PATENT ABSTRACT
The present invention relates to compounds of formula I 
                                 
wherein
   R 1 , R 2 ,   R 3 ,   R 4 , and   X are as defined herein or to pharmaceutically acceptable acid addition salts thereof, with the exception of   4-methoxy-N-[2-oxo-2-(phenylamino)ethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[5-chloro-2-methoxyphenyl)amino]-2-oxoethyl]-N-benzamide,   4-methyl-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-benzamide,   N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-methyl-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-benzamide and   N-[2-[(2,4-dimethoxyphenyl)amino]-2-oxoethyl]-N-[(2-fluorophenyl)methyl]-benzeneacetamide. The compounds are useful in the treatment of neurological and neuropsychiatric disorders.

PATENT DESCRIPTION
PRIORITY TO RELATED APPLICATION(S) 
     This application claims the benefit of European Patent Application No. 06119758.8, filed Aug. 30, 2006, which is hereby incorporated by reference in its entirety. 
     BACKGROUND OF THE INVENTION 
     Schizophrenia is a progressive and devastating neurological disease characterized by episodic positive symptoms such as delusions, hallucinations, thought disorders and psychosis and persistent negative symptoms such as flattened affect, impaired attention and social withdrawal, and cognitive impairments (Lewis D A and Lieberman J A,  Neuron,  2000, 28:325-33). For decades research has focused on the “dopaminergic hyperactivity” hypothesis which has led to therapeutic interventions involving blockade of the dopaminergic system (Vandenberg R J and Aubrey K R.,  Exp. Opin. Ther. Targets,  2001, 5 (4): 507-518; Nakazato A and Okuyama S, et al., 2000 , Exp. Opin. Ther. Patents,  10 (1): 75-98). This pharmacological approach poorly address negative and cognitive symptoms which are the best predictors of functional outcome (Sharma T.,  Br. J. Psychiatry,  1999, 174 (suppl. 28): 44-51). 
     A complementary model of schizophrenia was proposed in the mid-1960&#39; based upon the psychotomimetic action caused by the blockade of the glutamate system by compounds like phencyclidine (PCP) and related agents (ketamine) which are non-competitive NMDA receptor antagonists. Interestingly in healthy volunteers, PCP-induced psychotomimetic action incorporates positive and negative symptoms as well as cognitive dysfunction, thus closely resembling schizophrenia in patients (Javitt D C et al., 1999 , Biol. Psychiatry,  45: 668-679 and refs. herein). Furthermore transgenic mice expressing reduced levels of the NMDAR1 subunit displays behavioral abnormalities similar to those observed in pharmacologically induced models of schizophrenia, supporting a model in which reduced NMDA receptor activity results in schizophrenia-like behavior (Mohn A R et al., 1999 , Cell,  98: 427-236). 
     Glutamate neurotransmission, in particular NMDA receptor activity, plays a critical role in synaptic plasticity, learning and memory, such as the NMDA receptors appears to serve as a graded switch for gating the threshold of synaptic plasticity and memory formation (Hebb DO, 1949 , The organization of behavior , Wiley, N.Y.; Bliss T V and Collingridge GL, 1993 , Nature,  361: 31-39). Transgenic mice overexpressing the NMDA NR2B subunit exhibit enhanced synaptic plasticity and superior ability in learning and memory (Tang J P et al., 1999 , Nature:  401-63-69). 
     Thus, if a glutamate deficit is implicate in the pathophysiology of schizophrenia, enhancing glutamate transmission, in particular via NMDA receptor activation, would be predicted to produce both anti-psychotic and cognitive enhancing effects. 
     The amino acid glycine is known to have at least two important functions in the CNS. It acts as an inhibitory amino acid, binding to strychnine sensitive glycine receptors, and it also influences excitatory activity, acting as an essential co-agonist with glutamate for N-methyl-D-aspartate (NMDA) receptor function. While glutamate is released in an activity-dependent manner from synaptic terminals, glycine is apparently present at a more constant level and seems to modulate/control the receptor for its response to glutamate. 
     One of the most effective ways to control synaptic concentrations of neurotransmitter is to influence their re-uptake at the synapses. Neurotransmitter transporters by removing neurotransmitters from the extracellular space, can control their extracellular lifetime and thereby modulate the magnitude of the synaptic transmission (Gainetdinov R R et al, 2002, Trends in Pharm. Sci., 23 (8): 367-373). 
     Glycine transporters, which form part of the sodium and chloride family of neurotransmitter transporters, play an important role in the termination of post-synaptic glycinergic actions and maintenance of low extracellular glycine concentration by re-uptake of glycine into presynaptic nerve terminals and surrounding fine glial processes. 
     Two distinct glycine transporter genes have been cloned (GlyT-1 and GlyT-2) from mammalian brain, which give rise to two transporters with ˜50% amino acid sequence homology. GlyT-1 presents four isoforms arising from alternative splicing and alternative promoter usage (1a, 1b, 1c and 1d). Only two of these isoforms have been found in rodent brain (GlyT-1a and GlyT-1b). GlyT-2 also presents some degree of heterogeneity. Two GlyT-2 isoforms (2a and 2b) have been identified in rodent brains. GlyT-1 is known to be located in CNS and in peripheral tissues, whereas GlyT-2 is specific to the CNS. GlyT-1 has a predominantly glial distribution and is found not only in areas corresponding to strychnine sensitive glycine receptors but also outside these areas, where it has been postulated to be involved in modulation of NMDA receptor function (Lopez-Corcuera B et al., 2001 , Mol. Mem. Biol.,  18: 13-20). Thus, one strategy to enhance NMDA receptor activity is to elevate the glycine concentration in the local microenvironment of synaptic NMDA receptors by inhibition of GlyT-1 transporter (Bergereon R. Et al., 1998 , Proc. Natl. Acad. Sci. USA,  95: 15730-15734; Chen L et al., 2003 , J. Neurophysiol.,  89 (2): 691-703). 
     Glycine transporters inhibitors are suitable for the treatment of neurological and neuropsychiatric disorders. The majority of diseases states implicated are psychoses, schizophrenia (Armer R E and Miller D J, 2001 , Exp. Opin. Ther. Patents,  11 (4): 563-572), psychotic mood disorders such as severe major depressive disorder, mood disorders associated with psychotic disorders such as acute mania or depression associated with bipolar disorders and mood disorders associated with schizophrenia, (Pralong E T et al., 2002 , Prog. Neurobiol.,  67: 173-202), autistic disorders (Carlsson M L, 1998 , J. Neural Transm.  105: 525-535), cognitive disorders such as dementias, including age related dementia and senile dementia of the Alzheimer type, memory disorders in a mammal, including a human, attention deficit disorders and pain (Armer R E and Miller D J, 2001 , Exp. Opin. Ther. Patents,  11 (4): 563-572). 
     Thus, increasing activation of NMDA receptors via GlyT-1 inhibition may lead to agents that treat psychosis, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer&#39;s disease. 
     SUMMARY OF THE INVENTION 
     The present invention provides compounds of formula I 
                                
wherein
     R 1  is lower alkyl, aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted by halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cyano, amino, di-lower alkyl amino or morpholinyl;   R 2  is lower alkyl, —(CH 2 ) n -aryl, —(CH 2 ) n -heteroaryl or —(CH 2 ) n -cycloalkyl, wherein the aryl or heteroaryl groups are optionally substituted by one or more substituents selected from the group consisting of halogen, lower alkyl, cyano, or lower alkoxy;   R 3  is hydrogen or lower alkyl;   R 4  is aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of halogen, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl;   X is a bond or —OCH 2 —;   n is 0, 1 or 2;
 
or pharmaceutically acceptable acid addition salts thereof, with the exception of
   4-methoxy-N-[2-oxo-2-(phenylamino)ethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[5-chloro-2-methoxyphenyl)amino]-2-oxoethyl]-N-phenylmethyl-benzamide,   4-methyl-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-phenylmethyl-benzamide,   N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-methyl-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-phenylmethyl-benzamide and   N-[2-[(2, 4-dimethoxyphenyl)amino]-2-oxoethyl]-N-[(2-fluorophenyl)methyl]-benzeneacetamide.   
     The first excepted compound has been described in  Journal of the Chemical Society, Perkin Transactions  1:  Organic and Bio - Organic Chemistry  (1972), (7), 909-13 in a cyclisation process of α-acylamino-acids. The other excepted compounds have been listed in the CAS registry file. 
     Furthermore, the invention includes all racemic mixtures, all their corresponding enantiomers and/or optical isomers. 
     The present invention also provides pharmaceutical compositions containing a compound of formula I or a pharmaceutical salt thereof. The invention also provides methods for the preparation of the compounds and compositions of the invention. 
     Compounds of general formula I are good inhibitors of the glycine transporter 1 (GlyT-1) and have a good selectivity to glycine transporter 2 (GlyT-2) inhibitors. The invention provides methods for the treatment of diseases related to activation of NMDA receptors via GlyT-1 inhibition, such as psychoses, dysfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer&#39;s disease. The preferred indications of the present invention are schizophrenia, cognitive impairment and Alzheimer&#39;s disease. 
    
    
     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 saturated straight- or branched-chain hydrocarbon group containing from 1 to 7 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, 2-butyl, t-butyl and the like. Preferred alkyl groups are groups with 1-4 carbon atoms. 
     The term “cycloalkyl” denotes a saturated or partially saturated carbocyclic ring containing from 3 to 7 carbon atoms, for example cyclopropyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl or cycloheptenyl. 
     The term “halogen” denotes chlorine, iodine, fluorine and bromine. 
     The term “aryl” denotes a monovalent cyclic aromatic hydrocarbon radical having 6 to 12 ring atoms and consisting of one or more fused rings in which at least one ring is aromatic in nature, for example phenyl or naphthyl. 
     The term “heteroaryl” denotes a cyclic aromatic hydrocarbon radical, containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur or nitrogen wherein at least one ring is aromatic in nature, for example pyridyl, quinoxalinyl, dihydrobenzofuranyl, thiophenyl, benzothiophenyl, isoxazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, thiazolyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl and isothiazolyl. 
     The term “lower alkyl substituted by halogen” denotes a lower alkyl group as defined above, wherein at least one hydrogen atom is replaced by a halogen atom, for example the following groups: CF 3 , CHF 2 , CH 2 F, CH 2 CF 3 , CH 2 CHF 2 , CH 2 CH 2 F, CH 2 CH 2 CF 3 , CH 2 CH 2 CH 2 CF 3 , CH 2 CH 2 Cl, CH 2 CF 2 CF 3 , CH 2 CF 2 CHF 2 , CF 2 CHFCF 3 , C(CH 3 ) 2 CF 3 , CH(CH 3 )CF 3  or CH(CH 2 F)CH 2 F. 
     The term “lower alkoxy” denotes a alkyl group wherein the lower alkyl residue is as defined above and which is attached via an oxygen atom. 
     The term “lower alkoxy substituted by halogen” denotes an alkoxy group, wherein at least one hydrogen atom is replaced by halogen as defined above. 
     “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, methane-sulfonic 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 present invention provides compounds of formula I 
                                
wherein
     R 1  is lower alkyl, aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted by halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, cyano, amino, di-lower alkyl amino or morpholinyl;   R 2  is lower alkyl, —(CH 2 ) n -aryl, —(CH 2 ) n -heteroaryl or —(CH 2 ) n -cycloalkyl, wherein the aryl or heteroaryl groups are optionally substituted by one or more substituents selected from the group consisting of halogen, lower alkyl, cyano, or lower alkoxy;   R 3  is hydrogen or lower alkyl;   R 4  is aryl or heteroaryl, wherein aryl and heteroaryl are optionally substituted by one or more substituents selected from the group consisting of halogen, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl;   X is a bond or —OCH 2 —;   n is 0, 1 or 2;
 
or pharmaceutically acceptable acid addition salts thereof, with the exception of
   4-methoxy-N-[2-oxo-2-(phenylamino)ethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-[2-[5-chloro-2-methoxyphenyl)amino]-2-oxoethyl]-N-benzamide,   4-methyl-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-benzamide,   N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-methyl-N-[2-[(4-methylphenyl)amino]-2-oxoethyl]-N-phenyl-benzamide,   4-chloro-N-(2-oxo-2-[(2,4,6-trichlorophenyl)amino]ethyl]-N-benzamide and   N-[2-[(2,4-dimethoxyphenyl)amino]-2-oxoethyl]-N-[(2-fluorophenyl)methyl]-benzeneacetamide.   
     Preferred compounds of formula I are those, wherein X is a bond. 
     Preferred compounds of formula I of the present invention are further those, wherein R 1  and R 4  are both monosubstituted aryl, preferably halogen substituted phenyl, for example the following compounds:
     4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2,6-difluoro-benzyl)-benzamide,   4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2,3-difluoro-benzyl)-benzamide,   4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2-fluoro-benzyl)-benzamide,   4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-thiophen-2-ylmethyl-benzamide,   4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2-methoxy-benzyl)-benzamide,   4-Chloro-N-(3-chloro-benzyl)-N-[(3-chloro-phenylcarbamoyl)-methyl]-benzamide and   4-Chloro-N-(2-chloro-benzyl)-N-[(3-chloro-phenylcarbamoyl)-methyl]-benzamide.   

     Further preferred compounds are those, wherein R 1  and R 4  are both monosubstituted aryl, for R 1  preferably methoxy substituted phenyl and for R 4  preferably halogen substituted phenyl, for example the following compounds:
     N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(2,6-difluoro-benzyl)-4-methoxy-benzamide and   N-(3-Chloro-benzyl)-N-[(3-chloro-phenylcarbamoyl)-methyl]-4-methoxy-benzamide.   

     Preferred compounds of formula I of the present invention are further those, wherein R 1  is heteroaryl, preferably benzothiophenyl, for example the following compounds:
     Benzo[b]thiophene-2-carboxylic acid (2-chloro-benzyl)-[(3-trifluoromethyl-phenylcarbamoyl)-methyl]-amide,   Benzo[b]thiophene-2-carboxylic acid (2-chloro-benzyl)-[(3-fluoro-phenylcarbamoyl)-methyl]-amide,   Benzo[b]thiophene-2-carboxylic acid (3,5-difluoro-benzyl)-[(3-fluoro-phenylcarbamoyl)-methyl]-amide,   Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4-fluoro-phenylcarbamoyl)-methyl]-(2,6-difluoro-benzyl)-amide,   Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4-fluoro-phenylcarbamoyl)-methyl]-(2,3-difluoro-benzyl)-amide and   Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4-fluoro-phenylcarbamoyl)-methyl]-(3,5-difluoro-benzyl)-amide.   

     Preferred compounds of formula I of the present invention are further those, wherein R 1  and R 4  are monosubstituted aryl, preferably halogen substituted phenyl for R 1  and CF 3  substituted phenyl for R 4 , for example the following compound:
     N-(2-Chloro-benzyl)-4-fluoro-N-[(3-trifluoromethyl-phenylcarbamoyl)-methyl]-benzamide.   

     The present compounds of formula I and their pharmaceutically acceptable salts can be prepared by methods known in the art, for example, by processes described below, which processes comprise 
     a) reacting a compound of formula 
                                
with a compound of formula
 R 2 —NH 2   II 
and with a compound of formula
 
                                
in the presence of N-ethyldiisopropylamine
 
to produce a compound of formula
 
                                
wherein the substituents are as defined above, or
 
     b) reacting a compound of formula 
                                
with a compound of formula
 
                                
in presence of triethylamine
 
to produce a compound of formula
 
                                
wherein the substituents are as defined above or
 
     c) reacting a compound of formula
 
NHR 3 R 4   IX
 
with a compound of formula
 
                                
in the presence of N-ethyldiisopropylamine and HATU [O-(7-Azabenzotriazole-1-yl)-N, N,N′N′-tetramethyluronium hexafluorophosphate],
 
to produce a compound of formula
 
                                
wherein the substituents are as defined above, or
 
     d) reacting a compound of formula 
                                
with a compound of formula
 
                                
in the presence of triethylamine,
 
to produce a compound of formula
 
                                
wherein the substituents are as defined above
 
and
 
     if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts. 
     The acid addition salts of the basic compounds of formula I can be converted to the corresponding free bases by treatment with at least a stoichiometric equivalent of a suitable base such as sodium or potassium hydroxide, potassium carbonate, sodium bicarbonate, ammonia, and the like. 
     The compounds of formula I can be prepared in accordance with process variant a) to d), with the following schemes and with working examples 1-128. 
     The starting material is commercially available or can be prepared in accordance with known methods. 
     Procedure A 
     This procedure is used to prepare Example 34 (N-phenyl-N-(p-tolylcarbamoyl-methyl)-6-trifluoromethyl-nicotinamide). 
     
       
                 
         
             
             
         
      
     
     To a compound of formula III, for example 2-bromo-N-(4-methyl-phenyl)-acetamide, in THF is added a compound of formula II, for example aniline and N-ethyldiisopropylamine, and a compound of formula IV, for example 6-trifluoromethyl-nicotynoyl chloride, and the reaction mixture is stirred over night at reflux. Then the reaction is concentrated in vacuo, and the reaction mixture is purified in conventional manner. 
     Procedure B 
     This procedure is used to prepare Example 30: N-[(3,4-dichloro-phenylcarbamoyl)-methyl]-N-phenyl-3-trifluoromethyl benzamide. 
                                
Step 1: Compound of Formula V
 
     To a compound of formula III, for example 2-bromo-N-(3,4-dichloro-phenyl)-acetamide, in THF is added a compound of formula II, for example aniline and N-ethyldiisopropylamine, and the reaction mixture is stirred over night at reflux. The precipitated salt is then filtered off, and the filtrate was then concentrated in vacuo. The residue was then purified in conventional manner. 
     Step 2: Compound of Formula I 
     To a compound of formula V, for example N-(3,4-dichloro-phenyl)-2-phenylamino-acetamide, in THF is added triethylamine and a compound of formula IV, for example 3-trifluoromethylbenzoyl chloride, and the reaction mixture is stirred at room temperature for about 30 minutes. Water is then added to the mixture until precipitation occurred, and the mixture is stirred for 5 minutes. Then the precipitate is isolated by filtration and washed. 
     Procedure C 
     This procedure is used to prepare Example 30: 4-chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2-fluoro-benzyl)benzamide. 
                                
Step 1: Compound of Formula VII
 
     To a compound of formula VI, for example (2,6-dichloro-benzylamino)-acetic acid ethyl ester, in suspension THF is added triethylamine and a compound of formula IV, for example 4-methoxybenzoyl chloride, and the reaction mixture is stirred at room temperature for 10 min. Water is then added to the reaction mixture, and the aqueous phase is extracted with diethylacetate. The combined organic phases are then dried, concentrated in vacuo and purified. 
     Step 2: Compound of Formula VIII 
     To a compound of formula VII, for example N-(3,4-dichloro-phenyl)-2-phenylamino-acetamide, in ethanol is added NaOH, and the reaction mixture is stirred at room temperature for about 3 hours. The reaction mixture is then neutralized by addition of HCl, and the ethanol is eliminated by evaporation. Water and ethyl acetate is then added to the residue. The organic phase is separated, and the aqueous phase is extracted with ethylacetate. The combined organic phase is then washed again with water, dried and concentrated in vacuo. 
     Step 3: Compound of Formula I 
     To a solution of a compound of formula IX, for example 3-chloroaniline, in DMF is added N-ethyldiiopropylamine, a compound of formula VIII, for example [(2,6-dichloro-benzyl)-(4-methoxy-benzoyl)-amino]-acetic acid, and HATU; and the reaction mixture is stirred at room temperature over night. Then water is added until precipitation occurs, and the precipitate is isolated by filtration and washed with a mixture of water and ethanol to yield the title compound. 
     Procedure D 
     This procedure was used to prepare Example 1: 4-chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2,6-difluoro-benzyl)-benzamide. 
     
       
                 
         
             
             
         
      
     
     To a compound of formula III-1, for example N-1-(3-chlorophenyl)-2-chloroacetamide, in DMF is added a compound of formula II, for example 2,6-difluorobenzylamine and triethylamine, and a compound of formula IV, such as 4-chlorobenzoyl chloride. The reaction mixture is stirred at room temperature for about 15 min and then purified. 
     Procedure E 
     This procedure was used to prepare Example 97: N-[(3,4-dichloro-phenylcarbamoyl)-methyl]-N-isobutyl-4-methoxy-benzamide. 
                                
Step 1: Hydrobromide of a Compound of Formula V-1
 
     To a solution of a compound of formula III, for example 2-bromo-N-(3,4-dichloro-phenyl)-acetamide, in dichloromethane at 0° C. is slowly added isobutylamine in dichloromethane. The reaction mixture is allowed to warm up to room temperature and then stirred for another 24 hours. Then the salt is filtered off and the filtrate is concentrated in vacuo. The residue is then purified. 
     Step 2: Compound of Formula I-1. 
     To a solution of a compound of formula V-1, such as N-(3,4-dichloro-phenyl)-2-isobutylamino-acetamide hydrobromide, in THF are slowly added a solution of triethylamine in THF and a solution of a compound of formula IV, for example 4-methoxybenzoyl chloride, in THF, and the reaction mixture is stirred at room temperature for about 24 hours. Then water is added to the reaction mixture, and the precipitate is isolated by filtration and then purified. 
     The compounds of formula I and their pharmaceutically usable addition salts possess valuable pharmacological properties. Specifically, the compounds of the present invention are good inhibitors of the glycine transporter I (GlyT-1). 
     The compounds were investigated in accordance with the test given hereinafter. 
     Solutions and Materials 
     DMEM complete medium: Nutrient mixture F-12 (Gibco Life-technologies), fetal bovine serum (FBS) 5%, (Gibco life technologies), Penicillin/Streptomycin 1% (Gibco life technologies), Hygromycin 0.6 mg/ml (Gibco life technologies), Glutamine 1 mM Gibco life technologies) 
     Uptake buffer (UB): 150 mM NaCl, 10 mM Hepes-Tris, pH 7.4, 1 mM CaCl 2 , 2.5 mM KCl, 2.5 mM MgSO 4 , 10 mM (+) D-glucose. 
     Flp-in™-CHO (Invitrogen Cat n° R758-07) cells stably transfected with mGlyT1b cDNA. 
     Glycine Uptake Inhibition Assay (mGlyT-1b) 
     On day 1 mammalian cells, (Flp-in™-CHO), transfected with mGlyT-1b cDNA, were plated at the density of 40,000 cells/well in complete F-12 medium, without hygromycin in 96-well culture plates. On day 2, the medium was aspirated and the cells were washed twice with uptake buffer (UB). The cells were then incubated for 20 min at 22° C. with either (i) no potential competitor, (ii) 10 mM non-radioactive glycine, (iii) a concentration of a potential inhibitor. A range of concentrations of the potential inhibitor was used to generate data for calculating the concentration of inhibitor resulting in 50% of the effect (e.g. IC 50 , the concentration of the competitor inhibiting glycine uptake of 50%). A solution was then immediately added containing [ 3 H]-glycine 60 nM (11-16 Ci/mmol) and 25 μM non-radioactive glycine. The plates were incubated with gentle shaking and the reaction was stopped by aspiration of the mixture and washing (three times) with ice-cold UB. The cells were lysed with scintillation liquid, shaken 3 hours and the radioactivity in the cells was counted using a scintillation counter. 
     The compounds described in examples 1-128 have an IC 50  data &lt;1.0 μM. The IC 50  data (&lt;0.4 μM) for representative compounds 1-128 is be provided in table 2. 
     The present invention also provides pharmaceutical compositions containing compounds of the invention, for example compounds of formula I and their pharmaceutically suitable acid addition salts, and a pharmaceutically acceptable carrier. Such pharmaceutical compositions can be in the form of tablets, coated tablets, dragées, hard and soft gelatin capsules, solutions, emulsions or suspensions. The pharmaceutical compositions also can be in the form of suppositories or injectable solutions. 
     The pharmaceutical compounds 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 and organic carriers. Lactose, corn starch or derivatives thereof, talc, stearic acids or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragées and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like. Depending on the nature of the active substance no carriers are however usually required in the case of soft gelatine capsules. Suitable carriers for the production of solutions and syrups are, for example, water, polyols, glycerol, vegetable oil and the like. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like. 
     The pharmaceutical compositions can, moreover, 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 invention also provides a method for preparing compositions of the invention which comprises bringing one or more compounds of formula I and/or pharmaceutically acceptable acid addition salts and, if desired, one or more other therapeutically valuable substances into a galenical administration form together with one or more therapeutically inert carriers. 
     The most preferred indications in accordance with the present invention are those, which include disorders of the central nervous system, for example the treatment or prevention of schizophrenia, cognitive impairment and Alzheimer&#39;s disease. The invention provides a method for the treatment of schizophrenia, which comprises administering to an individual a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The invention also provides a method for the treatment of Alzheimer&#39;s disease, which comprises administering to an individual a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The invention further comprises a method for improving cognition, which comprises administering to an individual a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. 
     The dosage at which compounds of the invention can be administered can vary within wide limits and will, of course, have to be adjusted to the individual requirements in each particular case. In the case of oral administration the dosage for adults can vary from about 0.01 mg to about 1000 mg per day of a compound of general formula I or of the corresponding amount of a pharmaceutically acceptable salt thereof. The daily dosage can be administered as single dose or in divided doses and, in addition, the upper limit can also be exceeded when this is found to be indicated. 
     
       
         
               
             
               
               
             
               
               
               
               
               
               
             
               
             
               
               
             
               
             
               
               
             
               
               
               
               
               
               
             
               
             
               
               
             
           
               
                   
               
             
             
               
                 Tablet Formulation (Wet Granulation) 
               
               
                   
               
             
          
           
               
                   
                 mg/tablet 
               
             
          
           
               
                 Item 
                 Ingredients 
                 5 mg 
                 25 mg 
                 100 mg 
                 500 mg 
               
               
                   
               
               
                 1. 
                 Compound of formula I 
                 5 
                 25 
                 100 
                 500 
               
               
                 2. 
                 Lactose Anhydrous DTG 
                 125 
                 105 
                 30 
                 150 
               
               
                 3. 
                 Sta-Rx 1500 
                 6 
                 6 
                 6 
                 30 
               
               
                 4. 
                 Microcrystalline Cellulose 
                 30 
                 30 
                 30 
                 150 
               
               
                 5. 
                 Magnesium Stearate 
                 1 
                 1 
                 1 
                 1 
               
               
                   
                 Total 
                 167 
                 167 
                 167 
                 831 
               
               
                   
               
             
          
           
               
                 Manufacturing Procedure 
               
               
                   
               
             
          
           
               
                 1. 
                 Mix items 1, 2, 3 and 4 and granulate with purified water. 
               
               
                 2. 
                 Dry the granules at 50° C. 
               
               
                 3. 
                 Pass the granules through suitable milling equipment. 
               
               
                 4. 
                 Add item 5 and mix for three minutes; compress on a suitable press. 
               
               
                   
               
             
          
           
               
                 Capsule Formulation 
               
               
                   
               
             
          
           
               
                   
                 mg/capsule 
               
             
          
           
               
                 Item 
                 Ingredients 
                 5 mg 
                 25 mg 
                 100 mg 
                 500 mg 
               
               
                   
               
               
                 1. 
                 Compound of formula I 
                 5 
                 25 
                 100 
                 500 
               
               
                 2. 
                 Hydrous Lactose 
                 159 
                 123 
                 148 
                 — 
               
               
                 3. 
                 Corn Starch 
                 25 
                 35 
                 40 
                 70 
               
               
                 4. 
                 Talc 
                 10 
                 15 
                 10 
                 25 
               
               
                 5. 
                 Magnesium Stearate 
                 1 
                 2 
                 2 
                 5 
               
               
                   
                 Total 
                 200 
                 200 
                 300 
                 600 
               
               
                   
               
             
          
           
               
                 Manufacturing Procedure 
               
               
                   
               
             
          
           
               
                 1. 
                 Mix items 1, 2 and 3 in a suitable mixer for 30 minutes. 
               
               
                 2. 
                 Add items 4 and 5 and mix for 3 minutes. 
               
               
                 3. 
                 Fill into a suitable capsule. 
               
               
                   
               
             
          
         
       
     
     The following examples illustrate the present invention without limiting it. All temperatures are given in degree Celsius. 
     Procedure A 
     This procedure is used to prepare Example 34 
     N-Phenyl-N-(p-tolylcarbamoyl-methyl)-6-trifluoromethyl-nicotinamide 
     To 2-bromo-N-(4-methyl-phenyl)-acetamide (100 mg) in THF (3.0 mL) was added aniline (41 mg) and N-ethyldiisopropylamine and 6-trifluoromethyl-nicotynoyl chloride (110 mg) the reaction mixture was stirred over night at reflux. Then the reaction was concentrated in vacuo and the reaction mixture was purified by column chromatography to yield the title compound as a light brown solid (127 mg, 70%).
 
Procedure B
 
     This procedure was used to prepare Example 30 
     N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-phenyl-3-trifluoromethyl benzamide 
     Step 1: N-(3,4-Dichloro-phenyl)-2-phenylamino-acetamide 
     To 2-bromo-N-(3,4-dichloro-phenyl)-acetamide (2 g) in THF (80 mL) was added aniline (41 mg) and N-ethyldiisopropylamine and the reaction mixture was stirred over night at reflux. The precipitated salt was then filtered off and the filtrate was then concentrated in vacuo. The residue was then purified by column chromatography to give the title compound as a light brown solid (1.3 g, mp=110-112° C.). 
     Step 2: N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-phenyl-3-trifluoromethyl benzamide 
     To N-(3,4-dichloro-phenyl)-2-phenylamino-acetamide (73 mg) in THF (3.1 mL) was added tiethylamine (52 μL) and 3-trifluoromethylbenzoyl chloride (62 mg) and the reaction mixture was stirred at room temperature for 30 minutes. To the mixture was then added water under precipitation occurred and the mixture was stirred for 5 minutes. Then the precipitate was isolated by filtration and washed with a mixture water-ethanol (1:1) to yield the title compound as a white solid (64 mg, mp=130-132° C.). 
     Procedure C 
     This procedure was used to prepare Example 30 
     4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2-fluoro-benzyl)benzamide 
     Step 1: N-(3,4-Dichloro-phenyl)-2-phenylamino-acetamide 
     To (2,6-dichloro-benzylamino)-acetic acid ethyl ester (100 mg) in suspension THF (5 mL) was added triethylamine (0.08 mL) and 4-methoxybenzoyl chloride (78 mg) and the reaction mixture was stirred at room temperature for 10 min. After such time the water was added to the reaction mixture and the aqueous phase was extracted with diethylacetate. The combined organic phases were then dried over sodium sulfate, concentrated vacuo and purified by column chromatography to yield the title (128 mg). MS (m/e): 396.3 (M+H + ) 
     Step 2: [(2,6-Dichloro-benzyl)-(4-methoxy-benzoyl)-amino]-acetic acid 
     To N-(3,4-dichloro-phenyl)-2-phenylamino-acetamide in ethanol (10 mL) was added 1N NaOH (0.38 μL) and the reaction mixture was stirred at room temperature for 3 hours. After such time the reaction mixture was neutralized by addition of 3N HCl and the ethanol was eliminated by evaporation. To the residue was added more water and ethyl acetate. The organic phase was separated and the aqueous phase was extracted with ethylacetate. The combined organic phase was then washed again with water, dried over sodium sulfate and concentrated in vacuo to yield the title compound (90 mg). MS (m/e): 366.0 (M−H). 
     Step 3: 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2-fluoro-benzyl)benzamide 
     To a solution of 3-chloroaniline (20 mg) in DMF (1.5 mL) was added N-ethyldiiopropylamine (137 μL), [(2,6-Dichloro-benzyl)-(4-methoxy-benzoyl)-amino]-acetic acid (58 mg) and HATU (Across 365312) and the reaction mixture was stirred at room temperature over night. Then water was added until the precipitation occurs and the precipitate was isolated by filtration and washed with a mixture of water and ethanol (2:1) to yield the title compound (35 mg). MS (m/e): 479.2 (M+H + ). 
     Procedure D 
     This procedure was used to prepare Example 1 
     4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]-N-(2,6-difluoro-benzyl)-benzamide 
     To N1-(3-chlorophenyl)-2-chloroacetamide (61 mg) in DMF (1 mL) was added 2,6-difluorobenzylamine (38 mg) and triethylamine (0.1 mL) and 4-chlorobenzoyl chloride (58 mg) the reaction mixture was stirred at room temperature for 15 min and then purified by HPLC preparative to yield the title compound (55 mg). MS (m/e): 447.0 (M−H).
 
Procedure E
 
     This procedure was used to prepare Example 97 
     N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-isobutyl-4-methoxy-benzamide 
     Step 1: N-(3,4-Dichloro-phenyl)-2-isobutylamino-acetamide hydrobromide 
     To a solution of 2-bromo-N-(3,4-dichloro-phenyl)-acetamide (0.1 g) in dichloromethane (80 mL) at 0° C. was slowly added of isobutylamine (52 mg) in dichloromethane. The reaction mixture was allowed to warm up to room temperature and then stirred for another 24 hours. Then the salt was filtered off and the filtrate was concentrated in vacuo. The residue was then purified by column chromatography to yield the title compound as a white solid (0.1 g). MS (m/e): 357.1 (M+H + ). 
     Step 2: N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-isobutyl-4-methoxy-benzamide 
     To a solution of N-(3,4-dichloro-phenyl)-2-isobutylamino-acetamide hydrobromide (0.090 g) in THF were slowly added a solution of triethylamine (0.064 mg) in THF (5 mL) and a solution of 4-methoxybenzoyl chloride (47 mg) in THF (5 mL) and the reaction mixture was stirred at room temperature for 24 hours. Then water was added to the reaction mixture and the precipitate was isolated by filtration and then purified by column chromatography to yield the title compound (78 mg). MS (m/e): 409.2 (M−H, 100%). 
     The following starting materials for preparation of compounds of formula I have been used: 
     
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                 Amine/ 
                 Chloro amide or 
                   
               
               
                 Exp 
                 Procedure 
                 Aniline 
                 bromo amide 
                 Acyl chloride 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 1 
                 D 
                 2,6- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 2 
                 D 
                 3,4- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 3 
                 D 
                 3,5- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 4 
                 D 
                 2,3- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 5 
                 D 
                 2,4- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 6 
                 D 
                 2,5- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 7 
                 D 
                 4-Fluorobenzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 2-chloroacetamide 
                 chloride 
               
               
                 8 
                 D 
                 3-Fluorobenzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 2-chloroacetamide 
                 chloride 
               
               
                 9 
                 D 
                 2-Fluorobenzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 2-chloroacetamide 
                 chloride 
               
               
                 10 
                 D 
                 Thiophen-3-yl- 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 methylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 11 
                 D 
                 2,6- 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 Difluorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 12 
                 D 
                 3,5- 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 Dichlorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 13 
                 D 
                 2,6- 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 Dichlorobenzylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 14 
                 D 
                 3-Chlorobenzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 2-chloroacetamide 
                 chloride 
               
               
                 15 
                 D 
                 Benzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                   
                 2-chloroacetamide 
               
               
                 16 
                 D 
                 benzylamine 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 2-chloroacetamide 
                 chloride 
               
               
                 17 
                 D 
                 Thiophen-2-yl- 
                 N1-(3-Chlorophenyl)- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 methylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 18 
                 D 
                 Thiophen-2-yl- 
                 N1-(3-Chlorophenyl)- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 methylamine 
                 2-chloroacetamide 
                 chloride 
               
               
                 19 
                 C 
                 (2,6-Dichloro- 
                 3-Chloro aniline 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 benzylamino)-acetic 
                   
                 chloride 
               
               
                   
                   
                 acid ethyl ester 
               
               
                 20 
                 D 
                 3-Fluoroaniline 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 21 
                 D 
                 2-Fluoroaniline 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 22 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 23 
                 C 
                 Phenylamino-acetic 
                 3-Chloro-2- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                 Fluoroaniline 
                 chloride 
               
               
                 24 
                 C 
                 Phenylamino-acetic 
                 5-Amino-2,2-difluoro- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                 1,3-benzodioxole 
                 chloride 
               
               
                 25 
                 C 
                 Phenylamino-acetic 
                 3- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                 (Trifluoromethoxy)aniline 
                 chloride 
               
               
                 26 
                 C 
                 Phenylamino-acetic 
                 m-Toluidine 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                   
                 chloride 
               
               
                 27 
                 C 
                 Phenylamino-acetic 
                 3- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                 Aminobenzotrifluoride 
                 chloride 
               
               
                 28 
                 C 
                 Phenylamino-acetic 
                 3-Chloroaniline 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                   
                 chloride 
               
               
                 29 
                 C 
                 Phenylamino-acetic 
                 3-methoxybenzonitrile 
                 4-Methoxybenzoyl 
               
               
                   
                   
                 acid ethyl ester 
                   
                 chloride 
               
               
                 30 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 3-trifluoromethylbenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 31 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 3-cyanobenzoyl chloride 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
               
               
                   
                   
                   
                 acetamide 
               
               
                 32 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 2-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 33 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 3-Methylbenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 34 
                 A 
                 Aniline 
                 2-Bromo-N-(4-methyl- 
                 6-trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 nicotynoyl chloride 
               
               
                 35 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 3-Chlorobenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 36 
                 A 
                 Aniline 
                 2-Bromo-N-(4-fluoro- 
                 6-trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 nicotynoyl chloride 
               
               
                 37 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 6-Trifluoromethyl- 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 nicotinoyl chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 38 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
               
               
                   
                   
                   
                 acetamide 
               
               
                 39 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 2-Fluorobenzoyl chloride 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
               
               
                   
                   
                   
                 acetamide 
               
               
                 40 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 3-fluorobenzoyl chloride 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
               
               
                   
                   
                   
                 acetamide 
               
               
                 41 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 4-methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 42 
                 B 
                 Aniline 
                 2-Bromo-N-(3,4- 
                 4-fluorobenzoyl chloride 
               
               
                   
                   
                   
                 dichloro-phenyl)- 
               
               
                   
                   
                   
                 acetamide 
               
               
                 43 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 3-Methylbenzoyl 
               
               
                   
                   
                   
                 trifluoromethyl- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 44 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl- 
               
               
                   
                   
                   
                 trifluoromethyl- 
                 nicotynoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 45 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 3-Chlorobenzoyl 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 46 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl- 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
                 nicotynoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 47 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 6-Trifluoromethyl- 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
                 nicotinoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 48 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 49 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 2-Fluorobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 50 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 51 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                   
                 trifluoromethyl- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 52 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 3-fluorobenzoyl chloride 
               
               
                   
                   
                   
                 trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 53 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 trifluoromethyl- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 54 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4- 
               
               
                   
                   
                   
                 trifluoromethyl- 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 55 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                   
                 trifluoromethyl- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 56 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl benzyl 
               
               
                   
                   
                 benzylamine 
                 trifluoromethyl- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 57 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 carbonyl chloride 
               
               
                 58 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 3-fluorobenzoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 59 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 3-Methylbenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 60 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 4- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 61 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 62 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-fluoro- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 63 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 carbonyl chloride 
               
               
                 64 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 3-Methylbenzoyl 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 65 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 4- 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 66 
                 D 
                 3,4-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 carbonyl chloride 
               
               
                 67 
                 D 
                 3,4-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 3-Methylbenzoyl 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 68 
                 D 
                 3,4-difluoro- 
                 2-Chloro-N-(3-fluoro- 
                 4- 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 69 
                 D 
                 2,6-difluoro- 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 70 
                 D 
                 2,6-difluoro- 
                 2-Chloro-N-(3- 
                 3-Methylbenzoyl 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 71 
                 D 
                 2,6-difluoro- 
                 2-Chloro-N-(3- 
                 4- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 72 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 73 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 3-fluorobenzoyl chloride 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 74 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4-Chlrorobenzoyl 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 75 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4- 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 76 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 77 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 78 
                 D 
                 2,6-difluoro- 
                 2-Chloro-N-(3- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 79 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl benzyl 
               
               
                   
                   
                   
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 80 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 81 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 3-fluorobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 82 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 4-Chlrorobenzoyl 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 83 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 4- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 84 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 85 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 86 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl benzyl 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 87 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 88 
                 D 
                 2,6-difluoro- 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 89 
                 D 
                 2,3-Difluoro- 
                 2-Chloro-N-(3- 
                 3-Methylbenzoyl 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 90 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 4- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 trifluoromethoxybenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 91 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 92 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 4-cyanobenzoyl chloride 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 93 
                 D 
                 3,5-difluoro- 
                 2-Chloro-N-(3- 
                 6-trifluoromethyl benzyl 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 94 
                 D 
                 3,4-Difluoro- 
                 2-Chloro-N-(3- 
                 Benzo[b]thiophene-2- 
               
               
                   
                   
                 benzylamine 
                 Chloro,4-fluoro- 
                 carbonyl chloride 
               
               
                   
                   
                   
                 phenyl)-acetamide 
               
               
                 95 
                 D 
                 2,2-simethyl 
                 2-Chloro-N-(3-Chloro 
                 4-Chlrorobenzoyl 
               
               
                   
                   
                 propylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 96 
                 D 
                 3,3-dimethyl 
                 2-Chloro-N-(3-Chloro 
                 4-Chlrorobenzoyl 
               
               
                   
                   
                 butylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 97 
                 E 
                 iso butylamine 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 98 
                 E 
                 3-methyl butylamine 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 99 
                 B 
                 benzylamine 
                 2-Bromo-N-(3,4- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 dichloro phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 100 
                 D 
                 3-cyano-benzylamine 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 101 
                 D 
                 3-methoxy- 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 102 
                 D 
                 2-methoxy- 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 benzylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 103 
                 D 
                 3-methyl-benzylamine 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 104 
                 D 
                 2-methyl-benzylamine 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 105 
                 D 
                 3-Chloro-benzylamine 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 106 
                 D 
                 2-Chloro-benzylamine 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                   
                 phenyl)-acetamide 
                 chloride 
               
               
                 107 
                 D 
                 C-Furan-2-yl- 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 methylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 108 
                 C 
                 Phenylamino-acetic 
                 2-Bromo-N-(3,4- 
                 4-methoxy benzoyl 
               
               
                   
                   
                 acid ethyl ester 
                 dichloro phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 119 
                 B 
                 2-fluoro-benzylamine 
                 3-Chloro aniline 
                 6-Morpholin-4-yl- 
               
               
                   
                   
                   
                   
                 nicotinoyl chloride 
               
               
                 120 
                 B 
                 2-fluoro-benzylamine 
                 3-Chloro aniline 
                 6-Chloro-nicotinoyl 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 121 
                 B 
                 2-Fluoro-benzylamine 
                 3-Chloro aniline 
                 2-Chloro-isonicotinoyl 
               
               
                   
                   
                   
                   
                 chloride 
               
               
                 122 
                 B 
                 2-Fluoro-benzylamine 
                 3-Chloro aniline 
                 2,6-Dichloro- 
               
               
                   
                   
                   
                   
                 isonicotinoyl chloride 
               
               
                 123 
                 A 
                 C-Cyclohexyl- 
                 2-Chloro-N-(3-chloro- 
                 4-chlorobenzoyl chloride 
               
               
                   
                   
                 methylamine 
                 phenyl)-acetamide 
               
               
                 124 
                 A 
                 C-Cyclohexyl- 
                 2-Chloro-N-(3-chloro- 
                 4-Chlorobenzoyl 
               
               
                   
                   
                 methylamine 
                 phenyl)-acetamide 
                 chloride 
               
               
                 125 
                 A 
                 C-Cyclohexyl- 
                 2-Chloro-N-(3-chloro- 
                 4-Fluorobenzoyl chloride 
               
               
                   
                   
                 methylamine 
                 phenyl)-acetamide 
               
               
                 126 
                 A 
                 Cyclopentylamine 
                 2,4-Dichloro-N-(3- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 chloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 127 
                 A 
                 Cyclopropylamine 
                 2,4-Dichloro-N-(3- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 chloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                 128 
                 A 
                 Cyclohexylamine 
                 2,4-Dichloro-N-(3- 
                 4-Methoxybenzoyl 
               
               
                   
                   
                   
                 chloro-phenyl)- 
                 chloride 
               
               
                   
                   
                   
                 acetamide 
               
               
                   
               
             
          
         
       
     
     The following compounds have been prepared in accordance with table 1: 
     
       
         
               
             
               
             
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 I 
               
             
          
           
               
                 
                   
                             
                     
                         
                         
                     
                   
                 
               
               
                   
               
             
          
           
               
                 Procedure 
                 R 1   
                 R 2   
                 R 3   
                 R 4   
                 X 
                 IC 50   
                 Exp 
               
               
                   
               
             
          
           
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.052 
                 1 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.265 
                 2 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.184 
                 3 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.074 
                 4 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.16 
                 5 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.165 
                 6 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 7 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.128 
                 8 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.074 
                 9 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.285 
                 10 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.1 
                 11 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.243 
                 12 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.122 
                 13 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.024 
                 14 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.312 
                 15 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.156 
                 16 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.077 
                 17 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.257 
                 18 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.164 
                 19 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 20 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.315 
                 21 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 22 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 23 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 24 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 25 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 26 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.148 
                 27 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.267 
                 28 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 29 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 30 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.35 
                 31 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 32 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 33 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 34 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 35 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 36 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.154 
                 37 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 38 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.291 
                 39 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 40 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.276 
                 41 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 42 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.339 
                 43 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 44 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.298 
                 45 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 46 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 47 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 48 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 49 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 50 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.06 
                 51 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.153 
                 52 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.241 
                 53 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.196 
                 54 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.097 
                 55 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 56 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.088 
                 57 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 58 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.166 
                 59 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.107 
                 60 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 61 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.357 
                 62 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.07  
                 63 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 64 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.278 
                 65 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.167 
                 66 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 67 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 68 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.09 
                 69 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 70 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.107 
                 71 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.205 
                 72 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 73 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.142 
                 74 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.259 
                 75 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.159 
                 76 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.182 
                 77 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.282 
                 78 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 79 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.066 
                 80 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 81 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.108 
                 82 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.078 
                 83 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.178 
                 84 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.123 
                 85 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 86 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.036 
                 87 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.199 
                 88 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.306 
                 89 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.288 
                 90 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 91 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 92 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 93 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 94 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 95 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.359 
                 96 
               
               
                   
               
               
                 E 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 97 
               
               
                   
               
               
                 E 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 98 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 99 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.192 
                 100 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 101 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.06 
                 102 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.142 
                 103 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.209 
                 104 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.021 
                 105 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.025 
                 106 
               
               
                   
               
               
                 D 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.199 
                 107 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.182 
                 108 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 109 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.369 
                 110 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 111 
               
               
                   
               
               
                 C 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 112 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.15 
                 113 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.091 
                 114 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 115 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.191 
                 116 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.21 
                 117 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 OCH 2   
                 0.259 
                 118 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.355 
                 119 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.182 
                 120 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 121 
               
               
                   
               
               
                 B 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 122 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 CH 3   
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 123 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 124 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 125 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                 0.357 
                 126 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 127 
               
               
                   
               
               
                 A 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 H 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 bond 
                   
                 128 
               
               
                   
               
             
          
         
       
     
     
       
         
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
               
                   
               
               
                   
                   
                 MS 
                 MS 
                   
               
               
                 Compound name 
                 MW 
                 result 
                 mode 
                 Example 
               
               
                   
               
             
             
               
                   
               
             
          
           
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 447.0 
                 neg 
                 1 
               
               
                 N-(2,6-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 447.0 
                 neg 
                 2 
               
               
                 N-(3,4-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 447.0 
                 neg 
                 3 
               
               
                 N-(3,5-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 449.2 
                 pos 
                 4 
               
               
                 N-(2,3-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 449.2 
                 pos 
                 5 
               
               
                 N-(2,4-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 449.28 
                 449.2 
                 pos 
                 6 
               
               
                 N-(2,5-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 431.29 
                 431.4 
                 pos 
                 7 
               
               
                 N-(4-fluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 431.29 
                 431.4 
                 pos 
                 8 
               
               
                 N-(3-fluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 431.29 
                 431.4 
                 pos 
                 9 
               
               
                 N-(2-fluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-4- 
                 414.9 
                 415.3 
                 pos 
                 10 
               
               
                 methoxy-N-thiophen-3-ylmethyl-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(2,6- 
                 444.9 
                 443.2 
                 neg 
                 11 
               
               
                 difluoro-benzyl)-4-methoxy-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(3,5- 
                 477.8 
                 477.1 
                 pos 
                 12 
               
               
                 dichloro-benzyl)-4-methoxy-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(2,5- 
                 477.8 
                 479.2 
                 pos 
                 13 
               
               
                 dichloro-benzyl)-4-methoxy-benzamide 
               
               
                 N-(3-Chloro-benzyl)-N-[(3-chloro- 
                 443.3 
                 443.3 
                 pos 
                 14 
               
               
                 phenylcarbamoyl)-methyl]-4-methoxy-benzamide 
               
               
                 N-Benzyl-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 496.8 
                 497.1 
                 pos 
                 15 
               
               
                 4-fluoro-benzamide 
               
               
                 N-Benzyl-4-chloro-N-[(3-chloro-phenylcarbamoyl)- 
                 413.3 
                 413.2 
                 pos 
                 16 
               
               
                 methyl]-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 419.3 
                 419.1 
                 pos 
                 17 
               
               
                 N-thiophen-2-ylmethyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 449.4 
                 449.1 
                 pos 
                 18 
               
               
                 methoxy-N-thiophen-2-ylmethyl-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(2,6- 
                 477.8 
                 479.2 
                 pos 
                 19 
               
               
                 dichloro-benzyl)-4-methoxy-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-(3- 
                 447.3 
                 447.1 
                 pos 
                 20 
               
               
                 fluoro-phenyl)-4-methoxy-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N-(2- 
                 447.3 
                 447.1 
                 pos 
                 21 
               
               
                 fluoro-phenyl)-4-methoxy-benzamide 
               
               
                 Pentanoic acid [(3,4-dichloro-phenylcarbamoyl)- 
                 379.3 
                 379.3 
                 pos 
                 22 
               
               
                 methyl]-phenyl-amide 
               
               
                 N-[(3-Chloro-2-fluoro-phenylcarbamoyl)-methyl]- 
                 412.8 
                 413.4 
                 pos 
                 23 
               
               
                 4-methoxy-N-phenyl-benzamide 
               
               
                 N-[(2,2-Difluoro-benzo[1,3]dioxol-5-ylcarbamoyl)- 
                 440.4 
                 441.0 
                 pos 
                 24 
               
               
                 methyl]-4-methoxy-N-phenyl-benzamide 
               
               
                 4-Methoxy-N-phenyl-N-[(3-trifluoromethoxy- 
                 444.4 
                 445.1 
                 pos 
                 25 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 4-Methoxy-N-phenyl-N-(m-tolylcarbamoyl- 
                 374.4 
                 375.1 
                 pos 
                 26 
               
               
                 methyl)-benzamide 
               
               
                 4-Methoxy-N-phenyl-N-[(3-trifluoromethyl- 
                 428.4 
                 429.0 
                 pos 
                 27 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-4- 
                 394.9 
                 395.0 
                 pos 
                 28 
               
               
                 methoxy-N-phenyl-benzamide 
               
               
                 4-Methoxy-N-[(3-methoxy-phenylcarbamoyl)- 
                 390.4 
                 391.3 
                 pos 
                 29 
               
               
                 methyl]-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N- 
                 467.3 
                 467.0 
                 pos 
                 30 
               
               
                 phenyl-3-trifluoromethyl-benzamide 
               
               
                 3-Cyano-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 424.3 
                 467.0 
                 pos 
                 31 
               
               
                 methyl]-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-2- 
                 429.3 
                 429.2 
                 pos 
                 32 
               
               
                 methoxy-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-3- 
                 413.3 
                 413.2 
                 pos 
                 33 
               
               
                 methyl-N-phenyl-benzamide 
               
               
                 N-Phenyl-N-(p-tolylcarbamoyl-methyl)-6- 
                 413.4 
                 414.4 
                 pos 
                 34 
               
               
                 trifluoromethyl-nicotinamide 
               
               
                 3-Chloro-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 433.7 
                 433.0 
                 pos 
                 35 
               
               
                 methyl]-N-phenyl-benzamide 
               
               
                 N-[(4-Fluoro-phenylcarbamoyl)-methyl]-N-phenyl- 
                 417.4 
                 418.0 
                 pos 
                 36 
               
               
                 6-trifluoromethyl-nicotinamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N- 
                 468.3 
                 468.1 
                 pos 
                 37 
               
               
                 phenyl-6-trifluoromethyl-nicotinamide 
               
               
                 4-Cyano-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 424.3 
                 424.0 
                 pos 
                 38 
               
               
                 methyl]-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-2- 
                 417.3 
                 417.3 
                 pos 
                 39 
               
               
                 fluoro-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-3- 
                 417.3 
                 417.1 
                 pos 
                 40 
               
               
                 fluoro-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 429.3 
                 429.3 
                 pos 
                 41 
               
               
                 methoxy-N-phenyl-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 417.3 
                 417.1 
                 pos 
                 42 
               
               
                 fluoro-N-phenyl-benzamide 
               
               
                 N-(2-Chloro-benzyl)-4-cyano-N-[(3- 
                 471.9 
                 472.2 
                 pos 
                 43 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 N-(2-Chloro-benzyl)-3-trifluoromethyl-N-[(3- 
                 514.9 
                 515.2 
                 pos 
                 44 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (3,5-difluoro- 
                 504.5 
                 506.2 
                 pos 
                 45 
               
               
                 benzyl)-[(3-trifluoromethyl-phenylcarbamoyl)- 
               
               
                 methyl]-amide 
               
               
                 N-(3,5-Difluoro-benzyl)-3-fluoro-N-[(3- 
                 466.4 
                 467.2 
                 pos 
                 46 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 4-Chloro-N-(3,5-difluoro-benzyl)-N-[(3- 
                 482.8 
                 483.4 
                 pos 
                 47 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 N-(3,5-Difluoro-benzyl)-4-trifluoromethoxy-N-[(3- 
                 432.4 
                 433.2 
                 pos 
                 48 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 N-(3,5-Difluoro-benzyl)-4-fluoro-N-[(3- 
                 466.4 
                 467.2 
                 pos 
                 49 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 4-Cyano-N-(3,5-difluoro-benzyl)-N-[(3- 
                 473.4 
                 474.2 
                 pos 
                 50 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (2-chloro- 
                 502.9 
                 503.1 
                 pos 
                 51 
               
               
                 benzyl)-[(3-trifluoromethyl-phenylcarbamoyl)- 
               
               
                 methyl]-amide 
               
               
                 N-(2-Chloro-benzyl)-3-fluoro-N-[(3- 
                 464.9 
                 465.3 
                 pos 
                 52 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 4-Chloro-N-(2-chloro-benzyl)-N-[(3- 
                 481.3 
                 481.2 
                 pos 
                 53 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 #N!-(2-Chloro-benzyl)-4-trifluoromethoxy-#N!-[(3- 
                 530.9 
                 531.1 
                 pos 
                 54 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 N-(2-Chloro-benzyl)-4-fluoro-N-[(3- 
                 464.9 
                 465.3 
                 pos 
                 55 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 N-(3,5-Difluoro-benzyl)-3-trifluoromethyl-N-[(3- 
                 516.4 
                 517.2 
                 pos 
                 56 
               
               
                 trifluoromethyl-phenylcarbamoyl)-methyl]- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (2-chloro- 
                 452.9 
                 453.0 
                 pos 
                 57 
               
               
                 benzyl)-[(3-fluoro-phenylcarbamoyl)-methyl]-amide 
               
               
                 N-(2-Chloro-benzyl)-3-fluoro-N-[(3-fluoro- 
                 414.8 
                 415.3 
                 pos 
                 58 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 4-Chloro-N-(2-chloro-benzyl)-N-[(3-fluoro- 
                 431.3 
                 431.1 
                 pos 
                 59 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-(2-Chloro-benzyl)-N-[(3-fluoro- 
                 480.8 
                 481.1 
                 pos 
                 60 
               
               
                 phenylcarbamoyl)-methyl]-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 N-(2-Chloro-benzyl)-4-fluoro-N-[(3-fluoro- 
                 414.8 
                 415.2 
                 pos 
                 61 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-(2-Chloro-benzyl)-4-cyano-N-[(3-fluoro- 
                 421.9 
                 422.1 
                 pos 
                 62 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (3,5-difluoro- 
                 454.5 
                 455.2 
                 pos 
                 63 
               
               
                 benzyl)-[(3-fluoro-phenylcarbamoyl)-methyl]-amide 
               
               
                 4-Chloro-N-(3,5-difluoro-benzyl)-N-[(3-fluoro- 
                 432.8 
                 433.2 
                 pos 
                 64 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-(3,5-Difluoro-benzyl)-N-[(3-fluoro- 
                 482.4 
                 483.1 
                 pos 
                 65 
               
               
                 phenylcarbamoyl)-methyl]-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (3,4-difluoro- 
                 454.5 
                 455.2 
                 pos 
                 66 
               
               
                 benzyl)-[(3-fluoro-phenylcarbamoyl)-methyl]-amide 
               
               
                 4-Chloro-N-(3,4-difluoro-benzyl)-N-[(3-fluoro- 
                 432.8 
                 433.2 
                 pos 
                 67 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-(3,4-Difluoro-benzyl)-N-[(3-fluoro- 
                 482.4 
                 483.4 
                 pos 
                 68 
               
               
                 phenylcarbamoyl)-methyl]-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4- 
                 488.9 
                 489.1 
                 pos 
                 69 
               
               
                 fluoro-phenylcarbamoyl)-methyl]-(2,6-difluoro- 
               
               
                 benzyl)-amide 
               
               
                 4-Chloro-N-[(3-chloro-4-fluoro-phenylcarbamoyl)- 
                 467.3 
                 467.1 
                 pos 
                 70 
               
               
                 methyl]-N-(2,6-difluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 518.8 
                 517.1 
                 pos 
                 71 
               
               
                 N-(2,6-difluoro-benzyl)-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid (2-chloro- 
                 487.4 
                 487.2 
                 pos 
                 72 
               
               
                 benzyl)-[(3-chloro-4-fluoro-phenylcarbamoyl)- 
               
               
                 methyl]-amide 
               
               
                 N!-(2-Chloro-benzyl)-N!-[(3-chloro-4-fluoro- 
                 449.3 
                 449.1 
                 pos 
                 73 
               
               
                 phenylcarbamoyl)-methyl]-3-fluoro-benzamide 
               
               
                 4-Chloro-N-(2-chloro-benzyl)-N-[(3-chloro-4- 
                 465.7 
                 465.2 
                 pos 
                 74 
               
               
                 fluoro-phenylcarbamoyl)-methyl]-benzamide 
               
               
                 N-(2-Chloro-benzyl)-N-[(3-chloro-4-fluoro- 
                 515.3 
                 512.3 
                 pos 
                 75 
               
               
                 phenylcarbamoyl)-methyl]-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 N-(2-Chloro-benzyl)-N-[(3-chloro-4-fluoro- 
                 449.3 
                 449.1 
                 pos 
                 76 
               
               
                 phenylcarbamoyl)-methyl]-4-fluoro-benzamide 
               
               
                 N-(2-Chloro-benzyl)-N-[(3-chloro-4-fluoro- 
                 456.3 
                 456.3 
                 pos 
                 77 
               
               
                 phenylcarbamoyl)-methyl]-4-cyano-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 450.8 
                 451.1 
                 pos 
                 78 
               
               
                 N-(2,6-difluoro-benzyl)-4-fluoro-benzamide 
               
               
                 N-(2-Chloro-benzyl)-N-[(3-chloro-4-fluoro- 
                 499.3 
                 499.2 
                 pos 
                 79 
               
               
                 phenylcarbamoyl)-methyl]-3-trifluoromethyl- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4- 
                 488.9 
                 489.2 
                 pos 
                 80 
               
               
                 fluoro-phenylcarbamoyl)-methyl]-(2,3-difluoro- 
               
               
                 benzyl)-amide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 450.8 
                 451.1 
                 pos 
                 81 
               
               
                 N-(2,3-difluoro-benzyl)-3-fluoro-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-4-fluoro-phenylcarbamoyl)- 
                 467.3 
                 467.2 
                 pos 
                 82 
               
               
                 methyl]-N-(2,3-difluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 516.8 
                 517.1 
                 pos 
                 83 
               
               
                 N-(2,3-difluoro-benzyl)-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 450.8 
                 451.1 
                 pos 
                 84 
               
               
                 N-(2,3-difluoro-benzyl)-4-fluoro-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 457.8 
                 458.3 
                 pos 
                 85 
               
               
                 4-cyano-N-(2,3-difluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 500.8 
                 501.1 
                 pos 
                 86 
               
               
                 N-(2,3-difluoro-benzyl)-3-trifluoromethyl- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4- 
                 488.9 
                 499.1 
                 pos 
                 87 
               
               
                 fluoro-phenylcarbamoyl)-methyl]-(3,5-difluoro- 
               
               
                 benzyl)-amide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 457.8 
                 458.3 
                 pos 
                 88 
               
               
                 4-cyano-N-(2,6-difluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-4-fluoro-phenylcarbamoyl)- 
                 467.3 
                 467.4 
                 pos 
                 89 
               
               
                 methyl]-N-(3,5-difluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 516.8 
                 517.1 
                 pos 
                 90 
               
               
                 N-(3,5-difluoro-benzyl)-4-trifluoromethoxy- 
               
               
                 benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 450.8 
                 451.1 
                 pos 
                 91 
               
               
                 N-(3,5-difluoro-benzyl)-4-fluoro-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 457.8 
                 458.3 
                 pos 
                 92 
               
               
                 4-cyano-N-(3,5-difluoro-benzyl)-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 500.8 
                 501.1 
                 pos 
                 93 
               
               
                 N-(3,5-difluoro-benzyl)-3-trifluoromethyl- 
               
               
                 benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid [(3-chloro-4- 
                 488.9 
                 489.1 
                 pos 
                 94 
               
               
                 fluoro-phenylcarbamoyl)-methyl]-(3,4-difluoro- 
               
               
                 benzyl)-amide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 393.3 
                 393.1 
                 neg 
                 95 
               
               
                 N-(2,2-dimethyl-propyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 407.3 
                 408.3 
                 neg 
                 96 
               
               
                 N-(3,3-dimethyl-butyl)-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N- 
                 409.3 
                 409.2 
                 neg 
                 97 
               
               
                 isobutyl-4-methoxy-benzamide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 423.3 
                 421.0 
                 neg 
                 98 
               
               
                 methoxy-N-(3-methyl-butyl)-benzamide 
               
               
                 N-Benzyl-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 443.3 
                 441.2 
                 neg 
                 99 
               
               
                 methyl]-4-methoxy-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 438.3 
                 436.0 
                 neg 
                 100 
               
               
                 N-(3-cyano-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 443.3 
                 440.9 
                 neg 
                 101 
               
               
                 N-(3-methoxy-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 443.3 
                 440.9 
                 neg 
                 102 
               
               
                 N-(2-methoxy-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 427.3 
                 446.8 
                 neg 
                 103 
               
               
                 N-(3-methyl-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 427.3 
                 424.9 
                 neg 
                 104 
               
               
                 N-(2-methyl-benzyl)-benzamide 
               
               
                 4-Chloro-N-(3-chloro-benzyl)-N-[(3-chloro- 
                 447.8 
                 446.8 
                 neg 
                 105 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 4-Chloro-N-(2-chloro-benzyl)-N-[(3-chloro- 
                 447.8 
                 446.8 
                 neg 
                 106 
               
               
                 phenylcarbamoyl)-methyl]-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 403.3 
                 401.0 
                 neg 
                 107 
               
               
                 N-furan-2-ylmethyl-benzamide 
               
               
                 N-[(3-Chloro-4-fluoro-phenylcarbamoyl)-methyl]- 
                 412.9 
                 413.0 
                 pos 
                 108 
               
               
                 4-methoxy-N-phenyl-benzamide 
               
               
                 N-[(5-Chloro-2-methyl-phenylcarbamoyl)-methyl]- 
                 408.9 
                 409.2 
                 pos 
                 109 
               
               
                 4-methoxy-N-phenyl-benzamide 
               
               
                 N-[(3-Chloro-4-methyl-phenylcarbamoyl)-methyl]- 
                 408.9 
                 409.2 
                 pos 
                 110 
               
               
                 4-methoxy-N-phenyl-benzamide 
               
               
                 N-[(3,5-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 429.3 
                 429.3 
                 pos 
                 111 
               
               
                 methoxy-N-phenyl-benzamide 
               
               
                 N-[(4-Bromo-3-chloro-phenylcarbamoyl)-methyl]- 
                 473.8 
                 472.9 
                 pos 
                 112 
               
               
                 4-methoxy-N-phenyl-benzamide 
               
               
                 Benzo[b]thiophene-2-carboxylic acid [(3,4-dichloro- 
                 455.4 
                 454.9 
                 pos 
                 113 
               
               
                 phenylcarbamoyl)-methyl]-phenyl-amide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-N- 
                 483.3 
                 482.9 
                 pos 
                 114 
               
               
                 phenyl-4-trifluoromethoxy-benzamide 
               
               
                 Isoxazole-5-carboxylic acid [(3,4-dichloro- 
                 390.2 
                 390.0 
                 pos 
                 115 
               
               
                 phenylcarbamoyl)-methyl]-phenyl-amide 
               
               
                 N-[(3,4-Dichloro-phenylcarbamoyl)-methyl]-4- 
                 442.3 
                 442.0 
                 pos 
                 116 
               
               
                 dimethylamino-N-phenyl-benzamide 
               
               
                 N-(3-Chloro-phenyl)-N-[(3,4-dichloro- 
                 463.7 
                 462.8 
                 pos 
                 117 
               
               
                 phenylcarbamoyl)-methyl]-4-methoxy-benzamide 
               
               
                 2-(4-Chloro-phenoxy)-N-[(3,4-dichloro- 
                 463.7 
                 462.8 
                 pos 
                 118 
               
               
                 phenylcarbamoyl)-methyl]-N-phenyl-acetamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N-(2- 
                 462.9 
                 483.5 
                 pos 
                 119 
               
               
                 fluoro-benzyl)-6-morpholin-4-yl-nicotinamide 
               
               
                 6-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 432.3 
                 432.2 
                 pos 
                 120 
               
               
                 N-(2-fluoro-benzyl)-nicotinamide 
               
               
                 2-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 432.3 
                 432.1 
                 pos 
                 121 
               
               
                 N-(2-fluoro-benzyl)-isonicotinamide 
               
               
                 2,6-Dichloro-N-[(3-chloro-phenylcarbamoyl)- 
                 466.7 
                 468.1 
                 pos 
                 122 
               
               
                 methyl]-N-(2-fluoro-benzyl)-isonicotinamide 
               
               
                 4-Chloro-N-{[(3-chloro-phenyl)-methyl- 
                 445.3 
                 445.4 
                 pos 
                 123 
               
               
                 carbamoyl]-methyl}-N-(3-fluoro-benzyl)-benzamide 
               
               
                 4-Chloro-N-[(3-chloro-phenylcarbamoyl)-methyl]- 
                 419.4 
                 419.1 
                 pos 
                 124 
               
               
                 N-cyclohexylmethyl-benzamide 
               
               
                 N-[(3-Chloro-phenylcarbamoyl)-methyl]-N- 
                 402.9 
                 403.3 
                 pos 
                 125 
               
               
                 cyclohexylmethyl-4-fluoro-benzamide 
               
               
                 N-Cyclopentyl-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 421.3 
                 420.9 
                 pos 
                 126 
               
               
                 methyl]-4-methoxy-benzamide 
               
               
                 N-Cyclopropyl-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 393.3 
                 393.0 
                 pos 
                 127 
               
               
                 methyl]-4-methoxy-benzamide 
               
               
                 N-Cyclohexyl-N-[(3,4-dichloro-phenylcarbamoyl)- 
                 435.3 
                 435.1 
                 pos 
                 128 
               
               
                 methyl]-4-methoxy-benzamide