Abstract:
The present invention relates to a compound of formula I 
                                 
wherein R 1 , R 2 , R 3 , R 4 , R 7 , m and n are as defined herein. These compounds are high potential NK-3 receptor antagonists useful for the treatment of depression, pain, psychosis, Parkinson&#39;s disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

Description:
PRIORITY TO RELATED APPLICATION(S) 
     This application claims the benefit of European Patent Application No. 07100064.0, filed Jan. 3, 2007, which is hereby incorporated by reference in its entirety. 
     BACKGROUND OF THE INVENTION 
     The three main mammalian tachykinins, substance P(SP), neurokinin A (NKA) and neurokinin B (NKB) belong to the family of neuropeptides sharing the common COOH-terminal pentapeptide sequence of Phe-X-Gly-Leu-Met-NH 2 . As neurotransmitters, these peptides exert their biological activity via three distinct neurokinin (NK) receptors termed as NK-1, NK-2 and NK-3. SP binds preferentially to the NK-1 receptor, NKA to the NK-2 and NKB to the NK-3 receptor. 
     The NK-3 receptor is characterized by a predominant expression in CNS and its involvement in the modulation of the central monoaminergic system has been shown. These properties make the NK-3 receptor a potential target for central nervous system disorders such as anxiety, depression, bipolar disorders, Parkinson&#39;s disease, schizophrenia and pain ( Neurosci. Letters,  2000, 283, 185-188 ; Exp. Opin. Ther. Patents  2000, 10, 939-960 ; Neuroscience,  1996, 74, 403-414 ; Neuropeptides,  1998, 32, 481-488). 
     Neurokinin 3 receptors are expressed in the brain and strategically located along with NKB, i.e. its natural substrate, in noradrenergic and dopaminergic pathways. Indeed, CNS administration of senktide, a peptide agonist of NK-3 receptors, increases noradrenaline and dopamine in brain areas such as the prefrontal cortex. NK-3 receptors are less abundant in serotonergic pathways, nevertheless, intracerebroventricular administration of senktide elicits behavioural manifestations of serotonergic stimulation, such as forepaw treading, that were blocked by serotonin depletion (Stoessl et al., 1989 , Neurosci. Letters,  1987, 80(3), 321-6). 
     Thus, activation of NK-3 receptors stimulates noradrenergic, dopaminergic and serotonergic systems, i.e., those that are critically involved in the anti-depressant and anxiolytic effects of SSRI&#39;s (serotonin re-uptake inhibitors) and SNRI&#39;s (serotonin noradrenaline re-uptake inhibitors (Millan et al.,  Psychopharmacoogy  14 (2000), 114-138). Indeed, preliminary mice studies suggest that intraperitoneal administration of the NK-3 agonist aminosenktide exhibits anti-depressant-like effects in the forced swimming test (Panocka et al.,  Peptides,  2001, 22(7), 1037-42), and that intracerebroventricular administration of senktide exhibits anxiolytic-like effects in the elevated plus maze (Ribeiro and De Lima,  Neurosci Letters,  1998, 258(3), 155-8). 
     In addition, because cognitive impairment may be an important element of these diseases (Knapp et al.,  Br J Psychiatry,  2002, 18, 19-23), it is of great interest that senktide, after its local administration in the area of cholinergic cell bodies (septal area) stimulates acetylcholine in the hippocampus. Indeed, senktide ameliorates the scopolamine-induced impairment in a cognition test (Kameyama et al.,  Methods Find Exp Clin Pharmacol.,  1998, 20(7), 555-60). 
     In conclusion, based on biochemical and behavioral data, activation of NK-3 receptors is expected to lead to anti-depressant and anxiolytic-like effects, and in addition, to ameliorate possible cognitive deficits for the treatment of anxiety, depression, bipolar disorders, Parkinson&#39;s disease, schizophrenia and pain. 
     SUMMARY OF THE INVENTION 
     The present invention provides a compound of formula I 
                                
wherein
     R 1  is hydrogen or lower alkyl;   R 2  is lower alkyl, lower hydroxyalkyl or —(CHR 5 ) x -A;
       R 5  is hydrogen, lower alkyl, lower hydroxyalkyl, or heteroaryl optionally substituted by lower alkyl;   A is a cycloalkyl, aryl, heterocyclyl or heteroaryl ring, which rings are optionally substituted by one or more R 6 , wherein R 6  is lower alkyl, lower alkoxy, lower alkylsulfonyl, cyano, halogen, lower alkyl substituted by halogen or lower alkoxy substituted by halogen, or is aryl, heterocyclyl or heteroaryl optionally substituted by lower alkyl or is cycloalkyl optionally substituted by lower alkyl;   x is 0, 1, 2 or 3;
 
or R 1  and R 2  together with the N-atom to which they are attached form a heterocyclyl or heteroaryl ring, which rings are optionally substituted by one or more substituents selected from the group consisting of lower alkyl, lower alkoxy, lower alkylsulfonyl, halogen, cycloalkyl, benzyl and aryl;
   
       R 3  is hydrogen or halogen;   R 4  is hydrogen or lower alkyl;   R 7  is hydrogen, halogen or lower alkyl;   m is 1 or 2; when m is 2, each R 3  can be the same or different;   n is 1 or 2;   o is 1 or 2; when o is 2, each R 7  can be the same or different;
 
or to a pharmaceutically suitable acid addition salt thereof.
   
     The invention includes all stereoisomeric forms, including individual diastereoisomers and enantiomers of the compound of formula (I) as well as racemic and non-racemic mixtures thereof. 
     The invention also provides pharmaceutical compositions which contain a compound of the invention and a pharmaceutically acceptable carrier. The invention further provides methods for the manufacture of the compounds and compositions of the invention. 
     Compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson&#39;s disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD). Furthermore, the compounds have good activity toward the NK-1 and the NK-2 receptors. 
     The invention provides methods for the treatment of depression, anxiety disorders, bipolar disorder, attention deficit hyperactivity disorder, stress-related disorders, psychotic disorders such as schizophrenia, neurological diseases such as Parkinson&#39;s disease, neurodegenerative disorders such as Alzheimer&#39;s disease, epilepsy, migraine, hypertension, substance abuse and metabolic disorders such as eating disorders, diabetes, diabetic complications, obesity, dyslipidemia, disorders of energy consumption and assimilation, disorders and malfunction of body temperature homeostasis, disorders of sleep and circadian rhythm, and cardiovascular disorders. The preferred indications using the compounds of the present invention are depression, psychosis, Parkinson&#39;s disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD). 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The following definitions of the general terms used in the present description apply irrespective of whether the terms in question appear alone or in combination. It must be noted that, as used in the specification and the appended claims, the singular forms “a”, “an,” and “the” include plural forms unless the context clearly dictates otherwise. 
     As used herein, the term “lower alkyl” denotes a straight- or branched-chain alkyl group containing from 1-8 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl and the like. Preferred lower alkyl groups are groups with 1-4 carbon atoms. 
     The term “lower hydroxyalkyl” denotes an alkyl group as defined above, wherein at least one hydrogen atom is replaced by hydroxyl. Preferred lower hydroxyalkyl groups are groups with 1-4 carbon atoms and having one hydroxyl. 
     The term “lower alkyl substituted by halogen” denotes an alkyl group as defined above, wherein at least one hydrogen atom is replaced by halogen, for example —CF 3 , —CHF 2 , —CH 2 F, —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 CF 2 CF 3  and the like. Preferred lower alkyl substituted by halogen groups are groups having 1-4 carbon atoms. 
     The term “lower alkoxy” denotes a group wherein the alkyl residue is as defined above and which is attached via an oxygen atom, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, i-butoxy, 2-butoxy, t-butoxy and the like. Preferred alkoxy groups are groups with 1-4 carbon atoms. 
     The term “lower alkoxy substituted by halogen” denotes a group wherein the alkyl residue is as defined above “lower alkyl substituted by halogen” and which is attached via an oxygen atom. Preferred lower alkoxy substituted by halogen groups are groups having 1-4 carbon atoms. 
     The term “halogen” denotes chlorine, iodine, fluorine and bromine. 
     The term “cycloalkyl” denotes a saturated carbon ring containing from 3-7 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like. 
     The term “aryl” denotes a cyclic aromatic hydrocarbon radical consisting of one or more fused rings containing 6-14 carbon atoms in which at least one ring is aromatic in nature, for example phenyl, benzyl, naphthyl or indanyl. Preferred is the phenyl group. 
     The term “heteroaryl” denotes a cyclic aromatic hydrocarbon radical consisting of one or more fused rings containing 3-14 ring atoms, preferably containing 5-10 ring atoms, in which at least one ring is aromatic in nature, and which contains at least one heteroatom, selected from N, O and S, for example dihydroisoquinolinyl, pyrazinyl, pyrazolyl, pyridinyl, pyridyl, pyrimidyl, oxadiazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thienyl, furyl or imidazolyl. Preferred heteroaryl group is dihydroisoquinolinyl, furyl, pyrazolyl, pyridinyl, thiadiazolyl, thienyl or imidazolyl. 
     The term “heterocycle” denotes non-aromatic ring or a ring system containing 3-14 ring atoms, preferrably containing 5-6 ring atoms, wherein at least one ring atom is N, O or S, for example, pyrrol-1-yl, piperidin-1-yl, piperazin-1-yl, morpholin-4-yl, thiomorpholin-4-yl, 1-oxo-thiomorpholin-4-yl or 1,1-dioxo-thiomorpholin-4-yl. Preferred heterocycle group is piperizin-1-yl or morpholin-4-yl. 
     “Pharmaceutically acceptable,” such as pharmaceutically acceptable carrier, excipient, etc., means pharmacologically acceptable and substantially non-toxic to the subject to which the particular compound is administered. 
     The term “pharmaceutically acceptable acid addition salts” embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methanesulfonic acid, p-toluenesulfonic acid and the like. 
     “Therapeutically effective amount” means an amount that is effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. 
     The following groups of compounds of formula (I) are preferred: 
     A compound wherein one of R 1  or R 2  is lower alkyl. The following compounds relate to this group. 
     
         
         N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide hydrochloride; 
         N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide; 
         2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide; 
         N-butyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide; 
         N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(3-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide; 
         N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide; 
         N-(2-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide; 
         N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide; 
         2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide; 
         N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide; 
         4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(4-methylbenzyl)butanamide; 
         4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide; 
         N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide; 
         N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide; 
         2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide; 
         2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide; 
         2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; 
         N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide; 
         2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]pentanamide; 
         2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]pentanamide; 
         2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide; 
         2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)pentanamide; 
         (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; and 
         (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide. 
       
    
     A compound wherein one of R 1  or R 2  represents —(CHR 5 ) x -A, where A is aryl or heteroaryl and X is 1. The following compounds relate to this group.
     N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide hydrochloride;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(5-methyl-2-furyl)methyl]butanamide;   2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(3-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-(2-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2,4-dichlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(4-methylbenzyl)butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[3-(trifluoromethyl)benzyl]butanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-[(4-chlorophenyl) (1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(3-methyl-2-thienyl)methyl]pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]pentanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]pentanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl) pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]pentanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethyl)benzyl]pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)pentanamide;   (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1S)-1-phenylethyl]butanamide hydrochloride;   (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide.   

     A compound wherein R 1  and R 2  together with the N-atom to which they are attached form a heterocyclyl or heteroaryl ring, which rings are substituted by one or more halogen. The following compounds relate to this group.
     1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; and   1′-[3-(3,4-dichlorophenyl)-4-(4-fluoropiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one.   

     A compound wherein R 3  is halogen. More preferably, a compound wherein R 3  is chlorine and m is 2. The following compounds relate to this group.
     N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide hydrochloride;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(5-methyl-2-furyl)methyl]butanamide;   2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-butyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   1′-[3-(3,4-dichlorophenyl)-4-(4-fluoropiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(3-methyl-2-thienyl)methyl]pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]pentanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]pentanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]pentanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethyl)benzyl]pentanamide;   2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)pentanamide;   (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1S)-1-phenylethyl]butanamide hydrochloride;   (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; and   (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide.   

     A compound, wherein R 4  is lower alkyl. The following compounds relate to this group.
     N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   1′-[3-(3,4-dichlorophenyl)-4-(4-fluoropiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; and   (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide.   

     A compound, wherein n is 1. The following compounds relate to this group.
     N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide hydrochloride;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(5-methyl-2-furyl)methyl]butanamide;   2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-butyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(3-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-(2-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide;   N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   1′-[3-(3,4-dichlorophenyl)-4-(4-fluoropiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one;   N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   N-(2,4-dichlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(4-methylbenzyl)butanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide;   4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[3-(trifluoromethyl)benzyl]butanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide;   2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide;   2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide;   N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide;   (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1S)-1-phenylethyl]butanamide hydrochloride;   (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide; and   (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide.   

     The preparation of compounds of formula I of the present invention can be carried out in sequential or convergent synthetic routes. Syntheses of the compounds of the invention are shown in the following scheme. The skills required for carrying out the reaction and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following description of the processes have the significance given herein before unless indicated to the contrary. 
     In more detail, the compounds of formula I can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. The reaction sequence is not limited to the one displayed in scheme 1, however, depending on the starting materials and their respective reactivity the sequence of reaction steps can be freely altered. Starting materials are either commercially available or can be prepared by methods analogous to the methods given below, by methods described in references cited in the description or in the examples, or by methods known in the art. 
     The present compounds of formula I and their pharmaceutically acceptable salts can be prepared by methods, known in the art, for example by the process described below, which process comprises 
     reacting a compound of formula 
                                
with an amine of formula
 
                                
wherein the substituents have the same meanings as described before, under coupling conditions to provide the spiropiperidine derivatives of formula
 
                                
and, if desired, converting a compound of formula I into a pharmaceutically acceptable salt.
 
     
       
                 
         
             
             
         
      
     
     In the above scheme 1, R 1 , R 2 , R 3 , R 4 , n and m have same meanings as described before. 
     a) Phenylacetic acid ester derivatives II are commercially available or can be accessed by methods described in literature. Reaction of ester derivatives II with hydroxy-protected alkyl halides (either commercially available or synthetically accessible by methods known in the art) under basic conditions lead upon cleavage of the hydroxyl protecting group to lactones III as described in literature (for reaction conditions described in literature affecting such reactions see for example:  Comprehensive Organic Transformations: A Guide to Functional Group Preparations,  2 nd Edition , Richard C. Larock. John Wiley &amp; Sons, New York, N.Y. 1999). However, it is convenient to react ester derivative II with 2-(2-bromoethoxy)tetrahydro-2-H-pyrane (commercially available in the presence of a base and a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include dimethylformamide (DMF), tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the base used in this stage, and any base commonly used in this type of reaction may equally be employed here. Examples of such bases include NaH and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield the hydroxy protected intermediate which can be subjected to acidic cleavage of the protecting group in the presence of a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include dimethylformamide (DMF), tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the acid used in this stage, and any acid commonly used in this type of reaction may equally be employed here. Examples of such acid include HCl and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield lactone derivatives III.
 
b) Lactone derivative III can conveniently transferred into the respective ester derivative IV by a two step reaction sequence. Any commonly used synthetic sequence is applicable, however, we find it convenient to open the lactone derivative III with HBr in the presence of an acid. Any commonly used acid which in combination with HBr affects such a reaction can be used. Examples of such acids include acetic acid and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield the intermediately built acid derivative which is subjected to esterification conditions. Common procedures are described in literature, however, we find it convenient to transform the intermediately built acid into the respective ester derivative IV by reaction with SOCl 2  in methanol. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield ester derivative IV.
 
c) Transformation of ester derivative IV with spiropiperidine derivatives V (synthetic access described in literature: see for instance  Journal of Medicinal Chemistry  (1983), 26(5), 657-61) to access spiropiperidine derivatives VI can be affected by any commonly used procedure. However, we find it convenient to react ester derivative IV with spiropiperidine derivatives V in the presence of a solvent and a base. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include dimethylformamide (DMF), tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the base used in this stage, and any base commonly used in this type of reaction may equally be employed here. Examples of such bases include DIPEA, NEt 3  and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield spiropiperidine derivative VI.
 
d) Transformation of spiropiperidine derivative VI into the final amide derivatives I can be done according to procedures described in literature. However, we find it convenient to employ a two step reaction sequence in which the ester functionality in VI is cleaved under aqueous basic conditions and the liberated acid functionality VIII or a salt thereof
 
     
       
                 
         
             
             
         
      
     
     [R 3 , R 4 , n, o and m have same meanings as described before] 
     converted with the respective amines IX 
                                
wherein R 1  and R 2  have same meanings as described before,
 
under coupling conditions to produce the spiropiperidine derivatives I. There is no particular restriction on the nature of the aqueous base to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable aqueous bases include NaOH, LiOH and the like. Any commonly used co-solvent can be employed. Examples include THF and the like. The coupling of carboxylic acids with amines is widely described in literature and the procedures are known to those in the art (For reaction conditions described in literature affecting such reactions see for example:  Comprehensive Organic Transformations: A Guide to Functional Group Preparations,  2 nd Edition , Richard C. Larock. John Wiley &amp; Sons, New York, N.Y. 1999). The intermediately built acid VIII can conveniently be transformed to the respective amide I through coupling with an amine IX (either commercially available or accessible by methods described in references or by methods known in the art; as appropriate) by employing the usage of coupling reagents. For example coupling reagents like N,N′-carbonyldiimidazole (CDI), N,N′-dicyclohexylcarbodiimide (DCC), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI), 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU), 1-hydroxy-1,2,3-benzotriazole (HOBT), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) and the like can equally well be employed to affect such transformation. We find it convenient to carry out the reaction in a solvent like dimethylformamide (DMF) and in the presence of a base. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include: DMF, dichloromethane (DCM), dioxane, THF, and the like. There is no particular restriction on the nature of the base used in this stage, and any base commonly used in this type of reaction may equally be employed here. Examples of such bases include triethylamine and diisopropylethylamine, and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. We find it convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield spiropiperidine derivatives I.
 
e) Reaction of ester derivatives II with protected bromo alkyl aldehydes (either commercially available or synthetically accessible by methods known in the art) under basic conditions lead to aldehyde derivatives VII as described analogously in literature (for reaction conditions described in literature affecting such reactions see for example:  Comprehensive Organic Transformations: A Guide to Functional Group Preparations,  2 nd Edition , Richard C. Larock. John Wiley &amp; Sons, New York, N.Y. 1999). However, it is convenient to react ester derivative II with the respective protected bromo alkyl aldehyde (commercially available or accessible by methods known) in the presence of a base and a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include dimethylformamide (DMF), tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the base used in this stage, and any base commonly used in this type of reaction may equally be employed here. Examples of such bases include NaH and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield the aldehyde protected intermediate which can be subjected to acidic cleavage of the protecting group in the presence of a solvent. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the acid used in this stage, and any acid commonly used in this type of reaction may equally be employed here. Examples of such acid include HCl and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield aldehyde derivatives VII.
 
f) Reductive animations are widely described in literature (for reaction conditions described in literature affecting such reactions see for example:  Comprehensive Organic Transformations: A Guide to Functional Group Preparations,  2 nd Edition , Richard C. Larock. John Wiley &amp; Sons, New York, N.Y. 1999). However, we find it convenient to transform aldehyde derivative VII with spiropiperidine derivatives V ( Journal of Medicinal Chemistry  (1983), 26(5), 657-61) under reductive conditions in the presence of a solvent to afford ester derivatives VI. There is no particular restriction on the nature of the solvent to be employed, provided that it has no adverse effect on the reaction or the reagents involved and that it can dissolve the reagents, at least to some extent. Examples for suitable solvents include tetrahydrofuran (THF) and the like. There is no particular restriction on the nature of the reducing agent used in this stage, and any reducing agent commonly used in this type of reaction may equally be employed here. Examples of such reducing agents include sodium triacetoxyborohydride and the like. The reaction can take place over a wide range of temperatures, and the precise reaction temperature is not critical to the invention. It is convenient to carry out the reaction with heating from ambient temperature to reflux. The time required for the reaction may also vary widely, depending on many factors, notably the reaction temperature and the nature of the reagents. However, a period of from 0.5 h to several days will usually suffice to yield ester derivative VI.
 
     The salt formation is effected at room temperature in accordance with methods which are known per se and which are familiar to any person skilled in the art. Not only salts with inorganic acids, but also salts with organic acids come into consideration. Hydrochlorides, hydrobromides, sulphates, nitrates, citrates, acetates, maleates, succinates, methane-sulphonates, p-toluenesulphonates and the like are examples of such salts. 
     As mentioned earlier, the compounds of formula I and their pharmaceutically usable addition salts possess valuable pharmacological properties. Compounds of the present invention are allosteric positive modulators of neurokinin 3 (NK-3) receptors. The compounds were investigated in accordance with the tests given hereinafter. 
     Experimental Procedure 
     The compounds were investigated in accordance with the tests given hereinafter. 
     [ 3 H]SR142801 Competition Binding Assay 
     hNK3 receptor binding experiment were performed using [ 3 H]SR142801 (Catalog No. TRK1035, specific activity: 74.0 Ci/mmol, Amersham, GE Healthcare UK limited, Buckinghamshire, UK) and membrane isolated from HEK293 cells transiently expressing recombinant human NK3 receptor. After thawing, the membrane homogenates were centrifuged at 48,000×g for 10 min at 4° C., the pellets were resuspended in the 50 mM Tris-HCl, 4 mM MnCl 2 , 1 μM phosphoramidon, 0.1% BSA binding buffer at pH 7.4 to a final assay concentration of 5 μg protein/well. For inhibition experiments, membranes were incubated with [ 3 H]SR142801 at a concentration equal to K D  value of radioligand and 10 concentrations of the inhibitory compound (0.0003-10 μM) (in a total reaction volume of 500 μl) for 75 min at room temperature (RT). At the end of the incubation, membranes were filtered onto unitfilter (96-well white microplate with bonded GF/C filter preincubated 1 h in 0.3% PEI+0.3% BSA, Packard BioScience, Meriden, Conn.) with a Filtermate 196 harvester (Packard BioScience) and washed 4 times with ice-cold 50 mM Tris-HCl, pH 7.4 buffer. Nonspecific binding was measured in the presence of 10 μM SB222200 for both radioligands. The radioactivity on the filter was counted (5 min) on a Packard Top-count microplate scintillation counter with quenching correction after addition of 45 μl of microscint 40 (Canberra Packard S.A., Zürich, Switzerland) and shaking for 1 h. Inhibition curves were fitted according to the Hill equation: y=100/(1+(x/IC 50 ) nH ), where n H =slope factor using Excel-fit 4 software (Microsoft). IC 50  values were derived from the inhibition curve and the affinity constant (K i ) values were calculated using the Cheng-Prussoff equation K i =IC 50 /(1+[L]/K D ) where [L] is the concentration of radioligand and K D  is its dissociation constant at the receptor, derived from the saturation isotherm. All experiments were performed in duplicate and the mean±standard error (SEM) of the individual K i  values was calculated. 
     Results of some representative compounds with a good hNK-3 receptor affinity are shown in Table 1. 
     
       
         
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                 Ex- 
                   
                   
               
               
                 am- 
                   
                 hNK 3   
               
               
                 ple 
                 Compound name 
                 Ki [μM] 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo- 
                 0.0112 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methylbutanamide hydrochloride 
               
               
                 6 
                 N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro- 
                 0.0628 
               
               
                   
                 2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)butanamide 
               
               
                 8 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.017 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 9 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0914 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[(5-methyl-2-furyl)methyl]butanamide 
               
               
                 12 
                 2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4- 
                 0.0312 
               
               
                   
                 (6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 14 
                 N-butyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo- 
                 0.0908 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 15 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0037 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 17 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0067 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 18 
                 2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2- 
                 0.0157 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-(4-methylbenzyl)butanamide 
               
               
                 19 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0052 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 25 
                 N-(3-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro- 
                 0.0594 
               
               
                   
                 1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4- 
               
               
                   
                 fluorophenyl)-N-methylbutanamide 
               
               
                 26 
                 N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro- 
                 0.0383 
               
               
                   
                 1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4- 
               
               
                   
                 fluorophenyl)-N-methylbutanamide 
               
               
                 27 
                 N-(2-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro- 
                 0.0385 
               
               
                   
                 1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4- 
               
               
                   
                 fluorophenyl)-N-methylbutanamide 
               
               
                 29 
                 N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro- 
                 0.0067 
               
               
                   
                 1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 31 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0058 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide 
               
               
                 32 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1- 
                 0.0039 
               
               
                   
                 methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 33 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0547 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[4- 
               
               
                   
                 (methylsulfonyl)benzyl]butanamide 
               
               
                 34 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0033 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 38 
                 1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4- 
                 0.0487 
               
               
                   
                 dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1- 
               
               
                   
                 methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)- 
               
               
                   
                 one 
               
               
                 39 
                 2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl- 
                 0.0042 
               
               
                   
                 2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide 
               
               
                 40 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0011 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 42 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0008 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 43 
                 1′-[3-(3,4-dichlorophenyl)-4-(4-fluoropiperidin-1-yl)- 
                 0.0619 
               
               
                   
                 4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-2(1H)-one 
               
               
                 44 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0016 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 47 
                 N-(2,4-dichlorobenzyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0827 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-2-(4-fluorophenyl)butanamide 
               
               
                 49 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
                 0.0909 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)- 
               
               
                   
                 N-[2-(trifluoromethoxy)benzyl]butanamide 
               
               
                 51 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
                 0.0322 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)- 
               
               
                   
                 N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide 
               
               
                 56 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
                 0.0664 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)- 
               
               
                   
                 N-methyl-N-(4-methylbenzyl)butanamide 
               
               
                 58 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
                 0.0949 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)- 
               
               
                   
                 N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide 
               
               
                 59 
                 N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro- 
                 0.0489 
               
               
                   
                 1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4- 
               
               
                   
                 fluorophenyl)-N-methylbutanamide 
               
               
                 61 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
                 0.0885 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)- 
               
               
                   
                 N-[3-(trifluoromethyl)benzyl]butanamide 
               
               
                 62 
                 N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.01 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 64 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo- 
                 0.0125 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 65 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0707 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-(2-phenylethyl)butanamide 
               
               
                 66 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0288 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[2-(trifluoromethoxy)benzyl]butanamide 
               
               
                 67 
                 2-(3,4-dichlorophenyl)-N-[3- 
                 0.019 
               
               
                   
                 (difluoromethoxy)benzyl]-4-(6-fluoro-2-oxo-1,2- 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)butanamide 
               
               
                 68 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0014 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-[4- 
               
               
                   
                 (trifluoromethyl)benzyl]butanamide 
               
               
                 70 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.098 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide 
               
               
                 72 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0187 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide 
               
               
                 74 
                 2-(3,4-dichlorophenyl)-N-(3-fluoro-4- 
                 0.0055 
               
               
                   
                 methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H- 
               
               
                   
                 spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 75 
                 2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3- 
                 0.0077 
               
               
                   
                 methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H- 
               
               
                   
                 spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 76 
                 2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6- 
                 0.0046 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 77 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0046 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-(4-methylbenzyl)butanamide 
               
               
                 78 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0154 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[3-(trifluoromethoxy)benzyl]butanamide 
               
               
                 79 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0066 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-[3- 
               
               
                   
                 (trifluoromethyl)benzyl]butanamide 
               
               
                 80 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6- 
                 0.0044 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 81 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6- 
                 0.0116 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 82 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0197 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-(4-methoxybenzyl)butanamide 
               
               
                 83 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0129 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[3-(trifluoromethyl)benzyl]butanamide 
               
               
                 84 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0116 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide 
               
               
                 85 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0699 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[4-(trifluoromethoxy)benzyl]butanamide 
               
               
                 86 
                 N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0121 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 87 
                 N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0021 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 88 
                 N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2- 
                 0.0722 
               
               
                   
                 yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1- 
               
               
                   
                 methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)butanamide 
               
               
                 89 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1- 
                 0.0008 
               
               
                   
                 methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 90 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.008 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-(2- 
               
               
                   
                 phenylethyl)butanamide 
               
               
                 91 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0065 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[2- 
               
               
                   
                 (trifluoromethoxy)benzyl]butanamide 
               
               
                 92 
                 2-(3,4-dichlorophenyl)-N-[3- 
                 0.0028 
               
               
                   
                 (difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2- 
               
               
                   
                 oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)butanamide 
               
               
                 93 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0006 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-[4- 
               
               
                   
                 (trifluoromethyl)benzyl]butanamide 
               
               
                 94 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0877 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[4-(1H-pyrazol-1- 
               
               
                   
                 yl)benzyl]butanamide 
               
               
                 95 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0288 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4- 
               
               
                   
                 ylbenzyl)butanamide 
               
               
                 97 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0094 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4- 
               
               
                   
                 ylbenzyl)butanamide 
               
               
                 99 
                 2-(3,4-dichlorophenyl)-N-(3-fluoro-4- 
                 0.0024 
               
               
                   
                 methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2- 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methylbutanamide 
               
               
                 100 
                 2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3- 
                 0.0026 
               
               
                   
                 methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2- 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methylbutanamide 
               
               
                 101 
                 2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6- 
                 0.0013 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 102 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0021 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-(4- 
               
               
                   
                 methylbenzyl)butanamide 
               
               
                 103 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0037 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[3- 
               
               
                   
                 (trifluoromethoxy)benzyl]butanamide 
               
               
                 104 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0016 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-methyl-N-[3- 
               
               
                   
                 (trifluoromethyl)benzyl]butanamide 
               
               
                 105 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6- 
                 0.001 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 106 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6- 
                 0.0027 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 107 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0054 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide 
               
               
                 108 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.003 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[3- 
               
               
                   
                 (trifluoromethyl)benzyl]butanamide 
               
               
                 109 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.019 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4- 
               
               
                   
                 yl)benzyl]butanamide 
               
               
                 110 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo- 
                 0.0032 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′- 
               
               
                   
                 piperidin]-1′-yl)-N-[4- 
               
               
                   
                 (trifluoromethoxy)benzyl]butanamide 
               
               
                 111 
                 N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0031 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
               
               
                 116 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0668 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[(3-methyl-2-thienyl)methyl]pentanamide 
               
               
                 118 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0644 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[2-(trifluoromethoxy)benzyl]pentanamide 
               
               
                 120 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6- 
                 0.0463 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylpentanamide 
               
               
                 121 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0647 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-[4- 
               
               
                   
                 (trifluoromethyl)benzyl]pentanamide 
               
               
                 125 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6- 
                 0.0983 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)pentanamide 
               
               
                 130 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0919 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-[3- 
               
               
                   
                 (trifluoromethyl)benzyl]pentanamide 
               
               
                 131 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6- 
                 0.0692 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylpentanamide 
               
               
                 132 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6- 
                 0.0657 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)pentanamide 
               
               
                 135 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0903 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[4-(trifluoromethyl)benzyl]pentanamide 
               
               
                 138 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2- 
                 0.0954 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methyl-N-(4-methylbenzyl)pentanamide 
               
               
                 146 
                 (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2- 
                 0.0057 
               
               
                   
                 dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-[(1S)-1-phenylethyl]butanamide hydrochloride 
               
               
                 147 
                 (2R)—N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0018 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 148 
                 (2S)—N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.0004 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                   
               
             
          
         
       
     
     Furthermore, as indicated above, compounds of the present invention have also good activities toward the NK-1 and NK-2 receptors. 
     Some examples of such activity are given in Table 2: 
     
       
         
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                 hNK1 
                 hNK2 
               
               
                 Example 
                 Compound name 
                 μM 
                 μM 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo- 
                 0.171 
                 0.009 
               
               
                   
                 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′- 
               
               
                   
                 yl)-N-methylbutanamide hydrochloride 
               
               
                 17 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.111 
                 0.0053 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 19 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.066 
                 0.0081 
               
               
                   
                 fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine- 
               
               
                   
                 4,4′-piperidin]-1′-yl)-N-methylbutanamide 
               
               
                 40 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.035 
                 0.0052 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 42 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.116 
                 0.012 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                 44 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6- 
                 0.118 
                 0.0028 
               
               
                   
                 fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1- 
               
               
                   
                 benzoxazine-4,4′-piperidin]-1′-yl)-N- 
               
               
                   
                 methylbutanamide 
               
               
                   
               
             
          
         
       
     
     The present invention also provides pharmaceutical compositions containing compounds of the invention, for example compounds of formula I, or pharmaceutically acceptable salts thereof and a pharmaceutically acceptable carrier. Such pharmaceutical compositions can be in the form of tablets, coated tablets, dragées, hard and soft gelatine capsules, solutions, emulsions or suspensions. The pharmaceutical compositions also can be in the form of suppositories or injectable solutions. 
     The pharmaceutical compositions of the invention, in addition to one or more compounds of the invention, contain a pharmaceutically acceptable carrier. Suitable pharmaceutically acceptable carriers include pharmaceutically inert, inorganic or organic carriers. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc can be used as such excipients e.g. for tablets, dragées and hard gelatine capsules. 
     Suitable excipients for soft gelatine capsules are e.g. vegetable oils, waxes, fats, semi-solid and liquid polyols etc. 
     Suitable excipients for the manufacture of solutions and syrups are e.g. water, polyols, saccharose, invert sugar, glucose etc. Suitable excipients for injection solutions are e.g. water, alcohols, polyols, glycerol, vegetable oils etc. Suitable excipients for suppositories are e.g. natural or hardened oils, waxes, fats, semi-liquid or liquid polyols etc. 
     Moreover, the pharmaceutical compositions can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. 
     The dosage at which compounds of the invention can be administered can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, in the case of oral administration a daily dosage of about 10 to 1000 mg per person of a compound of general formula (I) should be appropriate, although the above upper limit can also be exceeded when necessary. 
     EXAMPLE A 
     Tablets of the following composition can be manufactured in the usual manner: 
     
       
         
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 mg/tablet 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Active substance 
                 5 
               
               
                   
                 Lactose 
                 45 
               
               
                   
                 Corn starch 
                 15 
               
               
                   
                 Microcrystalline cellulose 
                 34 
               
               
                   
                 Magnesium stearate 
                 1 
               
               
                   
                 Tablet weight 
                 100 
               
               
                   
                   
               
             
          
         
       
     
     EXAMPLE B 
     Capsules of the following composition can be manufactured: 
     
       
         
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 mg/capsule 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Active substance 
                 10 
               
               
                   
                 Lactose 
                 155 
               
               
                   
                 Corn starch 
                 30 
               
               
                   
                 Talc 
                 5 
               
               
                   
                 Capsule fill weight 
                 200 
               
               
                   
                   
               
             
          
         
       
     
     The active substance, lactose and corn starch can be firstly mixed in a mixer and then in a comminuting machine. The mixture can be returned to the mixer, the talc can be added thereto and mixed thoroughly. The mixture can be filled by machine into hard gelatine capsules. 
     EXAMPLE C 
     Suppositories of the following composition can be manufactured: 
     
       
         
               
               
             
               
               
               
             
           
               
                   
                   
               
               
                   
                 mg/supp. 
               
               
                   
                   
               
             
             
               
                   
               
             
          
           
               
                   
                 Active substance 
                 15 
               
               
                   
                 Suppository mass 
                 1285 
               
               
                   
                 Total 
                 1300 
               
               
                   
                   
               
             
          
         
       
     
     The suppository mass can be melted in a glass or steel vessel, mixed thoroughly and cooled to 45° C. Thereupon, the finely powdered active substance can be added thereto and stirred until it has dispersed completely. The mixture can be poured into suppository moulds of suitable size, left to cool, the suppositories then can be removed from the moulds and packed individually in wax paper or metal foil. 
     The following Examples illustrate the present invention without limiting it. All temperatures are given in degrees Celsius. 
     Abbreviations 
     
         
         DCM=dichloromethane; 
         DIPEA=N,N-diisopropylethylamine; 
         DMF=N,N-dimethylformamide; 
         HPLC=high-performance liquid chromatography; 
         MS=mass spectroscopy; 
         THF=tetrahydrofurane. 
       
    
     Intermediate 1 
     6-Fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride 
     A mixture of 48.96 g (232 mmol) (4-fluoro-phenyl)-carbamic acid tert-butyl ester and 300 mL tert-BuLi (1.7 M in hexane) in 380 mL THF at −70° C. was stirred for 50 min and afterwards 2.5 h at −20° C. 44.3 g (223 mmol) 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (commercially available) in 180 mL THF was added at −70° C. and 60 mg KOtBu at 15° C. The mixture was stirred at room temperature for 14 h. NH 4 Cl aq. was added, the organic phase was washed with saturated NaCl aq., and the aqueous phase was extracted with a mixture of THF and ethyl acetate. The combined organic phases were dried with Na 2 SO 4  and evaporated to dryness. The residue was titurated with diethyl ether, filtered off, washed with diethyl ether and dried to yield 31 g of tert-butyl 6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidine]-1′-carboxylate (MS (m/e): 335.5 (MH − )) which was used without further purification in the consecutive step. 300 mL dioxane and 136 mL 4N HCl in dioxane was added and stirred at room temperature for 18 h. The precipitate was filtered off, washed with dioxane and diethyl ether and dried in vacuum. 21 g (36%) of the title compound was yielded as light yellow solid. MS (m/e): 237.1 (MH + ). 
     Intermediate 2 
     6-Fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride 
     
       
                 
         
             
             
         
      
     
     A mixture of 3.67 g (11 mmol) tert-butyl 6-fluoro-2-oxo 1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidine]-1′-carboxylate, 3.09 g (21.8 mmol) methyl iodide (commercially available) and 5.33 g (16 mmol) Cs 2 CO 3  in 30 mL DMF was stirred at room temperature for 17 h. The mixture was poured onto ice/water and extracted with ethyl acetate. The combined organic phases were dried with Na 2 SO 4  and evaporated to dryness. 40 mL dioxane and 15 mL 4 N HCl in dioxane was added and the mixture was stirred at room temperature for 3 h. The precipitate was filtered off, washed with diethyl ether and dried in vacuum to yield 2.5 g (80%) of the title compound as off-white solid. MS (m/e): 251.3 (MH + ). 
     EXAMPLE 1 
     N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide hydrochloride 
     
       
                 
         
             
             
         
      
     
     a) Step 1 
     3-(3,4-Dichloro-phenyl)-dihydro-furan-2-one 
     
       
                 
         
             
             
         
      
     
     A mixture of 30 g (137 mmol) (3,4-Dichloro-phenyl)-acetic acid methyl ester (commercially available), 6.47 g (151 mmol) NaH (55%) and 35.8 g (171 mmol) 2-(2-Bromo-ethoxy)-tetrahydro-pyran in 100 mL DMF was stirred at room temperature for 17 h. The mixture was evaporated to dryness and partitioned between water and ethyl acetate. The combined organic phases were washed with NaCl aq., dried with Na 2 SO 4  and evaporated. The residue was treated with 400 mL 4N HCl in dioxane in 250 mL methanol and stirred for 16 h at room temperature. The mixture was evaporated to dryness and subjected to column chromatography on silica eluting with a gradient formed from ethyl acetate and heptane. The combined product fractions were evaporated to yield 18.5 g (58%) of the title compound as yellow oil. 
     b) Step 2 
     4-Bromo-2-(3,4-dichloro-phenyl)-butyric acid methyl ester 
     
       
                 
         
             
             
         
      
     
     A mixture of 10.2 g (44 mmol) 3-(3,4-dichloro-phenyl)-dihydro-furan-2-one, 55 mL HBr in acetic acid (33%) in 20 mL acetic acid was stirred at room temperature for 16 h. The mixture was poured onto ice/water and extracted with isopropylethyl acetate. The combined organic phases were washed with NaCl aq., dried with Na 2 SO 4  and evaporated. 26.3 g (221 mmol) SOCl 2  and 200 mL toluene was added and heated to 80° C. for 3 h. The mixture was evaporated to dryness and 100 mL methanol was added and stirred at room temperature for 30 min. The mixture was evaporated and subjected to column chromatography on silica eluting with a gradient formed from ethyl acetate and heptane. The combined product fractions were evaporated to yield 12.7 g (88%) of the title compound as light brown oil. MS (m/e): 335.5 (MH − ). 
     c) Step 3 
     Methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate 
     
       
                 
         
             
             
         
      
     
     A mixture of 1.5 g (4.6 mmol) 4-bromo-2-(3,4-dichloro-phenyl)-butyric acid methyl ester, 1.38 g (5 mmol) 6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride (intermediate 1) and 1.3 g (10 mmol) DIPEA in 30 mL DMF was stirred at room temperature for 16 h. The mixture was evaporated and subjected to column chromatography on silica eluting with a gradient formed from DCM, methanol and NEt 3 . The product containing fractions were evaporated to yield 0.4 g (18%) of the title compound as light yellow foam. MS (m/e): 481.1 (MH + ). 
     d) Step 4 
     Intermediate 3 
     2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid; hydrochloride 
     
       
                 
         
             
             
         
      
     
     A mixture of 0.38 g (0.79 mmol) methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate, 0.166 g (3.96 mmol) LiOH.H 2 O in 15 mL THF and 15 mL water was heated to reflux for 2 h. The mixture was concentrated and acidified with 4N HCl aq. The precipitate was filtered off, dried under vacuum and used in the consecutive step without further purification. MS (m/e): 467.1 (MH + ). 
     e) Step 5 
     A mixture of 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid; hydrochloride, 0.38 g (1.18 mmol) TBTU, 0.61 g (4.7 mmol) DIPEA and 0.12 g (1 mmol) N-methylbenzylamine in 30 mL DMF was stirred at room temperature for 16 h. The mixture was evaporated and subjected to column chromatography on silica eluting with a gradient formed from DCM, methanol and NEt 3 . The product containing fractions were evaporated, dissolved in methanol and treated with HCl in methanol. The mixture was evaporated, dissolved in methanol, charcoal was added, filtered and again evaporated and dried to yield 0.19 g (39%) of the title compound as light brown foam. MS (m/e): 570.3 (MH + ). 
     EXAMPLE 2 
     N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
     
       
                 
         
             
             
         
      
     
     a) Step 1 
     2-(3,4-Dichloro-phenyl)-4-oxo-butyric acid methyl ester 
     
       
                 
         
             
             
         
      
     
     A mixture of 25 g (114 mmol) (3,4-dichloro-phenyl)-acetic acid methyl ester (commercially available), 5.7 g (131 mmol) NaH (55%) and 23.1 g (137 mmol) bromoacetaldehyde dimethylacetal in 80 mL DMF was stirred at room temperature for 3 h. The mixture was poured onto ice/water and extracted with ethyl acetate. The combined organic phases were washed with NaCl aq., dried with Na 2 SO 4  and evaporated to dryness. The residue was dissolved in 250 mL THF and treated with 300 mL 1 N HCl at room temperature for 20 h. Water was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with NaCl aq., dried with Na 2 SO 4 , evaporated to dryness and subjected to column chromatography on silica eluting with a gradient formed from heptane and ethyl acetate. The product containing fractions were evaporated to yield 9.7 g (32%) of the title compound as light yellow oil. MS (m/e): 260.1/262.2 (MH + ). 
     b) Step 2 
     Methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate 
     
       
                 
         
             
             
         
      
     
     A mixture of 6.45 g (24.7 mmol) 2-(3,4-dichloro-phenyl)-4-oxo-butyric acid methyl ester, 6.42 g (27 mmol) 6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one, 7.85 g (47 mmol) sodium triacetoxyborohydride and 2.22 g acetic acid in 200 mL THF was stirred at room temperature for 16 h. Na 2 CO 3  aq and water was added and the mixture was extracted with ethyl acetate. The combined organic phases were washed with NaCl aq., dried with Na 2 SO 4  and evaporated to dryness. The residue was subjected to column chromatography on silica eluting with a gradient formed from DCM, methanol and NEt 3 . The product containing fractions were evaporated to yield 10.2 g (86%) of the title compound as off-white yellow foam. MS (m/e): 481.1 (MH + ). 
     c) Step 3 
     2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for example 1, step 4, the title compound was prepared from methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate through saponification with LiOH.H 2 O and hydrochloride formation with HCl aq. MS (m/e): 467.1 (MH + ). 
     d) Step 4 
     In analogy to the coupling procedure described for example 1, step 5, the title compound was prepared from 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride and benzylamine (commercially available) and subsequent subjection to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt 3 . The combined product fractions were evaporated to yield the title compound as off-white solid. MS (m/e): 556.1 (MH + ). 
     Intermediate 4 
     2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride 
     
       
                 
         
             
             
         
      
     
     a) Step 1 
     2-(4-Fluoro-phenyl)-4-oxo-butyric acid methyl ester 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for the synthesis of 2-(3,4-Dichloro-phenyl)-4-oxo-butyric acid methyl ester (example 2, step 1) the title compounds was prepared from 4-fluoro-phenyl-acetic acid methyl ester (commercially available), and bromoacetaldehyde dimethylacetal and subsequent treatment with HCl aq. MS (m/e): 209.3 (MH − ). 
     b) Step 2 
     Methyl 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for the synthesis of methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate (example 2, step 2) the title compound was prepared from 2-(4-fluoro-phenyl)-4-oxo-butyric acid methyl ester and 6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride (intermediate 1). MS (m/e): 431.3 (MH + ). 
     c) Step 3 
     In analogy to the procedure described for example 1, step 4, the title compound was prepared from methyl 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate through saponification with LiOH.H 2 O and hydrochloride formation with HCl aq. MS (m/e): 417.4 (MH + ). 
     Intermediate 5 
     2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride 
     
       
                 
         
             
             
         
      
     
     a) Step 1 
     Methyl 2-(3,4-dichlorophenyl)-4-(1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for the synthesis of methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate (example 2, step 2) the title compound was prepared from 2-(3,4-dichloro-phenyl)-4-oxo-butyric acid methyl ester and 6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride (intermediate 2). MS (m/e): 495.4 (MH + ). 
     b) Step 2 
     In analogy to the procedure described for example 1, step 4, the title compound was prepared from methyl 2-(3,4-dichlorophenyl)-4-(1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate through saponification with LiOH.H 2 O and hydrochloride formation with HCl aq. MS (m/e): 481.1 (MH + ). 
     a) Step 1 
     2-(3,4-Dichloro-phenyl)-5-oxo-pentanoic acid methyl ester 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for the synthesis of 2-(3,4-dichloro-phenyl)-4-oxo-butyric acid methyl ester (example 2, step 1) the title compounds was prepared from 3,4-dichloro-phenyl-acetic acid methyl ester (commercially available), and 3-bromopropionaldehyde dimethylacetal and subsequent treatment with HCl aq. MS (m/e): 274.1/276.1 (MH + ). 
     b) Step 2 
     Methyl 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoate 
     
       
                 
         
             
             
         
      
     
     In analogy to the procedure described for the synthesis of methyl 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoate (example 2, step 2) the title compound was prepared from 2-(3,4-dichloro-phenyl)-5-oxo-pentanoic acid methyl ester and 6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one; hydrochloride (intermediate 1). MS (m/e): 495.4 (MH + ). 
     c) Step 3 
     In analogy to the procedure described for example 1, step 4, the title compound was prepared from methyl 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1-yl)pentanoate through saponification with LiOH.H 2 O and hydrochloride formation with HCl aq. MS (m/e): 481.1 (MH + ). 
     In analogy to the synthesis of example 2 further 6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin derivatives have been prepared from their respective starting materials mentioned in table 2. Table 2 comprises example 3 to example 148. Optionally final compounds can be purified by column chromatography on silica eluting with appropriate solvent mixtures. Optionally final compounds can be transferred into their respective salts by treatment with appropriate acids. Diastereomeric or racemic mixtures can be separated into their respective diastereoisomer or enantiomer by chromatographic techniques as appropriate. 
     
       
         
               
               
               
               
               
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                   
                   
                   
                 MW 
               
               
                   
                   
                   
                   
                   
                 found 
               
               
                 Exp 
                 MW 
                 Structure 
                 Compound name 
                 Starting materials 
                 MH+ 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 3 
                 557.45 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(pyridin-4-ylmethyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andC-Pyridin-4-yl-methylamine(commerciallyavailable) 
                 557.2 
               
               
                   
               
               
                 4 
                 582.5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and1,2,3,4-Tetrahydro-isoquinoline(commerciallyavailable) 
                 582.3 
               
               
                   
               
               
                 5 
                 505.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andBenzylamine(commerciallyavailable) 
                 506.1 
               
               
                   
               
               
                 6 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andBenzyl-ethyl-amine(commerciallyavailable) 
                 586.1 
               
               
                   
               
               
                 7 
                 634.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Methanesulfonyl-benzylamine(commerciallyavailable) 
                 634.3 
               
               
                   
               
               
                 8 
                 590.91 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Chloro-benzylamine(commerciallyavailable) 
                 590.3 
               
               
                   
               
               
                 9 
                 560.45 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(5-methyl-2-furyl)methyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andC-(5-Methyl-furan-2-yl)methylamine(commerciallyavailable) 
                 560.3 
               
               
                   
               
               
                 10 
                 576.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(3-methyl-2-thienyl)methyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid,hydrochloride(intermediate 3) andC-(3-Methyl-thiophen-2-yl)-methylamine(commerciallyavailable) 
                 576.3 
               
               
                   
               
               
                 11 
                 585.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-pyridin-2-ylethyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and2-Pyridin-2-yl-ethylamine(commerciallyavailable) 
                 585.2 
               
               
                   
               
               
                 12 
                 602.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-ethyl-N-(2-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andEthyl-(2-fluoro-benzyl)-amine(commerciallyavailable) 
                 602.5 
               
               
                   
               
               
                 13 
                 644.57 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[2-(3,4-dimethoxyphenyl)ethyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and[2-(3,4-Dimethoxy-phenyl)-ethyl]-methyl-amine(commerciallyavailable) 
                 644.5 
               
               
                   
               
               
                 14 
                 536.47 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-butyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andButyl-methyl-amine(commerciallyavailable) 
                 536.3 
               
               
                   
               
               
                 15 
                 604.94 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Chloro-benzylamine(commerciallyavailable) 
                 606.3 
               
               
                   
               
               
                 16 
                 624.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[4-(4-benzylpiperidin-1-yl)-3-(3,4-dichlorophenyl)-4-oxobutyl]-6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Benzyl-piperidine(commerciallyavailable) 
                 624.3 
               
               
                   
               
               
                 17 
                 604.94 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(2-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 606.3 
               
               
                   
               
               
                 18 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butnamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andEthyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 19 
                 604.94 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(3-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 606.2 
               
               
                   
               
               
                 20 
                 600.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and7-Fluoro-1,2,3,4-tetrahydro-isoquinoline(commerciallyavailable) 
                 600.3 
               
               
                   
               
               
                 21 
                 533.62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andBenzyl-ethyl-amine(commerciallyavailable) 
                 534.3 
               
               
                   
               
               
                 22 
                 519.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-(4-methylbenzyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and4-Methyl-benzylamine(commerciallyavailable) 
                 520.2 
               
               
                   
               
               
                 23 
                 540.01 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and4-Chloro-benzylamine(commerciallyavailable) 
                 540.2 
               
               
                   
               
               
                 24 
                 547.65 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-ethyl-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-(4-methylbenzyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andEthyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 548.3 
               
               
                   
               
               
                 25 
                 554.04 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(3-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 554.1 
               
               
                   
               
               
                 26 
                 554.04 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(4-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 554.3 
               
               
                   
               
               
                 27 
                 554.04 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2-chlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(2-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 554.3 
               
               
                   
               
               
                 28 
                 576.54 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(cyclopropylmethyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′piperidin]-1′-yl)-N-propylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andCyclopropylmethyl-propyl-amine(commerciallyavailable) 
                 576.3 
               
               
                   
               
               
                 29 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andBenzyl-ethyl-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 30 
                 617.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[4-(4-cyclopentyl-piperazin-1-yl)-3-(3,4-dichlorophenyl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and1-cyclopentyl-piperazine(commerciallyavailable) 
                 617.5 
               
               
                   
               
               
                 31 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Methyl-benzylamine(commerciallyavailable) 
                 584.3 
               
               
                   
               
               
                 32 
                 570.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andBenzylamine(commerciallyavailable) 
                 570.3 
               
               
                   
               
               
                 33 
                 648.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(methylsulfonyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Methanesulfonyl-benzylamine(commerciallyavailable) 
                 648.2 
               
               
                   
               
               
                 34 
                 604.94 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′piperidin]-1′-yl)-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Chloro-benzylamine(commerciallyavailable) 
                 606.1 
               
               
                   
               
               
                 35 
                 578.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(4-methoxypiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Methoxy-piperidine(commerciallyavailable) 
                 578.3 
               
               
                   
               
               
                 36 
                 536.47 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N,N-diethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) anddiethylamine(commerciallyavailable) 
                 536.3 
               
               
                   
               
               
                 37 
                 593.53 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorphenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(2-morpholin-4-ylethyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and2-Morpholin-4-yl-ethylamine(commerciallyavailable) 
                 593.2 
               
               
                   
               
               
                 38 
                 614.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and7-Fluoro-1,2,3,4-tetrahydro-isoquinoline(commerciallyavailable) 
                 614.2 
               
               
                   
               
               
                 39 
                 612.57 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorphenyl)-N-ethyl-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andEthyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 612.3 
               
               
                   
               
               
                 40 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(3-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 41 
                 562.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(4-methylpiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Methylpiperidine(commerciallyavailable) 
                 562.1 
               
               
                   
               
               
                 42 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(4-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 43 
                 566.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-(4-fluropiperidin-1-yl)-4-oxobutyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Fluoro-piperidine(commerciallyavailable) 
                 566.2 
               
               
                   
               
               
                 44 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(2-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 45 
                 627.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-{3-(3,4-dichlorophenyl)-4-[4-(methylsulfonyl)piperazin-1-yl)-4-oxobutyl}-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and1-Methanesulfonylpiperazine(commerciallyavailable) 
                 627.3 
               
               
                   
               
               
                 46 
                 625.57 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[3-(3,4-dichlorophenyl)-4-oxo-4-(4-phenylpiperazin-1-yl)butyl]-6-fluoro-1-methylspiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and1-Phenyl-piperazine(commerciallyavailable) 
                 627.3 
               
               
                   
               
               
                 47 
                 574.45 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2,4-dichlorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide. 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and2,4-Dichloro-benzylamine(commerciallyavailable) 
                 576.2 
               
               
                   
               
               
                 48 
                 533.62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(2-phenylethyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andMethyl-phenethyl-amine(commerciallyavailable) 
                 534.2 
               
               
                 49 
                 589.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-(trifluoromethoxy)benzyl]butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and2-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 590.3 
               
               
                   
               
               
                 50 
                 571.57 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and3-Difluoromethoxy-benzylamine(commerciallyavailable) 
                 572.3 
               
               
                   
               
               
                 51 
                 587.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andMethyl-(4-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 588.2 
               
               
                   
               
               
                 52 
                 596.68 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andMethyl-(4-pyridin-4-yl-benzyl)-amine(commerciallyavailable) 
                 597.4 
               
               
                   
               
               
                 53 
                 567.61 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(3-Fluoro-4-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 568.3 
               
               
                   
               
               
                 54 
                 615.62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4)and (4-Difluoromethoxy-(3-methoxy-benzyl)methyl-amine(commerciallyavailable) 
                 616.3 
               
               
                   
               
               
                 55 
                 537.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(3-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 538.4 
               
               
                   
               
               
                 56 
                 533.62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-(4-methylbenzyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andMethyl-(4-methylbenzyl)-amine(commerciallyavailable) 
                 534.2 
               
               
                   
               
               
                 57 
                 589.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[3-(trifluoromethoxy)benzyl]butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and3-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 590.3 
               
               
                   
               
               
                 58 
                 587.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methyl-N-[3-(trifluoromethoxy)benzyl]butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) andMethyl-(3-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 588.3 
               
               
                   
               
               
                 59 
                 537.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-methylbutanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and(4-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 538.5 
               
               
                   
               
               
                 60 
                 523.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and4-Fluoro-benzylamine(commerciallyavailable) 
                 524.5 
               
               
                   
               
               
                 61 
                 573.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[3-(trifluoromethyl)benzyl]butanamide 
                 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 4) and3-Trifluoromethyl-benzylamine(commerciallyavailable) 
                 574.5 
               
               
                   
               
               
                 62 
                 625.35 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 22-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and2,4-Dichloro-benzylamine(commerciallyavailable) 
                 626.1 
               
               
                   
               
               
                 63 
                 671 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andC-(4-Chloro-phenyl)-C-(1-methyl-1H-imidazol-2-yl)-methylamine(commerciallyavailable) 
                 670.2 
               
               
                   
               
               
                 64 
                 570.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andBenzyl-methyl-amine(commerciallyavailable) 
                 570.3 
               
               
                   
               
               
                 65 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-phenethyl-amine(commerciallyavailable) 
                 586.3 
               
               
                   
               
               
                 66 
                 640.46 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and2-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 640.2 
               
               
                   
               
               
                 67 
                 622.47 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and3-Difluoromethoxy-(commerciallyavailable) 
                 622.3 
               
               
                   
               
               
                 68 
                 638.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(4-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 638.2 
               
               
                   
               
               
                 69 
                 622.53 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Pyrazol-1-yl-benzylamine(commerciallyavailable) 
                 622.4 
               
               
                   
               
               
                 70 
                 655.6 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(4-morpholin-4-yl-benzyl)-amine(commerciallyavailable) 
                 655.4 
               
               
                   
               
               
                 71 
                 653.63 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-piperidin-1-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(4-piperidin-1-yl-benzyl)-amine(commerciallyavailable) 
                 653.4 
               
               
                   
               
               
                 72 
                 647.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(4-piperidin-4-yl-benzyl)-amine(commerciallyavailable) 
                 647.5 
               
               
                   
               
               
                 73 
                 652.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-[4-(5-methyl[1,2,4]oxadiazol-3-yl)-benzyl]-amine(commerciallyavailable) 
                 652.3 
               
               
                   
               
               
                 74 
                 618.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(3-Fluoro-4-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 618.4 
               
               
                   
               
               
                 75 
                 666.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[4(difluoromethoxy)-3-methoxybenzyl]4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3)and (4-Difluoromethoxy-3-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 666.3 
               
               
                   
               
               
                 76 
                 588.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(3-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 588.1 
               
               
                   
               
               
                 77 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 586.2 
               
               
                   
               
               
                 78 
                 640.46 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(3-trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and3-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 640.2 
               
               
                   
               
               
                 79 
                 638.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) andMethyl-(3-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 638.3 
               
               
                   
               
               
                 80 
                 588.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(4-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 588.1 
               
               
                   
               
               
                 81 
                 574.45 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-butanamide. 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Fluoro-benzylamine(commerciallyavailable) 
                 576.3 
               
               
                   
               
               
                 82 
                 586.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Methoxy-benzylamine(commerciallyavailable) 
                 586.3 
               
               
                   
               
               
                 83 
                 624.46 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and3-Trifluoromethyl-benzylamine(commerciallyavailable) 
                 624.3 
               
               
                   
               
               
                 84 
                 640.56 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-[1,2,3]Thiadiazol-4-yl-benzylamine(commerciallyavailable) 
                 640.2 
               
               
                   
               
               
                 85 
                 640.46 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and3-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 640.2 
               
               
                   
               
               
                 86 
                 581.47 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and4-Aminomethyl-benzonitrile(commerciallyavailable) 
                 581.3 
               
               
                   
               
               
                 87 
                 639.38 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2,4-dichlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and2,4-Dichloro-benzylamine(commerciallyavailable) 
                 640.3 
               
               
                   
               
               
                 88 
                 685.03 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andC-(4-Chloro-phenyl)-C-(1-methyl-1H-imidazol-2-yl)-methylamine(commerciallyavailable) 
                 686.4 
               
               
                   
               
               
                 89 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andBenzyl-methyl-amine(commerciallyavailable) 
                 586.3 
               
               
                   
               
               
                 90 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-metyl-N-(2-phenylethyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-phenethyl-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 91 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and2-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.3 
               
               
                   
               
               
                 92 
                 636.5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and3-Difluoromethoxy-benzylamine(commerciallyavailable) 
                 636.3 
               
               
                   
               
               
                 93 
                 652.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(4-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 652.3 
               
               
                   
               
               
                 94 
                 636.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1H-pyrazol-1-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Pyrazol-1-yl-benzylamine(commerciallyavailable) 
                 636.3 
               
               
                   
               
               
                 95 
                 669.62 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-morpholin-4-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(4-morpholin-4-yl-benzyl)-amine(commerciallyavailable) 
                 669.4 
               
               
                   
               
               
                 96 
                 667.65 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-piperidin-1-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(4-piperidin-1-yl-benzyl)-amine(commerciallyavailable) 
                 667.3 
               
               
                   
               
               
                 97 
                 661.6 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(4-piperidin-1-yl-benzyl)-amine(commerciallyavailable) 
                 661.4 
               
               
                   
               
               
                 98 
                 666.58 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(5-methyl-1,2,4-oxadiazol-3-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-benzyl]-amine(commerciallyavailable) 
                 666.3 
               
               
                   
               
               
                 99 
                 632.53 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(3-Fluoro-4-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 632.5 
               
               
                   
               
               
                 100 
                 680.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(4-Difluoro-methoxy-3-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 680.3 
               
               
                   
               
               
                 101 
                 602.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(3-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 604.3 
               
               
                   
               
               
                 102 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 103 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and3-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.4 
               
               
                   
               
               
                 104 
                 652.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) andMethyl-(3-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 652.3 
               
               
                   
               
               
                 105 
                 602.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(4-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 604.3 
               
               
                   
               
               
                 106 
                 588.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Fluoro-benzylamine(commerciallyavailable) 
                 588.1 
               
               
                   
               
               
                 107 
                 600.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′H-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Methoxy-benzylamine(commerciallyavailable) 
                 600.3 
               
               
                   
               
               
                 108 
                 638.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethyl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and3-Trifluoromethyl-benzylamine(commerciallyavailable) 
                 638.3 
               
               
                   
               
               
                 109 
                 654.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-[1,2,3]Thiadiazol-4-yl-benzylamine(commerciallyavailable) 
                 654.4 
               
               
                   
               
               
                 110 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.4 
               
               
                   
               
               
                 111 
                 595.5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and4-Aminomethyl-benzonitrile(commerciallyavailable) 
                 595.4 
               
               
                   
               
               
                 112 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andBenzyl-methyl-amine(commerciallyavailable) 
                 584.2 
               
               
                   
               
               
                 113 
                 639.38 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2,4-dichloro-benzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and2,4-Dichloro-benzylamine(commerciallyavailable) 
                 640.3 
               
               
                   
               
               
                 114 
                 685.03 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-[(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andC-(4-Chloro-phenyl)-C-(1-methyl-1H-imidazol-2-yl)-methylamine(commerciallyavailable) 
                 686.3 
               
               
                   
               
               
                 115 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(2-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(2-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 116 
                 590.54 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(3-methyl-2-thienyl)methyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andC-(3-Methyl-thiophen-2-yl)-methylamine(commerciallyavailable) 
                 590.2 
               
               
                   
               
               
                 117 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-benzyl-2-(3,4-dichlorophenyl)-N-ethyl-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andBenzyl-ethyl-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 118 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[2-(trifluoromethoxy)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.3 
               
               
                   
               
               
                 119 
                 636.5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[3-(difluoromethoxy)benzyl]-5-(6-fluoro-2-oxo1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and3-Difluoromethoxy-benzylamine(commerciallyavailable) 
                 636.2 
               
               
                   
               
               
                 120 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(4-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 121 
                 652.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[4-(trifluoromethyl)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-(4-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 652.2 
               
               
                   
               
               
                 122 
                 618.96 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(3-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(3-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 123 
                 667.65 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-piperidin-1-ylbenzyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-(4-piperidin-1-yl-benzyl)-amine(commerciallyavailable) 
                 667.3 
               
               
                   
               
               
                 124 
                 661.6 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-pyridin-4-ylbenzyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-(4-pyridin-4-yl-benzyl)-amine(commerciallyavailable) 
                 661.3 
               
               
                   
               
               
                 125 
                 604.94 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Chloro-benzylamine(commerciallyavailable) 
                 604.3 
               
               
                   
               
               
                 126 
                 632.53 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluoro-4-methoxybenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(3-Fluoro-4-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 632.4 
               
               
                   
               
               
                 127 
                 680.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-[4-(difluoromethoxy)-3-methoxybenzyl]-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(4-Difluoro-methoxy-3-methoxy-benzyl)-methyl-amine(commerciallyavailable) 
                 680.3 
               
               
                   
               
               
                 128 
                 602.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(3-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(3-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 602.3 
               
               
                   
               
               
                 129 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[3-(trifluoromethoxy)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and3-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.4 
               
               
                   
               
               
                 130 
                 652.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-[3-(trifluoromethoxy)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-(3-trifluoromethyl-benzyl)-amine(commerciallyavailable) 
                 652.3 
               
               
                   
               
               
                 131 
                 602.51 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylpentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(4.Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 602.3 
               
               
                   
               
               
                 132 
                 588.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-N-(4-fluorobenzyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Fluoro-benzylamine(commerciallyavailable) 
                 588.1 
               
               
                   
               
               
                 133 
                 600.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methoxybenzyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Methoxy-benzylamine(commerciallyavailable) 
                 600.2 
               
               
                   
               
               
                 134 
                 584.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-(4-methylbenzyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Methyl-benzylamine(commerciallyavailable) 
                 584.2 
               
               
                   
               
               
                 135 
                 638.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethyl)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Trifluoromethyl-benzylamine(commerciallyavailable) 
                 638.3 
               
               
                   
               
               
                 136 
                 654.59 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(1,2,3-thiadiazol-4-yl)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-[1,2,3]Thiadiazol-4-yl-benzylamine(commerciallyavailable) 
                 654.4 
               
               
                   
               
               
                 137 
                 654.49 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[4-(trifluoromethoxy)benzyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Trifluoromethoxy-benzylamine(commerciallyavailable) 
                 654.3 
               
               
                   
               
               
                 138 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(4-methylbenzyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-(4-methyl-benzyl)-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 139 
                 614.52 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 1′-[4-(3,4-dichlorophenyl)-5-(7-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-5-oxopentyl]-6-fluorospiro[3,1-benzoxazine-4,4′-piperidin]-2(1H)-one 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and7-Fluoro-1,2,3,4-tetrahydro-isoquinoline(commerciallyavailable) 
                 614.1 
               
               
                   
               
               
                 140 
                 574.48 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(5-methyl-2-furyl)methyl]pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andC-(5-Methyl-furan-2-yl)-methylamine(commerciallyavailable) 
                 576.3 
               
               
                   
               
               
                 141 
                 598.55 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methyl-N-(2-phenylethyl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) andMethyl-phenethyl-amine(commerciallyavailable) 
                 598.3 
               
               
                   
               
               
                 142 
                 595.5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 N-(4-cyanobenzyl)-2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanamide 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and4-Aminomethyl-benzonitrile(commerciallyavailable) 
                 595.3 
               
               
                   
               
               
                 143 
                 606.95 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2S)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1R)-1-phenylethyl]butanamidehydrochloride 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(R)-1-Phenyl-ethylamine(commerciallyavailable) 
                   
               
               
                   
               
               
                 144 
                 606.95 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1R)-1-phenylethyl]butanamidehydrochloride 
                 2-(3,4-dichlorophenyl)-5-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)pentanoicacid, hydrochloride(intermediate 6) and(R)-1-Phenyl-ethylamine(commerciallyavailable) 
                   
               
               
                   
               
               
                 145 
                 606.95 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2S)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1S)-1-phenylethyl]butanamidehydrochloride 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(S)-1-Phenyl-ethylamine(commerciallyavailable) 
                 570.3 
               
               
                   
               
               
                 146 
                 606.95 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2R)-2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1S)-1-phenylethyl]butanamidehydrochloride 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 3) and(S)-1-Phenyl-ethylamine(commerciallyavailable) 
                 570.3 
               
               
                   
               
               
                 147 
                 618.961 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2R)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(4-Fluoro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
               
                 148 
                 618.961 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 (2S)-N-(4-chlorobenzyl)-2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-methylbutanamide 
                 2-(3,4-dichlorophenyl)-4-(6-fluoro-1-methyl-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoicacid, hydrochloride(intermediate 5) and(4-Chloro-benzyl)-methyl-amine(commerciallyavailable) 
                 618.3 
               
               
                   
               
             
          
         
       
     
     EXAMPLE 149 
     2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-N-[(1R)-2-hydroxy-1-phenylethyl]butanamide hydrochloride 
     
       
                 
         
             
             
         
      
     
     In analogy to the coupling procedure described for example 1, step 5, the title compound was prepared from 2-(3,4-dichlorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride and S-2-amino-2-phenyl ethanol (commercially available) and subsequent subjection to purification by flash chromatography (2% MeOH/CH 2 Cl 2 ). The combined product fractions were evaporated to yield the title compound. MS (m/e): 516 (MH + ). 
     EXAMPLE 150 
     4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[(1R)-1-(hydroxymethyl)-3-methylbutyl]butanamide 
     
       
                 
         
             
             
         
      
     
     In analogy to the coupling procedure described for example 1, step 5, the title compound was prepared from 2-(4-fluoro)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride and (R)-4-methyl-2-amino-pentanol (commercially available) and subsequent subjection to purification by flash chromatography (2% MeOH/CH 2 Cl 2 ) to yield two diastereomers. The combined product fractions of each were evaporated to yield the title compounds. Both showed MS (m/e): 516 (MH + ). 
     EXAMPLE 151 
     4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)-2-(4-fluorophenyl)-N-[(1R)-2-hydroxy-1-phenylethyl]butanamide 
     
       
                 
         
             
             
         
      
     
     In analogy to the coupling procedure described for example 1, step 5, the title compound was prepared from 2-(4-fluorophenyl)-4-(6-fluoro-2-oxo-1,2-dihydro-1′H-spiro[3,1-benzoxazine-4,4′-piperidin]-1′-yl)butanoic acid, hydrochloride and (R)-2-amino-2-phenyl ethanol (commercially available) and subsequent subjection to purification by flash chromatography (2% MeOH/CH 2 Cl 2 ). The diastereomers were separated in this way and each of the combined product fractions were evaporated to yield the title compound. MS (m/e): 536 (MH + ).