups include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl or dichloropropyl. 
     As used herein, the term “heteroalkyl” refers to a straight or branched alkyl chain, wherein one, two, or three carbons forming the alkyl chain are each replaced by a heteroatom independently selected from the group consisting of O, N, and S, and wherein the nitrogen and/or sulfur heteroatom(s) (if present) may optionally be oxidized and the nitrogen heteroatom(s) (if present) may optionally be quaternized. The heteroatom(s) O, N and S may, for example, be placed at the end(s) or at an interior position of the heteroalkyl group, i.e., the heteroalkyl may be bound to the remainder of the molecule via a heteroatom or a carbon atom. Up to two heteroatoms may be consecutive, such as, for example, —CH 2 —NH—OCH 3 . Accordingly, a further example for a “heteroalkyl” group is a straight or branched alkyl group, in which two consecutive carbon atoms are replaced by the heteroatoms S and N, respectively, and the sulfur heteroatom is furthermore oxidized, resulting in moieties such as, e.g., —S(═O) 2 —NH 2 , —S(═O) 2 —NH(alkyl) or —S(═O) 2 —N(alkyl)(alkyl). 
     As used herein, the term “heteroC 1-4  alkylene” refers to a straight or branched C 1-4  alkylene group (i.e., a straight or branched C 1-4  alkanediyl group) linked to one heteroatom selected from O, N and S and also refers to a straight or branched C 1-4  alkylene group wherein one or more (e.g., 1, 2 (if present) or 3 (if present)) of the carbon atoms of said alkylene group are each replaced by a heteroatom independently selected from O, N or S. The nitrogen and/or sulfur heteroatom(s) (if present) may optionally be oxidized and the nitrogen heteroatom(s) (if present) may optionally be quaternized. The heteroatom(s) O, N and S may be placed at the end(s) and/or at an interior position of the heteroC 1-4  alkylene group. It is to be understood that the presence of hydrogen atoms will depend on the valence of the heteroatom replacing the respective carbon atom. If, for example, the carbon atom in a —CH 2 — group is replaced by O or S, the resulting group will be —O— or —S—, respectively, while it will be —N(H)— when the carbon atom is replaced by N. Likewise, if the central carbon atom in a group —CH 2 —CH(—CH 3 )—CH 2 — is replaced by N, the resulting group will be —CH 2 —N(—CH 3 )—CH 2 —. An example for a “heteroC 1-4 alkylene” group is a straight or branched C 1-4  alkylene group, in which two consecutive carbon atoms are replaced by the heteroatoms S and N, respectively, and the sulfur heteroatom is furthermore oxidized, resulting in moieties such as, e.g., —S(═O) 2 —N(H)— or —S(═O) 2 —N(CH 3 )—. 
     As used herein, the term “heteroaryl” refers to a 5 to 6 membered unsaturated monocyclic ring, or a fused bicyclic or tricyclic ring system in which the rings are aromatic and in which at least one ring contains at least one heteroatom selected from the group consisting of O, S, and N. Preferred heteroaryl groups are 5- to 6-membered monocyclic or 9- to 10-membered bicyclic heteroaryl groups. Examples of heteroaryl groups include, but are not limited to, pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, or furopyridinyl. 
     As used herein, the term “heterocyclyl” or “heterocycle” or “heterocyclic ring” each refer to a saturated, partially unsaturated, or fully unsaturated monocyclic, bicyclic, or tricyclic heterocyclic group containing at least one heteroatom as a ring member, wherein each of said at least one heteroatoms may be independently selected from the group consisting of nitrogen, oxygen, and sulfur wherein the nitrogen or sulfur atoms may be oxidized (e.g., —N═O, —S(═O)—, or —S(═O) 2 —). Additionally, 1, 2, or 3 of the carbon atoms of the heterocyclyl may be optionally oxidized (e.g., to give an oxo group or ═O). One group of heterocyclyls has from 1 to 4 heteroatoms as ring members. Another group of heterocyclyls has from 1 to 2 heteroatoms as ring members. One group of heterocyclyls has from 3 to 8 ring members in each ring. Yet another group of heterocyclyls has from 3 to 7 ring members in each ring. Again another group of heterocyclyls has from 5 to 6 ring members in each ring. “Heterocyclyl” is intended to encompass a heterocyclyl group fused to a carbocyclyl or benzo ring systems. Examples of heterocyclyl groups include, but are not limited to, pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidino, morpholino, thiomorpholino, thioxanyl, piperazinyl, homopiperazinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl, oxepanyl, thiepanyl, oxazepinyl, diazepinyl, thiazepinyl, 2-pyrrolinyl, 3-pyrrolinyl, indolinyl, 2H-pyranyl, 4H-pyranyl, dioxanyl, 1,3-dioxolanyl, pyrazolinyl, dithianyl, dithiolanyl, dihydropyranyl, dihydrothienyl, dihydrofuranyl, pyrazolidinylimidazolinyl, or imidazolidinyl. Examples of heteroaryls that are heterocyclyls include, but are not limited to, pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, or furopyridinyl. 
     As used herein, the term “heterocycloalkyl” refers to a heterocyclyl group that is not fully unsaturated e.g., one or more of the rings systems of a heterocycloalkyl is not aromatic. Examples of heterocycloalkyls include piperazinyl, morpholinyl, piperidinyl, or pyrrolidinyl. 
     As used herein, the term “hydroxyl” or “hydroxy” refers to —OH. 
     As used herein, the term “lower” where not otherwise specifically defined, means containing from 1 to and including 6 carbon atoms. 
     As used herein, the term “nitro” refers to —NO 2 . 
     As used herein, the term “saturated” in relation to a ring means that the ring does not contain any unsaturation. 
     As used herein, the terms “sulfonate” “sulfonic acid” and “sulfonic” refer to the —SO 3 H group and its anion as the sulfonic acid is used in salt formation. 
     As used herein, the term “sulfinyl” refers to —S(═O)(R), with R as defined herein. 
     As used herein, the term “sulfonyl” refers to —S(═O) 2 R, with R as defined herein. 
     As used herein, the term “sulfonamide” refers to an N-sulfonamido or S-sulfonamido group as defined herein. 
     As used herein, the term “N-sulfonamido” refers to a RS(═O) 2 N(R′)— group with R and R′ as defined herein. Exemplary, non-limiting N-sulfonamido groups are —NHSO 2 alkyl such as —NHSO 2 CH 3 , —NHSO 2 CH 2 CH 3  or —NHSO 2 (isopropyl), and —NHSO 2  (optionally substituted aryl) such as —NHSO 2 phenyl —NHSO 2 -(2-cyanophenyl), —NHSO 2 -(3-cyanophenyl), —NHSO 2 -(4-cyanophenyl), —NHSO 2 -(2-aminophenyl), —NHSO 2 -(3-aminophenyl) or —NHSO 2 -(4-aminophenyl). 
     As used herein, the term “S-sulfonamido” refers to a —S(═O) 2 NRR′, group, with R and R′ as defined herein. 
     As used herein, the term “urea” refers to a —N(R)C(═O)N(R)(R′) group wherein R and R′ are as defined herein. 
     The term R or the term R′, appearing by itself and without a number designation, unless otherwise defined, refers to a moiety selected from the group consisting of hydrogen, alkyl, cycloalkyl, heteroalkyl, aryl, heteroaryl and heterocycloalkyl. 
     Whether an R group has a number designation or not, every R group, including R, R′ and R z  where z=(1, 2, 3, . . . z), every substituent, and every term should be understood to be independent of every other in terms of selection from a group. Should any variable, substituent, or term (e.g., aryl, heterocycle, R, etc.) occur more than one time in a formula or generic structure, its definition at each occurrence is independent of the definition at every other occurrence. Those of skill in the art will further recognize that certain groups may be attached to a parent molecule or may occupy a position in a chain of elements from either end as written. Thus, by way of example only, an unsymmetrical group such as —C(═O)N(R)— may be attached to the parent moiety at either the carbon or the nitrogen. 
     As used herein, the term “optionally substituted” means the preceding or anteceding group may be substituted or unsubstituted. When substituted and unless otherwise specified, the substituents of an “optionally substituted” group may include, without limitation, one or more substituents independently selected from the following groups or a particular designated set of groups, alone or in combination: lower alkyl, lower alkenyl, lower alkynyl, lower alkanoyl, lower heteroalkyl, lower heterocycloalkyl, lower haloalkyl, lower cycloalkyl, phenyl, aryl, heteroaryl, pyridyl, aryloxy, lower alkoxy, lower haloalkoxy, oxo, lower acyloxy, carbonyl, carboxyl, lower alkylcarbonyl, lower carboxyester, lower carboxamido, cyano, halogen, hydroxyl, amino, amido, nitro, thiol, lower alkylthio, lower haloalkylthio, lower perhaloalkylthio, arylthio, sulfonate, sulfonic acid, trisubstituted silyl, N 3 , SH, SCH 3 , C(O)CH 3 , CO 2 CH 3 , CO 2 H, carbamate, and urea. Two substituents may be joined together to form a fused five-, six-, or seven-membered carbocyclic or heterocyclic ring consisting of zero to three heteroatoms, for example forming methylenedioxy or ethylenedioxy. An optionally substituted group may be unsubstituted (e.g, —CH 2 CH 3 ), fully substituted (e.g., —CF 2 CF 3 ), monosubstituted (e.g., —CH 2 CH 2 F) or substituted at a level anywhere in-between fully substituted and monosubstituted (e.g., —CH 2 CF 3 ). Where substituents are recited without qualification as to substitution, both substituted and unsubstituted forms are encompassed. Where a substituent is qualified as “substituted,” the substituted form is specifically intended. Additionally, different sets of optional substituents to a particular moiety may be defined as needed; in these cases, the optional substitution will be as defined, often immediately following the phrase, “optionally substituted with.” In one specific definition, the optional substituents are chosen from hydroxyl, halo, alkyl, alkoxy, haloalkyl, haloalkoxy, —N(C 1-3  alkyl) 2 , —NH(C 1-3  alkyl), —NHC(═O)(C 1-3  alkyl), —C(═O)OH, —C(═O)O(C 1-3  alkyl), —C(═O)(C 1-3  alkyl), —C(═O)NH 2 , —C(═O)NH(C 1-3  alkyl), —C(═O)NH(cycloalkyl), —C(═O)N(C 1-3  alkyl) 2 , —S(═O) 2 (C 1-3  alkyl), —S(═O) 2 NH 2 , —S(═O) 2 N(C 1-3  alkyl) 2 ,—S(═O) 2 NH(C 1-3  alkyl), —CHF 2 , —OCF 3 , —OCHF 2 , —SCF 3 , —CF 3 , —CN, —NH 2 , —NO 2 , or tetrazolyl. 
     As used herein, the term “optional substituent” denotes that the corresponding substituent may be present or may be absent. Accordingly, a compound having 1, 2 or 3 optional substituents may be unsubstituted or may be substituted with 1, 2 or 3 substituents. 
     As used herein, the term “treating a disease” refers to a slowing of or a reversal of the progress of the disease. Treating a disease includes treating a symptom and/or reducing the symptoms of the disease. 
     As used herein, the term “preventing a disease” refers to a slowing of the disease or of the onset of the disease or the symptoms thereof. Preventing a disease or disorder can include stopping the onset of the disease or symptoms thereof. 
     As used herein, the term “dosage unit” refers to a physically discrete unit, such as a capsule or tablet suitable as a unitary dosage for a human patient. Each unit contains a predetermined quantity of a compound of Formula I which was discovered or believed to produce the desired pharmacokinetic profile which yields the desired therapeutic effect. The dosage unit is composed of a compound of Formula I in association with at least one pharmaceutically acceptable carrier, salt, excipient, or combination thereof. 
     As used herein, the term “subject” or “patient” or “individual”, such as the subject in need of treatment or prevention, may be a eukaryote, an animal, a vertebrate animal, a mammal, a rodent (e.g., a guinea pig, a hamster, a rat, a mouse), a murine (e.g., a mouse), a canine (e.g., a dog), a feline (e.g., a cat), an equine (e.g. a horse), a primate, a simian (e.g., a monkey or ape), a monkey (e.g., a marmoset, a baboon), an ape (e.g., gorilla, chimpanzee, orangutang, gibbon), or a human. The meaning of the terms “eukaryote”, “animal”, “mammal”, etc. is well known in the art and can, for example, be deduced from Wehner und Gehring (1995; Thieme Verlag). In the context of this invention, it is particularly envisaged that animals are to be treated which are economically, agronomically or scientifically important. Scientifically important organisms include, but are not limited to, mice, rats, and rabbits. Lower organisms such as, e.g., fruit flies like  Drosophila melagonaster  and nematodes like  Caenorhabditis elegans  may also be used in scientific approaches. Non-limiting examples of agronomically important animals are sheep, cattle and pig, while, for example, cats and dogs may be considered as economically important animals. Preferably, the subject/patient/individual is a mammal; more preferably, the subject/patient/individual is a human or a non-human mammal (such as, e.g., a guinea pig, a hamster, a rat, a mouse, a rabbit, a dog, a cat, a horse, a monkey, an ape, a marmoset, a baboon, a gorilla, a chimpanzee, an orangutang, a gibbon, a sheep, cattle, or a pig); even more preferably, the subject/patient/individual is a human. 
     As used herein, the term “dose” or “dosage” refers to the amount of active ingredient that an individual takes or is administered at one time. For example, a 40 mg dose of a compound of Formula I refers to, in the case of a twice-daily dosage regimen, a situation where the individual takes 40 mg of a compound of Formula I twice a day, e.g., 40 mg in the morning and 40 mg in the evening. The 40 mg of a compound of Formula I dose can be divided into two or more dosage units, e.g., two 20 mg dosage units of a compound of Formula I in tablet form or two 20 mg dosage units of a compound of Formula I in capsule form. 
     As used herein, the term “therapeutically effective amount”, such as the therapeutically effective amount of a compound of the present invention, refers to the amount sufficient to produce a desired biological effect (e.g., a therapeutic effect) in a subject. Accordingly, a therapeutically effective amount of a compound may be an amount which is sufficient to treat or prevent a disease or disorder, and/or delay the onset or progression of a disease or disorder, and/or alleviate one or more symptoms of the disease or disorder, when administered to a subject suffering from or susceptible to that disease or disorder. 
     As used herein, a “pharmaceutically acceptable prodrug” is a compound that may be converted under physiological conditions or by solvolysis to the specified compound or to a pharmaceutically acceptable salt of such compound. 
     As used herein, a “pharmaceutically acceptable salt” is intended to mean a salt that retains the biological effectiveness of the free acids and bases of the specified compound and that is not biologically or otherwise undesirable. A compound for use in the invention may possess a sufficiently acidic, a sufficiently basic, or both functional groups, and accordingly react with any of a number of inorganic or organic bases, and inorganic and organic acids, to form a pharmaceutically acceptable salt. Exemplary pharmaceutically acceptable salts include those salts prepared by reaction of the compounds of the present invention with a mineral or organic acid, such as hydrochlorides, hydrobromides, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, phosphates, monohydrophosphates, dihydrophosphates, metaphosphates, pyrophosphates, chlorides, bromides, iodides, nitrates, acetates, propionates, decanoates, caprylates, acrylates, formates, isobutyrates, caproates, heptanoates, propiolates, oxalates, malonates, succinates, suberates, sebacates, fumarates, maleates, butyne-1,4 dioates, hexyne-1,6-dioates, benzoates, chlorobenzoates, methylbenzoates, dinitrobenzoates, hydroxybenzoates, methoxybenzoates, phthalates, sulfonates, xylenesulfonates, phenylacetates, phenylpropionates, phenylbutyrates, citrates, lactates, gamma-hydroxybutyrates, glycollates, tartrates, methane-sulfonates, ethane-sulfonates, propanesulfonates, benzenesulfonates, toluenesulfonates, trifluoromethansulfonates, naphthalene-1-sulfonates, naphthalene-2-sulfonates, or mandelates, pyruvates, stearates, ascorbates, or salicylates. When the compounds of the invention carry an acidic moiety, suitable pharmaceutically acceptable salts thereof may include alkali metal salts, e.g. sodium or potassium salts; alkaline earth metal salts, e.g. calcium or magnesium salts; and salts formed with suitable organic ligands such as ammonia, alkylamines, hydroxyalkylamines, lysine, arginine, N-methylglucamine, procaine and the like. Pharmaceutically acceptable salts are well known in the art. 
     As used herein, a “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” refers to a non-API (API refers to Active Pharmaceutical Ingredient) substances such as disintegrators, binders, fillers, and lubricants used in formulating pharmaceutical products. They are generally safe for administering to humans according to established governmental standards, including those promulgated by the United States Food and Drug Administration and the European Medical Agency. Pharmaceutically acceptable carriers or excipients are well known to those skilled in the art. 
     In the chemical drawings used herein, such as in the drawings for specific D rings disclosed above, the wavy line represents the point of attachment to the remainder of the compound. 
     As is understood by the skilled artisan, certain variables in the list of substituents are repetitive (different name for the same substituent), generic to other terms in the list, and/or partially overlap in content with other terms. In the compounds of the invention, the skilled artisan recognizes that substituents may be attached to the remainder of the molecule via a number of positions and the preferred positions are as illustrated in the Examples. 
     The compounds of the invention are unexpectedly potent and selective inhibitors of LSD1. Avoiding inhibition of “off-targets” can avoid unwanted or undesirable side-effects like the cheese effect associated with MAO-A. The compounds of the invention are thus useful for the treatment or prevention of any disease or disorder associated with LSD1. This includes cancer, neurological diseases and viral infections, among others. 
     Preferably, the compounds of formula I, including compounds of formula Ia, Ia-1, Ib and Ic, as well as any salts and solvates thereof, are used for the treatment or prevention of cancer, and most preferably for the treatment of cancer. Cancers that may be treated (or prevented) with the compounds of the invention include, but are not limited to cancers such as: 
     Hematologic cancers (also designated herein as blood cancers), including cancers of the blood, bone marrow and lymph nodes such as leukemias (e.g. acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia), myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome, and lymphomas (e.g. Hodgkin&#39;s disease, non-Hodgkin&#39;s lymphoma (malignant lymphoma));
 
Breast cancer, including invasive ductal carcinoma, in situ ductal carcinoma, lobular carcinoma, and mixed ductal and lobular carcinoma;
 
Lung cancer such as bronchogenic carcinoma (e.g. squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hamartoma, and mesothelioma;
 
Gastrointestinal cancers such as esophagus (e.g. squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (e.g. carcinoma, lymphoma, leiomyosarcoma), pancreas (e.g. ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (e.g. adenocarcinoma, lymphoma, carcinoid tumors, Kaposi&#39;s sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), and large bowel (e.g. adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma);
 
Genitourinary tract cancers such as kidney (e.g. adenocarcinoma, Wilm&#39;s tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (e.g. squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (e.g. adenocarcinoma, sarcoma), and testis (e.g. seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma);
 
Liver cancer such as hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, and hemangioma;
 
Bone cancer such as osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing&#39;s sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors;
 
Nervous system cancers such as skull (e.g. osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (e.g. meningioma, meningiosarcoma, gliomatosis), brain (e.g. astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, and sarcoma;
 
Gynecological cancers such as uterus (e.g. endometrial carcinoma), cervix (e.g. cervical carcinoma, pre-tumor cervical dysplasia), ovaries (e.g. ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (e.g. squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (e.g. clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma)), and fallopian tubes (carcinoma);
 
Cardiac cancer such as sarcoma (e.g. angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipma and teratoma;
 
Skin cancer such as malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi&#39;s sarcoma; and
 
Adrenal glands cancer such as neuroblastoma.
 
     Accordingly, in one embodiment, the compounds of the invention are used for the treatment or prevention of cancer, particularly for the treatment of cancer, wherein said cancer is chosen from blood cancer, leukemia, lymphoma, breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, neuroblastoma, bladder cancer, liver cancer, sarcoma, myeloma and skin cancer. In another embodiment, the compounds of the invention are used for the treatment or prevention (particularly for the treatment) of blood cancers (also known as hematological cancers), including leukemias (for example, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), or hairy cell leukemia), lymphomas and myeiomas, prostate cancer, breast cancer, lung cancer, colorectal cancer, brain cancer or skin cancer. In a preferred embodiment, the compounds of formula I, including compounds of formula Ia, Ia-1, Ib and Ic, are used for the treatment of a blood cancer. More preferably, the compounds of formula I, including compounds of formula Ia, Ia-1, Ib and Ic, are used for the treatment of leukemia, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia, chronic eosinophilic leukemia, chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), and hairy cell leukemia. 
     Typically, compounds according to Formula I, Ia, Ia-1, Ib or Ic can be effective at an amount of from about 0.01 μg/kg to about 100 mg/kg per day based on total body weight. The active ingredient may be administered at once, or may be divided into a number of smaller doses to be administered at predetermined intervals of time. The suitable dosage unit for each administration can be, e.g., from about 1 μg to about 2000 mg, preferably from about 5 μg to about 1000 mg. Even more preferably, the amount of active ingredient administered is from about 5 μg to about 100 mg per day. These doses will depend on the pharmacokinetic parameters of the particular compound and other ADME properties as well as the efficacy of the compound in a particular disease setting. 
     It should be understood that the dosage ranges set forth above are exemplary only and are not intended to limit the scope of this invention. The therapeutically effective amount for each active compound can vary with factors including but not limited to the activity of the compound used, stability of the active compound in the patient&#39;s body, the severity of the conditions to be alleviated, the total weight of the patient treated, the route of administration, the ease of absorption, distribution, and excretion of the active compound by the body, the age and sensitivity of the patient to be treated, and the like, as will be apparent to a skilled artisan. The amount of administration can be adjusted as the various factors change over time. 
     While it is possible that a compound of the invention may be administered for use in therapy directly as such, it is typically administered in the form of a pharmaceutical composition, which comprises said compound as active pharmaceutical ingredient together with one or more pharmaceutically acceptable excipients or carriers. 
     The compounds of the invention may be administered by any means that accomplish their intended purpose. Examples include administration by the oral, parenteral, intravenous, subcutaneous or topical routes. 
     For oral delivery, the active compounds can be incorporated into a formulation that includes pharmaceutically acceptable carriers such as binders (e.g., gelatin, cellulose, gum tragacanth), excipients (e.g., starch, lactose), lubricants (e.g., magnesium stearate, silicon dioxide), disintegrating agents (e.g., alginate, Primogel, and corn starch), and sweetening or flavoring agents (e.g., glucose, sucrose, saccharin, methyl salicylate, and peppermint). The formulation can be orally delivered in the form of enclosed gelatin capsules or compressed tablets. Capsules and tablets can be prepared in any conventional techniques. The capsules and tablets can also be coated with various coatings known in the art to modify the flavors, tastes, colors, and shapes of the capsules and tablets. In addition, liquid carriers such as fatty oil can also be included in capsules. 
     Suitable oral formulations can also be in the form of suspension, syrup, chewing gum, wafer, elixir, and the like. If desired, conventional agents for modifying flavors, tastes, colors, and shapes of the special forms can also be included. In addition, for convenient administration by enteral feeding tube in patients unable to swallow, the active compounds can be dissolved in an acceptable lipophilic vegetable oil vehicle such as olive oil, corn oil and safflower oil. 
     The active compounds can also be administered parenterally in the form of solution or suspension, or in lyophilized form capable of conversion into a solution or suspension form before use. In such formulations, diluents or pharmaceutically acceptable carriers such as sterile water and physiological saline buffer can be used. Other conventional solvents, pH buffers, stabilizers, anti-bacteria agents, surfactants, and antioxidants can all be included. For example, useful components include sodium chloride, acetates, citrates or phosphates buffers, glycerin, dextrose, fixed oils, methyl parabens, polyethylene glycol, propylene glycol, sodium bisulfate, benzyl alcohol, ascorbic acid, and the like. The parenteral formulations can be stored in any conventional containers such as vials and ampoules. 
     Routes of topical administration include nasal, bucal, mucosal, rectal, or vaginal applications. For topical administration, the active compounds can be formulated into lotions, creams, ointments, gets, powders, pastes, sprays, suspensions, drops and aerosols. Thus, one or more thickening agents, humectants, and stabilizing agents can be included in the formulations. Examples of such agents include, but are not limited to, polyethylene glycol, sorbitol, xanthan gum, petrolatum, beeswax, or mineral oil, lanolin, squalene, and the like. A special form of topical administration is delivery by a transdermal patch. Methods for preparing transdermal patches are disclosed, e.g., in Brown, et al. (1988)  Ann. Rev. Med.  39:221-229 which is incorporated herein by reference. 
     Subcutaneous implantation for sustained release of the active compounds may also be a suitable route of administration. This entails surgical procedures for implanting an active compound in any suitable formulation into a subcutaneous space, e.g., beneath the anterior abdominal wall. See, e.g., Wilson et al. (1984)  J. Clin. Psych.  45:242-247. Hydrogels can be used as a carrier for the sustained release of the active compounds. Hydrogels are generally known in the art. They are typically made by crosslinking high molecular weight biocompatible polymers into a network, which swells in water to form a gel like material. Preferably, hydrogels are biodegradable or biosorbable. For purposes of this invention, hydrogels made of polyethylene glycols, collagen, or poly(glycolic-co-L-lactic acid) may be useful. See, e.g., Phillips et al. (1984)  J. Pharmaceut. Sci.,  73: 1718-1720. 
     The active compounds can also be conjugated, to a water soluble non-immunogenic non-peptidic high molecular weight polymer to form a polymer conjugate. For example, an active compound is covalently linked to polyethylene glycol to form a conjugate. Typically, such a conjugate exhibits improved solubility, stability, and reduced toxicity and immunogenicity. Thus, when administered to a patient, the active compound in the conjugate can have a longer half-life in the body, and exhibit better efficacy. See generally, Burnham (1994)  Am. J. Hosp. Pharm.  15:210-218. PEGylated proteins are currently being used in protein replacement therapies and for other therapeutic uses. For example, PEGylated interferon (PEG-INTRON A®) is clinically used for treating Hepatitis B. PEGylated adenosine deaminase (ADAGEN®) is being used to treat severe combined immunodeficiency disease (SCIDS). PEGylated L-asparaginase (ONCAPSPAR®) is being used to treat acute lymphoblastic leukemia (ALL). It is preferred that the covalent linkage between the polymer and the active compound and/or the polymer itself is hydrolytically degradable under physiological conditions. Such conjugates known as “prodrugs” can readily release the active compound inside the body. Controlled release of an active compound can also be achieved by incorporating the active ingredient into microcapsules, nanocapsules, or hydrogels generally known in the art. Other pharmaceutically acceptable prodrugs of the compounds of this invention include, but are not limited to, esters, carbonates, thiocarbonates, N-acyl derivatives, N-acyloxyalkyl derivatives, quaternary derivatives of tertiary amines, N-Mannich bases, Schiff bases, amino acid conjugates, phosphate esters, metal salts and sulfonate esters. 
     Liposomes can also be used as carriers for the active compounds of the present invention. Liposomes are micelles made of various lipids such as cholesterol, phospholipids, fatty acids, and derivatives thereof. Various modified lipids can also be used. Liposomes can reduce the toxicity of the active compounds, and increase their stability. Methods for preparing liposomal suspensions containing active ingredients therein are generally known in the art. See, e.g., U.S. Pat. No. 4,522,811; Prescott, Ed., Methods in Cell Biology, Volume XIV, Academic Press, New York, N.Y. (1976). 
     The active compounds can also be administered in combination with another active agent that synergistically treats or prevents the same symptoms or is effective for another disease or symptom in the patient treated so long as the other active agent does not interfere with or adversely affect the effects of the active compounds of this invention. Such other active agents include but are not limited to anti-inflammatory agents, antiviral agents, antibiotics, antifungal agents, antithrombotic agents, cardiovascular drugs, cholesterol lowering agents, anti-cancer drugs, hypertension drugs, and the like. 
     Combination therapy includes administration of a single pharmaceutical dosage formulation which contains a compound of the invention and one or more additional active agents, as well as administration of the compound of the invention and each additional active agent in its own separate pharmaceutical dosage formulation. If administered separately, the administration can be simultaneous, sequential or separate, and the compound of the invention and the additional therapeutic agent(s) can be administered via the same administration route or using different administration routes, for example one compound can be administered orally and the other intravenously. 
     In particular, when a compound of formula I, Ia, Ia-1, Ib or Ic is used for the treatment or prevention of cancer, said compound can be administered in combination with one or more further agents known to be useful in the treatment or prevention of cancer, including chemotherapy or radiotherapy. 
     Typically, for combination therapy with a compound of the invention any antineoplastic agent that has activity versus a cancer being treated or prevented with a compound of the invention may be used. Examples of antineoplastic agents that can be used in combination with the compounds and methods of the present invention include, in general, and as appropriate, alkylating agents, anti-metabolites, epidophyllotoxins, antineoplastic enzymes, topoisomerase inhibitors, procarbazines, mitoxantrones, platinum coordination complexes, biological response modifiers and growth inhibitors, hormonal/anti-hormonal therapeutic agents and haematopoietic growth factors. Exemplary classes of antineoplastic agents include the anthracyclines,  vinca  drugs, mitomycins, bleomycins, cytotoxic nucleosides, epothilones, discodermolides, pteridines, diynenes and podophyllotoxins. Particularly useful members of those classes include, for example, carminomycin, daunorubicin, aminopterin, methotrexate, methopterin, dichloromethotrexate, mitomycin C, porfiromycin, 5-fluorouracil, 6-mercaptopurine, gemcitabine, cytosine arabinoside, podophyllotoxin or podo-phyllotoxin derivatives such as etoposide, etoposide phosphate or teniposide, melphalan, vinblastine, vincristine, leurosidine, vindesine, leurosine, paclitaxel and the like. Other useful antineoplastic agents include estramustine, carboplatin, cyclophosphamide, bleomycin, gemcitibine, ifosamide, melphalan, hexamethyl melamine, thiotepa, cytarabin, idatrexate, trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11, topotecan, ara-C, bicalutamide, flutamide, leuprolide, pyridobenzoindole derivatives, interferons and interleukins. 
     Thus, a compound of formula I, Ia, Ia-1, Ib or Ic according to the present invention can be used for the treatment or prevention of cancer, wherein said compound is to be administered in combination with one or more antineoplastic agents. The antineoplastic agents to be administered for combination therapy may be selected, as appropriate, from: a tumor angiogenesis inhibitor (for example, a protease inhibitor, an epidermal growth factor receptor kinase inhibitor, or a vascular endothelial growth factor receptor kinase inhibitor); a cytotoxic drug (for example, an antimetabolite, such as purine and pyrimidine analog antimetabolites); an antimitotic agent (for example, a microtubule stabilizing drug or an antimitotic alkaloid); a platinum coordination complex; an anti-tumor antibiotic; an alkylating agent (for example, a nitrogen mustard or a nitrosourea); an endocrine agent (for example, an adrenocorticosteroid, an androgen, an anti-androgen, an estrogen, an anti-estrogen, an aromatase inhibitor, a gonadotropin-releasing hormone agonist, or a somatostatin analog); or a compound that targets an enzyme or receptor that is overexpressed and/or otherwise involved in a specific metabolic pathway that is misregulated in the tumor cell (for example, ATP and GTP phosphodiesterase inhibitors, histone deacetylase inhibitors, protein kinase inhibitors (such as serine, threonine and tyrosine kinase inhibitors (for example, Abelson protein tyrosine kinase)) and the various growth factors, their receptors and kinase inhibitors therefor (such as epidermal growth factor receptor kinase inhibitors, vascular endonthelial growth factor receptor kinase inhibitors, fibroblast growth factor inhibitors, insulin-like growth factor receptor inhibitors and platelet-derived growth factor receptor kinase inhibitors)); aminopeptidase inhibitors; proteasome inhibitors; cyclooxygenase inhibitors (for example, cyclooxygenase-1 or cyclooxygenase-2 inhibitors); topoisomerase inhibitors (for example, topoisomerase I inhibitors or topoisomerase II inhibitors); or retinoid agents. 
     An alkylating agent which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, a nitrogen mustard (such as cyclophosphamide, mechlorethamine (chlormethine), uramustine, melphalan, chlorambucil, ifosfamide, bendamustine, or trofosfamide), a nitrosourea (such as carmustine, streptozocin, fotemustine, lomustine, nimustine, prednimustine, ranimustine, or semustine), an alkyl sulfonate (such as busulfan, mannosulfan, or treosulfan), an aziridine (such as hexamethylmelamine (altretamine), triethylenemelamine, ThioTEPA (N,N′N′-triethylenethiophosphoramide), carboquone, or triaziquone), a hydrazine (such as procarbazine), a triazene (such as dacarbazine), or an imidazotetrazines (such as temozolomide). 
     A platinum coordination complex which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, cispiatin, carboplatin, nedapiatin, oxalipiatin, satraplatin, or triplatin tetranitrate. 
     A cytotoxic drug which can be used as an antineopiastic agent in combination with a compound of the present invention may be, for example, an antimetabolite, including folic acid analog antimetabolites (such as aminopterin, methotrexate, pemetrexed, or raltitrexed), purine analog antimetabolites (such as cladribine, clofarabine, fludarabine, 6-mercaptopurine (including its prodrug form azathioprine), pentostatin, or 6-thioguanine), and pyrimidine analog antimetabolites (such as cytarabine, decitabine, azacytidine, 5-fluorouracil (including its prodrug forms capecitabine and tegafur), floxuridine, gemcitabine, enocitabine, or sapacitabine). 
     An antimitotic agent which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, a taxane (such as docetaxel, larotaxel, ortataxel, paclitaxel/taxol, or tesetaxel), a  Vinca  alkaloid (such as vinbiastine, vincristine, vinflunine, vindesine, vinzolidine, or vinoreibine), an epothilone (such as epothilone A, epothilone B, epothilone C, epothilone D, epothilone E, or epothilone F) or an epothilone B analog (such as ixabepilone/azaepothilone B). 
     An anti-tumor antibiotic which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, an anthracycline (such as aclarubicin, daunorubicin, doxorubicin, epirubicin, idarubicin, amrubicin, pirarubicin, valrubicin, or zorubicin), an anthracenedione (such as mitoxantrone, or pixantrone) or an anti-tumor antibiotic isolated from  Streptomyces  (such as actinomycin (including actinomycin D), bleomycin, mitomycin (including mitomycin C), or plicamycin). 
     A tyrosine kinase inhibitor which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, axitinib, bosutinib, cediranib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, lestaurtinib, nilotinib, semaxanib, sorafenib, sunitinib, or vandetanib. 
     A topoisomerase-inhibitor which can be used as an antineoplastic agent in combination with a compound of the present invention may be, for example, a topoisomerase I inhibitor (such as irinotecan, topotecan, camptothecin, belotecan, rubitecan, or lamellarin D) or a topoisomerase II inhibitor (such as amsacrine, etoposide, etoposide phosphate, teniposide, or doxorubicin). 
     Further antineoplastic agents may be used in combination with a compound of the present invention. The antineoplastic agents may include biological or chemical molecules, such as TNF-related apoptosis-inducing ligand (TRAIL), tamoxifen, toremifene, fluoxymesterol, raloxifene, diethylstibestrol, bicalutamide, nilutamide, flutamide, aminoglutethimide, anastrozole, tetrazole, luteinizing hormone release hormone (LHRH) analogues, ketoconazole, goserelin acetate, leuprolide, megestrol acetate, prednisone, mifepristone, amsacrine, bexarotene, estramustine, irofulven, trabectedin, cetuximab, panitumumab, tositumomab, alemtuzumab, bevacizumab, edrecolomab, gemtuzumab, alvocidib, seliciclib, aminolevulinic acid, methyl aminolevulinate, efaproxiral, porfimer sodium, talaporfin, temoporfin, verteporfin, anagrelide, arsenic trioxide, atrasentan, bortezomib, carmofur, celecoxib, demecolcine, elesclomol, elsamitrucin, etoglucid, lonidamine, lucanthone, masoprocol, mitobronitol, mitoguazone, mitotane, oblimersen, omacetaxine, sitimagene, ceradenovec, tegafur, testolactone, tiazofurine, tipifarnib, and vorinostat. 
     Examples of retinoid agents include all natural, recombinant, and synthetic derivatives or mimetics of vitamin A, for example, retinyl palmitate, retinoyl-beta-glucuronide (vitamin A1 beta-glucuronide), retinyl phosphate (vitamin A1 phosphate), retinyl esters, 4-oxoretinol, 4-oxoretinaldehyde, 3-dehydroretinol (vitamin A2), 11-cis-retinal (11-cis-retinaldehyde, 11-cis or neo b vitamin A1 aldehyde), 5,6-epoxyretinal (5,6-epoxy vitamin A1 alcohol), anhydroretinol (anhydro vitamin A1) and 4-ketoretinol (4-keto-vitamin A1 alcohol), all-trans retinoic acid (ATRA; Tretinoin; vitamin A acid; 3,7-dimethyl-9-(2,6,6,-trimethyl-1-cyclohenen-1-yl)-2,4,6,8-nonatetraenoic acid [CAS No. 302-79-4]), lipid formulations of all-trans retinoic acid (e.g., ATRA-IV), 9-cis retinoic acid (9-cis-RA; Alitretinoin; Panretin™; LGD1057), 13-cis retinoic acid (Isotretinoin), (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl]-benzoic acid, 3-methyl-(E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propenyl]-benzoic acid, Fenretinide (N-(4-hydroxyphenyl)retinamide; 4-HPR), Etretinate ((all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid ethyl ester; Tegison), Acitretin ((all-E)-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonatetraenoic acid; Ro 10-1670; Soriatane; Neotigason), Tazarotene (ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate; Tazorac; Avage; Zorac), Tocoretinate (9-cis-tretinoin; Tocoferil), Adapalene (6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid; Differin), Motretinide (trimethylmethoxyphenyl-N-ethyl retinamide; Trasmaderm), retinaldehyde (Retinal), CD437 (6-[3-(1-adamantyl)-4-hydroxyphenyl)-2-naphthalene carboxylic acid; AHPN), CD2325, ST1926 ([E-3-(4′-hydroxy-3′-adamantylbiphenyl-4-yl)acrylic acid), ST1878 (methyl 2-[3-[2-[3-(2-methoxy-1,1-dimethyl-2-oxoethoxy)phenoxy]ethoxy]phenoxy]isobutyrate), ST2307, ST1898, ST2306, ST2474, MM11453, MM002 (3-Cl-AHPC), MX2870-1, MX3350-1, MX84, and MX90-1, docosahexaenoic acid (DHA), phytanic acid (3,7,11,15-tetramethyl hexadecanoic acid), MS6682 (methoprene acid), LG100268 (LG268), LG100324, SR11203 ([2-(4-carboxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1,3-dithiane), SR11217 (4-(2-methyl-1-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)propenyl)benzoic acid), SR11234, SR11236 (2-(4-carboxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1,3-dioxane), SR11246, AGN194204, derivatives of 9-cis-RA such as LGD1069 (3-methyl TTNEB; Bexarotene; Targretin®; 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl) ethenyl]benzoic acid). 
     Examples of histone deacetylase inhibitors include, without limitation, MS-275 (SNDX-275; Entinostat), FK228 (FR901228; depsipeptide; Romidepsin), CI-994 (Acetyldinaline; Tacedinaline), Apicidin (cyclo[(2S)-2-amino-8-oxodecanoyl-1-methoxy-L-tryptophyl-L-isoleucyl-(2R)-2-piperidinexcarbonyl]), A-161906 (7-[4-(4-cyanophenyl)phenoxy]-heptanohydroxamic acid), Scriptaid (6-(1,3-Dioxo-1H,3H-benzo[de]isoquinolin-2-yl)-hexanoic acid hydroxyamide), PXD-101 (Belinostat), CHAP (cyclic hydroxamic acid-containing peptide), LAQ-824 (Dacinostat), BML-EI319 (Depudecin), O3139 (Oxamflatin), NSC 696085 (Pyroxamide), MW2796; MW2996, T2580 (Trapoxin A), AN-9 (Pivanex), W222305 (Tributyrin) Trichostatin A, Trichostatin C, Butyric acid, Valproic acid (VPA), Suberoylanilide hydroxamic acid (SAHA; Vorinostat), m-Carboxycinnamic acid bishydroxamide (CBHA), Salicylbishydroxamic acid (S607; SHA; SHAM); Suberoyl bishydroxamic acid (SBHA); Azelaic bishydroxamic acid (ABHA); Azelaic-1-hydroxamate-9-anilide (AAHA); 3Cl-UCHA (6-(3-chlorophenylureido) caproic hydroxamic acid); and sodium butyrate, 4-phenylbutyrate, phenylacetate, valerate, isovalerate, butyramide, isobutyramide, 3-bromopropionate, and valproate. 
     Also biological drugs, like antibodies, antibody fragments, antibody constructs (for example, single-chain constructs), and/or modified antibodies (like CDR-grafted antibodies, humanized antibodies, “full humanized” antibodies, etc.) directed against cancer or tumor markers/factors/cytokines involved in cancer can be employed in cotherapeutic approaches with the compounds of the invention. Examples of such biological molecules are alemtuzumab, apolizumab, aselizumab, atlizumab, bapineuzumab, bevacizumab, bivatuzumab mertansine, cantuzumab mertansine, cedelizumab, certolizumab pegol, cidfusituzumab, cidtuzumab, daclizumab, eculizumab, efalizumab, epratuzumab, erlizumab, felvizumab, fontolizumab, gemtuzumab ozogamicin, inotuzumab ozogamicin, ipilimumab, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, motovizumab, natalizumab, nimotuzumab, nolovizumab, numavizumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pecfusituzumab, pectuzumab, pertuzumab, pexelizumab, ralivizumab, ranibizumab, reslivizumab, reslizumab, resyvizumab, rituximab, rovelizumab, rolizumab, sibrotuzumab, siplizumab, sontuzumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, trastuzumab, tucotuzumab celmoleukin, tucusituzumab, umavizumab, urtoxazumab, and visilizumab. 
     Other biologic agents include, but are not limited to, immunomodulating proteins such as cytokines (such as interleukin-2 (IL-2, Aldesleukin), Epoietin-alpha.; EPO), granulocyte-CSF (G-CSF; Filgrastin), and granulocyte-macrophage-CSF (GM-CSF; Sargramostim) and interferons, (e.g., interferon-alpha, interferon-beta and interferon-gamma),  bacillus  Calmette-Guerin, levamisole, and octreotide, endostatin, tumor suppressor genes (e.g., DPC4, NF-1, NF-2, RB, p53, WT1, BRCA1, and BRCA2), and cancer vaccines (e.g., tumor associated antigens such as gangliosides (GM2), prostate specific antigen (PSA), alpha-fetoprotein (AFP), carcin embryonic antigen (CEA) (produced by colon cancers and other adenocarcinomas, e.g., breast, lung, gastric, and pancreatic cancers), melanoma-associated antigens (MART-I, gap100, MAGE 1,3 tyrosinase), papillomavirus E6 and E7 fragments, whole cells or portions/lysates of autologous tumor cells and allogeneic tumor cells. 
     General Synthetic Route Description 
     Compounds of Formula I can be synthesized in accordance with or in analogy to the general routes described below. Unless otherwise stated, in the methods described below the meanings of the different substituents in each synthetic intermediate and compound of formula I are the meanings described above with regard to a compound of formula I. Other routes known by the ordinary skilled artisan, as well as other reactants and intermediates, can also be used to arrive at the compounds of Formula I. The reaction schemes described below are only meant to represent examples of the invention and are in no way meant to be a limit of the invention. In some of the processes described below it may be necessary or advisable to protect reactive or labile groups with conventional protecting groups. Both the nature of these protecting groups and the procedures for their introduction and removal are well known in the art (see for example Greene T W and Wuts PGM -“Greene&#39;s Protecting Groups in Organic Synthesis”,4 th  edition, Wiley, 2006). Whenever a protecting group is present, a subsequent deprotection step will be required, which can be performed under standard conditions well known in the art, such as those described in the above reference. 
     In general, the compounds of formula I can be prepared by reductive alkylation of a cyclopropylamino derivative of formula II with a ketone of formula IIIa or and aldehyde of formula IIIb or IIIc, as shown below in Scheme 1: 
                         
Wherein A, B, D, R w , R x , R y , R z  and L 2  have the meaning disclosed above in relation to a compound of formula I.
 
     Said reductive alkylation can be performed under standard conditions for reductive alkylations, well known in the art. For example, a suitable set of conditions is reacting II with IIIa, IIIb or IIIc using a reducing agent such as a borohydride (e.g. sodium triacetoxyborohydride or sodium borohydride) in a suitable solvent such as dichloroethane or methanol, optionally in the presence of an acid such as acetic acid. In order to conduct the reaction, it is necessary that any other amino group that may be present either in II or in IIIa, IIIb or IIIc be protected using conventional amino-protecting groups to avoid any side reactions; a subsequent deprotection step will be required then if such amino protecting group is present, in order to obtain a compound of formula I. Any suitable amino-protecting group may be used, such as for example a tert-butoxycarbonyl (Boc) group. If Boc is used, deprotection can be carried out under standard conditions, for example under acidic conditions using HCl in an organic solvent such as diethyl ether or 1,4-dioxane, or trifluoroacetic acid (TFA) in dichloromethane. When HCl is used in the last step of the synthesis, compounds of formula I are obtained as a hydrochloride salt. Likewise, if TFA is used, the compounds will be obtained as a trifluoroacetate. 
     The cyclopropylamino derivatives of formula II and the ketones of formula IIIa and the aldehydes of formula IIIb or IIIc are commercially available or can be prepared following methods disclosed in the literature. 
     More detailed methods to obtain compounds of formula I are described below. 
     The compounds of Formula I wherein R w , R x , R y  and R z ═H can be synthesized, for example, by the general route described in Scheme 2. This route is particularly suitable for compounds wherein B═H or R 1  since the corresponding aldehyde (1) is either commercially available or can be readily obtained. In Scheme 2 below, for schematic purposes “B” has been omitted. 
     
       
         
         
             
             
         
       
     
     Aldehydes of Formula (1) are subjected to a Horner-Wadsworth-Emmons reaction using triethyl phosphono acetate and a base preferably potassium tert-butoxide in a suitable solvent such as tetrahydrofuran to get the ethyl acrylate derivatives of formula (2) which are then subjected to cyclopropanation reaction using trimethylsulfoxonium iodide and sodium hydride in dimethyl sulfoxide as a solvent leading to (trans)-ethyl cyclopropanecarboxylate derivatives of formula (3) (obtained as a trans ((1S,2R) and (1R,2S)) racemic mixture). Hydrolysis to the corresponding (trans)-cyclopropanecarboxylic acid derivatives of formula (4) can be performed under basic conditions using for example NaOH in a suitable solvent such as MeOH. The subsequent reaction of compound (4), first with ethyl chloroformate and triethylamine in acetone and later with sodium azide in water leads to the formation of (trans)-cyclopropanecarbonyl azide derivatives of formula (5). Reaction with tert-butanol results in the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6). Alkylation with alkyl halides of formula (7) under basic conditions using for example NaH in a suitable solvent such as DMF leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (8). Deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or using HCl in 1,4-dioxane leads to the formation of the (trans)-cyclopropanamine derivatives of formula (9), which corresponds to a compound of formula I, and particularly Ia, wherein B is H or R 1 . 
     Alternatively, the (trans)-cyclopropanamine derivatives of formula (12) can be synthesized by reaction of aldehydes of formula (1) with nitromethane and ammonium acetate using tetrahydrofuran as a solvent, leading to the formation of nitrostyrene of formula (10). Later cyclopropanation reaction using trimetilsuifoxonium iodide and potassium tert-butoxide results in the formation of trans nitrocyclopropyl derivatives of formula (11) (obtained as a trans ((1S,2R), (1R,2S)) racemic mixture) and final reduction using zinc in hydrochloric acid affords the (trans)-cyclopropanamine derivatives of formula (12). 
     Reductive alkylation of the derivatives of formula (12) with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under standard conditions, for example using sodium triacetoxyborohydride or sodium borohydride as reducing agent in a suitable solvent such as dichloroethane or methanol leads to the formation of (trans)-cyclopropylamino derivatives of formula (14a), (14b) or (14c) respectively, which corresponds to a compound of formula I, and particularly Ia, wherein R w , R x , R y  and R z ═H. In case the ketones of formula (13a) or aldehydes of formula (13b) or (13c) containing a protected amino group, for example a Boc-protected amine (Boc: tert-Butyloxycarbonyl), an additional deprotection reaction step will be required to render a compound (14a), (14b) or (14c) respectively, which can be performed in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether, or using HCl in 1,4-dioxane. 
     Aldehydes of formula (1), alkyl halides of formula (7), ketones of formula (13a) and aldehydes of formula (13b) and (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     The compounds of Formula I wherein B=-L 1 -E, and R w , R x , R y  and R z ═H and L 1 =—(CH 2 )—O— (wherein x is as defined previously) can be synthesized, for example, by the general route described in Scheme 3 
     
       
         
         
             
             
         
       
     
     The alkylation of aldehydes of formula 1 (where R 1 ═—OH) using bromo derivatives of formula (15) (other halo derivatives could also be used) and a base, preferably potassium carbonate in a suitable solvent such as N,N-dimethylformamide leads to the formation of the aldehyde derivatives of formula (16). These are subjected to a Horner-Wadsworth-Emmons reaction under the same conditions disclosed in Scheme 2 to get the ethyl acrylate derivatives of formula (17) which are then subjected to cyclopropanation reaction under the same conditions disclosed in Scheme 2 to give the (trans)-ethyl cyclopropanecarboxylate derivatives of formula (18). Following the same conditions disclosed for the conversion of a compound (3) to a compound (6) in scheme 2, a compound (18) is converted into the (trans)-cyclopropanamine derivative of formula (21). Later alkylation with alkyl halides of formula (7) under basic conditions using for example NaH in a suitable solvent such as DMF leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (22). Deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether leads to the formation of the (trans)-cyclopropanamine derivatives of formula (23), which corresponds to a compound of formula I wherein B=-L 1 -E, R w , R x , R y  and R z ═H and L 1 =—(CH 2 )—O—. 
     Alternatively, the (trans)-cyclopropanamine derivatives of formula (26) can be synthesized from aldehydes of formula (16) by conversion into a nitrostyrene of formula (24), subsequent cyclopropanation to give a compound (25) and reduction of the nitro group under the same conditions disclosed in scheme 2 for the conversion of a compound (1) into a compound (12) via compounds (10) and (11). 
     Reductive alkylation of the derivatives of formula (26) with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under the conditions disclosed in scheme 1 or 2 yields compounds (27a), (27b) or (27c) respectively, which corresponds to a compound of formula I wherein B=-L 1 -E, and R w , R w , R y  and R z ═H and L 1 =—(CH 2 ) x —O—. In case the ketones of formula (13a) or aldehydes of formula (13b) or (13c) containing a protected amino group, for example a Boc-protected amine (Boc: tert-butoxycarbonyl), an additional deprotection reaction step will be required to render compounds (27a), (27b) or (27c) respectively, which can be performed in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or using HCl in 1,4-dioxane. 
     Aldehydes of formula (1, where R 1 ═—OH), bromo derivatives of formula (15) and ketones of formula (13a) or aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     The compounds of Formula I where B=-L 1 -E, and R w , R x , R y  and R z ═H and L 1 =—O— can be synthesized, for example, by the general route described in Scheme 4 
     
       
         
         
             
             
         
       
     
     Aldehydes of Formula (1, where R 1 ═Br) are subjected to a Horner-Wadsworth-Emmons reaction under the conditions disclosed in Scheme 2 to get the ethyl acrylate derivatives of formula (2, where R 1 ═Br) which are then subjected to cyclopropanation reaction under the same conditions disclosed in Scheme 2 for converting a compound (2) into (3), leading to the (trans)-ethyl cyclopropanecarboxylate derivatives of formula (3, where R 1 ═Br). Compounds of formula (3) (where R 1 ═Br) are converted into the corresponding (trans)-cyclopropanecarboxylic acid derivatives of formula (4, where R 1 ═Br), which are then converted into the (trans)-cyclopropanecarbonyl azide derivatives of formula (5, where R 1 ═Br) and then into the tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6, where R 1 ═Br) following the same conditions disclosed in Scheme 2. The reaction of the compounds (6, where R 1 ═Br) with hydroxy-derivatives of formula (28) using a palladium catalyst such as Tris(dibenzylideneacetone)dipalladium(0), Xantphos and a base such as sodium tert-butoxide in a suitable solvent such as dioxane leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (29). Alkylation with alkyl halides of formula (7) under basic conditions using for example NaH in a suitable solvent such as DMF leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (30). Deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane leads to the formation of the (trans)-cyclopropanamine derivatives of formula (31), which correspond to a compound of formula I wherein B=-L 1 -E, and R w , R x , R y  and R z ═H and L 1  is O. 
     Alternatively, deprotection of the Boc-group of derivatives of formula (29) in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane leads to the formation of the (trans)-cyclopropanamine derivatives of formula (32). Reductive alkylation with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under the conditions disclosed in Scheme 1 or 2 leads to the formation of (trans)-cyclopropylamino derivatives of formula (33a), (33b) or (33c) respectively, which correspond to a compound of formula I wherein B=-L 1 -E, R w , R x , R y  and R z ═H and L 1  is O. In case the ketones of formula (13a) or aldehydes of formula (13b) or (13c) containing a protected amino group, for example a Boc-protected amine (Boc:tert-butoxycarbonyl), an additional deprotection reaction step will be required to render compounds (33a), (33b) or (33c) respectively, which can be performed in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane. 
     Aldehydes of formula (1, where R 1 ═Br), hydroxy-derivatives of formula (28) and ketones of formula (13a) or aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     The compounds of Formula I wherein B=-L 1 -E, and R w , R x , R y  and R z ═H and L 1 =—NH— or —(CH 2 )—NH— can be synthesized, for example, by the general route described in Scheme 5. 
     
       
         
         
             
             
         
       
     
     Tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6, where R 1 ═Br), obtained following the same procedure disclosed in Scheme 4, are converted into the (trans)-cyclopropanamine derivatives of formula (34) by alkylation with alkyl halides of formula (7) under basic conditions using for example NaH in a suitable solvent such as DMF leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (34), which are then reacted with amino-derivatives of formula (35) using a palladium catalyst such as Tris(dibenzylideneacetone)dipalladium(0), Xantphos and a base such as sodium tert-butoxide in a suitable solvent such as dioxane to give the tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (36). Deprotection of the Boc-group of a compound (36) in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or using HCl in 1,4-dioxane leads to the formation of the (trans)-cyclopropanamine derivatives of formula (37), which correspond to compound of formula I wherein B=-L 1 -E, R w , R x , R y  and R z ═H and L 1 =—NH— or —(CH 2 ) x —NH—. 
     Alternatively, tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6, where R 1 ═Br), obtained following the same procedure disclosed in Scheme 4, are converted into the (trans)-cyclopropanamine derivatives of formula (12, where R 1 ═Br) by deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane. Reductive alkylation of compounds (12, R 1 ═Br) with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under the conditions disclosed in Scheme 1 leads to the formation of (trans)-cyclopropylamino derivatives of formula (38a), (38b) or (38c) respectively. Later reaction with di-t-butyl dicarbonate under basic conditions using for example triethylamine in a suitable solvent such tetrahydrofuran leads to the Boc-protected derivatives of formula (39a), (39b) or (39c) respectively. Reaction with amino-derivatives of formula (35) using a palladium catalyst such as Tris(dibenzylideneacetone)dipalladium(0), Xantphos and a base such as sodium tert-butoxide in a suitable solvent such as dioxane to give the tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (40a), (40b) or (40c) respectively. Deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane leads to the formation of the (trans)-cyclopropanamine derivatives of formula (41a), (41b) or (41c) respectively, which correspond to compound of formula I wherein B=-L 1 -E, R w , R x , R y  and R z ═H and L 1 =—NH— or —(CH 2 ) x —NH—. 
     Aldehydes of formula (1, where R 1 ═Br), amino-derivatives of formula (35) and ketones of formula (13a) or aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     The compounds of Formula I wherein R w ═F can be synthesized, for example, by the general route described in Scheme 6. This method is useful to obtain compounds having either a trans- or cis-configuration at the cyclopropyl ring (i.e. wherein the B-A- and —NH-D groups are in trans or cis configuration), or mixtures thereof, since the cyclopropanation reaction used yields a mixture of cis/trans isomers, as represented by the wavy line in Scheme 6, which can be used as such to obtain compounds of the invention as cis/trans mixtures, or can be separated if desired to yield at the end of the synthesis the desired cis or trans products. 
     
       
         
         
             
             
         
       
     
     Bromofluorination of derivatives of formula (42) using N-Bromosuccinimide and triethylamine trihydrofluoride in a suitable solvent such as dichloromethane leads to the formation of fluoro-derivatives of formula (43). Elimination reaction using a base, as for example potassium tert-butoxide in a suitable solvent, as for example pentane leads to fluoro-derivatives of formula (44). Cyclopropanation using ethyl diazoacetate and copper (II) acetylacetonate, as catalyst, in a suitable solvent such as dichloromethane leads to a 1:1 mixtures of cis- and trans-derivatives of formula (45). The diastereomers can be separated at this point either chromatographically or, after saponification (performed under basic conditions using for example NaOH in a suitable solvent such as MeOH), by recrystallisation of the corresponding carboxylic acids of formula (46). Curtius degradation to Boc-protected cyclopropylamines of formula (47) can be performed by using a base, as for example, triethylamine, diphenylphosphoryl azide and di-tert-butyl dicarbonate in a suitable solvent, as for example, tert-butanol. Deprotection of the Boc-group in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or HCl in 1,4-dioxane leads to the formation of the cyclopropanamine derivatives of formula (48). Reductive alkylation of the derivatives of formula (48) with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under standard conditions, for example using sodium triacetoxyborohydride as reducing agent in a suitable solvent such as dichloroethane leads to the formation of (trans)-cyclopropylamino derivatives of formula (49a), (49b) or (49c) respectively, which corresponds to a compound of formula I, wherein R w  ═F. In case the ketones of formula (13a) or aldehydes of formula (13b) or (13c) containing a protected amino group, for example a Boc-protected amine (Boc: tert-Butyloxycarbonyl), an additional deprotection reaction step will be required to render a compound (49a), (49b) or (49c) respectively, which can be performed in acidic conditions, for example using HCl 2M in diethyl ether in a suitable solvent such as diethyl ether or using HCl in 1,4-dioxane. 
     Compounds of formula (42) and ketones of formula (13a) or aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     Compounds of Formula I wherein R w  is H, fluoro or C 1-4  alkyl and R x , R y , R z ═H can be synthesized, for example, by the general route described in Scheme 7 below. This method is useful to obtain compounds wherein R w  is different from hydrogen having either a trans- or cis-configuration at the cyclopropyl ring (i.e. wherein the B-A- and —NH-D groups are in trans or cis configuration), as well as compounds of formula I wherein R w ,R x , R y , R z ═H (i.e. a compound of formula Ia) having a cis configuration, since the cyclopropanation reaction used yields a mixture of cis/trans isomers, as represented by the wavy line in Scheme 7, which can be separated to yield the desired cis or trans compounds of the invention. 
     
       
         
         
             
             
         
       
     
     Derivatives of formula (50) are subjected to cyclopropanation using ethyl diazoacetate and copper (I) chloride, as catalyst, in a suitable solvent as chloroform affording to a 1:1 mixtures of cis- and trans-derivatives of formula (51). Alternatively, the copper catalyst disclosed in Scheme 6 can be used. The diastereomers can be separated at this point either chromatographically or, after saponification (performed under basic conditions using for example NaOH in a suitable solvent such as MeOH), by recrystallisation of the corresponding carboxylic acids of formula (52). Curtius degradation to Boc-protected cyclopropylamines of formula (54) can be performed, first by using ethyl chloro formate and a base, as for example, triethylamine in a suitable solvent, as for example, acetone, and subsequent reaction with sodium azide in water leading to cyclopropanecarbonyl azide derivatives of formula (53). Reaction with tert-butanol results in the formation of Boc-protected cyclopropylamines of formula (54). Deprotection of the Boc-group in acidic conditions, for example using HCl in 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent leads to the formation of the cyclopropanamine derivatives of formula (55). Reductive alkylation with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under the same conditions disclosed in Scheme 2 leads to the formation of cyclopropylamino derivatives of the invention, designated as compounds of formula (56a), (56b) or (56c) in the above scheme, which corresponds to a compound of formula I, wherein R w  is H, fluoro or C 1-4  alkyl and R x , R y , R z ═H. In case the ketone of formula (13a) or the aldehydes of formula (13b) or (13c) contain a protected amino group, for example a Boc-protected amine (Boc: tert-butoxycarbonyl), an additional deprotection reaction step will be required to render a compound (56a), (56b) or (56c), which can be performed in acidic conditions, for example using HCl in 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent. 
     Compounds of formula (50), ketones of formula (13a) and the aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     The compounds of Formula I wherein B=-L 1 -E, and R w , R x , R y , R z ═H and L 1 =bond can be synthesized, for example, by the general route described in Scheme 8. 
     
       
         
         
             
             
         
       
     
     Tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6, where R 1 ═Br), obtained following the same procedure disclosed in Scheme 4, are converted into the (trans)-cyclopropanamine derivatives of formula (60) by reaction with boronic acid or ester derivatives of formula (59) using a suitable solvent such as acetonitrile and water, a base, such as for example potassium carbonate, and a palladium catalyst such as tetrakis(triphenylphospine)palladium (0). Deprotection of the Boc-group in acidic conditions, for example using HCl 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent leads to the formation of the (trans)-cyclopropanamine derivatives of formula (61). Reductive alkylation with ketones of formula (13a) or aldehydes of formula (13b) or (13c) under the same conditions disclosed in Scheme 2 leads to the formation of (trans)-cyclopropylamino derivatives of formula (62a), (62b) or (62c) which correspond to compounds of formula I wherein B=-L 1 -E, R w , R x , R y , R z ═H and L 1 =bond. When the ketones of formula (13a) or aldehydes of formula (13b) or (13c) contain a protected amino group, for example a Boc-protected amine (Boc: tert-butoxycarbonyl), an additional deprotection reaction step will be required to render a compound (62a), (62b) or (62c). The deprotection can be performed in acidic conditions, for example using HCl 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent. 
     Alternatively, (trans)-cyclopropylamino derivatives of formula (62a), (62b) or (62c) can be synthesized by reaction of Boc-protected derivatives of formula (39a), (39b) or (39c) with boronic acid or ester derivatives of formula (59) using a suitable solvent such as acetonitrile and water, a base, such as for example potassium carbonate, and a palladium catalyst such as tetrakis(triphenylphosphine)palladium (0) affording (trans)-cyclopropanamine derivatives of formula (63a), (63b) or (63c). Deprotection of the Boc-group in acidic conditions, for example using HCl 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent leads to the formation of the (trans)-cyclopropylamino derivatives of formula (62a), (62b) or (62c), which correspond to a compound of formula I, wherein B=-L 1 -E, R w , R x , R y , R z ═H and L 1 =bond. 
     Alternatively, alkylation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (6, where R 1 ═Br) with alkyl halides of formula (7) under basic conditions using for example NaH in a suitable solvent such as DMF leads to the formation of tert-butyl (trans)-cyclopropylcarbamate derivatives of formula (34). Reaction with boronic acid or ester derivatives of formula (59) using a suitable solvent such as acetonitrile and water, a base, such as for example potassium carbonate, and a palladium catalyst such as tetrakis(triphenylphospine)palladium (0) leads to the formation of compounds of formula (57). Deprotection of the Boc-group in acidic conditions, for example using HCl 1,4-dioxane in a suitable solvent such as 1,4-dioxane or HCl in Et 2 O using Et 2 O as solvent leads to the formation of the (trans)-cyclopropanamine derivatives of formula (58), which also correspond to a compound of formula I, wherein B=-L 1 -E, R w , R x , R y , R z ═H and L 1 =bond. 
     Aldehydes of formula (1), boronic acid or ester derivatives of formula (59) and ketones of formula (13a) or aldehydes of formula (13b) or (13c) are commercially available or can be prepared using well known synthetic procedures starting from readily available starting materials. 
     Furthermore, some compounds of the invention can be obtained from other compounds of formula I by appropriate interconversion reactions of functional groups present in a compound of formula I in one or several steps, using well known reactions in organic synthesis under standard experimental conditions. Said transformations can be carried out upon R 1 , R 2  and/or R 3  and may include, for example, the substitution of a primary or secondary amine or of an alcohol by treatment with an alkylating agent, the conversion of an amine into an amide, sulfonamide, carbamate or urea, the palladium-catalyzed cross-coupling of aryl halides with diboranes, boronic acids or esters or with amines, etc. Such interconversion reactions can be performed upon a compound of formula I as well as upon any suitable synthetic intermediate described in the above Schemes. 
     The salts of a compound of formula I can be obtained during the final isolation and purification of the compounds of the invention or can be prepared by treating a compound of formula I with a sufficient amount of the desired acid (or base) to give the salt in a conventional manner. 
     In the above schemes 2 to 5 the cyclopropanation reaction under the conditions disclosed always leads to a racemic mixture of the trans-isomers of compounds (3), (11), (18) and (25). If the synthetic procedures are continued using the trans racemic mixture thus obtained, the corresponding compounds of formula I are obtained as mixtures of trans-isomers. Likewise, in scheme 6 and 7 the cyclopropanaton reaction under the conditions disclosed leads to a mixture of cis/trans isomers of compounds (45) and (51). If the synthetic procedure is continued using said isomer mixture, the corresponding compounds of formula I are obtained as mixtures of cis/trans isomers. As used herein, cis and trans refers to the disposition of groups -A-B versus —NH-L2-D on the cyclopropyl ring. 
     Where the processes for the preparation of the compounds of the invention give rise to mixtures of stereoisomers, individual stereoisomers of a compound of formula I can be obtained by separation from a compound of formula I obtained as a mixture of stereoisomers, using well known methods such as formation of diastereomeric pairs by salt formation with an optically active acid followed by fractional crystallization and regeneration of the free base, or by chiral preparative chromatography. Alternatively, it is possible to obtain optically pure or enantiomerically enriched synthetic intermediates, which can then be used as such in subsequent steps, at various stages of the synthetic procedures described above, using any known method for chiral resolution. Preferably, the chiral separation is performed upon trans-cyclopropylamines of formula (12), (26), (32), (48), (55) and (61). Separation can also be performed at other stages of the procedure, for example upon a compound of formula (45). A suitable method to obtain the enantiomers of the trans cyclopropylamines (12), (26), (32), (48), (55) and (61) comprises contacting a trans-substituted cyclopropylamine with a chiral recrystallization agent in a solvent (particularly under conditions that are sufficient for the crystallization of the salt of the chiral recrystallization agent and the trans substituted cyclopropylamine); and isolating the crystallized salt of the chiral recrystallization agent and the trans substituted cyclopropylamine, thereby preparing an enatiomer of a trans N-substituted cyclopropylamine. A suitable chiral recrystallization agent is S (+) mandelic acid, D (−) tartaric acid, L (+) tartaric acid, L (−) di-p-toluoyl tartaric acid, or R (−) mandelic acid. Suitable solvents are tetrahydrofuran, ethanol or mixtures thereof with H 2 O. 
     Alternatively, it is possible for a person skilled in the art to obtain optically pure or enantiomerically enriched final compounds (or synthetic intermediates) by using chiral chromatography. 
     EXAMPLES 
     Unless stated otherwise, in the compounds of all Examples of the present specification the stereochemical configuration is defined by the chemical name indicated for the respective compound, even though the drawn structure may represent a more specific configuration. Nevertheless, the invention relates to all stereoisomers of the compounds described and defined herein. Accordingly, the invention encompasses the compounds described in the Examples as defined by their chemical names and, in addition thereto, also the corresponding compounds having the absolute configuration shown in the respective drawn structures. 
     The following abbreviations have been used: 
     ACN: acetonitrile, AcOH: acetic acid, aq: aqueous, Boc: tert-butyloxycarbonyl, (Boc) 2 O: di-tert-butyl dicarbonate, brm: broad multiplet, brs: broad singlet, Cu(acac) 2 : copper(II) acetylacetonate, d: doublet, DCE: 1,2-dichloroethane, DCM: dichloromethane, DMF: N,N-dimethylformamide, DMSO: dimethylsulfoxide, DPPA: diphenylphosphoryl azide, Et 2 O: diethyl ether, EtOAc: ethyl acetate, HPLC: high performance liquid chromatography, m: multiplet, MEM: methoxy methyl ether, MeOH: methanol, NBS: N-bromosuccinimide, NMR: nuclear magnetic resonance, Pd 2 (dba) 3 : tris(dibenzylideneacetone)dipalladium(0), Pet ether: petroleum ether, q: quadruplet, Rf: retention factor, RT: room temperature, s: singlet, sat.: saturated, t: triplet, TEA: triethylamine, THF: tetrahydrofuran, TLC: thin layer chromatography, vbrs: very broad singlet, Xantphos: 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene. 
     Intermediate A: 1-(benzyloxy)-4-[(trans)-2-nitrocyclopropyl]benzene 
     
       
         
         
             
             
         
       
     
     Trimethylsulfoxonium iodide (0.62 g, 2.82 mmol) was added in portions to a solution of t-BuOK (0.32 g, 2.82 mmol) in dry DMSO (5 mL). After 10 min a solution of 1-(benzyloxy)-4-[(E)-2-nitrovinyl]benzene (0.60 g, 2.35 mmol) in DMSO (5 mL) was transferred via canula and the mixture was stirred at room temperature for 6 h. The reaction was poured over water (10 mL) and extracted with Et 2 O (3×10 mL); the organic layers were washed with brine (2×15 mL), dried over anhydrous Na 2 SO 4  and filtered. After removal of the solvent, the residual orange oil was purified by column chromatography on silica gel (5% EtOAc/hexanes) affording 0.16 g of 1-(benzyloxy)-4-[(trans)-2-nitrocyclopropyl]benzene [Rf=0.5 (20% EtOAc/hexanes), white solid, 26% yield]. 
     Intermediate B: Trans-2-[4-(benzyloxy)phenyl]cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Zn dust (1.97 g, 30 mol) was added in small portions, over a period of 30 min, to a vigorously stirred solution of 1-(benzyloxy)-4-[(trans)-2-nitrocyclopropyl]benzene (intermediate A, 0.81 g, 3.0 mmol) in i-PrOH (25 mL) and HCl (11 mL of aqueous solution 2.7 N, 30 mmol). After 17 h the mixture was filtered through a pad of celite, that was washed with 10 mL of methanol. The filtrate was concentrated and 10 mL of water were added, washing with CH 2 Cl 2  (3×15 mL). The organic layers were dried over anhydrous Na 2 SO 4  and filtered. After removal of the solvent, the crude product was purified by column chromatography on silica gel (10% MeOH/CH 2 Cl 2 ) affording 0.50 g of (trans)-2-[4-(benzyloxy)phenyl]cyclopropanamine [Rf=0.2 (10% MeOH/CH 2 Cl 2 ), white solid, 70% yield]. 
       1 H-NMR (MeOH, 250 MHz, δ): 7.45-7.27 (m, 5H, ArH); 6.96 (d, J=8.5 Hz, 2H, ArH); 6.86 (d, J=8.5 Hz, 2H, ArH); 5.03 (s, 2H, CH2); 2.41-2.34 (m, 1H, CH); 1.86-1.76 (m, 1H, CH); 0.98-0.85 (m, 2H, CH2). 
     Intermediate C: 4-(benzyloxy)benzaldehyde 
     
       
         
         
             
             
         
       
     
     Potassium Carbonate (678 g, 4.91 mol) was added to a solution of 4-hydroxybenzaldehyde (200 g, 1.63 mol) in DMF (2 L) followed to the addition of benzyl bromide (214 mL, 1.80 mol) at 0° C. and stirred for 18 h at RT. After completion, the reaction mixture was poured into ice water (3 L), filtered the solid and dried to get 4-(benzyloxy)benzaldehyde (230 g, 66%). 
     Intermediate D: (E)-ethyl 3-(4-(benzyloxy)phenyl)acrylate 
     
       
         
         
             
             
         
       
     
     Triethyl phosphonoacetate (259 mL, 1.3 mol) was added slowly dropwise to a solution of Potassium-tert-butoxide (145 g, 1.29 mol) in dry THF (2 L) at −5° C. and stirred for 30-45 mins. Then a solution of 4-(benzyloxy)benzaldehyde (Intermediate C, 230 g, 1.08 mol) in dry THF (1.5 L) was added slowly dropwise at −10° C. over a period of 15 mins and stirred for 30 mins. After completion, the reaction mixture was poured into ice water (1 L) and extracted with EtOAc (2×1.5 L). The combined organic extracts were washed with sat NaHCO 3  solution (1 L), water (1 L), brine (1 L), dried over anhydrous Na 2 SO 4 , filtered and evaporated to get crude (E)-ethyl 3-(4-(benzyloxy)phenyl)acrylate (290 g, 95%). The crude was carried to next step without further purification. 
     Intermediate E: (Trans)-ethyl 2-(4-(benzyloxy)phenyl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (224 g, 1.02 mol) was added portion wise to a suspension of NaH (40.8 g, 1.02 mol) in dry DMSO (2 L) at RT over a period of 20 min and stirred for 1 h till the formation of a clear solution. A solution of (E)-ethyl 3-(4-(benzyloxy) phenyl) acrylate (intermediate D, 240 g, 0.85 mol) in dry DMSO (2 L) was added dropwise and stirred at RT for 30 mins. After completion, the reaction mixture was poured into ice water (2 L), extracted with EtOAc (2×1 L). Combined organic extracts were washed with ice water (1 L), brine (1 L), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (Trans)-ethyl 2-(4-(benzyloxy)phenyl)cyclopropanecarboxylate (142 g, 58.6%) as an off white solid. The crude was carried to next step without further purification. 
     Intermediate F: (Trans)-2-(4-(benzyloxy)phenyl)cyclopropanecarboxylic Acid 
     
       
         
         
             
             
         
       
     
     4N NaOH solution (4 L) was added to a solution of (trans)-ethyl 2-(4-(benzyloxy)phenyl)cyclopropanecarboxylate (Intermediate E, 250 g, 0.844 mol) in Methanol (1.2 L) at 0° C. and stirred at RT for 4 h. After completion, the solvent was evaporated, the residue was diluted with water (1 L), acidified with 4 N HCl solution, extracted with EtOAc (2×2 L). Combined organic extracts were washed with water (1 L), brine (1 L), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-2-(4-(benzyloxy)phenyl)cyclopropanecarboxylic acid (190 g, 84%) as off white solid. The crude was carried to next step without further purification. 
     Intermediate G: (Trans)-2-(4-(benzyloxy)phenyl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (143 mL, 1.48 mol) was added to a solution of (trans)-2-(4-(benzyloxy) phenyl) cyclopropanecarboxylic acid (Intermediate F, 190 g, 0.70 mol), Triethyl amine (229 mL, 1.63 mol) in acetone (2.8 L) at −20° C. and stirred for 1 h, then a solution of NaN 3  (138 g, 2.1 mol) in water (200 mL) was added and stirred at RT for 30 mins. After completion, the solvent was evaporated, residue was dissolved in EtOAc (2 L), washed with water (2 L), brine (1 L), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-2-(4-(benzyloxy)phenyl)cyclopropanecarbonyl azide (178 g, 85.9%). 
     Intermediate H: Tert-butyl ((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of (trans)-2-(4-(benzyloxy)phenyl)cyclopropanecarbonyl azide (Intermediate G, 178 g, 0.64 mol) in tert-butanol (2.6 L) was heated at 90° C. for 16 h. After completion, the solvent was evaporated and the crude residue was purified by column chromatography by using (SiO 2 ) EtOAc: Pet ether (4:96) to get tert-butyl ((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)carbamate (78 g, 37.8%) as off-white solid. 
     Intermediate I: (E)-ethyl 3-(6-bromopyridin-3-yl)acrylate 
     
       
         
         
             
             
         
       
     
     Triethyl phosphonoacetate (26.6 g, 118.8 mmol) was added slowly dropwise to a mixture of Potassium-tert-butoxide (14.5 g, 129.6 mmol) in dry THF (200 mL) at −5° C., stirred for 20 min and then a solution of 6-bromopyridine-3-carboxaldehyde (20 g, 108 mmol) in dry THF (100 mL) was added slowly dropwise at −5° C. and stirred for 30 min. After completion, the reaction mixture was poured into ice water (350 mL) and extracted with EtOAc (2×300 mL). The combined organic extracts were washed with saturated NaHCO 3  solution (250 mL), water (250 mL) and brine (250 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated to get (E)-ethyl 3-(6-bromopyridin-3-yl) acrylate (20 g, 72.9%) as brown color liquid. This is carried to next step without further purification. 
     Intermediate J: (Trans)-ethyl-2-(6-bromopyridin-3-yl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (20.8 g, 94.7 mmol) was added in small portions to a suspension of sodium hydride (4 g, 170.6 mmol) in dry DMSO (400 mL) at rt., stirred for 1 h until clear solution was obtained. A solution of (E)-ethyl 3-(6-bromopyridin-3-yl) acrylate (Intermediate I, 20 g, 78.7 mmol) in dry DMSO (20 mL) was added and stirred for 4 h. After completion, the reaction mixture was poured into ice water (700 mL), extracted with EtOAc (2×350 mL). The combined organic extracts were washed with water (250 mL), brine (250 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated to give (trans)-ethyl-2-(6-bromopyridin-3-yl)cyclopropanecarboxylate (10 g, 47%) as brown liquid. 
     Intermediate K: (Trans)-2-(6-bromopyridin-3-yl)cyclopropanecarboxylic acid hydrochloride 
     
       
         
         
             
             
         
       
     
     NaOH 4N solution (60 mL) was added to a solution of (trans -ethyl-2-(6-bromopyridin-3-yl)cyclopropanecarboxylate (Intermediate J, 10 g, 37.1 mmol) in methanol (100 mL) and the reaction mixture was stirred at RT for 4 h. After completion, the solvent was evaporated and the residue was diluted with ice water (250 mL) and acidified with 4 N HCl solution, the aqueous layer was extracted with EtOAc (2×350 mL). The combined organic extracts were washed with water (250 mL), brine (250 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated to give (trans)-2-(6-bromopyridin-3-yl)cyclopropanecarboxylic acid hydrochloride (5 g, 55.8%) as a light brown color solid. 
     Intermediate L: (Trans)-2-(6-bromopyridin-3-yl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (5.8 mL, 62 mmol) was added to a solution of (trans)-2-(6-bromopyridin-3-yl)cyclopropanecarboxylic acid hydrochloride (Intermediate K, 5 g, 20.7 mmol) and Et 3 N (14.2 mL, 103.7 mmol) in Acetone (100 mL) at −5° C., then reaction mixture was stirred at −5° C. for 1 h, then a solution of NaN 3  (2.7 g, 41.4 mmol) in water (10 mL) was added and stirred for 30 mins at RT. After completion the solvent was evaporated under vacuum. The crude residue was dissolved in ethyl acetate (200 mL), washed with water (80 mL), brine (80 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to get (trans)-2-(6-bromopyridin-3-yl)cyclopropanecarbonyl azide (2.5 g, 45.5%) as a brown color gummy liquid. 
     Intermediate M: tert-butyl (trans)-2-(6-bromopyridin-3-yl)cyclopropylcarbamate 
     
       
         
         
             
             
         
       
     
     A solution of (trans)-2-(6-bromopyridin-3-yl)cyclopropanecarbonyl azide (Intermediate L, 2.5 g, 9.36 mmol) in tert-butanol (80 mL) was heated at 90° C. for 16 h. After completion, the solvent was evaporated under vacuum and the residue was taken in water (100 mL) and extracted with EtOAc (2×100 mL). The combined organic extracts were washed with water (100 mL), brine (100 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by flash column chromatography (SiO 2 ) by eluting with EtOAc: Hexane (2:8) t o get tert-butyl (trans)-2-(6-bromopyridin-3-yl)cyclopropylcarbamate (1.1 g, 37.5%) as a light yellow solid. 
       1 H-NMR (CDCl 3 ) δ (ppm): 1.16 (q, 1H), 1.23 (quin, 1H), 1.45 (s, 9H), 2.01 (m, 1H), 2.69 (in, 1H), 4.88 (br, 1H), 7.36 (s, 2H), 8.20 (s, 1H). 
     Intermediate N: (E)-ethyl 3-(4-bromophenyl)acrylate 
     
       
         
         
             
             
         
       
     
     A solution of triethyl phosphonoacetate (13.1 g, 0.0589 mol) was added slowly (dropwise) to a solution of Potassium-tert-butoxide (6.9 g, 0.0589 mol), in dry THF (150 mL) at -5° C., stirred for 30-45 mins at the same temperature, then a solution of 4-Bromo benzaldehyde (10 g, 0.054 mol), in dry THF (50 mL) was slowly added dropwise at −5° C. over a period of 15 mins, stirred the reaction mixture for 30 mins at the same temperature. After completion of reaction by TLC, the reaction mixture was poured into ice water (300 mL), extracted with EtOAc (2×200 mL). The combined organic extracts were washed with sat NaHCO 3  solution (200 mL), water (200 mL), brine (200 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated to get crude (E)-ethyl 3-(4-bromophenyl) acrylate (10 g, 72%) as pale green liquid. This is carried to next step without further purification. 
     Intermediate 0: (Trans)-ethyl 2-(4-bromophenyl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (5.19 g, 0.0236 mol) was added slowly in small portions over a period of 20 min. to a suspension of sodium hydride (0.44 g, 0.0236 mol) in dry DMSO (80 mL) at rt, stirred for 1 h, till the formation of clear solution. Then a solution of (E)-ethyl 3-(4-bromophenyl) acrylate (Intermediate N, 5 g, 0.01968), in dry DMSO (20 mL) was added slowly dropwise, stirred at rt for 30 mins. After completion of reaction, checked by TLC, the reaction mixture was poured into ice water (200 mL), extracted with EtOAc (2×150 mL). Combined organic extracts were washed with ice water (2×150 mL), brine (150 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to get (trans)-ethyl 2-(4-bromophenyl)cyclopropanecarboxylate (4 g, 75.9%) as a green liquid. The crude is carried to next step without further purification. 
     Intermediate P: (Trans)-2-(4-bromophenyl)cyclopropanecarboxylic acid 
     
       
         
         
             
             
         
       
     
     NaOH 4N (20 mL) was added to a solution of (trans)-ethyl 2-(4-bromophenyl)cyclopropanecarboxylate (Intermediate O, 4 g, 0.0149 mol), in Methanol (40 mL) and stirred at rt for 2 h. After completion of reaction, checked by TLC, the solvent was evaporated and the residue was diluted with water (50 mL), acidified with HCl 4 N solution, the solid formed was filtered and dried to get (trans)-2-(4-bromophenyl)cyclopropanecarboxylic acid (2.59 g, 72%), as a white solid. 
     Intermediate Q: (Trans)-2-(4-bromophenyl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (1.9 mL) was added to a solution of (trans)-2-(4-bromophenyl) cyclopropanecarboxylic acid (Intermediate P, 4 g, 0.0165 mol) and Et 3 N (2.51 mL, 0.0199 mol) in acetone (60 mL) at −20° C., stirred at same temperature for 1 h, then a solution of NaN 3  (1.3 g, 0.0199 mol) in water (5 mL), was added and stirred for 30 mins at rt. After completion of reaction, checked by TLC, the solvent was evaporated and crude residue was dissolved in ethyl acetate (100 mL), washed with water (40 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to get (trans)-2-(4-bromophenyl)cyclopropanecarbonyl azide (4 g). The crude residue is carried to next step without further purification. 
     Intermediate R: tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate 
     
       
         
         
             
             
         
       
     
     A solution of (trans)-2-(4-bromophenyl) cyclopropanecarbonyl azide (Intermediate Q, 4 g) in tert-Butanol (40 mL) was heated at 90° C. for 16 h. After completion of reaction, checked by TLC, the solvent was evaporated residue was poured into water (50 mL), extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ) by eluting with EtOAc: Petroleum ether (2:98), to get tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (2.5 g, 48% overall 2 steps) as a white solid. 
       1 H-NMR (CDCl 3 , 250 MHz) δ: 1.07-1.19 (m, 2H), 1.44 (s, 9H); 2.05-1.94 (m, 1H); 2.72-2.62 (m, 1H); 4.85 (br, 1H,); 7.09-6.96 (m, 2H); 7.44-7.33 (m, 2H). 
     Intermediate S: (E)-ethyl 3-(pyridin-3-yl)acrylate 
     
       
         
         
             
             
         
       
     
     A solution of triethyl phosphonoacetate (66.75 mL, 336.44 mmol) was added dropwise to a solution of Potassium-tert-butoxide (37.7 g, 280.37 mmol) in dry THF (300 mL) at −5° C. over a period of 10 mins and stirred at 0° C. for 30 mins. Then a solution of nicotinaldehyde (30 g, 280.37 mmol) in dry THF (50 mL) was added dropwise at 0° C. over a period of 15 mins and stirred at RT for 2 h. After completion, the reaction mixture was poured into ice water (150 ml) and extracted with EtOAc (2×300 mL). The combined extracts were washed with sat NaHCO 3  solution (200 mL), water (200 mL), brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford crude liquid (E)-ethyl 3-(pyridin-3-yl) acrylate (42 g, 84.67%). The crude was carried to next step without further purification. 
     Intermediate T: (Trans)-ethyl 2-(pyridin-3-yl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (14.90 g, 67.76 mmol) was added portion wise to a suspension of NaH (2.71 g, 67.76 mmol) in dry DMSO (100 mL) at RT over a period of 20 min. and stirred for 1 h till the formation of a clear solution. A solution of (E)-ethyl 3-(pyridin-3-yl) acrylate (Intermediate S, 10 g, 56.47 mmol) in dry DMSO (50 mL) was added dropwise and stirred at RT for 20 min. After completion, the reaction mixture was poured into ice water (200 mL), extracted with EtOAc (2×200 mL). Combined organic extracts were washed with ice water (150 mL), brine (150 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-ethyl 2-(pyridin-3-yl)cyclopropanecarboxylate (4 g, 37.07%) as pale brown liquid. The crude was carried to next step without further purification. 
     Intermediate U: (Trans)-2-(pyridin-3-yl)cyclopropanecarboxylic Acid 
     
       
         
         
             
             
         
       
     
     A solution of NaOH (7.116 g in 45 mL of H 2 O, 177.92 mmol) was added to a solution of (trans)-ethyl 2-(pyridin-3-yl) cyclopropanecarboxylate (Intermediate T, 17 g, 88.96 mmol) in Methanol (170 mL) at 0° C. and stirred at RT for 16 h. After completion, the solvent was evaporated, the residue was diluted with water (50 mL), neutralized with Acetic acid and extracted with EtOAc (4×100 mL). The combined extracts were washed with water (100 mL), brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-2-(pyridin-3-yl)cyclopropanecarboxylic acid (9 g, 62.06%) as off white solid. The crude was carried to next step without further purification. 
     Intermediate V: (Trans)-2-(pyridin-3-yl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (6.89 mL, 71.15 mmol) was added to a solution of (trans)-2-(pyridin-3-yl)cyclopropanecarboxylic acid (Intermediate U, 9 g, 55.194 mmol) and triethyl amine (11.03 mL, 82.79 mmol) in acetone (90 mL) at −20° C. and stirred for 1 h, then a solution of NaN 3  (5.38 g, 82.79 mmol) in water (25 mL) was added and stirred at RT for 30 mins. After completion, the solvent was evaporated, residue was dissolved in EtOAc (100 mL), washed with water (2×50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-2-(pyridin-3-yl)cyclopropanecarbonyl azide (8.4 g, 81%). The crude was carried to next step without further purification. 
     Intermediate W: tert-butyl ((trans)-2-(pyridin-3-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of (trans)-2-(pyridin-3-yl)cyclopropanecarbonyl azide (Intermediate V, 8.4 g, 44.66 mmol) in tert-butanol (85 mL) was heated at 90° C. for 16 h. After completion, the solvent was evaporated and crude residue was purified by column chromatography (SiO 2 ) using EtOAc: Petroleum ether (25:75) to afford tert-butyl (trans)-2-(pyridin-3-yl) cyclopropylcarbamate (3.9 g, 37.32%) as colourless liquid. 
     Intermediate X: (Trans)-2-(pyridin-3-yl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in Dioxane (10 mL) was added to a solution of tert-butyl (trans)-2-(pyridin-3-yl)cyclopropylcarbamate (Intermediate W, 2 g, 8.54 mol) in 1,4-dioxane (10 mL) at 0° C. and stirred at RT for 12 h After completion, the solvent was evaporated and the residue was triturated with diethyl ether (20 mL) followed by hexane (20 mL) to get (trans)-2-(pyridin-3-yl)cyclopropanamine hydrochloride (1.2 g, 82.7%). 
     Intermediate Y: (E)-ethyl 3-(thiazol-5-yl)acrylate 
     
       
         
         
             
             
         
       
     
     A solution of triethyl phosphonoacetate (11.88 g, 53.03 mmol) was added dropwise to a solution of Potassium-tert-butoxide (5.94 g, 53.03 mmol) in dry THF (100 mL) at −5° C. and stirred for 30 mins. A solution of thiazole-5-carbaldehyde (5 g, 44.19 mmol) in dry THF (25 mL) was then added dropwise at -5° C. over a period of 15 mins and stirred for 30 mins. After completion, the reaction mixture was poured into ice water (150 mL), extracted with EtOAc (2×100 mL). The combined extracts were washed with sat NaHCO 3  solution (100 mL), water (100 mL), brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford crude (E)-ethyl 3-(thiazol-5-yl)acrylate (10 g, 82.3%) as a white solid. The crude was carried to next step without further purification 
     Intermediate Z: (Trans)-ethyl 2-(thiazol-5-yl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (14.40 g, 65.49 mmol) was added portionwise to a suspension of NaH (2.61 g, 108.75 mmol) in dry DMSO (200 mL) at RT over a period of 20 min and stirred for 1 h till the formation of clear solution. A solution of (E)-ethyl 3-(thiazol-5-yl)acrylate (Intermediate Y, 10 g, 54.57 mmol) in dry DMSO (50 mL) was then added dropwise and stirred at RT for 30 mins. After completion, the reaction mixture was poured into ice water (100 mL) and extracted with EtOAc (2×100 mL). Combined organic extracts were washed with water (2×50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford trans-ethyl 2-(thiazol-5-yl)cyclopropanecarboxylate (8 g, 61.9%) as a reddish brown liquid. The crude was carried to next step without further purification. 
     Intermediate AA: (Trans)-2-(thiazol-5-yl)cyclopropanecarboxylic acid 
     
       
         
         
             
             
         
       
     
     A 4N NaOH solution (40 mL) was added to a solution of trans-ethyl 2-(thiazol-5-yl)cyclopropanecarboxylate (Intermediate Z, 8 g, 40.55 mmol) in methanol (80 mL) and stirred at RT for 4 h. After completion, the solvent was evaporated, the residue was diluted with water (50 mL), acidified with Acetic acid and extracted with EtOAc (2×75 mL). The combined extracts were washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford trans-2-(thiazol-5-yl)cyclopropanecarboxylic acid (4 g, 58.30%). The crude was carried to next step without further purification. 
     Intermediate AB: (Trans)-2-(thiazol-5-yl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (3.34 g, 30.76 mmol) was added to a solution of trans-2-(thiazol-5-yl)cyclopropanecarboxylic acid (Intermediate AA, 4 g, 26.3 mmol) and triethylamine (3.62 g, 35.50 mmol) in acetone (40 mL) at −20° C., stirred at same temperature for 1 h. A solution of NaN 3  (2.84 g, 47.33 mmol) in water (10 mL) was then added and stirred at RT for 30 mins. After completion, the solvent was evaporated, the crude residue was dissolved in EtOAc (100 mL), washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford trans-2-(thiazol-5-yl)cyclopropanecarbonyl azide (3 g, 58.7%) as brown liquid. The crude was carried to next step without further purification. 
     Intermediate AC: tert-butyl ((trans)-2-(thiazol-5-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of trans-2-(thiazol-5-yl)cyclopropanecarbonyl azide (Intermediate AB, 3 g, 15.44 mmol) in tert-butanol (60 mL) was heated at 90° C. for 16 h. After completion, the solvent was evaporated and the residue was taken in water (50 mL), extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ) by using EtOAc: Petroleum ether (20:80) to get tert-butyl trans-2-(thiazol-5-yl)cyclopropylcarbamate (1.1 g, 29.64%) as a pale yellow liquid. 
     Intermediate AD: (Trans)-2-(thiazol-5-yl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in dioxane (10 mL) was added to a solution of tert-butyl trans-2-(thiazol-5-yl)cyclopropylcarbamate (intermediate AC, 1.1 g, 45.83 mmol) in dioxane (10 mL) at 15° C. and stirred at RT for 3 h. After completion, the solvent was evaporated, the residue was triturated with EtOAc to afford trans-2-(thiazol-5-yl)cyclopropanamine hydrochloride (600 mg, 74.8%) as pale yellow solid. 
     Intermediate AE: tert-butyl ((trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of tert-butyl (trans)-2-(6-bromopyridin-3-yl)cyclopropylcarbamate (Intermediate M, 100 mg, 0.32 mmol), potassium carbonate (132 mg, 0.96 mmol) and 3-trifluoromethylbenzeneboronic acid (72 mg, 0.38 mmol) in CH 3 CN:H 2 O (4:1) (10 mL) was degassed for 30 mins. Tetrakis triphenylphosphine palladium (37 mg, 0.032 mmol) was added and degassed for 10 mins and the reaction mixture was heated at reflux temperature for 2 h. After completion, the reaction mixture was poured in ice water (100 mL), extracted with ethyl acetate (5×40 mL). The combined extract was washed with water (70 mL), brine (70 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ), by using EtOAc:Petroleum ether (1:9) to get tert-butyl (trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropylcarbamate (70 mg, 58.3%) as a white solid. 
       1 H-NMR (CDCl 3 ) δ (ppm): 1.26 (m, 2H), 1.46 (s, 9H), 2.10 (m, 1H), 2.78 (m, 1H), 4.86 (br, 1H), 7.55 (m, 2H), 7.65 (t, 2H), 8.14 (d, 1H), 8.24 (s, 1H), 8.54 (s, 1H). MS (M+H): 379.1. 
     Intermediate AF: (Trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropanamine dihydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in diethyl ether (5 mL) was added to a solution of tert-buty (trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropylcarbamate (Intermediate AE, 70 mg, 0.185 mmol) in diethyl ether (10 mL) at 0° C. slowly dropwise over a period of 10 mins and then stirred for 2 h. After completion, the reaction mixture was filtered under inert atmosphere and washed with hexane (10 mL), EtOAC (5 mL), and dried under reduced pressure to get (trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropanamine dihydrochloride (50 mg, 86.2%) as a pale yellow powder. 
       1 H-NMR (D 2 O) δ (ppm): 1.52 (q, 1H), 1.63 (quin, 1H), 2.66 (m, 1H), 3.08 (m, 1H), 7.72 (t, 1H), 7.89 (d, 1H), 7.98 (d, 1H), 8.09 (s, 1H), 8.14 (d, 1H), 8.27 (d, 1H), 8.61 (s, 1H). MS (M+H): 279.1. 
     Intermediate AG: tert-butyl ((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate R, 1 g, 3.2 mmol), potassium carbonate (1.31 g, 9.6 mmol) and 3-(trifluoromethyl) phenylboronic acid (0.73 g, 3.8 mmol) in acetonitrile:water (4:1) was degassed for 30 mins. Tetrakis triphenylphosphine palladium (36 mg, 0.032 mmol) was then added, degassed again for 10 mins and the reaction mixture was heated at reflux temperature for 5 h. After completion, the reaction mixture was poured in ice water (50 mL) and extracted with ethyl acetate (2×50 mL). Combined extracts were washed with water (70 mL), brine (70 mL), dried over anhydrous Na 2 SO 4  and then filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ), by using EtOAc: Petroleum ether (2:8) to get tert-butyl ((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (0.8 g, 66%) as a white solid. 
     Intermediate AH: (Trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in diethyl ether (3 mL) was added slowly dropwise to a solution of tert-butyl ((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (Intermediate AG, 200 mg, 0.53 mmol) in diethyl ether (5 mL) at 10° C. over a period of 10 min and then stirred for 4 h. After completion, the solvent was evaporated and the residue was triturated with hexane (5 mL), diethyl ether (5 mL) and dried under reduced pressure to get (trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine hydrochloride (140 mg, 77.8%) as a white solid. 
       1 H-NMR (DMSO-d6) δ (ppm): 1.27 (q, 1H), 1.46 (quin, 1H), 2.41 (m, 1H), 2.86 (m, 1H), 7.29 (d, 2H), 7.69 (m, 4H), 7.96 (m, 2H), 8.53 (s, 1H), 8.61 (br, 2H). MS (M+H): 278.3 
     Intermediate AI: (1R,2S)-2-phenylcyclopropanamine 
     
       
         
         
             
             
         
       
     
     L (+) tartaric acid (15.7 g, 0.105 mmol) was added to a solution of (trans)-2-phenylcyclopropanamine (14 g, 0.105 mol) in EtOH (150 mL) at 0° C. and stirred at RT for 1 h. After completion, solid was filtered and dried to afford tartarate salt (28 g, 94.2%). The salt was taken in isopropanol: water (3:1) (260 mL) and stirred at 70° C. for 2 h. The clear solution was allowed to cool to RT. The solid separated was collected by filtration, taken in water (100 mL), basified with NaHCO 3  solution, and extracted with EtOAc (2×150 mL). The combined extracts were washed with water (150 mL), brine (150 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (1R,2S)-2-phenylcyclopropanamine (4.7 g, 67.1%). 
     Intermediate AJ: (1S,2R)-2-phenylcyclopropanamine 
     
       
         
         
             
             
         
       
     
     D (−) tartaric acid (6.7 g, 45.1 mmol) was added to a solution of (1S,2R)-2-phenylcyclopropanamine (crude of the reaction to get Intermediate AI)(6 g, 45.1 mmol) in EtOH (60 mL), at 0° C. and stirred at RT for 1 h. After completion, solid was filtered and dried to afford tartarate salt (12 g, 94.4%). The salt was taken in Isopropanol: water (3:1) (120 mL) and stirred at 70° C. for 2 h. The clear solution was allowed to cool to RT. The solid separated was collected by filtration, taken in water (75 mL), basified with NaHCO 3  solution, and extracted with EtOAc (2×75 mL). The combined extracts were washed with water (100 mL), brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (1S,2R)-2-phenylcyclopropanamine (3 g, 50%). 
     Intermediate AK: 4-((2-methoxyethoxy)methoxy)benzaldehyde 
     
       
         
         
             
             
         
       
     
     4-hydroxybenzaldehyde (50 g, 409 mmol) in THF (50 mL) was added dropwise and slowly over a period of 30 min to a suspension of sodium hydride (19.6 g, 817 mmol) in THF (750 mL) at 0° C. and stirred for 15 min, followed by addition of 1-(chloromethoxy)-2-methoxyethane (MEM chloride, 61.10 g, 490 mmol) at 0° C. The reaction mixture was stirred at RT for 30 min and, after completion, poured into ice water (500 mL) and extracted with EtOAc (2×750 mL). The combined organic extracts were washed with ice water (500 mL), brine (500 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated affording 4-((2-methoxyethoxy)methoxy)benzaldehyde (52 g, 60%) as a pale yellow liquid. The crude was used in the next step without further purification. 
     Intermediate AL: (E-ethyl 3-(4-((2-methoxyethoxy)methoxy)phenyl)acrylate 
     
       
         
         
             
             
         
       
     
     Triethyl phosphonoacetate (66.53 g, 296.8 mmol) was added to a solution of potassium-tert-butoxide (33.3 g, 296.8 mmol) in dry THF (500 mL) at −5° C. and stirred for 30-45 min at the same temperature. Then, a solution of 4-((2-methoxyethoxy)methoxy)benzaldehyde (Intermediate AK, 52 g, 247 mmol) in dry THF (100 mL) was added dropwise over a period of 15 min at −5° C. and stirred for 30 min at the same temperature. After completion, the reaction mixture was poured into ice water (600 mL) and extracted with EtOAc (2×600 mL). The combined extracts were washed with saturated aq. NaHCO 3  (300 mL), water (300 mL), brine (300 mL) and dried over anhydrous Na 2 SO 4 , filtered and concentrated yielding crude (E)-ethyl 3-(4-((2-methoxyethoxy)methoxy)phenyl)acrylate (58 g, 83%) as a thick viscous liquid. The crude product was used in the next step without further purification. 
     Intermediate AM: (Trans)-ethyl 2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylate 
     
       
         
         
             
             
         
       
     
     Trimethyl sulfoxonium iodide (53.7 g, 244 mmol) was added portionwise over a period of 20 min to a suspension of sodium hydride (9.58 g, 399 mmol) in dry DMSO (143 mL) and stirred at RT for 1 h, until a clear solution was formed. A solution of (E)-ethyl 3-(4-((2-methoxyethoxy)methoxy)phenyl)acrylate (Intermediate AL, 58 g (2×29 g), 207 mmol) in dry DMSO (20 mL) was added dropwise and stirred at RT for 30 min. After completion, the reaction mixture was poured into ice water (500 mL) and extracted with EtOAc (2×500 mL). The combined extracts were washed with ice water (2×250 mL), brine (250 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated yielding (trans)-ethyl 2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylate (35 g, 57%) as a brown liquid. The crude product was used in the next step without further purification. 
     Intermediate AN: (Trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylic acid 
     
       
         
         
             
             
         
       
     
     4N NaOH solution (175 mL) was added to a solution of (trans)-ethyl 2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylate (Intermediate AM, 35 g, 118.9 mmol) in methanol (350 mL) and stirred at RT for 6 h. After completion, the solvent was evaporated and the residue was taken up in water (150 mL), acidified with 4N HCl and extracted with EtOAc (2×400 mL). The combined extracts were washed with ice water (200 mL), brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated to render (trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylic acid (30 g, 95%) as a brown thick viscous liquid. The crude product was used in the next step without further purification. 
     Intermediate AO: (Trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarbonyl azide 
     
       
         
         
             
             
         
       
     
     Ethyl chloroformate (14.73 g, 135.73 mmol) was added to a solution of (trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarboxylic acid (Intermediate AN, 30 g, 112.6 mmol) and TEA (23.14 mL, 168.9 mmol) in acetone (300 mL) at −20° C. and stirred at same temperature for 1 h. Then, a solution of NaN 3  (14.64 g, 225.2 mmol) in water (15 mL) was added and stirred for 30 min at RT. After completion, the solvent was evaporated and the crude residue was dissolved in ethyl acetate (2×300 mL), washed with water (200 mL), brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated to yield (trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarbonyl azide (30.5 g, 93%). The crude product was used in the next step without further purification. 
     Intermediate AP: Tert-butyl ((trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     A solution of (trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropanecarbonyl azide (Intermediate AO, 30.5 g, 104.7 mmol) in tert-butanol (305 mL) was heated at 90° C. for 16 h. After completion, the solvent was evaporated and the residue was taken up in water (300 mL) and extracted with EtOAc (2×300 mL). The combined extracts were washed with water (200 mL), brine (200 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated. The crude residue was purified by column chromatography (SiO 2 , EtOAc/petroleum ether 1:9) affording tert-butyl ((trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropyl) carbamate (25 g, 71%) as a white solid. 
     Intermediate AQ: 4-((trans)-2-aminocyclopropyl)phenol hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in 1,4-dioxane (125 mL) was added to a solution of tert-butyl ((trans)-2-(4-((2-methoxyethoxy)methoxy)phenyl)cyclopropyl)carbamate (Intermediate AP, 25 mg, 74.18 mmol) in 1,4-dioxane (250 mL) at 10° C. and stirred at RT for 16 h. After completion, the solvent was evaporated and the solid residue was triturated with Et 2 O, filtered Off and dried affording 4-((trans)-2-aminocyclopropyl)phenol hydrochloride (13 g, 95%) as a brown solid. 
     Intermediate AR: Tert-butyl ((trans)-2-(4-hydroxyphenyl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     K 2 CO 3  (20.36 g, 147.56 mmol) and (Boc) 2 O (16.8 mL, 70.27 mmol) was added to a solution of 4-((trans)-2-aminocyclopropyl)phenol hydrochloride (Intermediate AQ, 13 g, 70.27 mmol) in 1,4-dioxane (78 mL) and water (195 mL) and stirred at RT for 16 h. After completion, the reaction mixture was poured into water (300 mL) and extracted with EtOAc (2×200 mL). The combined extracts were washed with water (75 mL), brine (75 mL), dried over anhydrous Na 2 SO 4 , filtered and concentrated. The crude residue was purified by column chromatography (SiO 2 , EtOAc/petroleum ether 3:7) affording tert-butyl ((trans)-2-(4-hydroxyphenyl)cyclopropyl)carbamate (14 g, 80%) as a brown thick viscous liquid. 
     Intermediate AS: Tert-butyl ((trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     2-fluorobenzyl bromide (5.83 mL, 48.13 mmol) was added to a solution of tert-butyl ((trans)-2-(4-hydroxyphenyl)cyclopropyl)carbamate (Intermediate AR 10.0 g, 40.11 mmol) and K 2 CO 3  (11.07 g, 80.22 mmol) in dry DMF (100 mL) at 0° C. and stirred at RT for 18 h. After completion, the reaction mixture was poured into ice water (350 mL) and extracted with EtOAc (2×200 mL). The combined extracts were washed with water (2×100 mL), brine (100 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by column chromatography (SiO 2 ) using EtOAc: petroleum ether (1:3) to afford tert-butyl ((trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropyl)carbamate (7.3 g, 51.01%) as an off white solid. 
     Intermediate AT: (Trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     HCl in 1,4-dioxane (50 mL) was added dropwise to a solution of tert-butyl ((trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropyl)carbamate (Intermediate AS, 7.3 g, 20.16 mmol) in 1,4-dioxane (100 mL) at 0° C. and stirred at RT for 12 h. After completion, the solvent was evaporated and the residue was taken in water, basified with NaHCO 3  and extracted with EtOAc (2×50 mL). The combined extracts were washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to afford (trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)cyclopropanamine (4.3 g, 81.90%) as an off white solid. 
     Intermediate AU: (Trans)-2-(4-bromophenyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     To a solution of tert-butyl trans-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate R, 10 g, 32.05 mmol) in 1,4-dioxane (100 mL) at 10° C. was added HCl in dioxane (50 m) and stirred at RT for 20 h. After completion, the solvent was evaporated and the residue was taken up in ice water, basified with saturated aq. NaHCO 3  and extracted with EtOAc (2×100 mL). The combined extracts were washed with water, brine, dried over anhydrous Na 2 SO 4 , filtered and concentrated to afford (trans)-2-(4-bromophenyl)cyclopropanamine (6.2 g, 91.5%). The crude was used in the next step without further purification. 
     Intermediate AV: (Tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     Tert-butyl 4-formylpiperidine-1-carboxylate (602 mg, 2.83 mmol) and AcOH (169.8 mg, 2.83 mmol) were added to a solution of trans 2-(4-bromophenyl)cyclopropanamine (Intermediate AU, 600 mg, 2.83 mmol) in DCE (12 mL) and stirred for 5 min. The reaction mixture was then cooled to 0° C. and sodium triacetoxy borohydride (1.07 g, 5.09 mmol) was added and stirred at RT for 5 h. After completion, the reaction mixture was poured into ice water and extracted with DCM (2×50 mL). The combined extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by column chromatography (SiO 2 ) using EtOAc: petroleum ether (2:8) to afford tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate (630 mg, 54.45%) as gummy liquid. 
     Intermediate AW: (Tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)(tert-butoxycarbonyl)amino)methyl)piperidine-1-carboxylate 
     
       
         
         
             
             
         
       
     
     NaOH (246 mg, 6.17 mmol) and Boc 2 O (839 mg, 3.85 mmol) were added to a solution of tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate (Intermediate AV, 630 mg, 1.54 mmol) in 1,4-dioxane (13 mL) and stirred at RT for 16 h. After completion, the reaction mixture was poured into water, and extracted with EtOAc (2×50 mL). The combined extracts were washed with water (50 mL), brine (50 mL) and dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by column chromatography (SiO 2 ) using EtOAc: petroleum ether (1:9) to afford (Tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)(tert-butoxycarbonyl)amino)methyl)piperidine-1-carboxylate (600 mg, 76.53%) as gummy liquid. 
     Intermediate AX: Tert-butyl 4-methylenepiperidine-1-carboxylate 
                         
t-BuOK (4.2 g, 37.63 mmol) was added portionwise to a solution of methyltriphenylphosphonium bromide (12.5 g, 35.13 mmol) in dry Et 2 O (40 mL) at 0° C. and stirred at 0° C. for 30 mins. Then a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5 g, 25.09 mmol) in dry Et 2 O (25 mL) was added and stirred at RT for 16 h. After completion, the reaction mixture was poured into saturated NH 4 Cl solution (25 mL) and extracted with EtOAc (2×50 mL). The combined extracts were washed with water (30 mL), brine (30 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ) using EtOAc:petroleum ether (5:95) to get tert-butyl 4-methylenepiperidine-1-carboxylate (3.8 g, 76.76%) as a white solid.
 
     Intermediate AY: Tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylate 
     
       
         
         
             
             
         
       
     
     Zn—Cu couple (15.6 g, 121.74 mmol) was added to a solution of tert-butyl 4-methylenepiperidine-1-carboxylate (Intermediate AX, 2 g, 10.14 mmol) in Diethyl ether (20 mL) followed by the addition of trichloroacetyl chloride (10.14 g, 55.77 mmol) in Dimethoxyethane (10 mL) at RT and stirred for 16 h. After completion the reaction mixture was poured into NaHCO 3  solution, filtered through celite and extracted with EtOAc (2×30 mL). The combined extracts were washed with water (20 mL), brine (20 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated to get tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (3 g crude, 96%). The crude was carried to next step without further purification. 
     Intermediate AZ: Tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate 
     
       
         
         
             
             
         
       
     
     Zinc powder (4.5 g, 1.5 weight equiv) was added portionwise to a solution of tert-butyl 1,1-dichloro-2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (Intermediate AY, 3 g, 9.77 mmol) in saturated NH 4 Cl (1.81 g, 34.20 mmol in Methanol 30 ml) at RT and stirred for 4 h. After completion, the reaction mixture was filtered through a pad of celite and the solvent was evaporated. The crude residue was purified by column chromatography (SiO 2 ) using EtOAc: petroleum ether (10:90) as the eluent to get tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate (750 mg, 32.18%) as a white solid 
     Intermediate BA: N-(3-bromo-4-methoxyphenyl)methanesulfonamide 
     
       
         
         
             
             
         
       
     
     Methanesulphonyl chloride (55.82 mL, 0.494 mmol) was added to a solution of 3-bromo-4-methoxyaniline (100 mg, 0.494 mmol) in pyridine (1 mL) at 0° C. and stirred at RT for 2 h. After completion, reaction mixture was poured into ice water (10 mL) and extracted with EtOAc (2×15 mL). The combined extracts were washed with water (3×10 mL), brine (15 mL) and dried over anhydrous Na 2 SO 4  filtered, and evaporated. The crude residue was purified by column chromatography (SiO 2 ) by using EtOAc:Hexane (3:7) to afford N-(3-bromo-4-methoxyphenyl)methanesulfonamide (137 mg, 99.2%) as a white solid 
     Intermediate BB: N-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide 
     
       
         
         
             
             
         
       
     
     A solution of N-(3-bromo-4-methoxyphenyl)methanesulfonamide (intermediate BA, 136 mg, 0.485 mmol), bispinacoldiborane (147 mg, 0.582 mmol) and KOAc (87.3 mg, 0.89 mmol) in dioxane (5.5 mL) was degassed for 30 min, then PdCl 2 (dppf) 2  (17.7 mg, 0.020 mmol) was added and the reaction mixture was heated at 100° C. for 3 h. After completion, the reaction mixture was poured into water (10 mL), extracted with EtOAc (2×15 mL). The combined extracts were washed with water (10 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The residue was purified by column chromatography (SiO 2 ) EtOAc: petroleum ether (1:9) to afford N-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)methanesulfonamide (100 mg, 63.2%) as a white solid. 
     Intermediate BC: Tert-butyl ((trans)-2-(2′-methoxy-5′-(methylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     K 2 CO 3  (246 mg, 1.923 mmol) was added to a solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate R, 200 mg, 0.641 mmol) and N-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-y) phenyl)methanesulfonamide (251 mg, 0.769 mmol) in ACN:water (8:2) (10 mL). The reaction mixture was degassed with argon for 20 min. and tetrakis(triphenylphosphine)palladium (0) (Pd(PPh 3 ) 4 ) (37 mg, 0.032 mmol) was then added to the reaction mixture and heated to reflux at 90° C. for 4 h. After completion, reaction mixture was poured into ice water (15 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (15 mL), brine (15 mL) and dried over anhydrous Na 2 SO 4  filtered, and evaporated under reduced pressure. The crude residue was purified by column chromatography (SiO 2 ) by using EtOAc: Hexane (20:80) to get tert-butyl ((trans)-2-(2′-methoxy-5′-(methylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (80 mg, 28.9%) as an off white solid. 
     Intermediate BD: N-(4′-((trans)-2-aminocyclopropyl)-6-methoxy-[1,1′-biphenyl]-3-yl)methanesulfonamide hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in 1,4-dioxane (0.8 ml) was added to a solution tort-butyl ((trans)-2-(2′-methoxy-5′-(methylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (Intermediate BC, 80 mg, 0.185 mmol) in 1,4-dioxane (1.6 mL) at 0° C. and stirred at RT for 6 h. After completion, the solvent was evaporated and the residue was triturated with diethyl ether (5 mL) followed by n-hexane (5 mL) to afford N-(4′-((trans)-2-aminocyclopropyl)-6-methoxy-[1,1′-biphenyl]-3-yl)methanesulfonamide hydrochloride (55 mg, 80.8%), a yellow solid. 
     Intermediate BE: Tert-butyl ((trans)-2-(3′-amino-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     K 2 CO 3  (331 mg, 2.403 mmol) was added to a solution of tert-butyl (trans)-2-(4-bromophenyl)cyclopropylcarbamate (Intermediate R, 250 mg, 0.801 mmol) and 3-Amino phenyl boronic acid (130.7 mg, 0.961 mmol) in ACN:water (8:2 mL), the reaction mixture was degassed with argon for 20 min. and tetrakis(triphenylphosphine)palladium (0) (Pd(PPh 3 ) 4 ) (9.2 mg, 0.008 mmol) was then added to the reaction mixture and heated to reflux at 90° C. for 4 h. After completion, reaction mixture was poured into ice water (15 mL) and extracted with EtOAc (2×20 mL). The combined extracts were washed with water (15 mL), brine (15 mL) and dried over anhydrous Na 2 SO 4  filtered, and evaporated. The crude residue was purified by column chromatography (SiO 2 ) using EtOAc: Hexane (3:7) to get tert-butyl ((trans)-2-(3′-amino-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (100 mg, 38.6%) as a light yellow solid. 
     Intermediate BF: Tert-butyl ((trans)-2-(3′-(1-methylethylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate 
     
       
         
         
             
             
         
       
     
     Propane-2-sulfonyl chloride (43.9 mg, 0.308 mmol) was added to a solution of tert-butyl ((trans)-2-(3′-amino-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (Intermediate BE, 100 mg, 0.308 mmol) in pyridine (1 mL) at 0° C. stirred at RT for 4 h. After completion, the reaction mixture was poured into ice water and extracted with EtOAc. The combined extracts were washed with water, brine, dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude residue was purified by column chromatography (SiO 2 ) using EtOAc: petroleum ether (3:7) to afford tert-butyl ((trans)-2-(3′-(1-methylethylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (100 mg, 75.75%) as a light brown solid. 
     Intermediate BG: N-(4′-((trans)-2-aminocyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide hydrochloride 
     
       
         
         
             
             
         
       
     
     HCl in 1,4-dioxane (0.5 mL) was added to a solution tert-butyl ((trans)-2-(3′-(1-methylethylsulfonamido)-[1,1′-biphenyl]-4-yl)cyclopropyl)carbamate (Intermediate BF, 100 mg, 0.232 mmol) in 1,4-dioxane (1 mL) and stirred at RT for 16 h. After completion, the solvent was evaporated. The solid residue was triturated with Et 2 O and dried to afford N-(4′-((trans)-2-aminocyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide hydrochloride (60 mg, 70.58%), as a pale yellow powder. 
     Example 1: N-((trans)-2-phenylcyclopropyl)piperidin-4-amine hydrochloride 
                         
Step 1:
 
     Tert-butyl 4-oxopiperidine-1-carboxylate (890 mg, 4.511 mmol) and sodium triacetoxy borohydride (2.2 g, 11.25 mmol) was added to a solution of trans-2-phenylcyclopropanamine (500 mg, 3.75 mmol) in DCE (10 mL) at 0° C. and stirred at RT for 16 h. After completion, solvent was evaporated, the crude residue was taken in water (25 mL) and extracted with EtOAc (2×25 mL). The combined extracts were washed with NaHCO 3 , water (25 mL), brine (25 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by column chromatography using (SiO 2 ) MeOH: CHCl 3 (2:98) to afford tert-butyl 4-(((trans)-2-phenylcyclopropyl)amino)piperidine-1-carboxylate (350 mg, 25.4%). 
     Step 2: 
     HCl in dioxane was added dropwise to a solution of tert-butyl tert-butyl 4-(((trans)-2-phenylcyclopropyl)amino)piperidine-1-carboxylate (150 mg, 0.0473 mol) in 1,4 dioxane at 10° C. and stirred at RT for 16 h. After completion, the solvent was evaporated, the solid was triturated with Et 2 O and dried to afford N-(trans)-2-phenylcyclopropyl)piperidin-4-amine hydrochloride (80 mg, 84.3%) as off white solid. 
       1 HNMR (400 MHz, DMSO D6) δ: 9.95 (brs, 2H), 9.09 (brs, 1H), 8.88 (brs, 1H), 7.33-7.28 (m, 2H), 7.24-7.17 (m, 3H), 3.49 (s, 1H), 3.40-3.36 (m, 3H), 2.95-2.91 (m, 3H), 2.57 (s, 1H), 2.23 (d, J=12 Hz, 2H), 1.94-1.90 (m, 2H), 1.61-1.56 (m, 1H), 1.31-1.26 (m, 1H); Mass (M+H): 217.3 
     Example 1 describes a racemic, which was the combination of the two different conformations regarding to the cyclopropyl ring ((1R,2S and 1 S,2R). The synthesis of each of these isomers was performed as follows: 
     Example 2: N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine hydrochloride 
                         
Step 1:
 
     Tert-butyl 4-oxopiperidine-1-carboxylate (1.49 g, 7.51 mmol), acetic acid (450 mg 7.51 mmol) and sodium triacetoxy borohydride (856 mg, 22.53 mmol) was added to a solution of (1S,2R)-2-phenylcyclopropanamine (Intermediate AJ, 1 g, 7.51 mmol) in DCE (20 mL) at 0° C., and stirred at RT for 3 h. After completion, solvent was evaporated, crude residue was taken in water (50 mL), treated with NaHCO 3 , and extracted with EtOAc (2×50 mL). The combined extracts were washed with water (50 mL), brine (50 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by column chromatography using SiO 2  by eluting EtOAc: pet ether(3:7) to afford tert-butyl 4-((1S,2R)-2-phenylcyclopropylamino)piperidine-1-carboxylate (1.2 g, 52%). 
     Step 2: 
     HCl in 1,4 dioxane (10 mL) was added to a solution of tert-butyl 4-((1S,2R)-2-phenylcyclopropylamino)piperidine-1-carboxylate (1.2 g, 3.78 mmol) in dioxane (12 mL) at 15° C. and stirred at RT for 16 h. After completion, the solvent was evaporated. The solid residue was triturated with Et 2 O and dried to afford N-((1S,2R)-2-phenylcyclopropyl)piperidin-4-amine hydrochloride (750 mg, 91.4%) as off white solid 
       1 HNMR (400 MHz, DMSO d6) δ: 9.86 (brs, 2H), 9.09 (brs, 1H), 8.80 (brs, 1H), 7.33-7.29 (m, 2H), 7.24-7.17 (m, 3H), 3.49 (s, 1H), 3.40-3.36 (m, 3H), 2.96-2.91 (m, 3H), 2.67 (s, 1H), 2.22 (d, J=12 Hz, 2H), 1.87 (brs, 2H), 1.55 (brs, 1H), 1.31-1.29 (m, 1H); Mass (M+H): 217.21; [α] D   27.6 : +72.11 (C=0.5% in DMSO) 
     Example 3: N-((1R,2S)-2-phenylcyclopropyl)piperidin-4-amine hydrochloride 
     
       
         
         
             
             
         
       
     
     This compound was synthesized following the same procedure described in example 2 but using the intermediate AI in Step 1, to afford 735 mg (89%) as off-white solid 
       1 HNMR (400 MHz, DMSO d6) δ: 9.91 (brs, 2H), 9.03 (brs, 1H), 8.84 (brs, 1H), 7.33-7.29 (m, 2H), 7.24-7.17 (m, 3H), 3.49 (s, 1H), 3.40-3.36 (m, 3H), 2.94-2.88 (m, 3H), 2.55 (s, 1H), 2.23 (d, J=12 Hz, 2H), 1.90-1.87 (m, 2H), 1.58-1.56 (m, 1H), 1.30-1.27 (m, 1H); Mass (M+H): 217.21; [α] D   27.4 : −63.82 (C=0.5% in DMSO). 
     The following compounds can be synthesized following the methodology described for example 1 by using the corresponding intermediates. The Step 2 was only performed in case the intermediate used in the reductive alkylation (Step 1) contained a Boc (tert-butyloxycarbonyl) protecting group 
     Example 4: N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine hydrochloride 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO D6) δ:9.80 (brs, 2H), 8.97 (brs, 1H), 8.81 (brs, 1H), 7.44-7.37 (m, 3H), 7.34-7.30 (m, 2H), 7.11 (d, J=8 Hz, 2H), 6.96 (d, J=8 Hz, 2H), 5.08, (s, 2H), 3.47-3.35 (m, 2H), 2.93-2.88 (m, 3H), 2.50 brs, 1H), 2.23-2.20 (d, J=8 Hz, 2H), 1.86-1.84 (m, 2H), 1.49 (brs, 1H), 1.25-1.20 (m, 1H); Mass (M+H): 323.4 
     Example 5: (Trans)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO D6) δ: 9.56 (brs, 2H), 8.91 (brs, 1H), 8.73 (brs, 1H), 7.33-7.28 (m, 2H), 7.24-7.17 (m, 3H), 3.27 (d, J=12 Hz, 1H), 3.00-2.83 (m, 5H), 2.59 (brs, 1H), 2.05 (brs, 1H), 1.96 (d, J=11 Hz, 2H), 1.63-1.59 (m, 1H), 1.46-1.37 (m, 1H), 1.28-1.23 (m, 1H); Mass (M+H): 231.27 
     Example 6: (Trans)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, CD3OD) δ: 7.39-7.31 (m, 2H), 7.23-7.21 (m, 1H), 7.21 (d, J=8 Hz, 2H), 3.38 (d, J=4 Hz, 2H), 3.38 (t, J=6 Hz, 2H), 3.29-3.21 (m, 2H), 3.00-2.92 (m, 3H), 2.57-2.46 (m, 1H), 1.98 (d, J=6 Hz, 2H), 1.57-1.51 (m, 1H), 1.49-1.42 (m, 1H), 1.41-1.31 (m, 3H); Mass: (M+H): 244.9. 
     Example 7: N-((trans)-2-(6-(3-(trifluoromethyl)phenyl)pyridin-3-yl)cyclopropyl)tetrahydro-2H-pyran-4-amine hydrochloride 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO D6) δ: 8.66 (brs, 1H), 8.66 (brs, 1H), 8.41 (brs, 1H), 8-38 (d, J=8 Hz, 1H), 8.10 (d, J=8 Hz, 2H), 7.72-7.82 (m, 3H), 3.93 (d, J=11 Hz, 1H), 3.469-3.46 (m, 1H), 3.32 (t, J=4 Hz, 2H), 3.12 (s, 1H), 2.70 (s, 1H), 2.09-1.98 (m, 2H), 1.70-1.74 (m, 3H); 1.49-1.46 (m, 1H); Mass (M+H): 363.1 
     Example 8: (Trans)-2-phenyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine hydrochloride 
                         
Step 1:
 
     NaH (108 mg, 2.69 mmol) was added to a solution of tert-butyl ((trans)-2-phenylcyclopropyl)carbamate (300 mg, 1.28 mmol) in dry DMF (12 mL) and stirred at RT for 4 h, then 4-(2-bromoethyl)tetrahydro-2H-pyran (281 mg, 1.41 mmol) was added and stirred at RT for 2 h. After completion, the reaction mixture was evaporated, then diluted with CH 2 Cl 2  (25 mL) and washed with a saturated NH 4 Cl solution. The organic layer was washed with brine (10 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The residue was purified by column chromatography (SiO 2 ) using Hexane: Methyl tert-butylether (60:40) to get tert-butyl ((trans)-2-phenylcyclopropyl)(2-(tetrahydro-2H-pyran-4-yl)ethyl)carbamate (314 mg, 71.2%) as a colorless oil 
     Step 2: 
     HCl in diethyl ether (5 mL) was added to a solution of tert-butyl ((trans)-2-phenylcyclopropyl)(2-(tetrahydro-2H-pyran-4-yl)ethyl)carbamate (314 g, 0.91 mmol) in diethyl ether (6 mL) and stirred at RT for 16 h. After completion, the solvent was evaporated. The solid residue was triturated with Et 2 O and dried to afford (Trans)-2-phenyl-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine hydrochloride (151 mg, 41.8%) as off white solid 
       1 HNMR (400 MHz, CD3OD) δ: 7.32-7.29 (m, 2H), 7.23-7.21 (m, 1H), 7.17 (d, J=8 Hz, 2H), 3.92 (dm, J=4 Hz, 2H), 3.41 (t, J=6 Hz, 2H), 3.21 (t, J=4 Hz, 2H), 2.97-2.90 (m, 1H), 2.52 (brs, 1H), 1.74-1.60 (m, 5H), 1.57-1.49 (m, 1H), 1.39-1.24 (m, 3H); Mass: (M+H): 246.3. 
     The following compound can be synthesized following the methodology described for example 8 by using the corresponding intermediates. 
     Example 9: (Trans)-2-(4′-chloro-[1,1′-biphenyl]-4-yl)-N-(2-(tetrahydro-2H-pyran-4-yl)ethyl)cyclopropanamine hydrochloride 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO D6) δ: 9.2-9.3 (brs, 2H), 7.67 (d, J=8 Hz, 2H), 7.61 (d, J=8 Hz, 2H), 7.50 (d, J=8 Hz, 2H), 7.28 (d, J=8 Hz, 2H), 3.82 (d, J=8 Hz, 2H), 3.25 (m, J=11 Hz, 2H), 3.08 (brs, 2H), 2.99 (brs, 1H), 2.55 (s, 1H), 1.61-1.57. (m, 6H), 1.33-1.30 (m, 1H), 1.12-1.19 (m, 1H); Mass: (M+H): 356.3. 
     The following compounds can be synthesized following the methodology described for example 1 by using the corresponding appropriate intermediates or commercially available reagents. Step 2 was only performed when the intermediate used in the reductive alkylation (Step 1) contained a Boc (tert-butyloxycarbonyl) protecting group. 
     Example 10: N-((trans)-2-phenylcyclopropyl)piperidin-3-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.52 (brs, 2H), 7.48-7.42 (m, 1H), 7.30 (brs, 2H), 3.89-3.81 (brm, 2H), 3.56-3.53 (m, 1H), 3.21 (brs, 1H), 3.12-3.02 (m, 2H), 2.61 (brs, 1H), 2.46 (brs, 1H), 2.23-2.17 (m, 1H), 1.93-1.78 (brm, 2H), 1.60 (brs, 2H); Mass (M+H): 217.28. This compound was obtained as a hydrochloride salt. 
     Example 11: N-((trans)-2-phenylcyclopropyl)pyrrolidin-3-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.57-7.46 (m, 2H), 7.43-7.39 (m, 1H), 7.36-7.31 (m, 2H), 4.39-4.32 (m, 1H), 3.97-3.89 (m, 1H), 3.73-3.51 (m, 3H), 3.10 (s, 1H), 2.68 (brs, 2H), 2.39-2.31 (m, 1H), 1.63 (brs, 1H), 1.57 (brs, 1H); Mass (M+H): 203.2. This compound was obtained as a hydrochloride salt. 
     Example 12: N-((trans)-2-phenylcyclopropyl)azetidin-3-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.57-7.46 (m, 2H), 7.43-7.39 (m, 1H), 7.36-7.31 (m, 2H), 4.79-4.72 (m, 1H), 4.55 (brs, 4H), 3.01 (brs, 1H), 2.60 (brs, 1H), 1.63 (brs, 1H), 1.52-1.43 (m, 1H); Mass (M+H): 189.20. This compound was obtained as hydrochloride salt 
     Example 13: N-((trans)-2-phenylcyclopropyl)-8-azabicyclo[3.2.1]octan-3-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.55-7.44 (brm, 3H), 7.37-7.34 (m, 2H), 4.31 (s, 2H), 3.94 (s, 1H), 3.23 (s, 1H), 2.76 (brs, 3H), 2.45-2.34 (brm, 4H), 2.22-2.18 (m, 2H), 1.78 (brs, 1H), 1.72-1.60 (m, 1H); Mass (M+H): 243.30. This compound was obtained as a hydrochloride salt. 
     Example 14: N-((trans)-2-phenylcyclopropyl)-3-azaspiro[5.5]undecan-9-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 9.37 (brs, 2H), 8.53 (brs, 2H), 7.38-7.29 (m, 2H), 7.22-7.18 (m, 3H), 3.18 (brs, 1H), 3.02 (brs, 5H), 2.92 (brs, 1H), 1.92-1.83 (m, 2H), 1.79-1.71 (m, 2H), 1.62-1.42 (m, 7H), 1.38-1.30 (m, 1H), 1.20-1.05 (m, 2H); Mass (M+H): 285.32. This compound was obtained as a hydrochloride salt. 
     Example 15: N-((trans)-2-phenylcyclopropyl)-7-azaspiro[3.5]nonan-2-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.45-7.39 (m, 2H), 7.38-7.32 (m, 1H), 7.27-7.21 (m, 2H), 4.11-4.04 (m, 1H), 3.26-3.18 (m, 4H), 2.96-2.94 (m, 1H), 2.57-2.43 (m, 3H), 2.20-2.15 (m, 2H), 1.98-1.85 (m, 4H), 1.42 (brs, 1H), 1.42-1.37 (m, 1H); Mass (M+H): 257.32. This compound was obtained as a hydrochloride salt. 
     Example 16: N-((trans)-2-phenylcyclopropyl)decahydroquinolin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 10.24-10.01 (m, 1H), 9.40-9.02 (m, 2H), 7.38-7.28 (m, 2H), 7.22-7.18 (m, 3H), 3.81-3.58 (m, 2H), 3.30-3.22 (m, 1H), 2.98-2.74 (m, 2H), 2.33-2.20 (m, 1H), 2.18-1.92 (m, 3H), 1.85-1.64 (m, 4H), 1.48-1.30 (m, 3H), 1.28-1-18 (m, 2H); Mass (M+H): 271.31. This compound was obtained as a hydrochloride salt. 
     Example 17: N-((trans)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (300 MHz, D 2 O) δ: 8.78-8.62 (m, 2H), 8.32 (d, J=8.2 Hz, 1H), 8.08-8.01 (m, 1H), 3.82-3.77 (m, 1H), 3.66-3.62 (m, 1H), 3.36-3.30 (m, 2H), 3.11-3.02 (m, 2H), 2.86-2.82 (m, 1H), 2.46-2.31 (m, 2H), 2.03-1.65 (m, 4H); Mass(M+H): 218.00. This compound was obtained as a hydrochloride salt. 
     Example 18: N-((trans)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 9.24 (s, 1H), 7.86 (s, 1H), 3.75-3.65 (m, 1H), 3.58-3.52 (m, 2H), 3.19-3.04 (brm, 3H), 2.83 (brs, 1H), 2.43-2.39 (m, 2H), 1.97-1.85 (brm, 2H), 1.77-1.72 (, 1H), 1.59-1.52 (m, 1H); Mass (M+H): 224.21. This compound was obtained as a hydrochloride salt. 
     Example 19: N-(2-(o-tolyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 10.13 (s, 1H), 9.99 (s, 1H), 9.26 (s, 1H), 8.99 (s, 1H), 7.19-7.12 (m, 3H), 7.01 (s, 1H), 3.49 (s, 1H), 3.34 (s, 2H), 2.95 (s, 3H), 2.72-2.69 (m, 1H), 2.50 (s, 3H), 2.29-2.25 (m, 2H), 1.99-1.91 (m, 2H), 1.57 (q, J=5.8 Hz, 1H), 1.80 (q, J=6.8 Hz, 1H); Mass (M+H): 231.3. This compound was obtained as a hydrochloride salt. 
     Example 20: N-(2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 10.04 (s, 2H), 9.09 (s, 1H), 8.87 (s, 1H), 7.32-7.25 (m, 1H), 7.22-7.11 (m, 3H), 3.32 (s, 3H), 3.04 (s, 1H), 2.93 (s, 2H), 2.71 (s, 1H), 2.23 (s, 2H), 1.89 (s, 2H), 1.60 (s, 1H), 1.32 (s, 1H); Mass (M+H): 235.3. This compound was obtained as a hydrochloride salt. 
     Example 21: N-(2-(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 9.41 (s, 1H), 8.74 (s, 1H), 8.54 (s, 1H), 7.39-7.22 (m, 2H), 7.06 (brs, 1H), 3.36 (brs, 3H), 2.93 (brs, 2H), 2.57-2.53 (m, 1H), 2.14 (brs, 2H), 1.70 (brs, 2H), 1.43 (s, 1H), 1.33 (s, 1H); Mass (M+H): 253.19. This compound was obtained as a hydrochloride salt. 
     Example 22: N-(2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 9.83 (s, 1H), 8.99 (s, 1H), 8.89 (s, 1H), 7.11 (d, J=8.8 Hz, 2H), 6.87 (d, J=8.8 Hz, 2H), 3.72 (s, 3H), 3.38 (brs, 1H), 2.93-2.85 (m, 3H), 2.33-2.30 (m, 2H), 1.87 (brs, 2H), 1.50 (s, 1H), 1.24-1.21 (m, 1H); Mass (M+H): 247.28. This compound was obtained as a hydrochloride salt. 
     Example 23: 4-(2-(piperidin-4-ylamino)cyclopropyl)phenol 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.10 (d, J=8.8 Hz, 2H), 6.86 (d, J=8.8 Hz, 2H), 3.74-3.67 (m, 1H), 3.61-3.57 (m, 2H), 3.15-3.07 (m, 2H), 2.94-2.90 (m, 1H), 2.49-2.41 (m, 3H), 1.94-1.88 (m, 2H), 1.50-1.38 (brm, 2H); Mass (M+H): 233.19. This compound was obtained as a hydrochloride salt. 
     Example 24: N-(2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.94-7.88 (m, 3H), 7.72 (s, 2H), 7.57-7.54 (m, 1H), 7.34 (d, J=8.8 Hz, 1H), 3.74-3.73 (m, 1H), 3.61-3.57 (m, 2H), 3.12-3.09 (m, 3H), 2.70-2.68 (m, 1H), 2.46-2.44 (m, 2H), 1.97-1.91 (m, 2H), 1.64-1.00 (m, 1H); Mass (M+H): 267.22. This compound was obtained as a hydrochloride salt. 
     Example 25: N-(2-methyl-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 9.97 (s, 1H), 9.49 (s, 1H), 8.98 (s, 1H), 8.87 (s, 1H), 7.34 (s, 4H), 7.23 (s, 1H), 3.55 (s, 1H), 3.29-3.24 (m, 1H), 2.95 (s, 2H), 2.76 (s, 1H), 2.38-2.29 (m, 2H), 1.97 (brs, 2H), 1.62 (s, 3H), 1.44-1.40 (m, 1H), 1.34-1.31 (m, 1H); Mass (M+H): 231.3. This compound was obtained as a hydrochloride salt. 
     Example 26: (Trans)-2-phenyl-N-(pyrrolidin-3-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.46-7.38 (m, 2H), 7.37-7.29 (m, 1H), 7.22-7.18 (m, 2H), 3.64-3.59 (m, 1H), 3.51-3.23 (brm, 4H), 3.07-3.02 (brm, 2H), 2.80-2.76 (m, 1H), 2.57 (brs, 1H), 2.36-2.32 (m, 1H), 1.84-1.78 (m, 1H), 1.58 (brs, 1H), 1.47-1.41 (brm, 1H); Mass (M+H): 217.3. This compound was obtained as a hydrochloride salt. 
     Example 27: (Trans)-2-(4-((2-fluorobenzyl)oxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 9.37 (s, 2H), 8.80 (s, 1H), 8.60 (s, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.46-7.39 (m, 1H), 7.25 (q, J=8.0 Hz, 2H), 7.13 (d, J=8.0 Hz, 2H), 6.97 (d, J=8.0 Hz, 2H), 5.11 (s, 2H), 3.27-3.21 (m, 2H), 3.02 (s, 2H), 2.91-2.80 (m, 3H), 2.52-2.48 (m, 1H), 2.02 (s, 1H), 1.94-1.99 (m, 2H), 1.52 (s, 1H), 1.41-1.32 (s, 2H), 1.22-1.18 (s, 1H); Mass (M+H): 416.18. This compound was obtained as a hydrochloride salt. 
     Example 28: (Trans)-N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 9.52-9.23 (brm, 3H), 8.78 (brs, 2H), 8.45 (brs, 2H), 7.98-7.94 (m, 2H), 7.70-7.63 (m, 4H), 7.31 (d, J=8.0 Hz, 2H), 3.3 (brs, 2H), 3.05 (s, 3H), 2.91-2.83 (m, 2H), 2.62-2.54 (m, 1H), 2.01-1.92 (m, 3H), 1.6 (brs, 1H), 1.42-1.25 (m, 3H); Mass (M+H): 375.30. This compound was obtained as a hydrochloride salt. 
     Example 29: N-(6-methoxy-4′-((trans)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)methanesulfonamide 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 10.01 (s, 2H), 9.48 (s, 1H), 9.12 (s, 1H), 8.91 (s, 1H), 7.39 (d, J=8.0 Hz, 2H), 7.23 (d, J=8.0 Hz, 2H), 7.19-7.08 (m, 3H), 3.73 (s, 3H), 3.51 (brs, 1H), 3.08-2.95 (m, 6H), 2.82 (s, 1H), 2.28-2.21 (m, 2H), 1.97 (s, 2H); Mass (M+H): 416.18. This compound was obtained as a hydrochloride salt. 
     Example 30: N-(4′-((trans)-2-(piperidin-4-ylamino)cyclopropyl)-[1,1′-biphenyl]-3-yl)propane-2-sulfonamide 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 7.63 (d, J=8.0 Hz, 2H), 7.52-7.47 (m, 3H), 7.30 (d, J=8.0 Hz, 3H), 3.76-3.70 (m, 1H), 3.62-3.58 (m, 2H), 3.49-3.43 (m, 1H), 3.15-3.03 (m, 3H), 2.58-2.55 (m, 1H), 2.46-2.43 (m, 2H), 1.97-1.94 (m, 2H), 1.62-1.51 (m, 2H), 1.39-1.29 (2s, 6H); Mass (M+H): 414.22. This compound was obtained as a hydrochloride salt. 
     Example 31: (Trans)-N-(azetidin-3-ylmethyl)-2-phenylcyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.48-7.41 (m, 2H), 7.40-7.35 (m, 1H), 7.27-7.21 (m, 2H), 4.28 (brs, 2H), 4.09-4.04 (m, 2H), 3.60-3.58 (m, 2H), 3.46-3.42 (m, 1H), 2.98 (s, 1H), 2.54 (s, 1H), 1.55 (brs, 1H), 1.46-1.40 (brm, 1H); Mass (M+H): 203.17. 
     Step 2 (Boc-deprotection) was performed with TFA in dichloromethane and the compound was obtained as a trifluoroacetate salt. 
     Example 32: 1-(methylsulfonyl)-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, CDCl 3 ) δ: 7.28-7.23 (m, 2H), 7.18-7.14 (m, 1H), 7.01 (d, J=7.2 Hz, 2H), 3.70-3.67 (m, 2H), 2.84-2.76 (m, 3H), 2.77 (s, 3H), 2.33-2.29 (m, 1H), 2.02-1.97 (m, 2H), 1.88-1.84 (m, 1H), 1.54-1.48 (m, 2H), 1.09-0.99 (m, 2H); Mass (M+H): 295.12. 
     This compound was obtained as free amine. 
     Example 33: 1-(4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)piperidin-1-yl)ethanone 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 7.39 (d, J=8.8 Hz, 2H), 6.99 (d, J=8.8 Hz, 2H), 4.11-4.07 (m, 1H), 3.71-3.67 (m, 1H), 3.03 (t, J=11.2 Hz, 1H), 2.76-2.67 (m, 2H), 2.20 (s, 1H), 1.96 (brs, 2H), 1.76-1.71 (m, 3H), 1.21-0.95 (m, 4H); Mass (M+H): 337.05. This compound was obtained as free amine 
     Example 34: 4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)piperidine-1-carboxamide 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 7.39 (d, J=8.8 Hz, 2H), 6.99 (d, J=8.8 Hz, 2H), 5.83 (s, 2H), 3.77 (d, J=13.6 Hz, 2H), 2.73-2.62 (m, 4H), 2.32-2.18 (m, 1H), 1.77-1.67 (m, 3H), 1.14-1.12 (m, 2H), 0.98-0.93 (m, 2H); Mass (M+H): 337.99. This compound was obtained as free amine 
     Example 35: N-((trans)-2-(4-bromophenyl)cyclopropyl)tetrahydro-2H-pyran-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, CDCl 3 ) δ: 7.35 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.8 Hz, 2H), 3.96 (dm, J=11.6 Hz, 2H), 3.42-3.35 (m, 2H), 2.86-2.79 (m, 1H), 2.32-2.28 (m, 1H), 1.86-1.81 (m, 3H), 1.48-1.37 (m, 2H), 1.12-1.07 (m, 1H), 0.99-0.94 (m, 1H); Mass (M+H): 296.10. This compound was obtained as free amine 
     Example 36: 2,2,6,6-tetramethyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 8.70 (vbrs, 1H), 7.70 (vbrs, 1H), 7.25-7.21 (m, 2H), 7.18-7.09 (m, 1H), 7.08-7.03 (m, 3H), 3.08 (m, 1H), 2.24 (s, 1H), 1.92-1.79 (brm, 3H), 1.33-1.14 (brm, 13H), 0.98-0.94 (s, 2H); Mass (M+H): 273.30. This compound was obtained as free amine. The reagent used in Step 1 (reductive alkylation) was directly 2,2,6,6-tetramethylpiperidin-4-one. 
     Example 37: 1-methyl-N-((trans -2,phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 10.60 (brs, 1H), 9.98 (brs, 2H), 7.38-7.30 (m, 2H), 7.23-7.18 (m, 3H), 3.56-3.38 (m, 3H), 3.02-2.96 (m, 3H), 2.78 (s, 3H), 2.57 (brs, 1H), 2.28 (brs, 2H), 2.05 (brs, 2H), 1.58 (brs, 1H), 1.28 (m, 1H); Mass (M+H): 231.22. After Step 1 (reductive alkylation), the compound was treated with HCl in 1,4-dioxane to afford the corresponding hydrochloride salt. 
     Example 38: 1-isopropyl-N-((trans)-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.44-7.41 (m, 2H), 7.39-7.35 (m, 1H), 7.26-7.21 (m, 2H), 3.75-3.57 (brm, 4H), 3.21-3.13 (m, 2H), 3.03 (s, 1H), 2.58-2.51 (m, 3H), 2.07-1.97 (m, 2H), 1.58-1.51 (m, 2H), 1.36 (2s, 6H); Mass (M+H): 259.30. After Step 1 (reductive alkylation), the compound was treated with HCl in 1,4-dioxane to afford the corresponding hydrochloride salt. 
     Example 39: N-((trans)-2-phenylcyclopropyl)-1-(2,2,2-trifluoroethyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.44-7.41 (m, 2H), 7.39-7.35 (m, 1H), 7.26-7.21 (m, 2H), 4.05-3.96 (brm, 2H), 3.82-3.68 (brm, 3H), 3.23 (brs, 2H), 3.06-3.02 (m, 1H), 2.61 (brs, 1H), 2.51 (brs, 2H), 2.10 (brs, 2H), 1.61-1.45 (m, 2H); Mass (M+H): 299.30. After Step 1 (reductive alkylation), the compound was treated with HCl in 1,4-dioxane to afford the corresponding hydrochloride salt. 
     Example 40: N-((trans)-2-phenylcyclopropyl)-1-(pyridin-4-yl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO-d 6 ) δ: 9.71 (brs, 2H), 8.27 (d, J=8.4 Hz, 2H), 7.32 (t, J=8.0 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 7.19 (d, J=7.2 Hz, 2H), 4.34 (d, J=13.6 Hz, 2H), 3.62 (brs, 1H), 3.28-3.18 (m, 2H), 2.98 (s, 1H), 2.67-2.55 (m, 2H), 2.50-2.49 (m, 2H), 2.32-2.18 (m, 2H), 1.69-1.74 (m, 2H), 1.56 (s, 1H), 1.35-1.30 (m, 1H); Mass (M+H): 294.3. After Step 1 (reductive alkylation), the compound was treated with HCl in 1,4-dioxane to afford the corresponding hydrochloride salt. 
     Example 41: 4-(((trans)-2-(4-bromophenyl)cyclopropyl)amino)tetrahydro-2H-thiopyran 1,1-dioxide 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.53 (d, J=8.8 Hz, 2H), 7.11 (d, J=8.8 Hz, 2H), 3.75-3.68 (m, 1H), 3.44-3.35 (m, 4H), 3.01 (s, 1H), 2.62-2.58 (m, 2H), 5.53-2.48 (m, 1H), 2.31-2.21 (m, 2H), 1.58-1.41 (m, 2H); Mass (M+H): 344.05. After Step 1 (reductive alkylation), the compound was treated with HCl in 1,4-dioxane to afford the corresponding hydrochloride salt. 
     Example 42: (Trans)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
                         
Step 1:
 
     A solution of tert-butyl 4-((((trans)-2-(4-bromophenyl)cyclopropyl)(tert-butoxycarbonyl)amino)methyl)piperidine-1-carboxylate (Intermediate AW, 500 mg, 0.98 mmol), cyclopropyl boronic acid (101 mg, 1.17 mmol) and K 2 CO 3  (405 mg, 2.94 mmol) in ACN:H 2 O (4:1) (10 mL) was degassed for 30 minutes, then Pd (PPh 3 ) 4 (56 mg, 0.049 mmol) was added and heated at reflux for 16 h. After completion, the reaction mixture was poured into water and extracted with EtOAc (2×25 mL). The combined extracts were washed with water (25 mL), brine (25 mL), dried over anhydrous Na 2 SO 4 , filtered and evaporated. The crude was purified by Preparative HPLC to afford tert-butyl 4-(((tert-butoxycarbonyl)((trans)-2-(4-cyclopropylphenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate (120 mg) as a white solid. 
     Step 2: 
     HCl in 1,4-dioxane (1 mL) was added to a solution of tert-butyl 4-(((tert-butoxycarbonyl)((trans)-2-(4-cyclopropylphenyl)cyclopropyl)amino)methyl)piperidine-1-carboxylate (120 mg, 0.23 mmol) in 1,4-dioxane (2 mL) at 10° C. and stirred at RT for 16 h. After completion, the solvent was evaporated. The solid was triturated with Et 2 O and dried to afford (trans)-2-(4-cyclopropylphenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine as a hydrochloride salt (80 mg), a white solid. 
       1 HNMR (400 MHz, DMSO d 6 ) δ: 9.49 (s, 1H), 8.89 (s, 1H), 8.70 (s, 1H), 7.06-6.98 (m, 4H), 3.40-3.34 (m, 2H), 2.98 (s, 2H), 2.89-2.80 (m, 3H), 2.08-1.82 (m, 4H), 1.59-1.53 (m, 1H), 1.47-1.38 (m, 2H), 1.18-1.22 (m, 1H), 0.95-0.84 (m, 2H), 0.75-0.62 (m, 2H); Mass (M+H): 271.29. 
     The following compounds can be synthesized following the methodology described for example 42 by using the corresponding intermediates or commercially available reagents. 
     Example 43: (Trans)-N-(piperidin-4-ylmethyl)-2-(4-(pyridin-3-yl)phenyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, DMSO d 6 ) δ: 9.16 (s, 1H), 8.89 (d, J=8.4 Hz, 2H), 8.82-8.80 (m, 2H), 8.16-8.12 (m, 1H), 7.80 (d, J=8.4 Hz, 2H), 7.45 (d, J=8.4 Hz, 2H), 3.45 (d, J=13.2 Hz, 2H), 3.23-3.01 (m, 5H), 2.76-2.68 (m, 1H), 2.19 (s, 1H), 2.08 (brd, J=12.8 Hz, 2H), 1.74-1.68 (m, 1H), 1.62-1.43 (m, 1H); Mass (M+H): 308.24. This compound was obtained as hydrochloride salt 
     Example 44: (Trans)-2-(4-(1H-pyrazol-5-yl)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
       1 HNMR (400 MHz, D 2 O) δ: 7.71 (brs, 3H), 7.23 (brs, 2H), 6.69 (brs, 1H), 3.44 (brs, 2H), 3.16 (brs, 1H), 2.96 (brs, 3H), 2.52 (brs, 1H), 2.28-2.05 (m, 4H), 1.54-1.42 (m, 4H); Mass (M+H): 297.25. This compound was obtained as hydrochloride salt 
     The following compounds can be synthesized following the general methods disclosed under the General Synthetic Route Description Section, including the methodologies described in Schemes 1,2,3, 4, 5,6, 7 and 8 and the examples above. 
     Example 45: N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 46: (Trans)-N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 47: (Trans)-N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 48: (Trans)-N-(4-(benzyloxy)phenyl)-N-piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 49: (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 50: (Trans)-N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 51: (Trans)-N-(2-(piperidin-4=yl)ethyl)-2-(3′ (trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 52: (Trans)-2-(4-(benzyl oxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 53: N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-3-amino 
     
       
         
         
             
             
         
       
     
     Example 54: N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-3-amino 
     
       
         
         
             
             
         
       
     
     Example 55: N-((trans)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)pyrrolidin-3-amine 
     
       
         
         
             
             
         
       
     
     Example 56: N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)pyrrolidin-3-amine 
     
       
         
         
             
             
         
       
     
     Example 57: N-((trans)-2-(3′-(trifluoromethyl)-[1 I -biphenyl]-4-yl)cyclopropyl)azetidin-3-amine 
     
       
         
         
             
             
         
       
     
     Example 58: N-((trans)-2-(4-(benzyloxy)phenyl)cyclopropyl)azetidin-3-amine 
     
       
         
         
             
             
         
       
     
     Example 59: N-((trans)-2 phenylcyclopropyl)azepan-3-amine 
     
       
         
         
             
             
         
       
     
     Example 60: N-((trans)-2-phenylcyclopropyl)-8-azabicyclo[3.21]octan-3-amine 
     
       
         
         
             
             
         
       
     
     Example 61: N-((trans)-2-phenylcyclopropyl)-1,2,3,4-tetrahydroquinolin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 62: N-((trans)-2-phenylcyclopropyl)-2-azaspiro[4.5]decan-8-amine 
     
       
         
         
             
             
         
       
     
     Example 63: N-((trans)-2-phenylcyclopropyl)-2,3-dihydrospiro[indene-1,4′-piperidin]-3-amine 
     
       
         
         
             
             
         
       
     
     Example 64: N-((1S,2R)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 65: N-((1R,2S)-2-(4-(benzyloxy)phenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 66: (1S,2R)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 67: (1R,2S)-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 68: (1S,2R)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 69: (1R,2S)-2-phenyl-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 70: N-((1S,2R)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 71: N-((1R,2S)-2-(pyridin-3-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 72: N-((1S,2S)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 73: N-((1R,2R)-2-(thiazol-5-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 74: N-((1S,2R)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 75: N-((1R,2S)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 76: (1S,2R)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 77: (1R,2S)—N-(piperidin-4-ylmethyl)-2-(pyridin-3-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 78: (1S,2S)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 79: (1R,2R)—N-(piperidin-4-ylmethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 80: (1S,2R)—N-(piperidin-4-ylmethyl)-2(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 81: (1R,2S)—N-(piperidin-4-ylmethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 82: (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 83: (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 84: (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(pyridin-3-y)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 85: (1R,2S)—N-(2-(piperidin-4-y)ethyl)-2-(pyridin-3-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 86: (1S,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 87: (1R,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(thiazol-5-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 88: (1S,2R)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 89: (1R,2S)—N-(2-(piperidin-4-yl)ethyl)-2-(3′-(trifluoromethyl)-[1,1-biphenyl]-4-yl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 90: (1S,2R)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 91: (1R,2S)-2-(4-(benzyloxy)phenyl)-N-(2-(piperidin-4-yl)ethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 92: N-((trans)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 93: N-((1S,2S)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 94: N-((1R,2R)-2-fluoro-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 95: N-((trans)-2-(naphthalen-2-yl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 96: (Trans)-2-(naphthalen-2-yl)-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 97: N-((trans)-2-methyl-2-phenylcyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 98: 2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 99: (trans)-2-methyl-2-phenyl-N-(piperidin-4-ylmethyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 100: (trans)-2-(4-(benzyloxy)phenyl)-N-(1-methylpiperidin-4-yl)methyl)cyclopropanamine 
     
       
         
         
             
             
         
       
     
     Example 101: N-((trans)-2-(o-tolyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 102: N-((trans)-2-(2-fluorophenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 103: N-((trans)-2(3,4-difluorophenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 104: N-((trans)-2-(4-methoxyphenyl)cyclopropyl)piperidin-4-amine 
     
       
         
         
             
             
         
       
     
     Example 105: Biological Assays—Inhibition of LSD1 
     The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc (catalog reference number 50100: human recombinant LSD1, GenBank accession no. NM_015013, amino acids 158-end with N-terminal GST tag, MW: 103 kDa). In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Anaspec) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H 2 O 2  produced during the catalytic process, using the Amplex® Red hydrogen peroxide/peroxidase assay kit (Invitrogen). 
     Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of at least eight 3-fold serial dilutions of the respective test compound (e.g., from 0 to 75 μM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in duplicate. After leaving the enzyme interacting with the inhibitor, K M  of di-methylated H3-K4 peptide was added to each reaction and the experiment was left for 30 minutes at 37° C. in the dark. The enzymatic reactions were set up in a 50 mM sodium phosphate, pH 7.4 buffer. At the end of the incubation, Amplex® Red reagent and horseradish peroxidase (HPR) solution were added to the reaction according to the recommendations provided by the supplier (Invitrogen), and left to incubate for 5 extra minutes at room temperature in the dark. A 1 μM H 2 O 2  solution was used as a control of the kit efficiency. The conversion of the Amplex® Red reagent to resorufin due to the presence of H 2 O 2  in the assay, was monitored by fluorescence (excitation at 540 nm, emission at 590 nm) using a microplate reader (Infinite 200, Tecan). Arbitrary units were used to measure level of H 2 O 2  produced in the absence and/or in the presence of inhibitor. 
     The maximum demethylase activity of LSD1 was obtained in the absence of inhibitor and corrected for background fluorescence in the absence of LSD1. The IC50 value of each inhibitor was calculated with GraphPad Prism Software. 
     The results presented in Table 1 below show the results of the LSD1 inhibition studies for a number of the Example compounds. In Table 2 the IC50 values for all examples tested in this assay are shown. Parnate (tranylcypromine; i.e., 2-trans phenylcyclopropylamine) was found to have a IC50 value of 35±10 micromolar. The studies show that the compounds of the invention have unexpectedly potent LSD1 inhibition. 
     Example 106: Biological Assays—Monoamine Oxidase Assays for Determining the Selectivity of the Compounds of the Invention for LSD1 
     Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of primary, secondary and tertiary amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescence-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropanamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAO-A and MAO-B activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product. 
     The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 μL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in duplicate within the same experiment. 
     Briefly, a fixed amount of MAO (0.25 μg for MAO-A and 0.5 μg for MAO-B) was incubated on ice for 15 minutes in the reaction buffer, in the absence and/or in the presence of at least eight 3-fold serial dilutions each. Clorgyline and Deprenyl (Sigma Aldrich) was used as a control for specific inhibition of MAO-A and MAO-B respectively. 
     After leaving the enzyme(s) interacting with the inhibitor, K M  of kynuramine was added to each reaction for MAO-B and MAO-A assay respectively, and the reaction was left for 1 hour at 37° C. in the dark. The oxidative deamination of the substrate was stopped by adding 50 μL of NaOH 2N. The conversion of kynuramine to 4-hydroxyquinoline, was monitored by fluorescence (excitation at 320 nm, emission at 360 nm) using a microplate reader (Infinite 200, Tecan). Arbitrary units were used to measure levels of fluorescence produced in the absence and/or in the presence of inhibitor. 
     The maximum of oxidative deamination activity was obtained by measuring the amount of 4-hydroxyquinoline formed from kynuramine deamination in the absence of inhibitor and corrected for background fluorescence in the absence of MAO enzymes. The IC50 values of each inhibitor were calculated with GraphPad Prism Software. 
     The results obtained with compounds of the invention in the biological assays of examples 105 and 106 are shown below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Summary of Data from MAO-A, MAO-B, 
               
               
                 and LSD1 Inhibition Studies 
               
            
           
           
               
               
               
               
            
               
                 Example 
                 MAO-A 
                 MAO-B 
                 LSD1 
               
               
                 No. 
                 (Ki) 
                 (Ki) 
                 (Ki) 
               
               
                   
               
               
                 1 
                 I 
                 I 
                 V 
               
               
                 2 
                 I 
                 I 
                 IV 
               
               
                 3 
                 I 
                 I 
                 V 
               
               
                 4 
                 II 
                 III 
                 V 
               
               
                 5 
                 I 
                 II 
                 V 
               
               
                 6 
                 II 
                 II 
                 V 
               
               
                 7 
                 II 
                 III 
                 IV 
               
               
                 8 
                 II 
                 II 
                 III 
               
               
                 9 
                 II 
                 III 
                 IV 
               
               
                   
               
            
           
         
       
     
     The ranges for the Ki value reported in Table 1 are for MAO-A, MAO-B and LSD1: I=higher than 100 μM; II=between 10 μM and 100 μM; III=between 1 μM and 10 μM; IV=between 0.1 μM and 1 μM; V=between 0.001 and 0.1 μM. The term Ki value is used herein as a designation for the IC50 value, i.e. the concentration required for a half-maximal (50%) inhibition of the corresponding target (MAO-A, MAO-B, or LSD1). 
     Generally compounds of the Examples were found to have particularly low IC50 values for LSD1, as compared to MAO-A and MAO-B. For some of the compounds of the Examples, IC50 values for LSD1 were lower than 0.1 μM. 
     The specific IC50 values obtained for the compounds disclosed in the Examples when tested in the assays of Examples 105 (LSD1 inhibition) and 106 (MAO-A and B inhibition) are provided in Table 2 below: 
     
       
         
           
               
               
               
               
               
             
               
                   
                   
               
               
                   
                 Example 
                 MAO-A 
                 MAO-B 
                 LSD1 
               
               
                   
                 no. 
                 (IC50 - μM) 
                 (IC50 - μM) 
                 (IC50 - μM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                   
                 1 
                 &gt;100 
                 &gt;100 
                 0.056 
               
               
                   
                 2 
                 &gt;100 
                 &gt;100 
                 0.491 
               
               
                   
                 3 
                 &gt;100 
                 &gt;100 
                 0.042 
               
               
                   
                 4 
                 39.86 
                 3.18 
                 0.019 
               
               
                   
                 5 
                 &gt;100 
                 35.37 
                 0.022 
               
               
                   
                 6 
                 38.32 
                 10.12 
                 0.038 
               
               
                   
                 7 
                 33.45 
                 0.70 
                 0.111 
               
               
                   
                 8 
                 &gt;100 
                 &gt;100 
                 2.18 
               
               
                   
                 9 
                 14.61 
                 5.60 
                 0.296 
               
               
                   
                 10 
                 &gt;100 
                 26.47 
                 0.119 
               
               
                   
                 11 
                 37.70 
                 46.78 
                 0.908 
               
               
                   
                 12 
                 23.75 
                 &gt;100 
                 1.942 
               
               
                   
                 13 
                 &gt;100 
                 &gt;100 
                 0.069 
               
               
                   
                 14 
                 &gt;100 
                 54.33 
                 0.071 
               
               
                   
                 15 
                 &gt;100 
                 ≈100 
                 0.048 
               
               
                   
                 16 
                 &gt;100 
                 &gt;100 
                 0.139 
               
               
                   
                 17 
                 &gt;100 
                 &gt;100 
                 0.107 
               
               
                   
                 18 
                 &gt;100 
                 &gt;100 
                 0.081 
               
               
                   
                 19 
                 &gt;100 
                 &gt;100 
                 0.105 
               
               
                   
                 20 
                 &gt;100 
                 &gt;100 
                 0.038 
               
               
                   
                 21 
                 &gt;100 
                 ≈100 
                 0.127 
               
               
                   
                 22 
                 ≈100 
                 ≈100 
                 0.111 
               
               
                   
                 23 
                 &gt;100 
                 &gt;100 
                 ≈100 
               
               
                   
                 24 
                 ≈50 
                 15.05 
                 0.047 
               
               
                   
                 25 
                 ≈100 
                 &gt;100 
                 0.097 
               
               
                   
                 26 
                 &gt;100 
                 20.79 
                 0.035 
               
               
                   
                 27 
                 3.58 
                 5.01 
                 0.008 
               
               
                   
                 28 
                 11.57 
                 1.02 
                 0.084 
               
               
                   
                 29 
                 ≈100 
                 ≈100 
                 0.023 
               
               
                   
                 30 
                 &gt;100 
                 &gt;100 
                 0.111 
               
               
                   
                 31 
                 &gt;100 
                 25.50 
                 0.042 
               
               
                   
                 32 
                 &gt;100 
                 &gt;100 
                 1.677 
               
               
                   
                 33 
                 ≈50 
                 ≈50 
                 0.212 
               
               
                   
                 34 
                 34.12 
                 32.40 
                 0.104 
               
               
                   
                 35 
                 45.41 
                 18.69 
                 0.549 
               
               
                   
                 36 
                 &gt;100 
                 &gt;100 
                 0.068 
               
               
                   
                 37 
                 &gt;100 
                 &gt;100 
                 0.153 
               
               
                   
                 38 
                 &gt;100 
                 &gt;100 
                 0.108 
               
               
                   
                 39 
                 &gt;100 
                 &gt;100 
                 4.499 
               
               
                   
                 40 
                 &gt;100 
                 35.96 
                 0.188 
               
               
                   
                 41 
                 &gt;50 
                 16.93 
                 0.177 
               
               
                   
                 42 
                 ≈100 
                 3.79 
                 0.037 
               
               
                   
                 43 
                 43.10 
                 ≈100 
                 0.032 
               
               
                   
                 44 
                 ≈100 
                 &gt;100 
                 0.072 
               
               
                   
                   
               
            
           
         
       
     
     As the data in the above table show, the compounds of the invention are very potent LSD1 inhibitors, with IC50 values in many cases below 100 nM or even below 50 nM. In addition, the compounds exhibit high selectivity versus MAO-A and MAO-B, with IC50 values for LSD1 in general ≥100-fold more potent than the corresponding IC50 values for MAO-A and MAO-B. 
     Example 107: Cellular Assay—Induction of Differentiation of THP-1 Leukemia Cells 
     Acute Myeloid Leukemia (AML) is characterized by the presence of leukemic cells with a maturation arrest that divide rapidly. With the induction of terminal differentiation, AML cells lose the ability to proliferate and end up dying without the need of a direct cytotoxic effect. 
     By analyzing the induction of CD11b membrane expression on THP-1 cells we are assessing the ability of LSD1 inhibitors to induce terminal monocytic differentiation of a MLL-AF9 AML cell line. 
     The assay was performed as follows: 
     THP-1 cells were established from the peripheral blood of a 1-year-old boy with acute monocytic leukemia at relapse in 1978. They carry t(9; 11)(p21; q23) leading to MLL-MLLT3 (MLL-AF9) fusion gene. This cell line can undergo monocytic differentiation upon treatment with the appropriate stimulus. THP-1 were purchased from DSMZ GmbH (Deutsche Sammlung von Mikroorganismen und Zellkulturen) and cultured in RPMI 1640 medium containing 10% of fetal bovine serum. 
     In this assay, 150,000 THP-1 cells were seeded in 1 ml of complete culture medium in 6-well tissue culture plates. Serial dilutions of the compounds were prepared in DMSO and then further diluted in complete medium to generate solutions of concentrations that are double of the final concentration at which the cells will be exposed. 1 ml of these 2× concentrated solutions was added to the cells. DMSO final content must be the same in all the wells and must be kept below 0.1% v/v (usually 0.01-0.02% v/v), since higher DMSO content can induce differentiation of THP-1 cells. 
     Cells were kept in the presence of compounds for 96 h at a 5% CO 2  atmosphere at 37° C. After this treatment period, cells were harvested, washed twice with PBS buffer and placed in a V-bottom 96-well plate. Each treated sample was split in two. One was stained with a phycoerythrin-labeled anti-CD11b antibody (clone ICRF44, purchased from eBiosciences) and the other with the relevant phycoerythrin-labeled isotype control antibody (mouse IgG 1 , purchased from eBiosciences). Samples were incubated in the dark at 4° C. for 30-60 minutes and washed three times in PBS buffer containing 1% fetal bovine serum. 
     Samples were analyzed in a flow cytometer equipped with a blue laser (488 nm). Emitted fluorescence was detected and quantified with a 575/30 nm filter. Percentage of CD11b positive cells, as an indicator of monocytic differentiation, was determined compared to isotype control antibody stained cells. EC50 values were calculated by non-linear regression analysis. 
     The results obtained with compounds of the invention in this test are shown in Table 3 below. 
     
       
         
           
               
               
               
             
               
                   
                   
               
               
                   
                 Example 
                 EC50 
               
               
                   
                 No 
                 (nM) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
            
               
                   
                 1 
                 2.1 
               
               
                   
                 3 
                 0.8 
               
               
                   
                 4 
                 1.9 
               
               
                   
                 5 
                 7.4 
               
               
                   
                 15 
                 2.1 
               
               
                   
                   
               
            
           
         
       
     
     These results show that compounds of the invention exhibit very potent activity in inducing differentiation of leukemia THP-1 cells, with EC50 values in the low nanomolar range, which indicates that these compounds are particularly useful for the treatment or prevention of leukemias. 
     Previous reports of LSD1 have found that it is involved in cell proliferation and growth. Some studies have implicated LSD1 as a therapeutic target for cancer. Huang et al. (2007)  PNAS  104:8023-8028 found that polyamine inhibitors of LSD1 modestly cause the reexpression of genes aberrantly silenced in cancer cells and particularly colorectal cancer (Huang et al.  Clin Cancer Res . (2009) Dec. 1; 15(23):7217-28. Epub 2009 Nov. 24. PMID: 19934284). Scoumanne et al. ((2007)  J. Biol. Chem . May 25; 282(21):15471-5) found that deficiency in LSD1 leads to a partial cell cycle arrest in G2/M and sensitizes cells to growth suppression induced by DNA damage. Kahl et al. ((2006)  Cancer Res.  66(23):11341-7.) found that LSD1 expression is correlated with prostate cancer aggressiveness. Metzger et al. ((2005) Nature, 437 (7057), 436-439) reported that LSD1 modulation by siRNA and pargyline regulates androgen receptor (AR) and may have therapeutic potential in cancers where AR plays a role, like prostate, testis, and brain cancers. Lee et al. ((2006)  Chem. Biol.  13:563-567) reported that tranylcypromine derepresses Egr-1 gene expression in some cancer lines. A body of evidence is accumulating that Egr-1 is a tumor suppressor gene in many contexts (see e.g., Calogero et al. (2004)  Cancer Cell International  4:1 exogenous expression of EGR-1 resulted in growth arrest and eventual cell death in primary cancer cell lines; Lucerna et al. (2006)  Cancer Research  66 (13), 6708-6713 show that sustained expression of Egr-1 causes antiangiogeneic effects and inhibits tumor growth in some models; Ferraro et al. ((2005)  J. Clin. Oncol . March 20; 23(9):1921-6) reported that Egr-1 is downregulated in lung cancer patients with a higher risk of recurrence and may be more resistant to therapy. Thus, increasing Egr-1 expression via inhibition of LSD1 is a therapeutic approach for some cancers. Recent studies have also implicated LSD1 in brain cancer (Schulte et al. (2009)  Cancer Res . March 1; 69(5):2065-71). Other studies have implicated LSD1 in breast cancer (Lim et al.  Carcinogenesis , (2010), 31(3): 512-20, Epub 2009 Dec. 30. [Epub ahead of print] PMID: 20042638), lung, bladder and colorectal cancers (Hayami et al (2011),  Int J Cancer,  128(3): 574-86, PMID:20333681) and leukemia (Binda et al (2010),  J Am Chem Soc,  132(19): 6827-33, PMID:20415477). 
     Thus, a body of evidence has implicated LSD1 in a number of cancers, which suggests that LSD1 is a therapeutic target for cancer. The instant inventors have discovered a class of LSD1 inhibitors that can be used to treat diseases where LSD1 is implicated as a therapeutic target like cancer. Accordingly, the (hetero)aryl cyclopropylamine compounds of the invention can be used to treat such diseases. 
     Recent studies have also implicated LSD1 in viral infection and reactivation. In particular it was shown that pharmacological inhibitors of LSD1 like parnate and siRNA knock down of LSD1 caused reduced viral infectivity and reduced reactivation after latency (Liang et al. (2009)  Nat. Med.  15(11):1312-1317). Therefore it is believed that the compounds of the invention can be used for treating or preventing viral infection. Furthermore, it is believed that the compounds of the invention can treat or prevent viral reactivation after latency. 
     Thus, without being bound by theory, the inventors have identified a new class of cyclopropanamine-based LSD1 inhibitors with unexpected potency and selectivity for LSD1, a biologically relevant target in oncology and other diseases. 
     All publications and patent applications mentioned in the specification are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The mere mentioning of the publications and patent applications does not necessarily constitute an admission that they are prior art to the instant application. 
     Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims.