TW200808727A - Aryloxyethylamine compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor - Google Patents

Abstract

The present invention relates to aryloxyethylamine compounds of the formula I and the physiologically tolerated acid addition salts thereof. The variables have the meanings given in the claims and the description. The invention also relates to the use of a compound of the formula I or a pharmaceutically acceptable salt thereof for preparing a pharmaceutical composition for the treatment of a medical disorder susceptible to treatment with a dopamine D3 receptor ligand.

Description

200808727 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to novel aryloxyethylamine compounds. These compounds have valuable therapeutic properties and are particularly suitable for the treatment of diseases responsive to modulation of the dopamine d3 receptor. [Prior Art] Among them, neurons obtain their information via receptors of G protein coupling. Many substances exert their effects via these receptors. One of them is dopamine. There are proven findings about the presence of dopamine and its physiological functions as neurotransmitters. Disorders of the dopaminergic system cause central nervous system disorders including, for example, schizophrenia, depression, and Parkinson's disease. These and other diseases are treated with drugs that interact with dopamine receptors. Until 1990, the two subtypes of dopamine receptors were pharmacologically defined, namely the D! receptor and the D2 receptor. Recently, a third subtype, the D3 receptor, has been found to appear to mediate the effects of some antipsychotics and anti-Parkinson's disease drugs (JC Schwartz et al., The Dopamine D3 Receptor as a Target for Antipsychotics, in Novel Antipsychotic Drugs, Η·Υ· Meltzer, Ed Raven Press, New York 1992, pp. 135-144; M. Dooley et al, Drugs and Aging 1998, 12, 495-514, JN Joyce, Pharmacology and Therapeutics 2001, 90, On pages 231-59, ''The Dopamine D3 Receptor as a Therapeutic Target for Antipsychotic and Antiparkinsonian Drugs") 0 Later, dopamine receptors were divided into two families. In one aspect, the D2 family, 119387.doc 200808727, consists of the D2 receptor, the D3 receptor, and the D4 receptor; and, on the other hand, is a Di group consisting of the D! receptor and the D5 receptor. Despite the widespread distribution of the Di&D2 receptor, the D3 receptor appears to be regioselectively expressed. Therefore, these receptors are preferred in the prominent areas of the limbic system and the midbrain dopamine system, especially in the nucleus accumbens, but are also found in other areas such as tonsils. Due to this relative regioselective behavior, the D3 receptor is considered to be a target with few side effects and it is assumed that although the selective D3 ligand will have the properties of a known antipsychotic, it will not have its dopamine D2 receptor. Mediated neurological side effects (p. Sokoloff et al., Localization and Function of the D3 Dopamine Receptor, Arzneim. Forsch./Drug Res. 42(1), 224 (1992); P. Sokoloff et al., Molecular Cloning and Characterization of a Novel Dopamine Receptor (D3) as a

Target for Neuroleptics, Nature, 347, 146 (1990)). SUMMARY OF THE INVENTION The present invention is based on the goal of providing a compound that acts as a highly selective dopamine D3 receptor ligand. Surprisingly, this object is achieved by means of an aryloxyethylamine compound of the formula I and physiologically tolerated acid addition salts of such compounds

among them

Ar is a heteroaromatic group in which a phenyl group or an aromatic 5 or 6 member C is bonded, wherein Ar may have 1 group Ra and wherein Ar may also have 1 or 2 groups Rb; 119387.doc 200808727

Ra is selected from the group consisting of CrCs alkyl, fluorinated Cr C6 alkyl, C2-C6 dilute, fluorinated C2-C6 dilute, C3-C6 cycloalkyl, fluorinated C3_C6 cycloalkyl ,Ci-C6 alkoxylate, fluorinated Ci-C6 alkoxy group, Ci_C6 via ketone group, Ci-C6 alkoxy-C1-C4 alkyl group, base-based gas-burning group, C1-C6-sintered base - C1 - C 4 oxime, C Ο Η Η, nr4r5, ch2nr4r5, ONR4R5, NHC(0)NR4R5, c(o)nr4r5, so2nr4r5, CVC6 alkylcarbonyl, fluorinated Cl-C6 alkyl, Ci- C6 alkylamino, oxyalkylamino, Ci-C6 alkyloxy, fluorinated CkCs alkyloxy, Ci-C6 alkoxycarbonyl, fluorinated Ci-Cs Oxycarbonyl, CVC6 alkylthio, fluorinated CrC6 alkylthio, Ci-Cs alkylsulfinyl, fluorinated C^C: 6 alkyl sulfinyl, alkyl sulfonyl, fluorinated Ci_C6 alkyl group, phenyl, phenyl, phenoxy, benzyloxy, acridine-2-yloxy and 3 to 7 membered heterocyclic groups, of which the last six The phenyl group, the η-pyridyl group and the heterocyclic group in the group may have 1, 2, 3 or 4 selected from the group consisting of halogen, cyano, oxime, pendant oxy, CN and the group Raa. Group, wherein

Raa is selected from the group consisting of (VC6 alkyl, fluorinated Cl_C6 alkyl, c2-C6 alkenyl, fluorinated C2-C6 alkenyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, CVC6 alkoxy, Fluorinated Ci-C6 alkoxy, Ci_c6 hydroxyalkyl, CVC6 alkoxy-CVC4 alkyl, CVC6 hydroxyalkoxy, CVC6 alkoxy A-C4 alkoxy, COOH, NR4R5, CH2NR4R5, 〇NR4R5, nhc (o) nr4r5, c(0)nr4r5, so2NR4R5, (^-(^alkylcarbonyl, fluorinated 119387.doc 200808727

Ci-C6 alkyl rotidyl, Ci-C6 alkylamino group, chloro group, hydrazino group, anoylamino group, Ci_C6 alkyl group, fluorinated c^_c6 alkylcarbonyl oxygen ,CrC6 alkoxycarbonyl, fluorinated Cl_C6^oxycarbonyl, CrC6 alkylthio, fluorinated Cl_c6 alkylthio, CrC6 alkylsulfinyl, fluorinated Cl-c6 alkylsulfinyl, Ci-C6 alkylsulfonyl, fluorinated c "c6 alkylsulfonyl, each Rb is selected from the group consisting of halogen, cyano, nitro, OH, methyl, methoxy, fluoromethyl, difluoromethyl a group, a trifluoromethyl group, a fluoromethoxy group, a difluoromethoxy group, and a trifluoromethoxy group, or when a group Ra and a group Rb are bonded to two adjacent carbon atoms of the phenyl group, A 5- or 6-membered heterocyclic ring or carbocyclic ring may be formed which is slightly and unsubstituted with a benzene ring or may have 1, 2 or 3 groups selected from the group consisting of halogen, N02, NH2, OH, CN. , CVC6 alkyl, fluorinated cvc6 alkyl, C3-C6 cycloalkyl, fluorinated C3-C6 cycloalkyl, CVC6 alkoxy, fluorinated Ci-C6 alkoxy, c!-c6 hydroxyalkyl, CrCi Alkoxy-C2-C4 alkyl, cvc6 via alkoxy, (^<4 alkoxy = c2 = C4 alkoxy, Ci-C6 burnt , CVC6 burnt base, C!-C6 alkylamino group, di-C1-C6 alkylamino group, Ci-Cs alkylamino group, a-Ci-C6 alkylamino group Ik base, Ci_C6 burn Alkylamino, fluorinated <^-(: 6 alkylcarbonylamino, CrG alkylcarbonyloxy, fluorinated Cl-C6 alkyloxy, CVC6 alkoxycarbonyl, alkylthio, Fluorinated Ci_C6 alkylthio, Ci_C6 alkyl sulphate, acylated Ci-C6 alkyl sulfinyl, CrCs alkyl sulfonyl and fluorinated alkyl thiol, 119387.doc 200808727 X is N Or CH; R1 is fluorene, CVC4 alkyl, C3-C4 cycloalkyl, c3-C4 cycloalkylfluorenyl, CVC4 alkenyl, fluorinated CKC4 alkyl, fluorinated c3-C4 cycloalkyl, fluorinated C^ C: 4 cycloalkylmethyl, fluorinated c3-C4 alkenyl, fluorenyl or Ci-Cs alkylcarbonyl;

Rla is 11, CVC4 alkyl, C3-C4 cycloalkyl, c3-C4 cycloalkylmethyl, CrC4 alkenyl, fluorinated c^C4 alkyl, fluorinated c3-C4 cycloalkyl, fluorinated C3_C4 ring burn Methyl or fluorinated c3-C4 alkenyl; or R1 and Rla together are (CR6R7)r, wherein ^3, 4 or 5; R2 and R2a are, independently of each other, fluorene, fluoro, q-C4 alkyl or fluorinated Ci_C4 alkyl or R2a and R2 together form a ring member (CR6R7)m, wherein the melon is 2, 3, 4 or 5;

Rla and R2a are in common (CR6R7)n, wherein b, 2, 3 or 4, R3 is deuterium or CVC4 alkyl; R4, R5 are independent of each other and are individually selected from H, CrC3 alkyl, Ci-C3 alkane. Oxyl and fluorinated Cl_c3 alkyl; R6, R7 are independent of each other and are individually selected as |H, fluorine, alkyl and fluorinated CrC* alkyl; R8, R8a are independently H, U--c4 An alkyl group or a fluorinated Cl_C4 alkyl group or R8 may form a ring member (CR6R7)q, wherein q is 2, 3, 4 or 5;

Rla and R8a are in common, R9 is hydrazine, CVC4 alkyl, and hydrazine-alkenyloxy. 'where s is 2 or 3; and fluorinated C1-C4 alkyl, C^C4 alkoxy or fluoro 119387.doc 200808727 Thus, the present invention relates to an aryloxyethylamine compound of the formula z and relates to its physiology A tolerable acid addition salt. The invention also relates to a pharmaceutical composition comprising at least one aryloxyethylamine compound of the formula I and/or at least one physiologically tolerated acid addition salt of J, suitably physiologically acceptable Carrier and / or auxiliary substances. The invention also relates to a method for treating a condition responsive to the effects of a dopamine D3 receptor antagonist or a dopamine D3 agonist, the method comprising administering an effective amount of at least one aryloxyethylamine compound and/or At least one physiologically tolerated acid addition salt of the worker is administered to a subject in need thereof. [Embodiment] Diseases responsive to the effects of dopamine D3 receptor antagonists or agonists include, in particular, diseases and diseases of the central nervous system, especially affective disorders, neurological premature dysfunction, stress disorders, and somatization spirits. Disorders and psychosis, especially schizophrenia and depression and, in addition, renal dysfunction, especially due to renal dysfunction of diabetes (see WO 00/67847). According to the invention, the above indications are treated using at least one compound of the formula I having the meaning indicated in the opening paragraph. It is a limitation that the compounds of formula I having a given configuration may exist in different spatial arrangements, for example, if they have one or more asymmetric centers, polysubstituted rings or double bonds, or as different tautomers, Especially enantiomeric mixtures, diastereomeric mixtures and tautomeric mixtures of the racemates. However, preferred are the substantially pure enantiomers of the compounds and/or their salts, Diastereomers and tautomers. 〃 119387.doc -11- 200808727 It is likewise possible to use physiologically tolerable salts of the compounds of formula i, especially acid addition salts with physiologically tolerable acids. Examples of suitable physiologically tolerable organic and inorganic acids are hydrochloric acid; hydrobromic acid; phosphoric acid; sulfuric acid; Ci-C4 alkyl acid, such as methyl anhydride; aromatic acids such as benzoic acid and Toluenesulfonic acid; oxalic acid; maleic acid; fumaric acid; lactic acid; tartaric acid; adipic acid and benzoic acid. Other available acids are described in Fortschritte der Arzneimittelforschung [Advances in drug research], Vol. 10, page 224 ff., BirkhSuser Verlag, Basel and Stuttgart, 1966. The organic moiety referred to in the above definition of the variables is (for example, the term halogen) used in the collective terms of the individual enumeration of individual group members. In each case, the prefix Cn-Cm indicates the number of possible carbon atoms in the group. In each case, the term halogen means fluorine, bromine, chlorine or iodine, especially deficient or gaseous. CVC4 alkyl (and also in CrCU hydroxyalkyl, alkoxyalkyl, Ci-C4 alkylcarbonyl, C^C4 alkylcarbonylamino, Cl-C4 alkylcarbonyloxy, C^C:4 alkyl The thio group, C^C: 4 alkyl sulfinyl group, CfCU alkyl fluorenyl group or the like) is a linear or branched alkyl group having 1 to 4 carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, 2-butyl, isobutyl or tert-butyl. CVC6 alkyl (and likewise in hydroxyalkyl, CVC6 alkoxy-CVC4 alkyl, C^C: 6 alkylcarbonyl, C^C: 6 alkylcarbonylamino, alkylcarbonyloxy, C^C: a 6 alkylthio group, (: anthracene-fluorenyl sulfinyl group, (^-(alkylalkyl group, etc.)) is a linear or branched alkyl group having 1 to 6 carbon atoms. .doc -12- 200808727 Examples include CrCU alkyl as described above and pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1,didecylpropyl, 1,2,dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-didecylbutyl, 1,2-dimethylbutyl, 1,3,dimethylbutyl, 2,2-dimethylbutyl, 2,3 - dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, i,2,2- Trimethylpropyl, ethyl 4-methylpropyl and 1-ethyl-2-methylpropyl; fluorinated CrC6 alkyl (and also in the fluorene fluoride 1-(:6 alkylcarbonyl, fluorine) C6 alkylamino group, fluorinated Cl_c6 alkylcarbonyloxy group, fluorinated group Sulfur-based, fluorinated C^C: 6-alkylsulfinylene, fluorinated Cl-c6 alkylsulfonyl, etc.) having from 1 to 6, especially from 1 to 4 carbon atoms, more preferably from 3 to 3 a linear or branched alkyl group of one carbon atom, wherein at least one, for example, 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom, such as fluoromethyl, difluoromethyl, trifluoromethyl Base, (RM·fluoroethyl, (S)-l-fluoroethyl, 2-fluoroethyl, fluorene-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl , (R)-1-fluoropropyl, (S)-l-fluoropropyl, 2-fluoropropyl, 3-fluoropropyl, M•difluoropropyl, 2,2-difluoropropyl, 3,3_difluoropropyl, 3,3,3_trifluoropropyl, (R)-2-fluoro-1-methylethyl, (s)_2_fluoro·b-methylethyl, (R)_2 , 2_二乱-1-methylethyl, (S)_2,2_difluoro·i•decylethyl, difluoro-1-indolylethyl, (S)_l,2-difluoromethane Methyl ethyl, (8) 2, 2, 2 · trifluoromethylene ethyl, (8)-2,2,2-trifluoromethylene ethyl, 2 bis! _(fluoromethyl)ethyl 1- (one gas methyl)_2,2_difluoroethyl, (8)·p-butyl butyl, (8)·p-butyl butyl, 2-fluorobutyl, 3-fluorobutyl, 4-fluorobutyl, difluorobutyl 119387.doc • 13 · 200808727 2,2-Difluorobutyl, 3,3-difluorobutyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, etc; Branched CrC6 The alkyl group is a group having 3 to 6 carbon atoms, at least one of which is a second or a divalent atom. Examples are isopropyl, tert-butyl, 2-butyl, isobutyl, 2-pentyl, 2 -hexyl, 3-methylpentyl, iota, dimethyldibutyl, 1,2-dimethylbutyl, 1-methylbeta-ethylpropyl.

Ci-C0 alkoxy (and likewise in c^C: 6 alkoxycarbonyl, Ci-Cs alkoxy-C1-C4 alkyl, CVC: 6 alkoxy-CVC: 4 alkoxy alkoxy Is a linear or branched alkyl group having from 1 to 6, especially from 1 to 4, carbon atoms bonded to the remainder of the molecule via an oxygen atom. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, 2-butoxy, isobutoxy, tert-butoxy, pentyloxy, b-butoxy 2—Methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropoxy, bethylpropoxy, hexyloxy, 1,1-dimethylpropoxy, 12 — Dimethylpropoxy, benzylidyloxy, 2-methylpentyloxy, methylpentyloxy, 4-methylpentyloxy, 1,1-didecylbutyloxy, LI dimethyl butyloxy, hydrazine, dimethyl butyloxy, 2,2-dimethylbutyloxy, 2, dimethyldimethyl butyloxy, 3,3 dimethyl butyl Alkoxy, oxime ethylbutyloxy, 2-ethylbutyloxy, 1,1,2-trimethylpropoxy, trimethylpropoxy, ethyl-1-methyl Propyloxy and 1-ethylmethylpropoxy; fluorinated c^c:6 alkoxy (and likewise in fluorinated Ci-C0 alkoxycarbonyl) having from 1 to 6, especially up to 4 a linear or branched alkoxy group of one carbon atom, wherein at least one, for example HgI '2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom, such as fluorocarbon , difluoromethoxy, trifluoromethoxy, 119387.doc -14- 200808727 (R)-l-fluoroethoxy, (S)-l-fluoroethoxy, 2-fluoroethoxy, I, 〗 〖Two gas ethoxy ' 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, (κ)]-allopropoxy, (S)-l· fluoropropyl Oxyl, 2-fluoropropoxy, 3-fluoropropoxy, difluoropropoxy, 2,2-difluoropropoxy, 3,3-di-propoxy, 3,3 3 -di Fluoropropoxy, (R)-2-fluoro-1-methylethoxy, (S)-2-fluoro-1-methylethoxy, (R)_2,2-difluoro_1_ Mercaptoethoxy, (S)-2,2-difluoro-1-methylethoxy, (R)-l,2-difluoro-1-methylethoxy, (S)-l, 2-difluoro-1-methylethoxy, (R)_2,2,2-trifluoro-1_methylethoxy, (S)-2,2,2-trifluoro-indolyl Ethoxy, 2-fluoro-1-(fluoromethyl)ethoxy, 1-(difluoromethyl)-2,2-diethoxyethoxy, (R)-l-fluorobutoxy, (S -l-fluorobutoxy, 2·fluorobutoxy, 3-fluorobutoxy, 4·fluorobutoxy, 1,1-difluorobutoxy, 2,2-difluorobutoxy, 3,3-difluorobutoxy, 4,4-difluorobutoxy, 4,4, 'trifluorobutoxy, etc.; 1

CyC: 6 cycloalkyl is a cycloaliphatic group having 3 to 6 atoms, such as cyclopropyl, cyclobutyl and cyclopentyl. The cycloalkyl group may be unsubstituted or may have 2, 3 or 4 (^44 alkyl groups, preferably methyl group. One alkyl group is preferably located at the 1-position of the cycloalkyl group, such as 1-methylcyclopropane Or a methylcyclobutyl group. Fluorinated CyC, a cycloalkyl group having 3 to 6 (: atomic cycloaliphatic groups such as cyclopropyl, cyclobutyl and cyclopentyl, at least one of which, for example, i , 2, 3, 4 or all hydrogen atoms are replaced by fluorine atoms, such as 1-fluorocyclopropanyl π fluoropropyl, 2,2-difluorocyclopropyl, j, 2 • difluorocyclopropane Base, 2,3_ ^ . ^ 2-aifT^ > 3- butyl, 2,2·difluorocyclo, 3,3-difluorocyclo 2-butyl, hydrazine butyl, 2,3-dioxocyclobutyl, 2,4_digas (tetra) H9387.doc •15- 200808727 or 1,2,2-tri-cyclobutyl. C3-C6 cycloalkylmethyl has the above a fluorenyl group having a cycloaliphatic group of 3 to 6 c atoms. The C3-C6 cycloalkylmethyl group of Dunhua is a methyl group having a cycloaliphatic earth group having 3 to 6 C atoms, wherein , for example, i, 2, 3, phase or all of the hydrogen atoms are replaced by a fluorine atom. The dilute group is a monounsaturated hydrocarbon group of 2'3, 4, 5 or 6 C atoms, Such as ethylene, propyl (2 - propylene small), i propylene small, 2 - propan-2-yl, T allyl (2 - methyl propyl - 2 - dilute) And a similar group. The C3-C4 alkenyl group is especially an allyl group, a propyl propyl group, a diphenyl group, a 2-butan-1-yl group, a 3-butene-1 group, a decylallyl group, and 2 _ pentene small group, % penten-1-yl, 4-penten-1-yl, 1 · methyl butyl 2 - dilute or 2-ethyl propyl _2 - dilute - yl. Fluorinated C 2 _ (:6 alkenyl is a monounsaturated nicotine group having 2, 3, 4, 5 or 6 c atoms, at least one of which, for example, 1, 2, 3, 4 or all hydrogen atoms are replaced by a fluorine atom 'such as vinylidene, 2-fluorovinyl, 2,2-fluorovinyl, 3,3,3-fluoropropenyl, fluorene, difluoro-2-propenyl, fluoro-2-propenyl And similar groups.

The Ci-C6 hydroxyalkyl group is a group having 1 to 6 carbon atoms as defined above, wherein one hydrogen atom is replaced by a hydroxyl group. Examples include hydroxymethyl, 2-ethyl, ethyl 1-ethylidene, 3-propylpropyl, 2-propylpropyl, 1-methyl-1-hydroxyethyl and the like.

The Ci-C6 hydroxyalkoxy group is an alkoxy group having 1 to 6, preferably 2 to 4 carbon atoms as defined above, wherein one hydrogen atom is replaced by a hydroxyl group. Example Package 119387.doc -16- 200808727 Contains 2-hydroxyethoxy, 3-hydroxypropoxy, 2-hydroxypropoxy, oxime methyl-2-hydroxyethoxy and the like.

The CrC6 alkoxy-CrC4 alkyl group is an alkyl group having a carbon atom as defined above, wherein one hydrogen atom is replaced by a Cl_C6 alkoxy group. Examples include methoxymethyl, 2-methoxyethyl, K methoxyethyl, 3-methoxypropyl, 2-methoxypropyl, ι 曱 · ι 曱 曱, ethoxymethyl, 2-ethoxyethyl, 1-ethoxyethyl, 3-ethoxypropyl, 2-ethoxypropyl, 1-mercapto-1-ethoxy Ethyl and its like.

The CrC6 alkoxy-CrC4 alkoxy group is an alkoxy group having 1 to 4 carbon atoms as defined above, wherein one hydrogen atom is replaced by a CrC6 alkoxy group. Examples include methoxymethoxy, 2-methoxyethoxy, 1-methoxyethoxy, 3-methoxypropoxy, 2-methoxypropoxy, 1-methyl-丨-methoxyethoxy, ethoxymethoxy, 2-ethoxyethoxy, 1-ethoxyethoxy, 3-ethoxypropoxy, 2-ethoxypropoxy Base, 1-methyl-i-ethoxyethoxy and the like. C "C6 alkylcarbonyl is a group of the formula RC(O)-, wherein R is an alkyl group as defined above having 1 to 6 carbon atoms. Examples include ethyl fluorenyl, propyl fluorenyl, n-butyl fluorenyl, 2-methyl a propyl fluorenyl group, a pentylene group and the like. The CVC6 alkylcarbonylamino group is a group of the formula RC(0)-NH_, wherein r is an alkyl group having 1 to 6 carbon atoms as defined above Examples include etidamine, acrylamide, n-butylammonium, 2-methylpropionamido, 2,2-dimethylpropanamine, and the like.

The Ci-Q alkylcarbonyloxy group is a group of the formula R-C(0)-0- wherein R is an alkyl group having 1 to 6 carbon atoms as defined above. Examples include acetamyloxy 119387.doc -17- 200808727, propyl decyloxy, n-butyl decyloxy, 2-methylpropenyloxy, 2,2-dimethylpropenyloxy and Similar group.

The Ci_C6 alkylthio group is a group of the formula R-S- wherein R is an alkyl group having 1 to 6 carbon atoms as defined above. Examples include methylthio, ethylthio, propylthio, butylthio, pentylthio, 1-methylbutylthio, 2-methylbutylthio, 3-methylbutyl Thiothio, 2,2-dimethylpropylthio, ethylpropylthio, hexylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio , 1-methylpentylthio, 2-decylpentylthio, 3-methylpentylthio, 4-methylpentylthio, 1,1-dimethylbutylthio, hydrazine , 2_ monomethylbutylthio, 1,3 -dimethylbutylthio, 2,2-dimethylbutylthio, 2,3-dimethylbutylthio, 3,3- Dimercaptobutylthio, i-ethylbutylthio, 2-ethylbutylthio, 1,1,2-trimethylpropylthio, 1,2,2-trimethylpropane a thiol group, a monoethyl-1-methylpropyl group and a hydrazine-ethyl 2-methyl propyl group; C "C6 alkyl sulfinyl group is a group of the formula RS (O)-, wherein r An alkyl group having 1 to 6 carbon atoms as defined above. Examples include methylsulfinyl, ethyl fluorenyl, propyl sulfite, butyl sulfite, pentyl sulfite, 1 -methylbutylsulfinyl, 2 - mercaptobutyl sulfinyl, 3-methylbutyl fluorenyl, 2,2-dimethylpropyl sulfite, 丨-ethyl propyl sulfhydryl, hexyl sulfinyl , dimethylpropylsulfinyl, 1,2-dimethylpropylsulfinyl, 丨-methylpentylsulfinyl, 2-methylpentylsulfinyl, 3-methyl Amyl sulfinyl, 4-methylpentyl sulfenyl, 1,1-dimethylbutylsulfinyl, anthracene, 2-dimethylbutylsulfinyl, 1,3 - dimethylbutylsulfinyl, 2,2-dimethylbutylsulfinium 119387.doc • 18 - 200808727, 2,3-dimethylbutylsulfinyl, 3,3- Dimethylbutylsulfinyl, 1-ethylbutylsulfinyl, 2-ethylbutylsulfinyl, 1,1,2-trimethylpropylsulfinyl, 1, 2,2-trimethylpropylsulfinyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

The Ci_C6 basestone is a group of the formula R-S(0)2- wherein R is an alkyl group having 1 to 6 carbon atoms as defined above. Examples include mercaptosulfonyl, ethylsulfonyl, propylsulfonyl, butylsulfonyl, pentylsulfonyl, 1-methylbutylsulfonyl, 2-methylbutylsulfonate Base, 3-methylbutylsulfonyl, 2,2-monopropylpropyl, 1-ethylpropyl fluorenyl, hexyl yellow, dimethyl propyl 1,2-Dimethylpropyl aryl, 1-methylpentylsulfonyl, 2-methylpentylsulfonyl, 3-methylpentylsulfonyl, 4-methylpentyl Sulfonyl, 1,1-dimethylbutylsulfonyl, iota, 2-dimethylbutylsulfonyl, 1,3-dimethylbutylsulfonyl, 2,2-dimethyl Butylsulfonyl, 2,3-dimethylbutylsulfonyl, 3,3-dimethylbutylsulfonyl, ethyl butylsulfonyl, 2-ethylbutylsulfonyl 1,1,2-Trimethylpropylsulfonyl, 1,2,2-trimethylpropylsulfonyl, 1-ethyl-1-methylpropyl and ethyl-2-yl The fluorinated CrC6 alkylcarbonyl group is a group of the formula rC(O)-, wherein R is a fluorinated alkyl group having 1 to 6 carbon atoms as defined above. Examples include fluoroacetamido, difluoroacetinyl, trifluoroethenyl, fluoroethylcarbonyl, 0)4·haloethyl, 2-fluoroethylcarbonyl, difluoroethylcarbonyl, 2,2 -difluoroethylcarboxy, 2,2,2-trifluoroethylcarbonyl, (R)-l-fluoropropylcarbonyl, fluoropropylcarbyl, 2-fluoropropylcarbonyl, 3-fluoropropylcarbonyl 1,1-difluoropropyl group, 2,2.difluoropropylcarbonyl, 3,3-difluoropropylcarbonyl, 3,3,3-119387.doc -19- 200808727 , (R)-2-Den-1-methylethylwei, (S)-2·fluoro-1-methylethylcarbonyl, (R)-2,2-difluoro-1-methyl Ethylcarbonyl, (S)-2,2-difluoromethylethyl, (R)-1,2-difluoro-1-methylethyl, (S)· 1,2-di Fluoro-1-methylethylcarbonyl, (r)-2,2,2-trifluoro-1-indenylethylcarbonyl, (S)_2,2,2-tri-IL-1-methylethyl , 2-fluoro-1-(fluoromethyl)ethyl Ik group, 1-(difluoromethyl)-2,2-difluoroethyl group, (R)-1 -fluorobutyl group, (S)-l-fluorobutylcarbonyl, 2-fluorobutylcarbonyl, 3-fluorobutylcarbonyl, 4-fluorobutylcarbonyl, 1,1-difluorobutylcarbonyl, 2,2-difluorobutyl Carbonyl, 3,3-di Butylcarbonyl, 4,4-difluorobutylcarbonyl, 4,4,4-trifluorobutylcarbonyl, etc.; fluorinated alkylcarbonylamino group is a group of the formula RC(0)-NH_, wherein R is A fluorinated alkyl group having 1 to 6 carbon atoms as defined above. Examples include fluoroacetamido, difluoroacetamido, trifluoroacetamido, (R)-l-fluoroethylcarbonylamino, (S)-l-fluoroethylcarbonylamino, 2- Fluoroethylcarbonylamino, 1,1-difluoroethylcarbonylamino, 2,2-difluoroethylcarbonylamino, 2,2,2-trifluoroethyl-Weiylamino, (R)- L-fluoropropylamino, (S)-l-d-propylamino, 2-fluoropropylcarbonylamino, 3-fluoropropylcarbonylamino, 1,1-difluoropropyl Carbonylamino, 2,2-difluoropropylcarbonylamino, 3,3-difluoropropylcarbonylamino, 3,3,3-trifluoropropylcarbonylamino, (1〇-2-fluoro- 1-methylethylcarbonylamino, (S)-2·fluoro-1-methylethylcarbonylamino, (R)-2,2·difluoro-1-methylethylcarbonylamino, ( S)-2,2-difluoro-1-methylethylcarbonylamino, (R)-l,2-difluoro-1-methylethylcarbonylamino, (S)-1,2-difluoro -1-methylethylcarbonylamino, (R)-2,2,2-trifluoro-1-methylethylcarbonylamino, (S)-2,2,2-digas-1-A Ethylethylaminoamine, 2-air-1-(oxymethyl)ethyl 119387.doc -20- 200808727 Carbonylamino, 1-(difluoromethyl)-2,2-difluoroethylcarbonyl Amine (R)-l-fluorobutylcarbonylamino, (S)-l-fluorobutylcarbonylamino, 2-fluorobutylcarbonylamino, 3-fluorobutylcarbonylamino, 4-fluorobutyl Carbonylamino, 1,1-difluorobutylcarbonylamino, 2,2-difluorobutylcarbonylamino, 3,3-difluorobutylcarbonylamino, 4,4-difluorobutylcarbonylamine a 4,4,4-trifluorobutylamino group or the like; the fluorinated alkylcarbonyloxy group is a group of the formula RC(0)-0-, wherein R is 1 to 6 carbon atoms as defined above A fluorinated alkyl group. Examples include fluoroacetamido, difluoroacetinyl, trifluoroethenyl, (R)-l-fluoroethylcarbonyloxy, (S)-l-fluoroethylcarbonyloxy , 2-fluoroethylcarbonyloxy, 1,1-difluoroethylcarbonyloxy, 2,2-difluoroethylcarbonyloxy, 2,2,2-trifluoroethylcarbonyloxy, (R -l-fluoropropylcarbonyloxy, (S)-l-fluoropropylcarbonyloxy, 2-fluoropropylalkyloxy, 3-fluoropropylweiloxy, 1,1-difluoro Propyl benzyloxy, 2,2-difluoropropylcarbonyloxy, 3,3-difluoropropylcarbonyloxy, 3,3,3-difluoropropylalkyloxy, (r)- 2-fluoro-1-indenyl-ethylphenyloxy, (S)-2·fluoro-1-methyl Alkylcarbonyloxy, (R) 2,2-difluoro-i-methylethyl Ik-yloxy, (S)-2,2-difluoro-1-methylethyloxy, (R -l,2-difluoro-1-methylethylcarbonyloxy, difluorodecylethylcarbonyloxy, (R)-2,2,2-trifluoro_1-methylethylcarbonyloxy Base, (s)_ 2,2,2-trifluoro-1·methylethylcarbonyloxy, 2-fluoro-1-(fluoromethyl)ethylcarbonyloxy, i-(difluorodecyl) _2,2-difluoroethylcarbonyloxy, (κ)_1ββfluorobutylcarbonyloxy, (S)-l-fluorobutylcarbonyloxy, 2-fluorobutylcarbonyloxy, 3-fluorobutyl Carbonyloxy, 4-fluorobutylcarbonyloxy, difluorobutylbenzyloxy, 2,2-difluorobutylcarbonyloxy, 3,3-difluorobutylcarbonyl 119387.doc -21 - 200808727 Oxyl, 4,4-difluorobutylcarbonyloxy, 4,4,4-trifluorobutylcarbonyloxy, etc.; disordered C1 -C6 alkylthio group is a group of the formula R-S- R is a fluorinated alkyl group having 1 to 6 carbon atoms as defined above. Examples include fluoromethylthio, difluoromethylthio, trifluoromethylthio, (R)-l-fluoroethylthio, (S)-l-fluoroethylthio, 2-fluoroethyl Thiothio, 1,1-difluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, (R)-l-fluoropropylthio , (s)· 1-fluoropropylthio, 2-fluoropropylthio, 3-fluoropropylthio, 1,1-difluoropropylstone, 2,2-propylidenethio, 3 , 3-diisopropylthio, 3,3,3 _trifluoropropylthio, (R)-2-fluoro-1-methylethylthio, (S)-2·fluoro-1· Methyl ethylthio, (R)-2,2-difluoro-1-methylethylthio, (S)-2,2-difluoro-1-methylethylthio, (11) -1,2-difluoro-1-methylethylthio, (8)-1,2-difluoro-1-methylethylthio, (R)_2,2,2-trifluoro-;甲基methylethylthio, (S)-2,2,2·difluoro_1-methylethylthio, 2-fluoro-1-(1indolyl)ethylthio, 1-(two Fluoromethyl)-2,2-difluoroethylthio, (R)-l-fluorobutylthio, (S)-l-fluorobutylthio, 2-fluorobutylthio, 3- Fluorobutylthio, 4-fluorobutylthio, 1,1-difluorobutylthio, 2,2-difluorobutylsulfide , 3,3-difluorobutylthio, 4,4-difluorobutylthio, 4,4,4-trifluorobutylthio, etc.; fluorinated CVC6 alkyl sulfite is a formula R_S (〇 a group wherein R is a fluorinated alkyl group having 1 to 6 carbon atoms as defined above. Examples include fluoromethylsulfinyl, difluoromethylsulfinyl, trifluoromethylsulfinyl, (R)-l-fluoroethylsulfinyl, (s)_i-fluoroethyl Sulfosyl, 2-fluoroethyl sulfenyl, 1,1-difluoroethylsulfinyl, 2,2-difluoroethylsulfinium 119387.doc -22- 200808727, 2, 2,2-difluoroethylsulfinyl, (--fluoropropylsulfinyl, (S)-l-fluoropropylsulfinyl, 2-fluoropropylsulfinyl, 3 _Fluoropropylsulfinyl, 1,1-difluoropropylsulfinylene, 2,2-difluoropropylsulfinylene, 3,3-difluoropropylsulfinyl, 3, 3,3_trifluoropropylsulfinyl, (r)_2_fluoro-1-methylethyl sulphate, (S)-2_fluoro-1-methylethyl sulphate, (R) -2,2-difluoro-1-indolylethyl sulphate, (s) 2,2-difluoromethylethylsulfinyl, (R)-l,2-difluoro-1-methyl Ethyl sulfinyl, (sylh difluoro-1-methylethylsulfinyl, (r) 2,2,2-trifluoro-1-indolyl sulfinyl, (S) -2,2,2-trifluoro-1_methylethylsulfinyl, fluorinated-fluorenyl (fluoroindolyl)ethylsulfinyl, 1-(difluoromethyl)_2,2_ Difluoro Ethylsulfinyl, (R)-l-fluorobutylsulfinyl, (S)·fluorobutylsulfinyl, 2-fluorobutylsulfinyl, 3-fluorobutyl Sulfonyl, 4-fluorobutylsulfinyl, 1,1-difluorobutyl sulfenyl, 2,2-difluorobutyl sulfhydryl, 3,3-difluorobutylsulfin Sulfhydryl, 4,4-difluorobutylsulfinyl, 4,4,4-trifluorobutylsulfinyl, etc.; fluorinated Ci-C6 alkylsulfonyl is of the formula RS(0)2- a group wherein R is a fluorinated alkyl group having 1 to 6 carbon atoms as defined above. Examples include fluoromethyl sulphate, -~ gas methyl stellite, tris, methyl stellite , (R) -1 - gas ethylsulfonyl, (S)-l-fluoroethylsulfonyl, 2-fluoroethylsulfonyl, 1,1-difluoroethylsulfonyl, 2, 2-difluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl, (R)-l-oxypropyl decyl, (S)-l-fluoropropyl fluorenyl, 2- Fluoropropylsulfonyl, 3-fluoropropylsulfonyl, i,;--difluoropropylsulfonyl, 2,2.difluoropropylsulfonyl, 3,3-difluoropropylsulfonate Indenyl, 3,3,3-trifluoropropylsulfonyl, (R)-2-fluoro-1-methylethyl, (s)-2-fluoro-1- Benzyl sulphate 119387.doc -23- 200808727 sulfhydryl, (Κ)·2 2 - ϋ m ^ ^ , a chaotic methyl ethyl sulfonyl group, (S) 2,2-difluoromethyl ethyl feldspar Stuffed _ > _ ), - a rat _1 - methyl ethyl sulphate, (S) - l, 2- 'T-ethyl ethyl thiol, (R) -2, 2, 2- trifluoro 1-methylethyl sulphate, (S)-2 9 , . , ^ , , - 齓β1_methylethyl sulfonyl, 2-fluoro-1-(fluoromethyl)ethylsulfonyl, W-翁田甘, ), 一气笮基)-2,2-difluoroethylsulfonyl, (R)-l·fluorobutene = to (S) small fluorobutyl gamma, 2-fluorobutyl Base group, 3-air butyl: K fluorenyl group, fluorenyl butyl sulfonyl group, M. difluorobutyl sulfonyl group, 2,2-dibutyl sulfonium ^ ^, - fluorobutyl sulfonate Sulfhydryl, 4,4-difluorobutyl sulfonate, 4,4,4·trifluorobutylsulfonyl, and the like. 3 to: a heterocyclic group containing usually 3, 4, 5, 6 or 7 ring-forming atoms (saturated heterocyclic group, usually having 5, 6 or · ring-forming atoms) The hetero group and the heteroaryl group having usually 5, 6 or 7 ring atoms may be bonded via a carbon atom (c bond) or a nitrogen atom. Preferably, the heterocyclic group contains (10) a nitrogen atom as a ring member atom and, as the case may be, i, 2 or 3 other hetero atoms independently selected from the group consisting of ruthenium, s and N as a ring member. Also, a preferred heterocyclic group contains 丄 as a ring member atom, a hetero atom selected from 0, S and N and optionally 2 or 3 other nitrogen atoms as a ring member. Examples of the 3- to 7-membered saturated heterocyclic group include a pyridinyl group or a 2-aziridine group, a 1-azetidinyl group, a 2-azetidinyl group, a 3-azetidinyl group, a pyrrolidinyl group, and a 2-pyrrolidinyl group. Or 3-pyrrolidinyl, 丨-piperidinyl, piperidinyl, % piperidinyl or 4-piperidinyl, 1-morpholinyl, 2-morpholinyl or 3-morpholinyl, thio Morpholinyl, 2-thiomorphinyl or 3-thiomorpholinyl, indole-piperidinyl, 2-piperazinyl or 3-piperazinyl, 1-oxazolidinyl, oxazolidinyl or Oxazole 119387.doc -24- 200808727 1-isoxazolidinyl, 3-isoxazolidinyl or 4·isoxazolidinyl, 2_lactyl, oxacyclobutane or 3·oxa Cyclobutanyl, 2 oxecyclo, or 3_halocyclopentyl, 2oxeine, 3 oxacyclohexyl or 4 oxacyclohexane, I3· Dioxol-2-yl or dioxolan and a similar group which may be unsubstituted or may have two or three of the above groups Ra and/or Rb. The unsaturated non-aromatic heterocyclic group is a heterocyclic group which usually has 5, 6 or 7 ring-forming atoms and has 1 or 2 double bonds which do not form an aromatic p-electron system. Examples are 2,3-dithiocarbazide, 3,4-dichloropropanyl, 2,3-dihydrobite. Nanji, hydrogenfolyl, 2,3-dihydrothiophenyl, 3,4-dihydrothiophenyl, Μ--wind silk, 2,3_dihydro „bite base, 3,4_two Hydrogen tonnage, m-tetrahydropyridyl, 2,3,4,5-tetrahydropyridyl and the like. The 5 or 6 membered heteroaromatic group is a heteroaromatic cyclic group, wherein The cyclic group has 5 or 6 ring-forming atoms (ring members) and wherein usually 丨, 2, 3 or 4 ring member atoms are selected from 〇, S&N, and other ring member atoms are carbon atoms. In the present invention, a heteroaromatic group contains, as a member of the ring, a hetero atom selected from 0, s and N and, optionally, a fluorene, 2 or 3 other N atoms as a ring member. The heteroaromatic group may be via carbon Atom (c-bonded) or a nitrogen atom (n-bonded) is bonded. Preferably, the heteroaromatic group contains one of the nitrogen atoms as a ring member atom and optionally contains as a ring member, 2 or 3 other independently from each other. Heteroatoms of hydrazine, S and N. Of course, only one of the other hetero atom ring members may be hydrazine or S and only 5 members of the heteroaromatic group may contain hydrazine or S as a ring member. Aromatic group a hetero atom selected from the group consisting of ruthenium, S and N as a ring member atom and optionally as a ring member, 2 or 3 119387.doc -25- 200808727 other nitrogen atoms. 5 or 6 member heteroaromatic Examples of the group include 2-pyridyl, 3-pyridyl or 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl or 5-pyrimidinyl, pyridazinyl, triazinyl or 4-pyridazinyl , 2_thienyl or thiophenyl, 2_ fluorenyl or 3-furanyl, 1_fluorenyl, 2-pyrrolyl or pyrrole, oxime, 2-imidazolyl or 4-imidazolyl, 1-pyrazolyl, 3-pyrazolyl or 4-[r-oxazolyl, 1-[1,2,4]-triazolyl or 3-[1,2,4]-triazolyl, ΐ-[ι , 2,3]·Tristimulus or 4-[1,2,3]-trimethyl, 1-tetradecyl, 2-tetradecyl or 5-tetradecyl, 2-oxazolyl, 3 -oxazolyl or 5-oxazolyl, 3-isoxazolyl, 4-isooxasyl or 5-isoxazolyl, 2-thiazolyl, 3-thiazolyl or 5-thiazolyl, 3- Isothiazolyl, 4-isothiazolyl or 5-isothiazolyl, 4-[1,2,3]-oxadiazolyl or 5-[1,2,3]-oxadiazolyl, oxadiazolyl (=furanyl), % [1,2,4]-oxadiazolyl or oxadiazolyl, oxadiazolyl, 4-[1 2,3]-thiadiazolyl or thiadiazolyl, [丨一一卜thiadiazolyl, 3_[1,2,4]-thiadiazolyl or 5·[1,2,4]·thio A oxadiazolyl or [1,3,4]-indenyl fluorenyl group which may be unsubstituted or may have one of the above groups Ra and, as the case may be, 1 or 2 of the above groups Rb. Those skilled in the art should understand The group R9 may be bonded to any of the carbon atoms of the pyridine or the nip portion of the formula I, thereby substituting a hydrogen atom. Preferably, R9 is at the 3-position with respect to the nitrogen ring atom and at the 3 position of the NR3_s〇2_Ar group. Preferably, Ar is a phenyl group or a hetero atom containing a nitrogen atom as a ring member and 0, 1, 2 or 3 other ring members independently selected from the group consisting of ruthenium, ruthenium and N as a ring member. The aromatic 5 or 6 member C is bonded to a heteroaromatic group which may be unsubstituted or may have 1, 2 or 3 of the above groups Ra and/or Rb. In these heteroaromatic groups H9387.doc -26- 200808727, the car father contains 1, 2 or 3 nitrogen atoms as ring member atoms and

Other heteroatoms are ring members, or one or two nitrogen atoms and one heteroaromatic group selected from the group consisting of ruthenium and S as a ring member. However, thienyl and furanyl groups are also preferred. Particularly preferably, the heteroaromatic group Ar is 2-thienyl or 3-thienyl, 2-pyridyl, 3-pyridyl or 4-pyridyl, 2·pyrimidinyl, pyrimidazolyl or 5 fluorene, 2_嗟0 sitting group, 3_mercapto or 5-n thiol, i, 2,4. oxazol-3-yl, 1,2,3-triazole-4-yl, thiadiazole 2—Based, especially 2—thienyl, 2-pyrimidinyl, 5-pyrimidinyl and 2-pyridyl, which may be unsubstituted or may have one of the above groups Ra and, as the case may be, 1 or 2 of the abovementioned groups Rb. More preferably, 'Ar is phenyl having one of the above groups Ra and, as the case may be, 1 or 2 of the above groups Rb2. Preferably, the 'aromatic group Ar' has one group Ra as described above and optionally one or two other groups Rb, Rb being especially selected from methyl, fluorinated methyl, halogen' more preferably selected from Fluorine or gas. The above 5-membered heteroaromatic group Ar preferably has a group Ra in the 3-position (related to the position of the s〇2_ group) and optionally has one or two other groups Rb, and Rb is preferably selected from halogen. Especially fluorine or gas. The phenyl group and the above 6-membered heteroaromatic group Ar preferably have a group Ra at the 4-position (related to the position of the S02- group) and optionally have one or two other groups Rb' Rb preferably selected from the group consisting of Halogen, especially fluorine or gas. In a preferred embodiment of the invention, Ar is a phenyl group having a group Ra group at the 4-position of the phenyl ring and optionally 1 or 2 other groups Rb, Rb preferably selected from halogen, especially selected from Fluorine or gas. In another preferred embodiment of the present invention, Ar is a 2-pyrimidinyl group having a group Ra at the 5 position of the biting of the 119387.doc -27- 200808727 and optionally having 1 or 2 other groups Rb Rb is preferably selected from halogens, especially from fluorine or chlorine. In another preferred embodiment of the present invention, the compound is a pyrimidyl group having a group Ra at the 2-position of the pyrimidine ring and optionally 1 or 2 other groups Rb, and Rb is preferably selected from the group consisting of Rb. Halogen, especially selected from fluorine or gas. In another preferred embodiment of the present invention, Ar is a 2-σ-sepeno group having a group Ra at the 3-position of the π-cetin ring and optionally 1 or 2 other groups Rb, Rb is preferred. It is selected from halogens, especially from fluorine or gas. In a preferred embodiment, Ar has 1 group Ra selected from the group consisting of: Cl_C6 alkyl, fluorinated Cl_c6 alkyl 'c3-C6 cycloalkyl, fluorinated CrC6 ring-fired Base, Ci-C6 alkoxylate, gasified CVC6 alkoxy, NR R, 1-mercaptopurine, ruthenium-based, σ-r-quinone-based, slightly sigma-based (where, finally The four groups mentioned may be fluorinated, phenyl and one nitrogen atom as a ring member and 0, 1, 2 or 3 other heteroatoms independently selected from the group consisting of ruthenium, S and N. The aromatic 5 or 6 member C combines a heteroaromatic group, wherein the last two groups have 1, 2, 3 or 4 groups selected from the group consisting of halogen, Ci-C6 alkyl. Fluorinated C--C6 alkyl, 〇3-(1:6 cycloalkyl, fluorinated CyC6 cycloalkyl, CrC6 alkoxy, fluorinated alkoxy and NR4R5; and wherein Ar may have 1 or 2 The other groups Rb, Rb are independently selected from the group consisting of _, cyano, methyl, fluoromethyl, difluoromethyl, trimethoxymethyl, difluoromethoxy and trifluoromethoxy. Wherein R4 and R5 are each independently selected from the group consisting of ruthenium, CrC2 alkyl and fluorinated CrCi alkyl. One of the groups R4 or R5 is not hydrogen. One of the groups R4 or R5 may also be an alkoxy group. 119387.doc -28- 200808727 In the U example, the group Ar is preferably Has a group Ra having the formula Ra

—Y \ 32 Ra.

Ra2 where Y is N, CH or CF,

Ral and Ra2 independently of each other select ICl_C2 alkyl, Ci_C2 alkoxy, fluorenium fluoride 1-(:2 alkyl, the restriction condition is ¥ (;: 11 or (:17, group 1^1 or 1^) One of 2 may also be hydrogen or fluorine, or R and R together form a group (CH2)k, wherein one or two hydrogen atoms may be a gas, a trans group, a pendant oxy group, a Crq alkyl group or a CVC2 alkoxy group. Substitution, wherein one CH2 moiety may be replaced by 0, s, s=0, S02 or N-Rc, R is hydrogen or alkyl and wherein k is 2, 3, 4, 5 or 6;

Ral or Ra2 are independently of each other selected from the group consisting of Cl_C2 alkyl, fluorinated Ci_C2 alkyl, especially fluoromethyl, difluoromethyl or trifluoromethyl, with the proviso that γ is CH or CF, in the group Ral or Ra2 One may also be hydrogen or fluorine, or Ral and Ra2 form a group (CH2)k, wherein one or two hydrogen atoms may be replaced by fluorine and wherein k is 2, 3 or 4, especially CH2-CH2, CHF-CH2CF2 CH2 ^ CH2-CH2-CH2 > CHF-CH2-CH2 > cf2-ch2.ch2 ^ ch2-chf_ch2, ch2-cf2-ch2. In the case where Ral and Ra2 are different from each other, the group of the above formula Ra· may have the (R) or (S) configuration with respect to the Y moiety. 119387.doc -29- 200808727 Examples of preferred groups Ra' include isopropyl, (R)-l-fluoroethyl, (S)-l-gas ethyl, 2-fluoroethyl, 1,1- Difluoroethyl, 2,2-difluoroethyl, 2,2,2-difluoroethyl, (R)-l-fluoropropyl, (S)-l-fluoropropyl, 2-fluoropropyl , 3-fluoropropyl, 1,1-difluoropropyl, 2,2-difluoropropyl, 3,3·difluoropropyl, 3,3,3-trifluoropropyl, (R)-2 -Fluoro-1-methylethyl, (8)-2-fluoro-1_mercaptoethyl, (R)-2,2-difluoro-1-methylethyl, (S)_2,2- Difluoro-1_methylethyl, (trans)-1,2-difluoro-1-methylethyl, (8)_1,2-difluoro_1-methylethyl, (chemical)-2 , 2,2_trifluoro-1-methylethyl, (s)-2,2,2-trifluoro-1-methylethyl, 2-fluorofluoromethyl)ethyl, 1-(difluoro Methyl)-2,2-difluoroethylcyclopropyl, cyclobutyl, 1-fluorocyclopropyl and 2-fluorocyclopropyl. Fortunately, the father is the group Ra 'where one of Ral or Ra2 is Ci_c2 alkoxy and the other of R or R is selected from Η, q-C2 alkyl, especially methyl, fluorinated C ^C: 2 alkyl, especially fluoromethyl, difluoromethyl or trifluoromethyl. Examples include N-methoxy-N-methylamino, N-methoxyamino and N-ethoxyamino groups. Preferred groups of the formula Ra' also include such groups wherein γ is nitrogen and wherein Rai and Ra2 form a group (CHA wherein 1 or 2 hydrogen atoms may be derived from fluorine, methyl, trifluoromethyl, methoxy Substituent or pendant oxy group substitution and wherein 1 is 2, 3, 4 or an example comprises azetidine-i-yl, 2-mercaptopyridinium-indenyl, (s)_2-methyl^butidine-1 -yl, (R)-2-methylazetidinyl, 3-fluoroazetidine-yl-yl, i-methoxyazetidin-1-yl, 3-hydroxyazetidinyl, indole, 3-oxazole 5•yl, pyrrolidin-1-yl, (S)-2-fluoropyrrolidin-1-yl, 忸)_2_fluoropyrrolidinyl, 3-fluoropyrrolidine-1-yl, (s)-3 -fluoropyrrolidine_ι_yl, (R)_3_fluorotrolidin-1-yl, 2,2-difluoropyrrolidin-1-yl, 3,3-difluoropyrrolidine 119387.doc -30- 200808727 Methylpyrrolidine β1_yl, (s)-2•methylpyrrolidine 4•yl, (r)_2-methyl-perylpyridine small base, 3-methyl sigma a group, (8) 1 methyl phosphonium-diyl, (R)-3-methylpyrrolidinyl, 2,2-dimethylpyrrolidine j-yl, 3,3-dimethylpyrrolidine 2_Trifluoromethylpyrrolidine^•, 〇_2_ trifluoromethyl 咣 啶 丨 丨 基 、, (R) _ 孓Fluoromethylpyrrolidine _ 丨 _ group, Hong San chaotic methyl pyrrolidine-fluorenyl group, (S) _3_ trifluoromethyl pyrrolidine-h group, (r) _3_ trifluoromethyl pyrrolidine-1- Base, 2· side oxypyrrolidine q•yl, piperidinyl 4·yl, 2-methylpiperidin-1-yl, (S)-2·methylpiperidinyl] and (R)_2·曱Isopiperidin-1-yl. Also preferred is a group Ra. wherein, together with Ra2, a group (CH2乂 wherein one or two hydrogen atoms may be replaced by fluorine, hydroxyl, pendant oxy, CVC2 alkyl or CVC2 alkoxy, one of which is ch2 Partially substituted by 〇, S, S=0, S024N-RC, Rc is hydrogen or Cl_c2 alkyl and wherein u is 2, 3, 4, 5 or 6. Examples of preferred groups of formula Ra' also include kernels Boryl group, cardiothiomorpholinyl, 4-(1,1-di-oxy)thiomorpholinyl, piperazine-yl-yl, 4-methylpiperazin-1-yl, 2-sided oxygen -oxazolidin-3-yl, pyrrolidin-2-yl, (S)-pyrrolidin-2-yl, (R)-pyrrolidin-2-yl, pyrrolidine-3-yl, (S) - 吡 各 -3 -3 -, (R) - 吼 π 定 -3- -3-, 2- fluoro β 洛 咬 -1- yl, 1 曱 。. Bilobidine-2 · base, (S )-l-methylpyrrolidin-2-yl, (R)-l-methylpyrrolidinium-2-yl, 1-methylpyrrolidin-3-yl, (S)-l-decylpyrrolidin-3 And a methylpyrrolidin-3-yl group. Among the groups of the formula Ra, those having 1, 2, 3 or 4 'particularly 1, 2 or 3 fluorine atoms are preferred. In a preferred embodiment, Ar has a group Ra which is 119387.doc -31· 200808727 is selected from a 5- or 6-membered heteroaromatic group having one hetero atom selected from the group consisting of fluorene, S and N and which may additionally have 1, 2 or 3 nitrogen atoms as ring members' and wherein The 5 or 6 membered heteroaromatic group may have 1, 2 or 3 substituents selected from the group consisting of halogen, N02, NH2, OH, CN, Cr C6 alkyl, C3-C6 cycloalkyl, CVC6 Alkoxy, fluorinated (VC6 alkyl, fluorinated c3-c6 cycloalkyl, fluorinated Cl_C6 alkoxy, Cl-C6 hydroxyalkyl, CV C4 alkoxyalkyl, CVC6 hydroxyalkoxy, CVC4 alkane Oxy-C2-C 4 alkoxy, Ci_C6 alkyl, Ci_C6 alkylamino, di-C1-C6 alkylamino, CrQ alkylaminocarbonyl, di-CrG alkylaminocarbonyl, fluorine Ci_C6 alkyl group _ thiol, Ci_C6 alkylamino group, gasified Ci_C6 alkylamino group, Ci-Q alkylcarbonyloxy group, fluorinated (^-0:6 alkylcarbonyloxy group, CrG Alkoxycarbonyl, CrCs alkylthio, fluorinated alkylthio, CrG alkylsulfinyl, CrCs alkylsulfonyl, fluorinated CrCs alkylsulfinyl and fluorinated alkylsulfonyl Among these groups Ra, preferred are groups selected from the following groups: 2-pyridyl, 3-pyridyl or 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl or 5-pyrimidinyl, pyrazinyl, 3-pyridazinyl or 4-indenyl, 2-thienyl Or 3-nonyl, 2-furyl or 3-furyl, 1-°-l-l base, 2-σ-l-lyl or 3-σ-pyryl, 1·micanyl, 2-11 m fluorenyl , 4-Miso-based or 5-terpenyl, 1-hydrazino, 3-° thiol, 4·σΛσ sitting or 5-carbazolyl, 1-[1,2,4]-triazole , 3-[1,2,4]-triazolyl or 5-[1,2,4]-triazolyl, 1-[1,2,3]-triazolyl, 4-[1,2 , 3]-triazolyl or 5-[1,2,3]-triazolyl, 1-(1Η)-tetrazolyl or 5-(1Η)-tetrazolyl, 2-(2Η)-tetradecyl Or 5-(2Η)·tetradecyl, 2-chymidyl, 4-mercapto or 5-oxamethyl, 3-isoxazolyl, 4-isoxazolyl or 5-isoxazolyl, 2-thiazolyl, 119387.doc -32- 200808727 4- Sodium or succinyl, 3-isoindazinyl, 4-isoxazolyl or 5-isoxazolyl, 4-[1,2, 3]-oxadiazolyl or 5-[1,2,3]-oxadiazolyl, 3-[1,2,5]-oxadiazolyl or 4-[1,2,5]-oxadiazole Base (=furanyl), oxadiazolyl or 5-[1,2,4]-oxadiazolyl, 2-[1,3,4]-oxadiazolyl or 5-[1 3,4]-oxadiazolyl, 4-[1,2,3]-thiadiazolyl or 5-[1,2,3]-thiadiazolyl, 3-[1,2,5]_ Thiadiazolyl or 4-[1,2,5]-thiadiazolyl, 3·[1,2,4]-thiadiazolyl or 5-[1,2,4]-thiadiazolyl or 2 -[1,3,4]-thiadiazolyl or 5-[1,3,4]-thiaditopyl is especially selected from 2-oxa or 3-indolyl, 2-°-septenyl or 3-nonyl, 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, 1-pyrazolyl, 3-pyrazolyl, 4-n-pyridyl or 5-oxazolyl, 1-imidazolyl , 2-imidazolyl, 4-oxazolyl or 5-imidazolyl, 2-oxazolyl, 4-oxazolyl or 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl or 5 -isoxazolyl, 2-[1,3,4]-thiadiazolyl or 5-[1,3,4]-thiadiazolyl, 1-[1,2,4]-triazolyl, 3-[1,2,4]-triazolyl or 5-[1,2,4]·triazolyl, 1-[1,2,3]-triazolyl, 4·[1,2,3 ]-Triazolyl or 5-[1,2,3]-trimethyl, 1-(111)-tetradecyl or 5-(111)-tetradecyl and 2-(211)-tetrazolyl or 5 -(2Η)-tetrazolyl, and especially selected from the group consisting of 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl or 5-pyrazolyl, especially 1-pyrazolyl and 2-oxazolyl, 4-oxanyl or 5-mouth sulfhydryl, especially 4-oxo Or 5-chewing. Sitting on the base. The heteroaromatic group may be unsubstituted or may have 1 to 3 substituents given above. Preferred substituents for the heteroaromatic Ra are selected from the group consisting of halogen, Ci-C* alkyl, alkoxy, fluorinated Crq alkyl and fluorinated CrG alkoxy. In another preferred embodiment, Ar has one group Ra selected from the group consisting of: (CH2)VCF3, (CH2)VCHF2, (CH2)VCH2F, 0(ch2)vcf3, o( Ch2) vchf2, o(ch2)vch2f, where V is ο, 119387.doc -33 - 200808727 1, 2 or 3. In this embodiment, Ar may also have two other groups Rb, which are independently selected from the group consisting of halogen, cyano, methyl, dimethyl, monofluoromethyl, difluoromethyl, A fluoromethoxy group and a trifluoromethoxy group. Preferably, Ar does not have other groups Rb. In this embodiment, Ar is preferably a phenyl group having i groups Ra selected from the group consisting of: (CH2) VCF3, (CH2) VCHF2, (CH2) VCH2F, 〇(CH2)vCF3 , 0(CH2)vCHF2, 0(CH2)vCH2F, where V is ο, i, 2 or 3. In this embodiment, Ar is preferably a phenyl group having Ra at the 4-position relative to the S〇2_ group. In another embodiment of the present invention, Ar has one group selected from the group consisting of R, CVG alkenyl, fluorinated c2_c6 alkenyl, Cl-c6-based alkyl, C "C6 alkane" Oxyalkyl, CVC6 hydroxyalkoxy 'Ci-C6 alkoxy-Ci-C^ alkoxy, COOH, CH2NR4R5, onr4r5, nhc(o)nr4r5, c(0)nr4r5, so2NR4R5, Cl_c6 Cyclic, fluorinated CyC: 6 alkylcarbonyl, CrC6 alkylcarbonylamino, fluorenylfluorenylalkylcarbonylamino, Ci_C6 alkylcarbonyloxy, fluorinated Ci-C6 alkylrotoryloxy, C "C6 alkoxy group, alkylthio group, fluorinated C6 alkylthio group, CrC: 6 alkyl sulfinyl group, Cl_C6 alkylsulfonyl group, fluorine tc^c: 6 alkyl sulfinyl group , fluorinated Cl_C6 alkylsulfonyl, phenylsulfonyl, phenyloxy, benzyloxy, indole-2-yloxy and 5 or 6 membered N bonded heteroaromatic groups' The six groups mentioned may have 1, 2, 3 or 4 groups selected from the group consisting of halogen, ν 〇 2, νη 2 ' 〇Η, CN, CVC6 alkyl, C3_C6 cycloalkyl, Ci_C6: oxy group, oximation Ci_C6 alkyl group, fluorinated c"c: 6 cycloalkyl group, fluorinated oxy group, Ci -C6 hydroxyalkane 119387.doc -34- 200808727 base, cvc4 alkoxy-C2_C4 alkyl, Cl_c6 hydroxyalkoxy, Cl-C^oxy-C2-C4 alkoxy, Cl_c6 alkylcarbonyl, 〇1- (: 6 alkylamino group, bis-CVC6 alkylamino group, Cl_c0 alkylaminocarbonyl group, di-Ci_c6 alkylamino group Ik group, annihilated Ci-C: 6 alkylcarbonyl group, CVC6 alkylcarbonylamino group , fluorinated Ci-C6 alkylcarbonylamino group, Cl-C6 alkylcarbonyloxy group, fluorinated Ci_C6 alkylcarbonyloxy group, Ci-C:6 alkoxycarbonyl group, alkylthio group, fluorinated alkyl sulfide Base, Ci-C6 alkylsulfinyl, Cl_c6 alkylsulfonyl, fluorinated c "C6 alkylsulfinyl and fluorinated Cl-C6 alkylsulfonyl. Another embodiment of the invention Wherein Ar is a phenyl group having one group R and at least one group Rb and wherein Ra and one group Rb are bonded to two adjacent carbon atoms of the phenyl group and form a 5 or 6 membered heterocyclic ring or carbocyclic ring , which is fused to the benzene ring and unsubstituted or may have 1, 2 or more groups given. Examples of benzene rings fused to a saturated or unsaturated 5 or 6 membered carbocyclic or heterocyclic ring include Mercapto, dihydroindenyl, naphthyl, tetralin, benzofuranyl, 2,3- Hydroquinonefuranyl, benzoquinone, fluorenyl, carbazolyl, benzoimidazolyl, benzoquinone oxime, benzoquinone sigma, benzoquinone, benzene幷 嗓 嗓 嗓, dihydrophenyloxazinyl, quinolyl, isoquinolyl, tetrahydroisoquinolyl, fluorenyl, chromanyl and the like, which may be unsubstituted or There may be 1, 2 or 3 of the above groups. Preferred substituents for a saturated or unsaturated 5 or 6 membered carbocyclic or heterocyclic ring fused to a benzene ring are selected from the group consisting of: halogen, Ci_c4 alkyl, q-C4 alkoxy, fluorinated Cl_C4 alkyl and fluoro Ci_C4 alkoxy group. Specifically, 'Ra is selected from CVC4 alkyl, fluorinated alkyl, especially (CH2)VCF3, (CH2)VCHF2 and (CH2)VCH2F, CVCU alkoxy and fluorinated alkoxy, especially 〇(ch2)vCF3 , 〇(CH2)vCHF2 and 119387.doc •35- 200808727 o(ch2)vch2f. Alternatively, Ra is especially selected from a 5- or 6-membered heteroaromatic group having one of the ring members selected from 0, S and N and further having 1, 2 or 3 nitrogen atoms as ring members. And wherein the 5 or 6 membered heteroaromatic group can be substituted as described above. Preferably, the 5 or 6 membered heteroaromatic group Ra and its preferred substituents are as described above. More specifically, Ar is preferably a phenyl group having a group Ra at the 4-position of the sulfonyl group, and the group is selected from a Ci_C4 alkyl group, a fluorinated CVC4 alkyl group, especially CH2) vCF3, (CH2)vCHF2 and (CH2) CH2F, CVC4 alkoxy, fluorinated Ci_C4 alkoxy 'especially θα%)/. And hydrazine (CH2) vCHF2 and hydrazine (CH2) vCH2F, and a 5 or 6 membered heteroaromatic group as described above. The group R1 is preferably H, Cl_c4 alkyl, C3_C4 ring, C3_C4 cycloalkyl, c3-c4, fluorinated C2_C4 alkyl, gasified c3_c, alkyl, fluorinated cvc4 ring Base, fluorinated C3_C4 dilute group, methyl ketone group or Cl% alkyl group, especially H, Cl_C4 alkyl group, alkenyl group, fluorinated C2_C^ group, fluorinated C3-C4 base group, more preferably H, methyl group , ethyl, n-propyl, fluorinated fluorene 2-(: 3 alkyl or propylene-3-yl (dilyl), especially h, methyl or n-propyl, especially n-propyl. The preferred embodiment relates to a compound wherein Rla is hydrogen. In the specific compound, R 1 and 丨V » ΛΑ . _ 2 八 have the meaning of upper and lower, and preferably not hydrogen. R is n-propyl. In this embodiment, 'β is preferably hydrogen and r2 is K is 虱, f group or fluorinated yin. ϋ ® h is both wind and the other is methyl. In the embodiment 119387.doc -36 - 200808727, both the ruthenium and the rS are preferably hydrogen. In another preferred embodiment, Rla is not hydrogen and preferably (tetra)alkyl, c3-c4 alkenyl , gasification of c2_c4 alkyl, fluorinated dilute, more preferably methyl n-propyl, fluorinated CVC3 Or a 1-propenyl-3-yl group, especially n-propyl. In these compounds, R1 has the meaning given above. In particular, R is H, methyl or n-propyl. In this embodiment Rl&Ria has the same 3- meaning and especially methyl or both n-propyl groups. In this embodiment, hydrogen is preferred and R2 is preferably hydrogen, methyl or fluorinated methyl. R2a and R2 are both hydrogen or the group mR2, which is hydrogen and the other is methyl. In this embodiment, both r and r8 are preferably hydrogen. In another preferred embodiment R2a&RU is (CR0R7)n, wherein n is 2, 3 or 4 and especially 3. R6 and R7 are preferably H. R2 is preferably hydrogen. Among these compounds, R1 has the above Meaning, in particular, ^ is n-propyl^propen-3-yl. In this embodiment, both RSa & R8 are preferably hydrogen. In another preferred embodiment, R8a & Rla are ( Cr6r7)s, wherein S is 2 or 3 and especially 2. Han 6 and Han 7 are preferably H. R2 and R2a are preferably H. R8 rut is hydrogen. Among these compounds, r1 has the above The meaning of the word. Details of the 'R, H, n-propyl, 1 · C In another preferred embodiment, R1 and Rla are in common (CR6R7)r, wherein I* is 34 or 5 and especially 4. R6 and R7 are more Preferably, in this embodiment, both R2a & R2 and R8a and R8 are preferably hydrogen. A preferred embodiment of the invention pertains to formula 119387.doc-37 wherein X is CH. - 200808727 Things. Another preferred embodiment of the invention pertains to a compound of formula J wherein χ is N. Preferably, R3 is hydrazine or methyl and more preferably η. A preferred embodiment of the invention relates to a compound of formula I, wherein R9 is selected from the group consisting of CrC4 alkyl, especially methyl, Cl_c4 alkoxy, especially methoxy, and in another preferred embodiment, R9 is bonded to pyridine And the pyrimidine moiety is ortho to the ring nitrogen and R9 is preferably a Cl_C4 alkoxy group, especially a methoxy group. In another preferred embodiment, R9 is bonded to the ortho to the ring nitrogen of the pyridine and pyrimidine moieties, respectively, and R9 is preferably a C1-C4 alkyl group, especially a methyl group. Another preferred embodiment is a compound wherein X is CH and Rla, r2, R2a, r8 and R8a are H, R9 is methoxy and Ra&Ar is as defined above. Another preferred embodiment relates to compounds wherein X is N, Rla, r2, R2a, 8 and R8a are oxime, R9 is methoxy, and ^ and ^ are as defined above. In a preferred embodiment, Ar (along with Ra) has one of the meanings given in Table B below. Preferred embodiments of the present invention are compounds of the following formulae and physiologically tolerable acid addition salts thereof la, Ib, Ie, Id, Ie, If, Ig, Ih,

Ii, Ij, Ik, II, Im, In, I〇, Ip, Iq, Ir, Is, only, ^,

Iv, Iw, IX, ly, and Iz. About carbon atoms with four different groups, formula! i, Formula Ik, Formula Ilk, Formula I, Formula In, Formula 1 , Formula & Formula Iq, Formula Ir, Formula Is, and Formula It may be R-enantiomer or s•opposite The conformation as well as a mixture of enantiomers, such as a racemic mixture, is present. 119387.doc -38 - 200808727 Preferred examples include the R-enantiomers and S-enantiomers of Ii, Ij, Ik, II, Im, In, Ιο, Ip, Iq, Ir, Is and It And a mixture of such enantiomers. In the formula la, lb, Ic, Id, Ie, Ef, Ig, Ih, Ii, Ij, Ik, I, I, I, I, ΐ, In the compounds of Iq, Formula Ir, Formula Is and Formula It, R1, Ar and Rla are as defined above, and particularly preferred are those wherein Ri, Ar& Rla has one of the preferred meanings.

119387.doc -39- 200808727

〇 N, R1—n

N Ar

I

H In the compounds of the formula Iu, the formula Iv, the formula Iw, the formula lx, the formula ly and the formula lz, the Ar is as defined above, particularly preferably wherein Ar has the preferred meaning of 119387.doc -40-200808727 One of their compounds.

Preferred compounds of the formula I are as follows: Α-1, Α-10, Α-Α_18, Α-cut examples are shown in the following tables: Α-2, Α-3, Α-4, α_5, Α6, ··7, α_8 α: 11, Α-12, Α-13, Α-14, Α-15, Α-16, Α-17 19, Α-20, Β·1, Β-2, Β-3, Β-4, Β-5 and Β-6. Table 1-1 - a compound of the formula la, wherein the ruler is "!! and Ar and R1 have the meanings given in one of the columns of Table 8. Table A-2: Compound of the formula lb where 111& is 11 and Ar and R1 It has the meaning given in one of the columns of Table a. Table A-3: Compound of the formula Ic, wherein 111 & is 11 and Ar and R1 have the meanings given in one of the columns of Table A. 119387. Doc-41 - 200808727 Table A-4: Compounds of the formula Id, wherein Ar and R1 have the meanings given in one of the columns of Table 8. Table A-5: Compound of the formula Ie, wherein Ar and R1 have the meanings given in one of the columns of Table 8. Table A-6: Compound of the formula If where the ruler is "!! and Ar and R1 have the meanings given in one of the columns of Table 8. Table A-7: Compound of the formula Ig, wherein Ar and R1 have one of the columns in Table A The meanings given are given in Table A-8. Compounds of the formula Ih, wherein Ar and R1 have the meanings given in one of the columns of Table A. Table A-9: Compounds of the formula Ii, which comprise the pure S-isomer, Pure r-isomer and racemic mixture, wherein Ar and R1 have the meanings given in one of the columns of Table A. Table A-10: Compound of formula Ij' which includes pure S-isomer, pure isomer And a racemic mixture wherein Ar and R1 have the meanings given in one of the columns of Table A. Table A-11: Compound of formula Ik comprising pure S-isomer, pure R-isomer and racemic a mixture wherein Ar and R1 have the meanings given in one of the columns of Table a. Table A-12: Compound of formula II 'which includes pure S-isomer, pure isomer and racemic mixture' wherein Ar and R1 It has the meaning given in one of the columns of Table a. Table A-13: Compound of the formula Im' which includes the pure s_isomer, the pure R_isomer and the racemic mixture 'wherein Ar and R have in Table a Given in one of the columns 1 19387. Doc -42- 200808727 Meaning. Table A-14: Compounds of the formula In which include pure s-isomers and racemic mixtures, wherein Ar and R1 have the meanings given in Table a. Table A-15: Formula 1 oxime compounds, including pure S-isomers and racemic mixtures, wherein Ar and R1 have the meanings given in Table a. Table A-16: Compounds of the formula Ip which comprise the pure S-isomer and the racemic mixture, wherein Ar and R1 have the meanings indicated in Table a. Table A-17: Compounds of formula Iq which include the pure S-isomers and racemic mixtures wherein Ar and R1 have the meanings given in Table A. Table A-18 · A compound of the formula Ir, which includes the pure s. isomer and a racemic mixture, wherein Ar and R1 have the meanings of Table A. Table A-19: Compounds of the formula Is, which include the pure s-isomers and racemic mixtures, wherein Ar and R1 have the meanings given in Table A. Table A-20: Compounds of the formula It, including the pure S-isomers and racemic mixtures, wherein Ar and R1 have the meanings given in Table A. Pure R-heterogeneity given in the pure H-isomer column given in the pure R-isomer column given in the pure R-isomer column The pure R-isomer column given in the column gives the 119387 given in the pure R-isomer column. Doc •43· 200808727 Table A No. R1 Ar 1.  Methyl 4-(trifluoromethoxy)-phenyl 2.  Mercapto 3-(trifluoromethoxy)-phenyl 3.  Methyl 4-cyanophenyl 4.  Methyl 4-mercaptophenyl 5.  Methyl 4-ethylphenyl 6.  Methyl 4-propylphenyl 7.  Methyl 4-methoxyphenyl 8.  Methyl 4-fluorophenyl 9·methyl 4-chlorophenyl 10.  Methyl 4-bromophenyl 11.  Methyl 3-(trifluoromethyl)phenyl 12.  Methyl 4_(trifluoromethyl)phenyl 13.  Methyl 2-(trifluoromethyl)phenyl 14.  Methyl 3,4-difluorophenyl 15.  Methyl 4->odor-3-fluorophenyl 16.  Methyl 4-isin-2-morphine phenyl 17.  Methyl 4-di-2,5-difluorophenyl 18.  Methyl 2-vapor-4-isopropylphenyl 19.  Methyl 4-hydroxyphenyl 20.  Mercapto 4-isopropylphenyl 21.  Mercapto 4-dibutylphenyl 22.  Mercapto 4-isobutylphenyl 23.  Methyl 4-(1,1-dimethylpropyl)-phenyl 24.  Methyl 4_vinylphenyl 25. .  Methyl 4-isopropenylphenyl 26.  Mercapto 4-(fluoromethyl)phenyl 27.  Methyl 3-(fluoromethyl)phenyl 28.  Methyl 2·(fluoromethyl)phenyl 29.  Methyl 4-(difluoroindolyl)phenyl 30.  Methyl 3-(difluoromethyl)phenyl 31.  Methyl 2-(difluoromethyl)phenyl 119387. Doc -44- 200808727 No. R1 Ar 32.  Methyl 4-(1_fluoroethyl)-phenyl 33.  Mercapto 4-((S)-1 -fluoroethyl)-phenyl 34.  Methyl 4-((R)-1 -1 ethylphenyl 35.  Methyl 4-(2-fluoroethyl)-phenyl 36.  Methyl 4-(1,1-difluoroethyl)-phenyl 37.  Methyl 4-(2,2-difluoro^ethyl)-phenyl 38.  Methyl 4-(2,2,2-trifluoroethyl)-phenyl 39.  Methyl 4-(3-fluoropropyl)-phenyl 40.  Methyl 4-(2-defyl)phenyl 41.  Methyl 4-((S)-2-1 propyl)-phenyl 42.  Methyl 4-((R)-2-1 propyl)-phenyl 43.  Methyl 4-(3,3-difluoropropyl)-phenyl 44.  Methyl 4_(3,3,3-trifluoropropyl)-phenyl 45.  Mercapto 4-(1-gas-1-methylethyl)-phenyl 46.  Methyl 4-(2-fluoro-1-methylethyl)-phenyl 47.  Methyl 4-((S)-2-fluoro-1-methylethyl)-phenyl 48.  Methyl 4-((R)-2-fluoro-1-methylethyl)"phenyl 49.  Methyl 4-(2,2-difluoro-1·methylethyl)-phenyl 50.  Methyl 4-((S)-2,2·diqi-1-methylethyl)-phenyl 51.  Methyl 4-((R)-2,2-difluoro-1-methylethyl)-phenyl 52.  Methyl 4-(2,2,2-trifluoro-1-methylethyl)-phenyl 53, methyl 4-((S)-2,2,2-difluoro-1-methylethyl )-Phenyl 54.  Methyl 4-((R)-2,2,2-trifluoro-1-methylethyl)-phenyl 55.  Mercapto 4-(2-fluoro-1-fluoroindolyl)phenyl.  Methyl 4-(1-difluoroindolyl-2,2-difluoroethyl)-phenyl 57.  Methyl 4_(1,1-dimethyl.2_fluoroethyl)-phenyl 58.  Methyl 4-ethoxyphenyl 59.  Methyl 4-propoxyphenyl 60.  Mercapto 4-isopropoxyphenyl 61.  Methyl 4-butoxyphenyl 62.  Methyl 4_(fluoromethoxy)·phenyl 63.  Methyl 4-(difluoromethoxy)-phenyl 64.  Methyl 4-(2-fluoroethoxy)-phenyl 119387. Doc -45- 200808727 No. R1 Ar 65.  Methyl 4-(2,2-dioxaethoxy)-phenyl 66.  Methyl 4-(2,2,2-trisethoxy)-phenyl 67.  Methyl 4-(1,1,2,2-tetrafluoroethoxy)-phenyl 68.  Methyl 4-cyclopropylphenyl 69.  Methyl 4-cyclobutylphenyl 70.  Methyl 4-cyclopentylphenyl 71.  Methyl 4-(2,2-difluorocyclopropyl)-phenyl 72.  Methyl 3-fluoro-4-isopropylphenyl 73.  Methyl 4-(1-carbo-1-methylethyl)-phenyl 74.  Methyl 4-(2-hydroxy-2-methylpropyl)-phenyl 75.  Methyl 4-ethylmercaptophenyl 76.  Methyl 4-carboxyphenyl 77.  Methyl 4-(0-benzyl)-phenyl 78.  Methyl 4-(2-methoxyethoxy)-phenyl 79.  Methyl 4-(CH2-N(CH3)2)-phenyl 80.  Methyl 4-(NH-CO-NH2)-phenyl 81.  Methyl 4-(methylthio)-phenyl 82.  Methyl 4-(fluoromethylthio)-phenyl 83.  Methyl 4-(difluoromethylthio)-phenyl 84.  Methyl 4-(trifluoromethylthio)-phenyl 85.  Methyl 4-(methylsulfonyl)-phenyl 86, methyl 4-(N-methoxymethyl-amino)-phenyl 87.  Methyl 4-(methoxyamino)-phenyl 88.  Methyl 4-(ethoxyamino)-phenyl 89.  Methyl 4-(N-decylaminooxy)-phenyl 90.  Methyl 4-(N,N-dimethylaminooxy)-phenyl 91.  Methyl 4-(°-butan-1-yl)-phenyl 92.  Methyl 4-(2-methyl σ 丫 σ -1- -1- -1-yl)-phenyl 93.  Methyl 4-((S)_2-methylazetidine-1-yl)-phenyl 94.  Methyl 4-((R)_2·methyl σ 丫 咬 _1 _1 yl)-phenyl 95.  Methyl 4-(3-fluoroazetidine small)-phenyl 96.  Methyl 4-(3-methoxyazetidin-1-yl)-phenyl 97.  Methyl 4-(3-pyridinium-1-yl)-phenyl 119387. Doc -46- 200808727 No. R1 Ar 98.  Methyl 4-(tonoxazolidine-1-phenyl)-phenyl 99.  Sulfhydryl 4-(°piroxime-2-yl)-phenyl 100.  Methyl 4-((8)-0 piroxicam-2-yl)-phenyl 101.  Methyl 4-((&)-° pyrolidine-2-yl)-phenyl 102.  Methyl 4-(indoprozol-3-but-3-yl)-stupyl 103.  Methyl 4-((S)·indolyl-3-yl)-phenyl 104.  Methyl 4-((R)-a than fluoren-3-yl)-phenyl 105.  Methyl 4-(2-pyrenepyrrolidin-1-yl)phenyl 106.  Methyl 4-((8)-2_气11比洛11定-1-yl)-phenyl 107.  Methyl 4-((R)-2- disorder 11 bis-l-l-yl)-phenyl 108.  Methyl 4-(3-ϋϋ比洛丁-1-yl)-phenyl 109.  Methyl 4-((S)-3- gas oxazolidine-1-yl)-phenyl 110.  Methyl 4-((R)-3 · gas π piroxicam-1 -yl)-phenyl 111.  Methyl 4-(2,2·digas 11 phloate-1-yl)-phenyl 112.  Methyl 4-(3,3-disorder σ 比 洛 σ -1- yl)-phenyl 113.  Methyl 4-(2-methylindolopyrazine-1-yl)-phenyl 114.  Methyl 4-((S)-2-methyl 0-Butyl-1-yl)-phenyl 115.  Methyl 4-((R)-2-methyl 0-loxazol-1-yl)-phenyl 116.  Mercapto 4-(3-methyltolfrolidine-1-yl)-phenyl 117.  Methyl 4-((S)-3-methyloxaridin-1-yl)-phenyl 118.  Mercapto 4-((R)-3-indolyl σ pirin-1-yl)-phenyl 119.  Methyl 4-(1-methyl.pyrrolidin-2-yl)-phenyl 120.  Methyl 4-((S)-l-methyloxaridin-2-yl)-phenyl 121.  Methyl 4-((R)-l-methyl.bipirin-2-yl)-phenyl 122.  Methyl 4-(1-methyl σpyrrolidine-3-yl)-phenyl 123.  Methyl 4-((S)-l-methylpyridin-3-yl)-phenyl 124.  Methyl 4-((尺)_1-methyl ° 洛洛 bit-3_)-phenyl 125.  Methyl 4-(2,2-dimercaptopyran-1-yl)-phenyl 126.  Methyl 4-(3,3-dimethylpyrrolidin-1-yl)-phenyl 127.  Methyl 4-(2-trifluoromethylpyridin-1-yl)-phenyl 128.  Methyl 4-((S)-2-dimethylmethyl 0-Butyl-1-yl)-phenyl 129.  Methyl 4-((R)-2-trifluoromethyloxaridin-1-yl)-phenyl 130.  Methyl 4-(3-trifluoromethyloxaridin-1-yl)-phenyl 119387. Doc -47- 200808727 No. R1 Ar 131.  Methyl 4-((S)-3_trifluoromethylpyrrolidin-1-yl)phenyl 132.  Methyl 4-((R)-3-dimethylmethylσpyramid-1-yl)-phenyl 133.  Methyl 4-(2-o-oxaoxaridin-1-yl)-phenyl 134.  Methyl 4-(2-o-oxy-σ oxime 17-but-3-yl)-phenyl 135.  Methyl 4·(Brigade σ-1-yl)-phenyl 136.  Indenyl 4_(2-methylpiperidin-1-yl)-phenyl 137.  Mercapto 4-((S)-2_methyl 唆-1_yl)-phenyl 138.  Methyl 4-((R)-2-methylpiperidin-1-yl)-phenyl 139.  Methyl 4-(Brigade-l-yl)_phenyl 140.  Methyl 4-(4-methyl-tung-1-yl)-phenyl 141.  Methyl 4-(morpholin-4-yl)-phenyl 142.  Methyl 4-(thiomorphin-4-yl)-phenyl 143.  Methyl 4-(1-flavoryl-thio- phenanthryl-4-yl)-phenyl 144.  Methyl 4-( 1,1-di-oxy-thio- phenothin-4-yl)-phenyl 145.  Methyl 4-(0-l-l-yl)-phenyl 146.  Mercapto 4-(σpyr-2-yl)-phenyl 147.  曱 4-(ϋ比洛_3_基)-phenyl 148.  Methyl 4-(1•methylindol-2-yl)-phenyl 149.  Methyl 4-(1-methyl 0-pyridin-3-yl)-phenyl 150.  Methyl 4-(indol-2-yl)-phenyl 151.  Methyl 4-(indol-3-yl)-phenyl 152.  Mercapto 4-(嗟-phen-2-yl)-phenyl 153.  Methyl 4-(11-secen-3-yl)-phenyl 154.  Methyl 4-(5-propyl hydrazin-2-yl)-phenyl 155.  Methyl 4-7-pyridin-1-yl)-phenyl 156.  Methyl 4 decazol-3-yl)-phenyl 157.  Methyl 4 decazol-4-yl)-phenyl 158.  Methyl 4-(1-methyl-1Η-oxazol-4-yl)-phenyl 159.  Methyl 4-(1-ethyl-1H-indazol-4-yl)-phenyl 160.  Methyl 4-(1-methyl-1H-indazol-5-yl)-phenyl 161.  Methyl 4-(1Η-imidazol-2-yl)-phenyl 162.  Methyl 4-(imidazolium-1yl)-phenyl 163.  Methyl 4-(1-methyl-n-methane s-yl-2-yl)-phenyl 119387. Doc -48- 200808727 No. R1 Ar 164.  Methyl 4-(oxazol-2-yl)-phenyl 165, fluorenyl 4_(oxazol-4-yl)-phenyl 166.  Mercapto 4-(oxazol-5-yl)-phenyl 167.  Methyl 4-(iso. Ester 11 -3-yl)-phenyl 168.  Methyl 4-(isoxazol-4-yl)-phenyl 169.  Methyl 4-(isoxazole-5-yl)-phenyl 170.  Methyl 4-([1,2,3]-triazol-1-yl)-phenyl 171.  Methyl 4-([1,2,4]-triazole small)-phenyl 172.  Methyl 4-([1,2,3]-triazol-2-yl)-phenyl 173.  Methyl 4-(4Η-[1,2,4]-triazol-3-yl)-phenyl 174.  Methyl 4-([1,2,4]-triazol-4-yl)-phenyl 175.  Methyl 4-(2Η-[1,2,3]-triazol-4yl)-phenyl 176.  Methyl 4-(4-methyl-4H-[1,2,4].triazol-3-yl)-phenyl 177.  Methyl 4-(2-methyl.2Η-[1,2,3]-triazol-3-yl)-phenyl 178.  Methyl 4-([1,3,4]-oxadiazol-2-yl)-phenyl 179.  Mercapto 4-([1,2,4]_oxadiazol-3-yl)-phenyl 180.  Methyl 4-([1,2,4]-oxadiazol-5-yl)-phenyl 181.  Methyl 4-([1,2,3]-oxadiazol-4-yl)-phenyl 182.  Methyl 4-([1,2,3]-oxadiazol-5-yl)-phenyl 183.  Methyl 4-([1,2,3]-thiadiazol-4-yl)-phenyl 184.  Methyl 4-(1Η-tetrazol-5-yl)-phenyl 185.  Methyl 4-(tetrazol-1-yl)-phenyl 186.  Methyl 4-(2-methyl-2-indole-tetrazol-5-yl)-phenyl 187.  Methyl 4-( 1 ·methyl-1H-tetrazole-5-yl)-phenyl 188.  Methyl 4-furazan-3-yl-phenyl 189.  Methyl 4 decapyridin-2-yl)-phenyl 190.  Indenyl 4 decapyridin-3-yl)-phenyl 191.  曱 ))-phenyl 192.  Methyl 4-(mouth sigma-2-yl)-phenyl 193.  Methyl 4-7-melt-4-yl)-phenyl 194.  Methyl 4-(♦ gnato-5-yl)-phenyl 195.  Methyl 5-isopropyl σ-cephen-2-yl 196.  Methyl 2-gas π-cephen-5-yl 119387. Doc -49- 200808727 No. R1 Ar 197.  Methyl 2,5-dichloroσsept-4-yl 198.  Methyl 2,3-dioxathiophen-5-yl 199.  Methyl 2-vapor-3-yetyl sigma-5-yl group 200.  Methyl 2-(phenyl)-porphin-5-yl.  Methyl 2-(0-bito-2-yl)σ-sept-5-yl 202.  Methyl 2-(5-(trifluoromethyl)isoxazol-3-yl)-thiophen-5-yl 203.  Methyl 2-(2-methylthiazol-4-yl)-thiophene-5.  Methyl 1·methyl-1H-imidazol-4-yl 205.  Methyl 1,2-dimethyl-1H-imidazol-4-yl 206.  Methyl 3,5-dimethylisoxazole-4-yl 207.  Methyl 嗟唆-2-yl 208.  Methyl 4-methylthiazol-2-yl 209.  Methyl 4-isopropylthiazole-2.  Methyl 4-trifluoromethylthiazol-2-yl 211.  Methyl 5-methylthiazol-2-yl 212.  Methyl 5-isopropylthiazol-2-yl 213.  Methyl 5-trifluoromethylthiazol-2-yl 214.  Methyl 2,4-dimethylthiazol-5-yl 215.  Methyl 2-ethylamino-4-pyrene. Sitting on a 5-base 216.  Methyl 4H-[1,2,4]triazol-3-yl 217.  Mercapto 5-methyl-4H_[1,2,4]triazol-3-yl 218.  Methyl 4-methyl-4H-[1,2,4]-triazol-3-yl 219.  Methyl 5-isopropyl-4H-[1,2,4]triazol-3-yl 220.  Methyl 5-trifluoroindolyl 4 Η_[1,2,4]triazole _3_yl 221.  Methyl 4,5-dimethyl-4Η-[1,2,4]triazol-3-yl 222.  Methyl 5-isopropyl-4-methyl-4-anthracene-[1,2,4]triazol-3-yl 223.  Methyl 5-trifluoromethyl-4_methyl-4Η-[1,2,4]triazole_3_yl 224.  Methyl [1,3,4]thiadiazole winter base 225.  Methyl 5-methyl-[1,3,4]thiadiazol-2-yl 226.  Methyl 5-isopropyl-[1,3,4]thiadiazol-2-yl 227.  Methyl 5-trifluoromethyl-[1,3,4]thiadiazol-2-yl 228.  Methyl 3-bromo-2-chloropyridin-5-yl 229.  Methyl 2-(4-morphinyl)-indenyl-5-yl 119387. Doc -50- 200808727 No. R1 Ar 230.  Methyl 2-phenoxypurine-5-based 231.  Methyl (2-isopropyl)-indole-5-based 232.  Methyl (5-isopropyl)-biting-2-yl 233.  Methyl 8-quinolinyl 234.  Methyl 5-isoindole 235.  Methyl 2-(trifluoroethenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl 236.  Methyl 5-chloro-3-phenylbenzothiophen-2-yl 237.  Methyl 3,4-dihydro-4-methyl-2Η-benzoquinone [b][l,4]oxazinyl 238.  Methyl benzothiazole-6-yl 239.  Methyl phenylhydrazine P, l, 3] oxadiazol-4-yl 240.  Methyl 5-chlorophenylhydrazone p,l,3]oxadiazol-4-yl 241.  Methyl 7-chlorophenylhydrazone p,l,3]oxadiazol-4-yl 242.  Methyl phenylhydrazine P, l, 3] thiadiazole-4-yl 243.  Methyl 6-chloroimidazolium [2,l-b]thiazolyl 244.  Ethyl 4-(trifluoromethoxy)-phenyl 245.  Ethyl 3-(trifluoromethoxy)-phenyl 246.  Ethyl 4-cyanophenyl 247.  Ethyl 4-methylphenyl 248.  Ethyl 4-ethylphenyl 249.  Ethyl 4-propylphenyl 250.  Ethyl 4-decyloxyphenyl 25L ethyl 4-fluorophenyl 252.  Ethyl 4-chlorophenyl 253.  Ethyl 4-bromophenyl 254.  Ethyl 3-(trifluoromethyl)phenyl 255.  Ethyl 4-(trifluoromethyl)phenyl 256.  Ethyl 2-(trifluoromethyl)phenyl 257.  Ethyl 3,4-difluorophenyl 258.  Ethyl 4->odor-3-fluorophenyl 259.  Ethyl 4-bromo-2-fluorophenyl 260.  Ethyl 4-bromo-2,5-difluorophenyl 261.  Ethyl 2-fluoro-4-isopropylphenyl 262.  Ethyl 4-phenylphenyl 119387. Doc -51- 200808727 No. R1 Ar 263.  Ethyl 4-isopropylphenyl 264.  Ethyl 4-t-butylphenyl 265 _ ethyl 4-isobutylphenyl 266.  Ethyl 4-(1,1-dimethylpropyl)-phenyl 267.  Ethyl 4-vinylphenyl 268.  Ethyl 4-isopropenylphenyl 269.  Ethyl 4-(fluoroindolyl)phenyl 270.  Ethyl 3-(fluoroindolyl)phenyl 271.  Ethyl 2-(fluoromethyl)phenyl 272.  Ethyl 4-(difluoromethyl)phenyl 273.  Ethyl 3-(difluoromethyl)phenyl 274.  Ethyl 2-(difluoroindolyl)phenyl 275.  Ethyl 4-(1-fluoroethyl)-phenyl 276.  Ethyl 4-((S)-l-fluoroethyl)-phenyl 277.  Ethyl 4-((R)-l-fluoroethyl)-phenyl 278.  Ethyl 4·(2_fluoroethyl)-phenyl 279.  Ethyl 4-(1,1-difluoroethyl)-phenyl 280.  Ethyl 4-(2,2-difluoroethyl)-phenyl 281.  Ethyl 4-(2,2,2-trifluoroethyl)-phenyl 282.  Ethyl 4-(3-a. propyl)-phenyl 283.  Ethyl 4-(2-a. propyl)-phenyl 284.  Ethyl 4-((S)-2-fluoropropyl)-phenyl 285.  Ethyl 4-((R)-2-1 propyl)-phenyl 286.  Ethyl 4-(3,3-difluoropropyl)-phenyl 287.  Ethyl 4-(3,3,3-trifluoropropyl)-phenyl 288.  Ethyl 4-(1-fluoro-1-methylethyl)-phenyl 289.  Ethyl 4-(2-fluoromethylethyl)-phenyl 290.  Ethyl 4-((S)-2- gas small methyl ethyl)-phenyl 291.  Ethyl 4-((R)-2-fluorosuccinylethyl)-phenyl 292.  Ethyl 4-(2,2-difluoromethylethyl)-phenyl 293.  Ethyl 4-((S)-2,2-difluoro 1-indolylethyl)-phenyl 294.  Ethyl 4-((R)-2,2-difluoro-1-methylethyl)-phenyl 295.  Ethyl 4-(2,2,2_tris-1 -methylethyl)-phenyl 119387. Doc -52- 200808727 No. R1 Ar 296.  Ethyl 4-((S)-2,2,2-difluoro-1-methylethyl)-phenyl 297.  Ethyl 4-((R)-2,2,2-trifluoromethylethyl)-phenyl 298.  Ethyl 4-(2-a-1)-methylethyl)-phenyl 299.  Ethyl 4-(1-difluoroindolyl-2,2-difluoroethyl)-phenyl 300.  Ethyl 4_(1,1-dimethyl-2-fluoroethyl)-phenyl 301.  Ethyl 4-ethoxyphenyl 302.  Ethyl 4-propoxyphenyl 303.  Ethyl 4-isopropoxyphenyl 304.  Ethyl 4-butoxyphenyl 305.  Ethyl 4-(fluorodecyloxy)-phenyl 306.  Ethyl 4-(difluoromethoxy)-phenyl 307.  Ethyl 4-(2-fluoroethoxy)-phenyl 308.  Ethyl 4-(2,2-difluoroethoxy)-phenyl 309.  Ethyl 4-(2,2,2-trifluoroethoxy)-phenyl 310.  Ethyl 4_(1,1,2,2-tetrafluoroethoxy)-phenyl 311.  Ethyl 4-cyclopropylphenyl 312.  Ethyl 4-cyclobutylphenyl 313.  Ethyl 4-cyclopentylphenyl 314.  Ethyl 4-(2,2-difluorocyclopropyl)-phenyl 315.  Ethyl 3-fluoro-4-isopropylphenyl 316.  Ethyl 4-(1-group-1-ylethyl)-phenyl 317.  Ethyl 4-(2-carbo-2-methylpropyl)-phenyl 318.  Ethyl 4-ethylmercaptophenyl 319.  Ethyl 4-mercaptophenyl 320.  Ethyl 4-(0-phenylhydrazinyl)-phenyl 321.  Ethyl 4-(2-methoxyethoxy)-phenyl 322.  Ethyl 4-(CHrN(CH3)2)-phenyl 323.  Ethyl 4-(NH-CO-NH2)·phenyl 324.  Ethyl 4-(methylthio)-phenyl 325.  Ethyl 4-(fluoromethylthio)-phenyl 326.  Ethyl 4-(difluoromethylsulfanyl)-phenyl 327.  Ethyl 4-(trifluoromethylthio)-phenyl 328.  Ethyl 4-(methylsulfonyl)-phenyl 119387. Doc -53- 200808727 No. R1 Ar 329.  Ethyl 4-(N-methoxy-N-methyl-amino)-phenyl 330.  Ethyl 4-(methoxyamino)-phenyl 331.  Ethyl 4-(ethoxyamino)-phenyl 332.  Ethyl 4-(N-methylaminooxy)-phenyl 333.  Ethyl 4-(N,N-dimethylaminooxy-phenyl 334.  Ethyl 4-(°丫丫-1-yl)-phenyl 335.  Ethyl 4-(2-methylindole-1-yl)-phenyl 336.  Ethyl 4-((8)-2-methyloxazolidine-1-yl)-phenyl 337.  Ethyl 4-((R)-2-methylindole-1-yl)-phenyl 338.  Ethyl 4-(3-fluorooxin-1-yl)-phenyl 339.  Ethyl 4-(3·methylmercaptopurine·1 -yl)-phenyl 340.  Ethyl 4-(3-hydroxyazetidin-1-yl)-phenyl 341.  Ethyl 4-(0 piroxicam-1 -yl)-phenyl 342.  Ethyl 4-(11-Butyl-2-yl)-phenyl 343.  Ethyl 4-((S)-indolyl-2-yl)-phenyl 344.  Ethyl benzyl-2-yl)-phenyl 345.  Ethyl 4-(σ pyrrole-3-yl)-phenyl 346.  Ethyl 4-((S)-(r-hexyl-3-yl)-phenyl 347.  Ethyl ‘·(^[^- 口比洛 bit-^-kibphenyl 348.  Ethyl 4-(2- gas ° 洛 咬 _1 _ base) - phenyl 349.  Ethyl 4-((S)-2_气11比洛0定-1-yl)_phenyl 350.  Ethyl 4-((R)-2- gastropyrrolidine-1-yl)-phenyl 351.  Ethyl 4-(3-carboindole-1-yl)phenyl 352.  Ethyl 4-((S)-3·chaos. bilodin-1 -yl)phenyl 353.  Ethyl 4-((R)-3- gas 11 piroxicam-1-yl) phenyl 354.  Ethyl 4-(2,2-digas 11 is more than 1 bit base)-phenyl 355.  Ethyl 4-(3,3-dioxol ratio 0 __1-yl)-phenyl 356.  Ethyl 4-(2-methyl 0-Bisole-1-_1)-phenyl 357.  Ethyl 4-((S)-2-methyl 0-pyrrolidine-1-yl)-phenyl 358.  Ethyl 4-((R)-2-mercapto-t-rheptin-1-yl)-phenyl 359.  Ethyl 4-(3-methylindoleridin-1-yl)-phenyl 360.  Ethyl 4-((S)-3-methyloxaridin-1-yl)-phenyl 361.  Ethyl 4-((R)_3_methylηpyrrolidin-1-yl)-phenyl 119387. Doc -54- 200808727 No. R1 Ar 362.  Ethyl 4-(1-methyl 0-pyramidine-2-yl)-phenyl 363.  Ethyl 4-((S)-l-methylindolebipyridin-2-yl)-phenyl 364.  Ethyl 4-((R)-l-methyl σ 比 洛 17 17 _2 _ _ _ phenyl) 365.  Ethyl 4-(1-methyloxaridin-3-yl)-phenyl 366.  Ethyl 4-((S)_l.methylpyrrolidin-3-yl)-phenyl 367.  Ethyl 4-((R)-l-methyloxaridin-3-yl)-phenyl 368.  Ethyl 4-(2,2·dimethyl-p-butlobutan-1-yl)-phenyl 369.  Ethyl 4-(3,3-dimercaptopyrrolidinyl)-phenyl 370.  Ethyl 4-(2-dimethyl fluorenyl hydrazide _1 yl) phenyl 371.  Ethyl 4-((8)_2_trifluoromethyl.pyrrolidinylphenyl 372.  Ethyl 4-((R)-2-trifluoromethyl oxaridin-1-yl)-phenyl 373.  Ethyl 4-(3-dimethylmethylpyridinium 0-but-1-yl)-phenyl 374.  Ethyl 4-((S)-3-disorganomethylindole-1-yl)-phenyl 375.  Ethyl 4-((R)-3-disindolylpyridinium pyridin-1-yl)-phenyl 376.  Ethyl 4-(2-o-oxopyrrolidin-1-yl)-phenyl 377.  Ethyl 4-(2-o-oxy-oxazolidine-3-yl)-phenyl 378.  Ethyl 4-(Big sigma-1-yl)-phenyl 379.  Ethyl 4-(2·methylpiperidin-1-yl)-phenyl 380.  Ethyl 4-((S)-2-methylpiperidin-1-yl)-phenyl 381.  Ethyl 4-((R)-2-methylpiperidin-1-yl)-phenyl 382.  Ethyl 4-(嗓嗓-1-yl)-phenyl 383.  Ethyl 4-(4-methyl succinyl-1 -yl)-phenyl 384.  Ethyl 4-(morpholin-4-yl)-phenyl 385.  Ethyl 4-(thiomorphin-4-yl)-phenyl 386.  Ethyl 4-(1-flavoryl-thio- phenanthyl 4-yl)-phenyl 387.  Ethyl 4-( 1,1-di-l-milyl-thio- phenanthren-4-yl)-phenyl 388.  Ethyl 4-tetrapyr-1-yl)-phenyl 389.  Ethyl 4-(^bi-l-yl)-phenyl 390.  Ethyl 4-indolyl-3-yl)-phenyl 391.  Ethyl 4-(1·methyl 0-pyridin-2-yl)-phenyl 392.  Ethyl 4-(1-methyl σ-pyrrol-3-yl)phenyl 393.  Ethyl 4-(furan-2-yl)-phenyl 394.  Ethyl 4-(bung-3-yl)-phenyl 119387. Doc -55- 200808727 No. R1 Ar 395.  Ethyl 4-(σsecen-2-yl)-phenyl 396.  Ethyl 4-(σsecen-3-yl)-phenyl 397.  Ethyl 4-(5-propyl 11 sec-2-yl)-phenyl 398.  Ethyl 4 decazol-1-yl)-phenyl 399.  Ethyl 4-(oxazol-3-yl)-phenyl 400.  Ethyl 4 Tetrapyran-4-yl)-phenyl 401.  Ethyl 4-(1-methyl-1H-indazol-4-yl)-phenyl 402.  Ethyl 4-(1-ethyl-1Η-σ ratio ° sitting _4-yl) phenyl 403.  Ethyl 4-(1-methyl-1Η-indazol-5-yl)-phenyl 404.  Ethyl 4-(1Η-imidazol-2-yl)-phenyl 405.  Ethyl 4-(imidazol-1-yl)-phenyl 406.  Ethyl 4-(1-methylimidazol-2-yl)-phenyl 407.  Ethyl 4-(oxazol-2-yl)-phenyl 408.  Ethyl 4-(oxazol-4-yl)-phenyl 409.  Ethyl 4-(oxazol-5-yl)-phenyl 410.  Ethyl 4-(isoindole·^-yl)-phenyl 411.  Ethyl 4-(isoxazole-4_yl)-phenyl 412.  Ethyl 4-(isoyl)-phenyl 413.  Ethyl 4-([1,2,3]-triazole-1_yl)-phenyl 414.  Ethyl 4_([1,2,4]·triazol-1-yl)-phenyl 415.  Ethyl 4-([1,2,3]-disial-2-yl)-phenyl 416.  Ethyl 4·(4Η-[1,2,4]-triazol-3-yl)phenyl 417.  Ethyl 4-([1,2,4]-triazole _4_yl)-phenyl 418.  Ethyl 4-(2Η-[1,2,3]-triazol-4-yl)-phenyl 419.  Ethyl 4-(4-methyl-4Η·[1,2,4]-triazole _3_yl)-phenyl 420.  Ethyl 4-(2-methyl-2Η-[1,2,3]-triazol-4-yl)-phenyl 421.  Ethyl 4-([1,3,4]-oxadiazol-2-yl)-phenyl 422.  Ethyl 4-([1,2,4]-oxadiazol-3-yl)-phenyl 423.  Ethyl 4-([1,2,4]-oxadiazol-5-yl)-phenyl 424.  Ethyl 4-([1,2,3]·oxadiazol-4-yl)-phenyl 425.  Ethyl 4-([1,2,3]-oxadiazol-5-yl)-phenyl 426.  Ethyl 4-([1,2,3]-thiadiazol-4-yl)-phenyl 427.  Ethyl 4-(1Η-tetrazol-5-yl)phenyl 119387. Doc -56- 200808727 No. R1 Ar 428.  Ethyl 4-(tetras-l-yl)-phenyl 429.  Ethyl 4-(2-mercapto-2H-tetrazol-5-yl)-phenyl 430.  Ethyl 4-(1-methyl-1H-tetraindole-5-yl)phenyl 431.  Ethyl 4-bito-3-yl-phenyl 432.  Ethyl 4-(deuterium.din-2-yl)-phenyl 433.  Ethyl 4-(σ ratio σ定-3_yl)·phenyl 434.  Ethyl 4-(° ratio 0--4-yl)-phenyl 435.  Ethyl 4 acetylene-2-yl)-phenyl 436.  Ethyl 4-(snack -4-yl)-phenyl 437.  Ethyl 4-bumpy-5-yl)-phenyl 438.  Ethyl 5-isopropyl π-cephen-2-yl 439.  Ethyl chloride ° ceto-5-based 440.  Ethyl 2,5-dioleothiophene-4-yl 441.  Ethyl 2,3-dichlorothiophen-5-yl 442.  Ethyl 2-chloror3-zeschyl porphin-5-yl 443.  Ethyl 2-(phenylsulfonyl) > thiophen-5-yl 444.  Ethyl 2-(π ratio σ-but-2-yl) decet-5-yl 445.  Ethyl 2-(5-(trifluoromethyl)isoxazole-3-yl)-thiophen-5-yl 446.  Ethyl 2-(2.methylthiazol-4-yl)-thiophen-5-yl 447.  Ethyl 1-methyl-1H-imidazol-4-yl 448.  Ethyl 1,2-dimethyl-1H-imidazol-4-yl 449.  Ethyl 3,5-dimethyliso 17 oxazeto _4_ base 450.  Ethyl 嗟嗤-2-yl 451.  Ethyl 4-mercaptothiazol-2-yl 452.  Ethyl 4-isopropylthiazol-2-yl 453.  Ethyl 4-trifluoromethylthiazol-2-yl 454.  Ethyl 5-methylthiazol-2-yl 455.  Ethyl 5-isopropylthiazol-2-yl 456.  Ethyl 5-trifluoromethylthiazol-2-yl 457.  Ethyl 2,4-dimethylthiazol-5-yl 458.  Ethyl 2-acetamido-4-methylthiazole-5-yl 459.  Ethyl 4H-[1,2,4]triazol-3-yl 460.  Ethyl 5-methyl·4Η_[1,2,4]triazol-3-yl 119387. Doc -57- 200808727 No. R1 Ar 461.  Ethyl 4-mercapto-4H-[1,2,4]triazole group 462.  Ethyl 5-isopropyl-4Η·[1,2,4]triazol-3-yl 463.  Ethyl 5-trifluoromethyl-4Η-[1,2,4]triazol-3-yl 464.  Ethyl 4,5-dimethyl-4Η-[1,2,4]triazol-3-yl 465.  Ethyl 5-isopropyl-indolemethyl-4Η-[1,2,4]triazol-3-yl 466.  Ethyl 5-trifluoromethyl-4-methyl-4Η-[1,2,4]triazol-3-yl 467.  Ethyl [1,3,4]thiadiazole-2. 468.  Ethyl 5-methyl-[1,3,4]thiadiazol-2-yl 469.  Ethyl 5-isopropyl-[1,3,4]thiadiazol-2-yl 470.  Ethyl 5-trifluoromethyl-[1,3,4]thiadiazol-2-yl 471.  Ethyl 3-> odor-di-gas^ is more than bite-based 472.  Ethyl 2-(4-?^木基)-11 唆_5·基 473.  Ethyl 2-phenyllactyl hydrazone 11--5-yl 474.  Ethyl (2-isopropyl)_feeding.定-5-基 475.  Ethyl (5-isopropyl)-11 dimethyl-2-yl 476.  Ethyl 8-indole 477.  Ethyl 5-isoquinolinyl 478.  Ethyl 2-(trifluoroethenyl)·1,2,3,4·tetrahydroisoquinolin-7-yl 479.  Ethyl 5-chloro-3-methylbenzoquinone σ-cephen-2-yl 480.  Ethyl 3,4-dihydro-4.methyl-2Η-benzoquinone [b][l,4]oxazinyl 481.  Ethyl benzoxazole _6-based 482.  Ethyl benzoquinone [2,1,3]oxadiazol-4-yl 483.  Ethyl 5-chlorobenzoquinone ρ,1,3]oxadiazole-4-yl 484.  Ethyl 7-gas benzoquinone P, l, 3] oxadiazole · 4 · 485.  Ethyl benzoquinone [2,1,3]thiadiazole-4-yl 486.  Ethyl 6-amidazolium [2,l-b]thiazolyl 487.  Propyl 4-(trifluoromethoxy)-phenyl 488.  Propyl 3-(trifluoromethoxy)-phenyl 489.  Propyl 4-cyanophenyl 490.  Propyl 4-methylphenyl 491.  Propyl 4-ethylphenyl 492.  Propyl 4-propylphenyl 493.  Propyl 4-methoxyphenyl 119387. Doc -58- 200808727 No. R1 Ar 494.  Propyl 4-fluorophenyl 495.  Propyl 4-chlorophenyl 496.  Propyl 4-> stinyl phenyl 497.  Propyl 3-(trifluoromethyl)phenyl 498.  Propyl 4-(trifluoromethyl)phenyl 499.  Propyl 2-(trifluoromethyl)phenyl 500.  Propyl 3,4-difluorophenyl 501.  Propyl 4-indol-3-fluorophenyl 502.  Propyl 4-bromo-2-fluorophenyl 503.  Propyl 4-di-2,5-difluorophenyl 504.  Propyl 2-fluoro-4-isopropylphenyl 505.  Propyl 4-phenylphenyl 506.  Propyl 4-isopropylphenyl 507.  Propyl 4-second butyl phenyl 508.  Propyl 4-isobutylphenyl 509.  Propyl 4-(1,1-dimethylpropyl)-phenyl 510.  Propyl 4-vinylphenyl 511.  Propyl 4-isopropenylphenyl 512.  Propyl 4-(fluoromethyl)phenyl 513.  Propyl 3-(fluoromethyl)phenyl 514.  Propyl 2-(fluoroindolyl)phenyl 515.  Propyl 4-(difluoroindolyl)phenyl 516.  Propyl 3-(difluoromethyl)phenyl 517.  Propyl 2·(difluoromethyl)phenyl 518.  Propyl 4-(1-fluoroethyl)-phenyl 519.  Propyl 4-((S)-l-fluoroethyl)-phenyl 520.  Propyl 4-((R)-l-fluoroethyl)-phenyl 521.  Propyl 4-(2·fluoroethyl)-phenyl 522.  Propyl 4-(1,1-difluoroethyl)-phenyl 523.  Propyl 4-(2,2-difluoroethyl)-phenyl 524.  Propyl 4-(2,2,2-trifluoroethyl)-phenyl 525.  Propyl 4-(3-fluoropropyl)-phenyl 526.  Propyl 4-(2-fluoropropyl)-phenyl 119387. Doc -59- 200808727 No. R1 Ar 527.  Propyl 4-((8)-2-fluoropropyl)-phenyl 528.  Propyl 4-(XR)-2-fluoropropyl)-phenyl 529.  Propyl 4-(3,3-di-propylpropyl)-phenyl 530.  Propyl 4-(3,3,3-discyl)-phenyl 531.  Propyl 4-(1-enyl α-l-methylethyl)-phenyl 532.  Propyl 4-(2-fail-1 -mercaptoethyl)-phenyl 533.  Propyl 4-((S)-2_gas-1 1-methylethyl)-phenyl 534.  Propyl 4-((R)-2-fluoro-1"methylethyl)-phenyl 535.  Propyl 4-(2,2-difluoro-1-methylethyl)-phenyl 536.  Propyl 4-((S)-2,2-difluoro-1-methylethyl)phenyl 537.  Propyl 4-((R)-2,2_diox-1-methylethyl)-phenyl 538.  Propyl 4-(2,2,2-difluoro-1-methylethyl)-phenyl 539.  Propyl 4-((S)-2,2,2-tris-l-l-decylethyl)-phenyl 540.  Propyl 4-((R)-2,2,2-trifluoro-1-methylethyl)-phenyl 541.  Propyl 4-(2-nitro-1-methylmethylethyl)-phenyl 542.  Propyl 4-(1-difluoromethyl-2,2·dioxaethyl)-phenyl 543.  Propyl 4-(1,1-dimethyl-2-cycloethyl)-phenyl 544.  Propyl 4-ethoxyphenyl 545.  Propyl 4-propoxyphenyl 546.  Propyl 4-isopropoxyphenyl 547.  Propyl 4-butoxyphenyl 548.  Propyl 4-(fluoromethoxy)-phenyl 549.  Propyl 4-(difluorodecyloxy)-phenyl 550.  Propyl 4-(2-fluoroethoxy)-phenyl 551.  Propyl 4-(2,2-difluoroethoxy)-phenyl 552.  Propyl 4-(2,2,2-difluoroethoxy)-phenyl 553.  Propyl 4_(1,1,2,2-tetrafluoroethoxy)-phenyl 554.  Propyl 4-cyclopropylphenyl 555.  Propyl 4-cyclobutylphenyl 556.  Propyl 4-cyclopentylphenyl 557.  Propyl 4-(2,2-difluorocyclopropyl)-phenyl 558.  Propyl 3-fluoro-4-isopropylphenyl 559.  Propyl 4-(1-hydroxy-1-methylethyl)-phenyl 119387. Doc -60- 200808727 No. R1 Ar 560.  Propyl 4-(2-carbo-2-methylpropyl)-phenyl 561.  Propyl 4-ethylmercaptophenyl 562.  Propyl 4-carboxyphenyl 563.  Propyl 4-(0-benzyl)-phenyl 564.  Propyl 4-(2·decyloxyethoxy)-phenyl 565.  Propyl 4-(CH2-N(CH3)2)-phenyl 566.  Propyl 4-(NH-CO-NH2)-phenyl 567.  Propyl 4-(mercaptothio)-phenyl 568.  Propyl 4-(fluoromethylthio)-phenyl 569.  Propyl 4-(difluorodecylthio)-phenyl 570.  Propyl 4-(trifluoromethylsulfanyl)-phenyl 571.  Propyl 4-(methylsulfonyl)-phenyl 572.  Propyl 4-(N-methyllacylmethyl-amino)-phenyl 573.  Propyl 4-(methoxyamino)-phenyl 574.  Propyl 4-(ethoxyamino)-phenyl 575.  Propyl 4-(N-decylaminooxy)-phenyl 576.  Propyl 4-(N,N-didecylaminooxy)-phenyl 577.  Propyl 4-(π丫丁咬-1-yl)-phenyl 578.  Propyl 4-(2·methylglycolidine.-1-yl)-phenyl 579.  Propyl 4-((S)-2·methyl oxime 17-den-1-yl)-phenyl 580.  Propyl 4-((R)-2-methylsulfonium σ-denyl-1-yl)-phenyl 581.  Propyl 4-(3-d-butyl succinyl-1-yl)-phenyl 582.  Propyl 4-(3-methoxyazetidine small)-phenyl 583.  Propyl 4-(3-hydroxyazetidin-1-yl)-phenyl 584.  Propyl 4-(σ 比洛丁-l-yl)-phenyl 585.  Propyl 4-(ϋΐί*) 2-phenyl)-phenyl 586.  Propyl 4-((S)-%b-bromo-2-yl)-phenyl 587.  Propyl 4-((R)-indolyl-2-yl)-phenyl 588.  Propyl 4-(°Bido-3-yl)-phenyl 589.  Propyl 4-((S)"pyrrolidine_3_yl)·phenyl 590.  Propylpyrrolidine-3-yl)-phenyl 591.  Propyl 4-(2-fluoropyridin-1-yl)-phenyl 592.  Propyl 4-((S)-2- gas 0 than 唆_1_1-yl)-phenyl 119387. Doc -61- 200808727 No. R1 Ar 593.  Propyl 4-((R)-2-gas σ than H bit _1-yl)-phenyl 594.  Propyl 4-(3- gas 11 than fluoren-1-yl)-phenyl 595.  Propyl 4-((S)_3-乱°比鸣定定-1-yl)-phenyl 596.  Propyl 4-((R)-3-gas 11 than fluoren-1-yl)-phenyl 597.  Propyl 4-(2,2-digas σ pyrrolidine-1-yl)phenyl 598.  Propyl 4-(3,3-disorder σ pirodi-1 base)-phenyl 599.  Propyl 4-(2-mercapto pyrrolidine small group)-phenyl 600.  Propyl 4_((S)-2-methyl-l-rheptan-1-yl)-phenyl 601.  Propyl 4-((R)-2-methylpyrrolidin-1-yl)-phenyl 602.  Propyl 4-(3-methyl-pyrrolidine-1-yl)-phenyl 603.  Propyl 4-((S)-3-methyl-l-bromo-1-yl)-phenyl 604.  Propyl 4-((R)-3-methyl 0bizorazine-1-yl)-phenyl 605.  Propyl 4-(1-methylindolebi-2-yl)-phenyl 606.  Propyl 4-((S) benzhydrazin-2-yl)-phenyl 607.  Propyl 4-((R)-l-methylpyrrolidin-2-yl)-phenyl 608.  Propyl 4-(1-methyl σpyrrolidine-3-yl)-phenyl 609.  Propyl 4-((S)-l-methyl °Biluo-3_yl)·phenyl 610.  Propyl 4-((R)-1 -methylindole^indol-3-yl)-phenyl 611.  Propyl 4-(2,2-dimethylindole-1-yl)-phenyl 612.  Propyl 4-(3,3.dimethyl)-phenyl 613.  Propyl 4-(2-dimethyl fluorenyl group 0 to bite_1·yl)-phenyl 614.  Propyl 4-((S)-2-dimethylmethyl ° pirate-1-yl) phenyl 615.  Propyl 4-((R)-2-dimethylmethyl 11 piroxicam-1 yl) phenyl 616.  Propyl 4-(3-difluoro^methyl σ pyrrolidine-1-yl)-phenyl 617.  Propyl 4-((S)-3_ bis-methyl 0 洛洛-l-yl)-phenyl 618.  Propyl 4-((R)-3-dimethylmethyl 0-Butyl-1-yl)-phenyl 619.  Propyl 4_(2-flank based on phenyl 17 1-1 yl)-phenyl 620.  Propyl 4-(2-o-oxy-oxazolidine-3-yl)-phenyl 621.  Propyl 4-(Brigade sigma-1 -yl)-phenyl 622.  Propyl 4-(2·methyl bunge-1-yl)-phenyl 623.  Propyl 4-((S)-2-methylpyridin-1-yl)-phenyl 624.  Propyl 4-((R)_2-methylpiperidinyl)-phenyl 625.  Propyl 4·(嗓嗓-l-yl)·phenyl 119387. Doc •62- 200808727 No. R1 Ar 626.  Propyl 4-(4-methyl brace σ Qin_1_yl)-phenyl 627.  Propyl 4-(morphin-4-yl)-phenyl 628.  Propyl 4·(thiomorphin-4-yl)-phenyl 629.  Propyl 4-(1_sideoxy-thiomorphin-4-yl)-phenyl 630.  Propyl 4-(1,1-di-l-milyl-thio- phenanthryl-4-yl)-phenyl 631.  Propyl 4 decapyr-1-yl)-phenyl 632.  Propyl 4 1,4-pyr-2-yl)-phenyl 633.  Propyl 4 deca-but-3-yl)-phenyl 634.  Propyl 4-(1-methylindol-2-yl)-phenyl 635.  Propyl 4-(1-methylindole-3-yl)-phenyl 636.  Propyl 4_(indol-2-yl)-phenyl 637.  Propyl 4-(indol-3-yl)-phenyl 638.  Propyl 4-(嗟-phen-2-yl)-phenyl 639.  Propyl 4-(thiophen-3-yl)-phenyl 640.  Propyl 4-(5-propylthiophene-2-yl)-phenyl 641.  Propyl 4 decazzozolyl)-phenyl 642.  Propyl 4-(π-p--3-yl)-phenyl 643.  Propyl 4-(° ratio ol-4-yl)-phenyl 644.  Propyl 4-(1-methyl-1Η-σΛσ坐-4-yl)-phenyl 645.  Propyl 4-(1-ethyl-sial-4-yl)-phenyl 646.  Propyl 4-(1-mercapto-1H-indazol-5-yl)-phenyl 647.  Propyl 4-(1Η-imidazol-2-yl)-phenyl 648.  Propyl 4-(imidon-1-yl)-phenyl 649.  Propyl 4-(1-mercaptoimidazole-2-yl)-phenyl 650.  Propyl 4-(oxazol-2-yl)-phenyl 651.  Propyl 4-(disindolyl-4-yl)-phenyl 652.  Propyl 4-(oxazol-5-yl)-phenyl 653.  Propyl 4-(isoxazol-3-yl)-phenyl 654.  Propyl 4-(iso-oxo. sit-4-yl)-phenyl 655.  Propyl 4-(isoxazole-5-yl)-phenyl 656.  Propyl 4_([1,2,3]-triazole small)-phenyl 657.  Propyl 4-([1,2,4]-triazol-1-yl)-phenyl 658.  Propyl 4-([1,2,3]·triazol-2-yl)-phenyl 119387. Doc -63- 200808727 No. R1 Ar 659.  Propyl 4-(4Η-[1,2,4]-triazol-3-yl)phenyl 660.  Propyl 4-([1,2,4]·triazol-4-yl)-phenyl 661.  Propyl 4-(2fan [1,2,3]-triazol-4-yl)-phenyl 662.  Propyl 4-(4-methyl-4H-[1,2,4]-triazol-3-yl)-phenyl 663.  Propyl 4-(2-methyl-2Η·[1,2,3]-triazol-4-yl)-phenyl 664.  Propyl 4-([1,3,4]-oxo 2 ° sit-2-yl)-phenyl 665.  Propyl 4-([1,2,4]-° dioxin-3-yl)-phenyl 666.  Propyl 4-([1,2,4]-oxadiazol-5-yl)-phenyl 667.  Propyl 4-([1,2,3]-0 oxazet-4-yl)-phenyl 668.  Propyl 4-([1,2,3]_°Ectophen-5-yl)-phenyl 669.  Propyl 4-([1,2,3]-thiadiazol-4-yl)-phenyl 670.  Propyl 4-(1Η-tetrazol-5-yl)-phenyl 671.  Propyl 4-(tetrazol-1-yl)-phenyl 672.  Propyl 4-(2-methyl-2Η-tetrazol-5-yl)-phenyl 673.  Propyl 4-(1-methyl-1H-tetrazol-5-yl)-phenyl 674.  Propyl 4-bito-3-yl-phenyl 675.  Propyl 4-(acridin-2-yl)-phenyl 676.  Propyl 4-G-pyridin-3-yl)-phenyl 677.  Propyl 4 decapyridin-4-yl)-phenyl 678.  Propyl 4-(pyrimidin-2-yl)-phenyl 679.  Propyl 4-(Naxid-4-yl)-phenyl 680.  Propyl 々-(mouth 唆-纟-based 丨-phenyl 681.  Propyl 5-isopropylthiophen-2-yl 682.  Propyl 2-chlorothiophen-5-yl 683.  Propyl 2,5-dioxythiophen-4-yl 684.  Propyl 2,3-dioxythiophen-5-yl 685.  Propyl 2-gas-3·Shishiki porphin-5-yl 686.  Propyl 2-(phenyl-phenyl)-σ-sept-5-yl 687.  Propyl 2-(ϋ比°定_2-cesecen-5-yl 688.  Propyl 2-(5-(trifluoromethyl)isoxazole·3·yl)-thiophen-5-yl 689.  Propyl 2-(2-methylthiazol-4-yl)-thiophen-5-yl 690.  Propyl 1-mercapto-1H-imidazol-4-yl 691.  Propyl 1,2-dimethyl-1H-imidazol-4-yl 119387. Doc -64- 200808727 No. R1 Ar 692.  Propyl 3,5-dimercaptooxazol-4-yl 693.  Propyl thiazol-2-yl 694.  Propyl 4-methylthiazol-2-yl 695.  Propyl 4-isopropyl hydrazine. Sitting-2-base 696.  Propyl 4-trifluoromethylthiazol-2-yl 697.  Propyl 5-mercaptothiazol-2-yl 698.  Propyl 5-isopropyl. Plug. Sitting -2-base 699.  Propyl 5-trifluoromethylthiazol-2-yl 700.  Propyl 2,4-dimethylthiazol-5-yl 701.  Propyl 2-acetamido-4-methylthiazole-5-yl 702.  Propyl 4H-[1,2,4]triazole-3. 703.  Propyl 5-methyl-4H-[1,2,4]triazol-3-yl 704.  Propyl 4-methyl-4H-[1,2,4]triazol-3-yl 705.  Propyl 5-isopropyl-4H-[1,2,4]triazol-3-yl 706.  Propyl 5-trifluoromethyl-4H-[1,2,4]triazol-3-yl 707.  Propyl 4,5-dimethyl-4H-[1,2,4]triazol-3-yl 708.  Propyl 5·isopropyl-4-methyl-4H-[1,2,4]triazole_3_yl 709.  Propyl 5-trifluoromethyl-4-methyl·4Η-[1,2,4]triazol-3-yl 710.  Propyl [1,3,4]thiadiazol-2-yl 711.  Propyl 5-methyl-[1,3,4]thiadiazol-2-yl 712.  Propyl 5-isopropyl-[1,3,4]thiadiazole-2. 713.  Propyl 5 · trifluoromethyl _ [1, 3, 4] thiadiazole winter base 714.  Propyl 715.  Propyl 2-(4-morphinyl)-π ratio σ--5-yl 716.  Propyl 2-stactyl base 0 ratio. Ding-5-based 717.  Propyl (2-isopropyl)-sneeze-5-yl 718.  Propyl (5-isopropyl)-03⁄411 定-2-yl 719.  Propyl 8-喧琳基 720.  Propyl 5-isoquinolinyl 721.  Propyl 2-(trifluoroethenyl)-1,2,3,4_tetrahydroisoquinolin-7-yl 722.  Propyl 5-chloro-3-methylbenzoquinone 11 cephen-2-yl 723.  Propyl 3,4-dihydro-4-methyl·2Η·benzoquinone [b][l,4]oxazinyl 724.  Propyl benzoquinone sits on a -6-base 119387. Doc -65- 200808727 No. R1 Ar 725.  Propyl benzoquinone [2,1,3]oxadiazol-4-yl 726.  Propyl 5-chlorophenylhydrazone p,l,3]oxadiazole bucket base 727.  Propyl 7-chlorophenylhydrazone [2,1,3]oxadiazole bucket base 728.  Propyl benzoquinone [2,1,3]thiadiazole-4-yl 729.  Propyl 6-chloroimidazolium p,l-b]thiazolyl 730.  3-apropyl propyl 4-methylphenyl 731.  3-fluoropropyl 4-ethylphenyl 732.  3- propyl propyl 4-propyl phenyl 733.  3-fluoropropyl 4-isopropylphenyl 734.  3-fluoropropyl 4-t-butylphenyl 735.  3-fluoropropyl 4-isobutylphenyl 736.  3-fluoropropyl 4-(1,1-dimethylpropyl)-phenyl 737.  3-apropyl propyl 4-vinylphenyl 738.  3-_Fluoropropyl 4-isopropenylphenyl 739.  3-fluoropropyl 4-fluorophenyl 740.  3-fluoropropyl 4-chlorophenyl 741.  3-fluoropropyl 4-bromophenyl 742.  3-fluoropropyl 4-(fluoromethyl)phenyl 743.  3-fluoropropyl 3-(fluoromethyl)phenyl 744.  3-fluoropropyl 2-(fluoromethyl)phenyl 745.  3-fluoropropyl 4-(difluoromethyl)phenyl 746.  3-D-propyl 3-(difluoroindolyl)phenyl 747.  3-fluoropropyl 2-(difluoromethyl)phenyl 748.  3-fluoropropyl 4_(trifluoromethyl)phenyl 749.  3-apropyl propyl 3-(trifluoromethyl)phenyl 750.  3-apropyl propyl 2-(trifluoromethyl)phenyl 751.  3-fluoropropyl 4·(1-fluoroethyl)-phenyl 752.  3-D-propyl 4-((s)-i-fluoroethyl)-phenyl 753.  3-fluoropropyl 4-((R)-l-fluoroethyl)-phenyl 754.  3-fluoropropyl 4-(2-fluoroethyl)-phenyl 755.  3-fluoropropyl 4-(1,1-difluoroethyl)-phenyl 756.  3-fluoropropyl 4-(2,2·difluoroethyl)-phenyl 757.  3-fluoropropyl 4-(2,2,2-trifluoroethyl)-phenyl 119387. Doc -66- 200808727 No. R1 Ar 758.  3-fluoropropyl 4-(3-dunyl)-phenyl 759.  3-fluoropropyl 4-(2-propyl)-phenyl 760.  3-fluoropropyl 4-((S)-2.fluoropropyl)-phenyl 761.  3-apropyl propyl 4-((R)-2- propyl)-phenyl 762.  3-fluoropropyl 4-(3,3-di-propyl)-phenyl 763.  3- propyl propyl 4-(3,3,3-dipropylpropyl)-phenyl 764.  3-apropyl propyl 4-(1-fluororl-methylethyl)-phenyl 765.  3-apropylpropyl 4-(2-fluoro-1-indenylethyl)-phenyl 766.  3-apropyl propyl 4-((S)-2- gas-1 -methylethyl)-phenyl 767.  Propyl 4-((R)-2.fluoro-1 -methylethyl)-phenyl 768.  3-fluoropropyl 4-(2,2-diox-1-methylethyl)-phenyl 769.  3-fluoropropyl 4-((S)-2,2-difluorosuccinylethyl)-phenyl 770.  3- propyl propyl 4-((R)-2,2-difluoro-1-methylethyl)-phenyl 771.  3-fluoropropyl 4-(2,2,2-difluoro-1-methylethyl)-phenyl 772.  3-1 propyl 4-((S)-2,2,2·trifluoro/4-methylethyl)-phenyl 773.  3-fluoropropyl 4-((R)-2,2,2-trifluoromethyleneethyl)-phenyl 774.  3- Said propyl 4-(2-fluoro-1-fluoromethylethyl)-phenyl 775.  3- propyl propyl 4_(1-difluoromethyl-2,2-difluoroethyl)-phenyl 776.  3- propyl propyl 4-(1,1-dimethyl-2_lethyl) phenyl 777.  3-fluoro*propyl 4-methoxyphenyl 778.  3-fluoro*propyl 4-ethoxyphenyl·779.  3-1 propyl 4-propoxyphenyl 780.  3-|1 propyl 4-isopropoxyphenyl 781.  3-fluoropropyl 4-butoxyphenyl 782.  3-1 propyl methoxy)-phenyl 783.  3- propyl propyl 4-(difluorodecyloxy)-phenyl 784.  3-apropylpropyl 4-(trifluoromethoxy)-phenyl 785.  3-fluoro*propyl 3-(trifluoromethoxy)-phenyl 786.  3- propyl propyl 4-(2fluoroethoxy)-phenyl 787.  3-fluoropropyl 4-(2,2-difluoroethoxy)-phenyl 788.  3-fluoropropyl 4-(2,2,2-trifluoroethoxy)-phenyl 789.  3-fluoropropyl 4-(1,1,2,2-tetrafluoroethoxy)-phenyl 790.  3-fluoropropyl 4-cyclopropylphenyl 119387. Doc -67- 200808727 No. R1 Ar 791.  3-fluoropropyl 4-cyclobutylphenyl 792.  3-fluoropropyl 4-cyclopentylphenyl 793.  3-fluoropropyl 4-(2,2-difluorocyclopropyl)-phenyl 794.  3-vapor propyl 3,4-difluorophenyl 795.  3-fluoropropyl 4-Desc-3-phenylphenyl 796.  3-fluoropropyl 4-bromo-2-fluorophenyl 797.  3-fluoropropyl 4-> odor-2,5-difluorophenyl 798.  3-fluoropropyl 2-fluoro-4-isopropylphenyl 799.  3-fluoropropyl 3-vapor-4-isopropylphenyl 800.  3-fluoropropyl 4-(1-yl-1-methylethyl)-phenyl 801.  3-fluoropropyl 4-(2-3⁄4yl-2-methylpropyl)-phenyl 802.  3-fluoropropyl 4-ethenylphenyl 803.  3-fluoropropyl 4-carboxyphenyl 804.  3-fluoropropyl 4-cyanophenyl 805.  3-fluoropropyl 4-hydroxyphenyl 806.  3-fluoropropyl 4-(0-benzyl)-phenyl 807.  3-fluoropropyl 4_(2-methoxyethoxy)-phenyl 808.  3-fluoropropyl 4-(CH2-N(CH3)2)-phenyl 809.  3-fluoropropyl 4-(NH-CO-NH2)-phenyl 810.  3-fluoropropyl 4-(methylthio)-phenyl 811.  3-fluoropropyl 4-(fluoromethylsulfanyl)-phenyl 812, 3-fluoropropyl 4-(dimethylthio)phenyl 813.  3-apropyl propyl 4-(trifluoromethylthio)-phenyl 814.  3- propyl propyl 4-(methylsulfonyl)-phenyl 815.  3-fluoropropyl 4-(N-methoxy-N-methyl-amino)-phenyl 816.  3-apropylpropyl 4-(methoxyamino)-phenyl 817.  3-fluoropropyl 4-(ethoxyamino)-phenyl 818.  3-fluoropropyl 4_(N-methylaminooxy)-phenyl 819.  3-fluoropropyl 4-(N,N-dimethylaminooxy)-phenyl 820.  3-fluoropropyl 4-(σ丫丁丁-1-yl)-phenyl 821.  3-fluoropropyl 4-(2-methylazetidin-1-yl)-phenyl 822.  3-Fluoropropyl 4-((S)-2-methylindole-1-yl)-phenyl 823.  3-fluoropropyl 4-((R)-2-methylazetidin-1-yl)-phenyl 119387. Doc -68- 200808727 No. R1 Ar 824.  3-apropyl propyl 4-(3-fluoroazetidine small) phenyl 825.  3-fluoropropyl 4-(3-decyloxybutyridin-1-yl)-phenyl 826.  3-fluoropropyl 4-(3-3⁄4-based succinyl-1-yl)-phenyl 827.  3-fluoropropyl-1-yl)-phenyl 828.  3-Fluoropropyl 4-(deuteroline-2-yl)·phenyl 829.  3-fluoropropyl 4-((S)-indolyl-2-yl)-phenyl 830.  3-fluoropropyl 4_((R)j than pyridin-2-yl)-phenyl 831.  3-vapor propyl 4-7-pyridyl-3-yl)-phenyl 832.  3-fluoropropyl 4-((8)-113 than fluoren-3-yl)-phenyl 833.  3-Failyl 4-((R)-indolyl-3-yl)-phenyl 834.  3-fluoropropyl 4-(2-qi σ phloate-1-yl)-phenyl 835.  3-Fluoropropyl 4-((S)_2-gas 0-Butyl-1-yl)-phenyl 836.  3-fluoropropyl 4-((R)-2-port ratio 洛口定-1-yl)-phenyl 837.  3-fluoropropyl 4_(3_gas 11 than slightly fluoren-1-yl)-phenyl 838.  3-Fluoropropyl 4-((S)-3-murine-Butyl-1-yl)-phenyl 839.  3- propyl propyl 4-((R)-3-fluoropyrrolidin-1_yl)phenyl 840.  3-fluoropropyl 4-(2,2·二吼吼洛洛定_1_1)-phenyl 841.  3-lactic propyl 4-(3,3-difluoropyridinium small group)-phenyl 842.  3-fluoropropyl 4-(2,methyl-p-butlo-but-1-yl)-phenyl 843.  3-fluoropropyl belovin-1-yl)phenyl 844.  3-_Fluoropropyl 4-((R)-2-methylindolyl-1-yl)-phenyl 845.  3-fluoropropyl 4-(3-methyl.pyrrolidine 4=yl)-phenyl 846.  3-fluoropropyl 4-((S)-3-methylindole 嘻σ定-1-yl)-phenyl 847.  3-fluoropropyl 4-((R)-3-methyl^bihasidine-1-yl)-phenyl 848.  3-apropyl propyl 4-(1-methyl σ-habit-2-yl)-phenyl 849.  3-fluoropropyl 4-((S)-l-methylpyrrolidin-2-yl)-phenyl 850.  3-apropyl propyl 4-((R)-l-methyltonolidine-2-yl)-phenyl 851.  3-Fluoropropyl 4-(1-methyl-portage than hakatidine-3-yl)-phenyl 852.  3-_Fluoropropyl 4-((S) small methyl tolyl-3-yl)-phenyl 853.  3-Denyl 4-((R)-l-methyl 0 to each of the -3 -yl)-phenyl 854.  3- propyl propyl 4-(2,2-dimethyl-port-specific -1-yl)-phenyl 855.  3-fluoropropyl 4-(3,3-dimethyl-7piroxidin-1-yl)-phenyl 856.  3-fluoropropyl 4-(2-trifluoromethyloxaridin-1-yl)-phenyl 119387. Doc -69- 200808727 No. R1 Ar 857.  3-fluoropropyl 4_((S)-2-dimethylmethyl π pirin-1-yl)-phenyl 858.  3-fluoropropyl 4-((R)-2-disorganomethyl ° pirodiazin-1-yl)-phenyl 859.  3-fluoropropyl 4-(3_dioxanyl)pyrazine-1-yl)-phenyl 860.  3-fluoropropyl 4-((S)-3-dimethylmethyl σ piroxime-1-yl)-phenyl 861.  3-Fluoropropyl 4-((R)-3_ bis-methyl-3-pyran-1-yl)-phenyl 862.  3-fluoropropyl 4-(2-salt-based σ 比 洛 σ _1 _1 _ yl) phenyl 863.  3-fluoropropyl 4-(2-sialyl-indenyl 11 sigma-3-yl)-phenyl 864.  3-fluoropropyl 4·(派17定-1 -yl)-phenyl 865.  3-fluoropropyl 4-(2-methyl sigma-1,yl)-phenyl 866.  3-fluoropropyl 4-((S)-2-methylbenzazepine·1-yl)-phenyl 867.  3-fluoropropyl 4-((R)-2-methyl ϋ -1--1-yl)-phenyl 868.  3-fluoropropyl 4-(indiyl-1-yl)-phenyl 869.  3-fluoropropyl 4-(4-indolyl-yl-l-yl)-phenyl 870.  3-fluoropropyl 4-(morpholin-4-yl)-phenyl 871.  3-fluoropropyl 4-(thio-indol-4-yl)-phenyl 872.  3-apropyl propyl 4-(1-y-lactyl-thio-indol-4-yl)-phenyl 873.  3-fluoropropyl 4-(1,1-di-oxy-thio- methionin-4-yl)-phenyl 874.  3-apropyl propyl 4-(σpyr-1-yl)-phenyl 875.  3-fluoropropyl 4-(debido-2-yl)-phenyl 876.  3-fluoropropyl 4 decapyr-3-yl)-phenyl 877.  3-fluoropropyl 4-(1-methylindol-2-yl)-phenyl 878.  3-fluoropropylmethylpyrrole = 3 = base) = phenyl 879.  3-D-propyl 4-(bung-2-yl)-phenyl 880.  3-fluoropropyl 4-(bung-3-yl)-phenyl 881.  3-fluoropropyl 4 Decet-2-yl)-phenyl 882.  3-apropylpropyl 4-(thiophen-3-yl)-phenyl 883.  3-_Fluoropropyl 4-(5-propyl sigma succinyl-2-yl) phenyl ^ 884.  3-fluoropropyl 4-(.Bizozol-1-yl)-phenyl 885.  3-fluoropropyl 4 decabazole-3-yl)-phenyl 886.  3-fluoropropyl 4 decathiazole-4·yl)-phenyl 887.  3-fluoropropyl 4-(1-methyl-1 Η-carbazole·4-yl)-phenyl 888.  3-fluoropropyl 4-(1-ethyl-1Η-pyrazol-4-yl)-phenyl 889.  3-fluoropropyl 4-(1-methyl-lH-α-biazole-5-yl)-phenyl 119387. Doc -70- 200808727 No. R1 Ar 890.  3-fluoropropyl 4-(1Η-imidazol-2-yl)-phenyl 891.  3-fluoropropyl 4-(imidazol-1-yl)-phenyl 892.  3-fluoropropyl 4-(1-methylimidazol-2-yl)-phenyl 893.  Propyl 4-(°oxan-2-yl)-phenyl 894.  3-vapor propyl 4-(° 恶 0 sit-4-yl)·phenyl 895.  3-apropyl propyl 4-(oxazol-5-yl)-phenyl 896.  3-fluoropropyl 4-(isoindole oxime-3-yl)-phenyl 897.  3-apropyl propyl 4-(isoxazol-4-yl)-phenyl 898.  3-fluoropropyl 4-(isoyl)-phenyl 899.  3-fluoropropyl 4-([1,2,3]-diin-1-yl)-phenyl 900.  3-fluoropropyl 4-([1,2,4]-triazol-1-yl)phenyl 901.  3-apropylpropyl 4-([1,2,3]-dioxa-2-yl)-phenyl 902.  3-apropylpropyl 4-(4H-[l,2,4]-triazol-3-yl)-phenyl 903.  3-1 propyl 4-([1,2,4]-triazole-4.yl)-phenyl 904.  3-murlypropyl 4-(2Η-[1,2,3]-triazol-4-yl)-phenyl 905.  3-fluoropropyl 4-(4-methyl-4H-[1,2,4]-triazol-3-yl)-phenyl 906.  3-fluoropropyl 4-(2-methyl_2H-[1,2,3]-triazol-4-yl)-phenyl 907.  3-ILpropyl 4-([ 1,3,4]· oxadihydro-2-yl)-phenyl 908.  3-fluoropropyl 4-([1,2,4]-oxadiazol-3-yl)-phenyl 909.  3-fluoropropyl 4-([1,2,4]-oxadiazol-5-yl)-phenyl 910.  3-apropylpropyl 4-([1,2,3]-oxadiazol-4-yl)-phenyl 911.  Propyl 4-([1,2,3]-°carbazy-5-yl)-phenyl 912.  3-Actylpropyl 4-([1,2,3]-thiadiazol-4-yl)-phenyl 913.  Propyl 4-(1Η-tetrazol-5-yl)-phenyl 914.  3-apropyl propyl 4-(tetrazole small) phenyl group 915.  3-ILpropyl 4-(2-methyl-2H-tetrazol-5-yl)phenyl 916.  3-fluoropropyl 4-(1-methyl-1H-tetrazol-5-yl)-phenyl 917.  3-apropyl propyl 4-indol-3-yl-phenyl 918.  3-fluoropropyl 4-7-but-2-yl)-phenyl 919.  3- propyl propyl 4-(0-indol-3-yl)-phenyl 920.  3-fluoropropyl 4-(ntba-1,4-yl)-phenyl 921.  3-apropylpropyl 4-(pyrimidin-2-yl)-phenyl 922.  3-fluoropropyl 4-(indole-4)-phenyl 119387. Doc -71 · 200808727 No. R1 Ar 923.  3-vapor propyl 4-(mouth 唆-5-yl)·phenyl 924.  3-fluoropropyl 5-isopropyl σ-cephen-2-yl 925.  3-fluoropropyl 2-chloro 11 ceto-5-yl 926.  3-fluoro*propyl 2,5-dichloroσsept-4-yl 927.  3-fluoropropyl 2,3-dioxythiophen-5-yl 928.  Propyl 2-chloro-3-decyl σ-secend-5-yl 929.  3-mercaptopropyl 2-(phenyl continuation)-porphin-5-yl 930.  3-fluoropropyl - 卜比咬^-基塞塞^-基 931.  3-Actylpropyl 2-(5-(trifluoromethyl)isoxazol-3-yl)-thiophen-5-yl 932.  Propyl 2-(2-methylthiazol-4-yl)-thiophen-5-yl 933.  3-fluoropropyl 1·methyl-1H-imidazole-4. 934.  3-fluoropropyl 1,2-dimercapto-1H-imidazole-4. 935.  3-vapor propyl 3,5-dimethylisoxazole-4-yl 936.  3_fluoropropyl thiazol-2-yl 937.  3_ propyl propyl 4-methylthiazole-2 yl.  3-fluoropropyl 4-isopropyl 0 stopper 0 sitting-2-yl 939.  3-fluoropropyl 4-trifluoromethylthiazol-2-yl 940.  3-fluoropropyl 5-methylthiazol-2-yl 941.  3-fluoropropyl 5-isopropyl hydrazine. Sitting -2-base 942.  3-Air propyl 5-trifluoromethylthiazol-2-yl 943.  3-fluoropropyl 2,4-dimethylthiazole·5· base 944.  3-Actylpropyl 2-acetamido-4-mercaptothiazol-5-yl 945.  3-1 propyl 4Η-[1,2,4]triazol-3-yl 946.  3_Fluoropropyl 5-indenyl·4Η-[1,2,4]triazol-3-yl 947.  3-fluoropropyl 4-indolyl-4Η-[1,2,4]triazol-3-yl 948.  3-isopropylpropyl 5-isopropyl-4Η-[1,2,4]triazole-3-yl 949.  3- propyl propyl 5-trifluoromethyl-4 fluorene-[1,2,4]triazole _3_yl 950.  Propyl 4,5-dimethyl·4Η-[1,2,4]triazol-3-yl 951.  3-fluoropropyl 5-isopropyl-4-indolyl·4Η-[1,2,4]triazol-3-yl 952.  3-fluoropropyl 5-trifluoromethyl-4-methyl-4Η-[1,2,4]triazol-3-yl 953.  3-failyl [1,3,4]thiadiazol-2-yl 954.  3-fluoropropyl 5-indolyl-[1,3,4]thiadiazol-2-yl 955.  3-fluoro*propyl 5-isopropyl-[1,3,4]thiadiazole-2-yl 119387. Doc -72- 200808727 No. R1 Ar 956.  3-D-propyl 5-trifluoromethyl-[1,3,4]thiadiazole_2-yl 957.  3-fluoropropyl 3 - > odorous 2 - chloro π ratio bite - 5 - yl.  3-Meryl 2-(4-?4 woody)-σΛσ定-5-yl 959.  3-meryl 2-benzene-based sigma ratio bite 5-base 960.  3-fluoropropyl (2-isopropyl)- 唆-5-yl 961.  3_Vinylpropyl (5-isopropyl)-ϋ密唆-2-yl 962.  3--propyl propyl 8-hydrazine 963.  3-fluoropropyl 5-isoquinolinyl 964.  3-lactylpropyl 2·(trifluoroethenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl 965.  3-fluoropropyl 5-chloro-3-mercaptobenzophen-2-yl 966.  3-fluoropropyl 3,4-dihydro-4.methyl-2-indole-benzoquinone [b][l,4]oxazinyl 967.  3-fluoropropyl benzoquinone-6-yl 968.  3- propyl phenyl hydrazine P, l, 3] oxadiazole ice base 969.  3-fluoropropyl 5_ gas benzoquinone [2,1,3] ° dioxin 0 -4- group 970.  3-fluoropropyl 7-chlorophenylhydrazone p,l,3]oxadiazole bucket base 971.  3-fluoropropyl benzoquinone [2,1,3]thiadiazole-4-yl 972.  3- propyl propyl 6-chloroimidazolium p, l-b] thiazolyl 973.  2-fluoroethyl 4-methylphenyl 974.  2-fluoroethyl 4·ethylphenyl 975.  2-fluoroethyl 4-propylphenyl 976.  2-gas ethyl 4-isopropylphenyl 977.  2-fluoroethyl 4-t-butylphenyl 978.  2-fluoroethyl 4-isobutylphenyl 979.  2-fluoroethyl 4-(1,1-dimethylpropyl)-phenyl 980.  2_fluoroethyl 4-vinylphenyl 981.  2-fluoroethyl 4-isopropenylphenyl 982.  2-fluoroethyl 4-fluorophenyl 983.  2-fluoroethyl 4-chlorophenyl 984.  2-fluoroethyl 4- Desert Phenyl 985.  2-fluoroethyl 4-(fluoromethyl)phenyl 986.  2_fluoroethyl 3-(fluoroindolyl)phenyl 987.  2-nonethyl 2-(fluoromethyl)phenyl 988.  2-fluoroethyl 4-(difluoromethyl)phenyl 119387. Doc -73- 200808727 No. R1 Ar 989.  2-oxoethyl 3-(difluoromethyl)phenyl 990.  2-Denyl 2-(difluoroindolyl)phenyl 991.  2-Denyl 4_(trifluoromethyl)phenyl 992.  2-gasethyl 3_(trifluoromethyl)phenyl 993.  2-Denyl 2-(trifluoromethyl)phenyl 994.  2-Denyl 4-(1-ethylethyl)-phenyl 995.  2-fluoroethyl 4-((S)-1 -fluoroethyl)-phenyl 996.  2-fluoroethyl 4-((R)-1 -fluoroethyl)-phenyl 997.  2-fluoro*ethyl 4-(2-fluoroethyl)-phenyl 998.  2-fluoroethyl 4-(1,1-dioxaethyl)-phenyl 999.  2-fluoroethyl 4-(2,2-difluoroethyl)-phenyl 1000.  2-fluoroethyl 4-(2,2,2-trifluoroethyl)-phenyl 1001.  2-fluoroethyl 4-(3-fluoropropyl)-phenyl 1002.  2-fluoroethyl 4-(2-fluoropropyl)-phenyl 1003.  2-fluoroethyl 4 - ((S) - 2 - 1 propyl) - phenyl 1004.  2-fluoroethyl 4-((R)-2-fluoropropyl)-phenyl 1005.  2-gasethyl 4-(3,3-difluoropropyl)-phenyl 1006.  2-Denyl 4-(3,3,3-trifluoropropyl)-phenyl 1007.  2_fluoroethyl 4-(1-fluoro-1-indenylethyl)-phenyl 1008.  2-fluoroethyl 4-(2·fluoro-1-methylethyl)-phenyl 1009.  2-fluoroethyl 4-((S)-2-气-1-methylethyl)-phenyl 1010.  2-fluoroethyl 4-((R)-2_fluoromethylethyl)-phenyl 1011.  2-fluoroethyl 4-(2,2-difluoro-1-indenylethyl)-phenyl 1012.  2-fluoroethyl 4-((S)-2,2-dioxa·1-methylethyl)-phenyl 1013.  2-fluoroethyl 4-((R)-2,2-difluoro-1-methylethyl)-phenyl 1014.  2-fluoroethyl 4·(2,2,2-trifluoro-1-methylethyl)-phenyl 1015.  2-gasethyl 4-((S)-2,2,2-tris-l-methylethyl)-phenyl 1016.  2-fluoroethyl 4-((R)-2,2,2·trifluoro-1-methylethyl)-phenyl 1017.  2-fluoroethyl 4-(2-fluoro-1-fluoromethylethyl)-phenyl 1018.  2-fluoroethyl 4-(1-difluoromethyl-2,2-difluoroethyl)-phenyl 1019.  2-fluoroethyl 4-(1,1·dimethyl-2-fluoroethyl)-phenyl 1020.  2-fluoroethyl 4-methoxyphenyl 1021.  2-fluoroethyl 4-ethoxyphenyl 119387. Doc -74- 200808727 No. R1 Ar 1022.  2_fluoroethyl 4-propoxyphenyl 1023.  2-fluoroethyl 4-isopropoxyphenyl 1024.  2-gas ethyl 4-butoxyphenyl 1025.  2-decyl ethyl 4-(fluoromethoxy)-phenyl 1026.  2-fluoroethyl 4-(difluoromethoxy)-phenyl 1027.  2-fluoroethyl 4-(tri-1methoxy)-phenyl 1028.  2-Denyl 3-(trifluoromethoxy)-phenyl 1029.  2-fluoroethyl 4-(2-fluoroethoxy)-phenyl 1030.  2-fluoroethyl 4-(2,2-difluoroethoxy)-phenyl 1031.  2-fluoroethyl 4-(2,2,2-trifluoroethoxy)-phenyl 1032.  2-fluoroethyl 4-(1,1,2,2-tetrafluoroethoxy)-phenyl 1033.  2-fluoroethyl 4-cyclopropylphenyl 1034.  2-fluoroethyl 4-cyclobutylphenyl 1035.  2-fluoroethyl 4-cyclopentylphenyl 1036.  2-1 ethyl 4-(2,2-difluorocyclopropyl)-phenyl 1037.  2-fluoroethyl 3,4-difluorophenyl 1038.  2-fluoroethyl 4-wet,-3-fluorophenyl 1039.  2-fluoroethyl 4-diethyl-2-fluorophenyl 1040.  2-fluoroethyl 4-> odor-2,5-difluorophenyl 1041.  2-decyl ethyl 2-random 4-isopropylphenyl 1042.  2-fluoroethyl 3-vapor-4-isopropylphenyl 1043.  2-fluoroethyl 4-(1-carbo-1-methylethyl)-phenyl 1044.  2-fluoroethyl 4-(2-hydroxy-2-methylpropyl)-phenyl 1045.  2-fluoroethyl 4-ethenylphenyl 1046.  2-fluoroethyl 4-repoylphenyl 1047.  2_fluoroethyl 4-cyanophenyl 1048.  2-gas ethyl 4-hydroxyphenyl 1049.  2-1 ethyl 4-(0-benzyl)-phenyl 1050.  2-oxoethyl 4-(2-methoxyethoxy)-phenyl 1051.  2-fluoroethyl 4-(CHrN(CH3)2)-phenyl 1052.  2-fluoroethyl 4-(NH-CO-NH2)-phenyl 1053.  2-fluoroethyl 4-(methylthio)-phenyl 1054.  2-fluoroethyl 4-(fluoromethylthio)-phenyl 119387. Doc -75- 200808727 No. R1 Ar 1055.  2-decyl ethyl 4-(di-methylthio)-phenyl 1056.  2-fluoroethyl 4-(trifluoromethylsulfanyl)-phenyl 1057.  2-fluoroethyl 4-(methylsulfonyl)-phenyl 1058.  2-fluoroethyl 4-(N-methoxy-N-methyl-amino)-phenyl 1059.  2-form ethyl 4-(methoxyamino)-phenyl 1060.  2-fluoroethyl 4-(ethoxyamino)-phenyl 1061.  2-Denyl 4-(N-methylaminooxy)-phenyl 1062.  2-fluoroethyl 4-(N,N-dimethylaminooxy)-phenyl 1063.  2-fluoroethyl 4-(0-butan-l-yl)-phenyl 1064.  2-fluoroethyl 4-(2-methylazetidine σ-decyl-1-yl)-phenyl 1065.  2-oxoethyl 4-((S)-2-methylazetidine-l-yl)phenyl 1066.  2-fluoroethyl 4-((R)-2-methylindole-1-yl)-phenyl 1067.  2-Denyl 4-(3-gaspinidine-1-yl)-phenyl 1068.  2-fluoroethyl 4-(3-methyllacyl succinyl-1-yl)-phenyl 1069.  2-fluoroethyl 4-(3-radio- 11-butyl succinyl-1-yl)-phenyl 1070.  2-gasethyl 4-(σ 洛 咬 -1 -yl)-phenyl 1071.  2-gasethyl 4-(σ ratio butyl-2-yl)-phenyl 1072.  2-gasethyl 4-((8)-σΛ^σ定-2-yl)·phenyl 1073.  2-oxoethyl 4-((R)-indolyl-2-yl)-phenyl 1074.  2-fluoroethyl 4-(11-Butyl-3-yl)-phenyl 1075.  2-fluoroethyl 4-((S)-npyrrolidin-3-yl)-phenyl 1076.  2-fluoroethyl 4-((R> fluoren-3-yl)-phenyl 1077.  2-gasethyl 4-(2-gas π 洛 咬-1-yl)-phenyl 1078.  2_Fluoroethyl 4-((S)-2-gas 11-pyridin-1-yl)-phenyl 1079.  2-Vethyl ethyl 4-((R)-2- gas ϋ 洛 淀 -1--1-yl)-phenyl 1080.  2-fluoroethyl 4-(3-gas 11 piroxicam-1-yl)phenyl 1081.  2-fluoroethyl 4-((S)-3-chaopyridine-1-yl)phenyl 1082.  2· defeat ethyl 4-((R)-3_qi 0 than butyl-1-yl)-phenyl 1083.  2-fluoroethyl 4-(2,2-dipyridin-1-yl)-phenyl 1084.  2-fluoroethyl 4_(3,3-difluoropyridinium-1-yl)phenyl 1085.  2-fluoroethyl 4-(2-methyl 11 piroxicam-1-yl)-phenyl 1086.  2-fluoroethyl 4-((S)-2-methylpyrrolidin-1-yl)-phenyl 1087.  2-fluoroethyl 4-((R)-2-methyloxaridinyl)-phenyl 119387. Doc •76- 200808727 No. R1 Ar 1088.  2-fluoroethyl 4-(3-methylpyrrolidin-1-yl)-phenyl 1089.  2-fluoroethyl 4-((S)-3-methyloxaridin-1-yl)-phenyl 1090.  2_Fluoroethyl 4-((R)-3-methylindolebiol 0-1,4-yl)-phenyl 1091.  2-fluoroethyl 4-(1-methyl 11-pyridin-2-yl)-phenyl 1092.  2-Denyl 4-((S)_l-methyllahydroidin-2-yl)-phenyl 1093.  2-fluoroethyl 4-((R)-l-methyl σ dine-2-yl)-phenyl 1094.  2-fluoroethyl 4-(1-methylindolobi alpha-3-yl)-phenyl 1095.  2-fluoroethyl 4_((S) benzhydrazin-3-yl)-phenyl 1096.  2-fluoroethyl 4-((R)-l-indenyl^pyrazine-3-yl)-phenyl 1097.  2-fluoroethyl 4-(2,2-dimethyl.bilo 0-1,4-yl)·phenyl 1098.  2-Denyl 4·(3,3-dimethylpyrrolidin-1-yl)-phenyl 1099.  2-fluoroethyl 4-(2·trifluoromethyloxaridin-1-yl)-phenyl 1100.  2-Denyl 4-((S)-2-dimethylmethyl^bilosin-1-yl)-phenyl 1101.  2-fluoroethyl 4-((R)-2-dimethylmethyl. Bilo.-1 -yl)-phenyl 1102.  2-fluoroethyl 4-(3-disindolylmethylpyrrolidine-1-yl)-phenyl 1103.  2-fluoroethyl 4-((S)_3_bis-methylmethylbipyridin-1-yl)-phenyl 1104.  2-Denylethyl 4_((R)-3-di-methylenemethyl 0-Butyl-1-yl)-phenyl 1105.  2-oxoethyl 4-(2-sialyl-based ntb-lorium-1-yl)-phenyl 1106.  2-aeroethyl 4-(2-sialyl- σ oxazeto-3-yl)-phenyl 1107.  2-fluoroethyl 4-(pyrene-1-yl)-phenyl 1108.  2-oxoethyl 4-(2-methylpiperidin-1-yl)-phenyl 1109.  2-fluoroethyl 4-((S)-2-fluorenylindole-1-yl)-phenyl 1110.  2-fluoroethyl 4-((R)-2-mercaptopiperidine-1-yl)-phenyl 1111.  2-fluoroethyl 4-(indol-1-yl)-phenyl 1112.  2-fluoroethyl 4-(4-indolyl-1-yl)-phenyl 1113.  2-fluoroethyl 4·(morpholin-4-yl)-phenyl 1114.  2-fluoroethyl 4-(thio-indol-4-yl)-phenyl 1115.  2-1 ethyl 4-(1-o-oxy-thiomorpholin-4-yl)-phenyl 1116.  2-oxoethyl 4-(1,1-di-oxy-thiomorpholino)-phenyl 1117.  2-fluoroethyl 4-(11-pyr-1-yl)phenyl 1118.  2-Denyl 4 Tetrapyr-2-yl)-phenyl 1119.  2-fluoroethyl 4 1,4-pyrrol-3-yl)-phenyl 1120.  2-fluoroethyl 4-(1-methylindol-2-yl)-phenyl 119387. Doc -77- 200808727 No. R1 Ar 1121.  2-fluoroethyl 4-(1-methylu-bi-l-yl)-phenyl 1122.  2-fluoroethyl 4-(bung-2-yl)-phenyl 1123.  2-fluoroethyl 4-(mouthmana-3-yl)-phenyl 1124.  2-fluoroethyl 4-(decenophen-2-yl)-phenyl 1125.  2-fluoroethyl 4-(σsecen-3-yl)-phenyl 1126.  2-fluoroethyl 4-(5-propylthiophen-2-yl)-phenyl 1127.  2-Denethyl 4 decazol-1-yl)-phenyl 1128.  2-fluoroethyl 4-(p than oxa-3-yl)-phenyl 1129.  2-Denyl 4 decapyrazol-4-yl)-phenyl 1130.  2-fluoroethyl 4-(1-methyl-lH-u-p--4-yl)-phenyl 1131.  2-oxoethyl 4-(1-ethyl-1H-pyrazole-4.yl)-phenyl 1132.  2-fluoroethyl 4-(1-methyl-1H-s--5-yl)-phenyl 1133.  2-fluoroethyl 4-(1Η-imidazol-2-yl)-phenyl 1134.  2-fluoroethyl 4-(imidazol-1-yl)-phenyl 1135.  2-fluoroethyl 4-(1-methylimidazolyl-2-yl)-phenyl 1136.  2_fluoroethyl 4-(oxo-2-yl)-phenyl 1137.  2-fluoroethyl 4-(oxazol-4-yl)-phenyl 1138.  2-fluoroethyl ‘-(. 唾 纟 纟-纟-yl 丨-phenyl 1139.  2-fluoroethyl 4-(isoxazol-3-yl)-phenyl 1140.  2-oxoethyl 4-(isoxazol-4-yl)-phenyl 1141.  2-Denyl 4-(iso 17 oxo sitting -5-yl)-phenyl 1142.  2-fluoroethyl 4-([152,3]-二° sit-1_yl)-phenyl 1143.  2-fluoroethyl 4·([1,2,4]-triazol-1-yl)-phenyl 1144.  2-fluoroethyl 4-([1,2,3]-triazol-2-yl)-phenyl 1145.  2-fluoroethyl 4-(4Η·[1,2,4]-triazol-3-yl)-phenyl 1146.  2-fluoroethyl 4-([1,2,4]-triazol-4-yl)-phenyl 1147.  2-fluoroethyl 4-(2Η-[1,2,3]-triazol-4-yl)-phenyl 1148.  2-fluoroethyl 4-(4-methyl-4Η-[1,2,4]·triazol-3-yl)-phenyl 1149.  2-fluoroethyl 4-(2-methyl-2Η-[1,2,3]-triazol-4-yl)-phenyl 1150.  2-fluoroethyl 4-([1,3,4]-oxadiazol-2-yl)-phenyl 1151.  2-fluoroethyl 4-([1,2,4]oxadiazol-3-yl)-phenyl 1152.  2-fluoroethyl 4-([1,2,4]-oxadiazole _5_yl)-phenyl 1153.  2-Denyl 4-([1,2,3]-oxadiazol-4-yl)phenyl 119387. Doc -78- 200808727 No. R1 Ar 1154.  2-fluoroethyl 4-([1,2,3]-oxadiazol-5-yl)phenyl 1155.  2-fluoroethyl 4-([1,2,3]-11-disindolyl-1-yl)-phenyl 1156.  2-oxoethyl 4-(1Η-tetrazol-5-yl)-phenyl 1157.  2-like ethyl 4-(tetradecyl-1 -yl)-phenyl 1158.  2-1 ethyl 4-(2-methyl-2H-tetrazol-5-yl)·phenyl 1159.  2-Nexyl 4-(1-methyl-1H.tetrazol-5-yl)-phenyl 1160.  2-air ethyl 4-furazan-3-yl-phenyl 1161.  2-decylethyl 唆-2-yl)-phenyl 1162.  2-fluoroethyl 4-7-pyridin-3-yl)-phenyl 1163.  2-fluoroethyl 4 1,4-pyridin-4-yl)-phenyl 1164.  2-fluoroethyl 4-(hypo-2-yl)-phenyl 1165.  2-fluoroethyl 4-(° 唆-4-yl)_phenyl 1166.  2-fluoroethyl 4-(tongshen-5-yl)-phenyl 1167.  2-fluoroethyl 5-isopropyl σ cephen-2-yl 1168.  2-Oxyl 2-Chloro 1® thiophene-5-yl 1169.  2-gasethyl 2,5-dichloroπ-cephen-4-yl 1170.  2-1 ethyl 2,3-dioxaphen-5-yl 1171.  2-fluoroethyl 2-chloro-3-decyl thiophene-5-yl 1172.  2-Nexyl 2-(phenyl fluorescein)-π-cephen-5-yl 1173.  2-fluoro^ethyl. -Bubi唆-^-基丨嗟---- 1174.  2-deethyl 2-(5-(trifluoromethyl)isoxazol-3-yl)-thiophen-5-yl 1175.  2-fluoroethyl 2-(2-methylthiazol-4-yl)-thiophen-5-yl 1176.  2-fluoroethyl 1·indolyl-1Η-imidazol-4-yl 1177.  2-fluoroethyl 1,2-dimercapto-1H-imidazole-4-yl 1178.  2-1 ethyl 3,5-dimercaptoisoxazole-4-yl 1179.  2-fluoroethyl hydrazine.圭-2-基 1180.  2-fluoroethyl 4-methylthiazol-2-yl 1181.  2-gasethyl 4-isopropylthiazol-2-yl 1182.  2-fluoroethyl 4·trifluoromethylthiazol-2-yl 1183.  2-fluoroethyl 5-methylthiazol-2-yl 1184.  2-decyl ethyl 5-isopropyl hydrazine. Sitting-2-base 1185.  2-fluoroethyl 5-trifluoromethylthiazol-2-yl 1186.  2-fluoroethyl 2,4-dimercaptothiazol-5-yl 119387. Doc •79- 200808727 No. R1 Ar 1187.  2-form ethyl 2-acetamido-4-methylthiazole-5-yl 1188.  2-gasethyl 4H-[1,2,4]triazol-3-yl 1189.  2-fluoroethyl 5-methyl-4H-[1,2,4]triazol-3-yl 1190.  2-fluoroethyl 4-mercapto-4H-[1,2,4]triazol-3-yl 1191.  2-Gasylethyl 5_isopropyl-4H-[1,2,4]triazol-3-yl 1192.  2-fluoroethyl 5-trifluoromethyl-4H-[1,2,4]triazol-3-yl 1193.  2-fluoroethyl 4,5-dimethyl-4H-[1,2,4]triazol-3-yl 1194.  2-fluoroethyl 5-isopropyl-4-methyl-4H-[1,2,4]triazol-3-yl 1195.  2-Gethyl ethyl 5-trifluoromethyl-4-methyl-4H-[1,2,4]triazole _3·yl 1196.  2-fluoroethyl [1,3,4]thiadiazol-2-yl 1197.  2-like ethyl 5-methyl-[1,3,4]thiadiazol-2-yl 1198.  2-Denyl 5-isopropyl-[1,3,4]thiadiazole-2-yl 1199.  2-Denyl 5-trifluoromethyl-[1,3,4]thiadiazol-2-yl 1200.  2-fluoroethyl 1201.  2-Fluoroethyl 2-(4_么吓基基)-17!^11定-5-基 1202.  2-fluoroethyl 2-benzene lactylpyrazine 唆-5-ylation 1203.  2-fluoroethyl (2-isopropyl)-mouth bite-5-based 1204.  2-fluoroethyl (5-isopropyl)-pyrimidin-2-yl 1205.  2-fluoroethyl 8-indolyl 1206.  2-fluoroethyl 5-isoindolyl 1207.  2-fluoroethyl 2-(dihydroethylene)-1,2,3,4-tetrazolium isoindole-7-yl 1208.  2-fluoroethyl 5-gas-3-methylphenylhydrazine. Cephen-2-yl 1209.  2-fluoroethyl 3,4-dihydro-4_methyl-2-indole-benzoquinone [b] [ 1,4]oxazinyl 1210.  2·fluoroethyl benzoquinone 17 sitting-6-based 1211.  2_fluoroethyl benzoquinone [2,1,3]oxadiazole bucket base 1212.  2-fluoroethyl 5-chlorophenylhydrazone [2,1,3]oxadiazole winter base 1213.  2-fluoroethyl 7-chlorophenylhydrazone [2,1,3]oxadiazole bucket base 1214.  2-fluoroethyl benzoquinone [2,1,3]thiadiazole-4-yl 1215.  2-fluoroethyl 6-chloroimidazolium [2,l-b]thiazolyl 1216.  Cyclopropylmethyl 4-methylphenyl 1217.  Cyclopropylmethyl 4-ethylphenyl 1218.  Cyclopropylmethyl 4-propylphenyl 1219.  Cyclopropyl decyl 4-isopropylphenyl 119387. Doc -80- 200808727 No. R1 Ar 1220.  Cyclopropylmethyl 4-t-butylphenyl 1221.  Cyclopropylmethyl 4-isobutylphenyl 1222.  Cyclopropylmethyl 4-(1,1-dimethylpropyl)-phenyl 1223.  Cyclopropylmethyl 4-ethylphenyl phenyl 1224.  Cyclopropylmethyl 4-isopropenylphenyl 1225.  Cyclopropylmethyl 4-fluorophenyl 1226.  Cyclopropylmethyl 4-chlorophenyl 1227.  Cyclopropylmethyl 4-diphenyl 1228.  Cyclopropylmethyl 4-(fluoroindolyl)phenyl 1229.  Cyclopropylmethyl 3-(fluoromethyl)phenyl 1230.  Cyclopropylmethyl 2-(fluoroindolyl)phenyl 1231.  Cyclopropylmethyl 4-(difluoromethyl)phenyl 1232.  Cyclopropylmethyl 3-(difluoromethyl)phenyl 1233.  Cyclopropyl decyl 2-(difluoromethyl)phenyl 1234.  Cyclopropylmethyl 4-(trifluoromethyl)phenyl 1235.  Cyclopropylmethyl 3-(trifluoromethyl)phenyl 1236.  Cyclopropylmethyl 2-(trifluoromethyl)phenyl 1237.  Cyclopropylmethyl 4_(1_fluoroethyl)-phenyl 1238.  Cyclopropylmethyl 4-((S)-l-fluoroethyl)-phenyl 1239.  Cyclopropylmethyl 4-((R)-fluoroethyl)-phenyl 1240.  Cyclopropylmethyl 4-(2-fluoroethyl)-phenyl 1241.  Cyclopropylmethyl 4-(1,1-difluoro(ethyl)-phenyl 1242.  Cyclopropylmethyl 4-(2,2·difluoroethyl)-phenyl 1243.  Cyclopropylmethyl 4-(2,2,2-trifluoroethyl)-phenyl 1244.  Cyclopropylmethyl 4-(3-fluoropropyl)-phenyl 1245.  Cyclopropylmethyl 4-(2-fluoropropyl)-phenyl 1246.  Cyclopropylmethyl 4-((S)-2·1propyl)phenyl 1247.  Cyclopropylmethyl 4-((R)-2·1propyl)-phenyl 1248.  Cyclopropylmethyl 4-(3,3-difluoropropyl)-phenyl 1249.  Cyclopropylmethyl 4-(3,3,3·trifluoropropyl)-phenyl 1250.  Cyclopropylmethyl 4-(1-fluoro-1-methylethyl)-phenyl 1251.  Cyclopropylmethyl 4·(2·fluoro-1-indolylethyl)-phenyl 1252.  Cyclopropylmethyl 4-((S)-2-fluorosodiummethylethyl)-phenyl 119387. Doc -81 - 200808727 No. 1253.  1254.  1255.  1256.  1257.  1258.  1259.  1260.  1261.  1262.  1263.  1264.  1265.  1266.  1267.  1268.  1269.  1270.  1271.  1272.  1273.  1274· 1275.  1276.  1277.  1278.  1279.  1280.  1281.  1282.  1283· 1284.  1285.  R1 cyclopropylmethylcyclopropyl decylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropyl decylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropyl Cyclopropylmethylcyclopropyl decylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropyl hydrazine Cyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylnonylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethylcyclopropylmethyl I propyl Methyl propyl methyl

Ar 4-((R)-2- gas-1-mercaptoethyl V stupid 4-(2,2-difluorosuccinylethyl)-phenyl 4-((S)_2,2_2 Fluorine·1 -methylethyl)-phenyl 4-(()-2,2-difluoro_1-methylethyl-dish 4-(2,2,2-trifluoro_1-methyl Ethyl)_stupid 4-((8)_2,2,2-trifluoro-1-indolylethyl)-etc. 4-((R)-2,2,2_trifluoro_1·A 4-ethyl(2-fluoro-1·fluoromethylethyl)phenyl__ 4-(1-difluoromethyl-2,2-diyl)-dimethyl fluoride Base)-styl 4-methoxyphenyl 4-ethoxyphenyl 4-propoxyphenyl 4-isopropoxyphenyl 4-butoxyphenyl 4-(fluoromethoxy)- Phenyl 4-(difluoromethoxy)-phenyl 4-(trifluoromethoxy) phenyl 3-(trifluoromethoxy)phenyl 4-(2,2-difluoroethoxy) - stupid base (252,2_~trifluoroethoxy)-benzene^ 4-cyclopropylphenyl 4-cyclobutylphenyl p,2-difluorocyclopropyl)-phenyl 3,4- Di-cyclopentyl 4-cyclopentylphenylcyclopropylmethylcyclopropylmethyl

Tufeng-2-fluorophenyldifluorophenylpropylphenylpropylphenyl 119387.doc -82 - 200808727 No. R1 Ar 1286. Cyclopropylmethyl 4-(1-pyridyl-1-indenyl) ))-phenyl 1287. Cyclopropylmethyl 4-(2-3⁄4-yl-2-methyl^propyl)-phenyl 1288. Cyclopropylmethyl 4-ethinylphenyl 1289. Cyclopropyl Mercapto 4-carboxyphenyl 1290. Cyclopropylmethyl 4-cyanophenyl 1291. Cyclopropylmethyl 4-hydroxyphenyl 1292. Cyclopropyl decyl 4-(0-benzyl)-benzene Base 1293. Cyclopropylmethyl 4-(2-decyloxyethoxy)-phenyl 1294. Cyclopropyl decyl 4-(CHrN(CH3)2)-phenyl 1295. Cyclopropylmethyl 4 -(NH-CO-NH2)-phenyl 1296. Cyclopropyl decyl 4-(methylthio)-phenyl 1297. Cyclopropyl decyl 4-(fluoromethylthio)-phenyl 1298. Cyclopropylmethyl 4-(difluoromethylsulfanyl)-phenyl 1299. Cyclopropyl decyl 4-(difluoromethylsulfanyl)-phenyl 1300. Cyclopropylmethyl 4-(methyl Sulfomethyl)-phenyl 1301. Cyclopropyl decyl 4-(N-methoxy-N-methyl-amino)-phenyl 1302. Cyclopropyl decyl 4-(methoxyamino) -phenyl 1303. cyclopropylmethyl 4_(ethoxyamino)-phenyl 1304. cyclopropylmethyl 4-( N-methylaminooxy)-phenyl 1305. Cyclopropylmethyl 4-(anthracene, dimethylaminooxy)-phenyl 1306. Cyclopropyl decyl 4- (ϋ丫丁定-1-yl)-phenyl 1307. Cyclopropylmethyl 4-(2-methyloxetidine.-1-yl)-phenyl 1308. Cyclopropylmethyl 4-(〇2- Methyl 丫 唆 唆 -1-yl) phenyl 1309. Cyclopropylmethyl 4-((R)-2-methylindole decyl-1-yl)-phenyl 1310. Cyclopropyl Methyl 4-(3-fluoropyristin-1-decyl-1-phenyl)-phenyl 1311. Cyclopropyldecyl 4-(3-decyloxypyridinium-1-yl)phenyl 1312. Cyclopropylmethyl 4-(3-pyridinium-1-yl)-phenyl 1313. Cyclopropylmethyl 4-(0-pyridin-1-yl)-phenyl 1314. Cyclopropyl Methyl 4-(.pyrrolidin-2-yl)phenyl 1315. Cyclopropylmethyl 4-((S)-indolyl-2-yl)-phenyl 1316. Cyclopropylmethyl' -((R)-11Bilo-2-yl)-phenyl 1317. Cyclopropylmethyl 4 decyl-3-yl)-phenyl 1318. Cyclopropylmethyl 4-((S )-n-Bile-3-yl)-phenyl 119387.doc -83 - 200808727 No. R1 Ar 1319. Cyclopropylmethylpyrrolidine-3-yl)-phenyl 1320. Cyclopropyl fluorenyl 4-(2-gas σ Ploat-1-yl)-phenyl 1 321. Cyclopropylmethyl 4-((S)_2-gas 0 bisoxazolidine-1-yl)-phenyl 1322. Cyclopropylmethyl 4-(())-2- gas 0 洛洛 bite -1-yl)-phenyl 1323. Cyclopropylmethyl 4-(3-indolyl-1-yl)-phenyl 1324. Cyclopropylmethyl 4-((S)_3- disordered σ ratio Cyclopropyl-1·yl)-phenyl 1325. Cyclopropylmethyl 4-((R)-3-gaspin-bito-indole-ylindole-phenyl 1326. Cyclopropylmethyl 4-(2, 2-dione ϋ 洛 σ σ -1- -1- yl) phenyl 1327. Cyclopropylmethyl 4-(3,3-diox 0 bis-l-yl)-phenyl 1328. Cyclopropyl Methyl 4-(2-methyl 0-pyrrolidine-1-yl)-phenyl 1329. Cyclopropylmethyl 4-((8)-2-methyl 0bizorazine-1-yl) -phenyl 1330. Cyclopropylmethyl 4-((R)-2-methyloxaridin-1-yl)-phenyl 1331. Cyclopropylmethyl 4-(3-methyl 0 to ^§定-1-yl)-phenyl 1332. Cyclopropylmethyl 4-((S)-3-methyl 0-habit-1-yl)-phenyl 1333. Cyclopropylmethyl 4-( (R)-3_methylindole σ -1--1-yl)-phenyl 1334. Cyclopropylmethyl 4-(1-methyl σ pirodi-2-yl)-phenyl 1335. Propylmethyl 4-((S)-l-methyl sigma-ha-ha--12-yl)-phenyl 1336. Cyclopropylmethyl 4-((R)-1 -methyl-pyridinidine- 2-yl)-phenyl 1337. Cyclopropylmethyl 4-(1-methylindole- -3-yl)-phenyl 1338. Cyclopropylmethyl 4-((S)-l-methylpyrrolidin-3-yl ·Phenyl 1339. Cyclopropylmethyl 4-((R)-l-methyl 0bilorizin-3-yl)-phenyl 1340. Cyclopropyl fluorenyl 4-(2,2-di Methyl ϋpyrrolidin-1-yl)=phenyl 1341. Cyclopropylmethyl 4-(3,3-dimethylpyrrolidin-1-yl)-phenyl 1342. Cyclopropylmethyl 4 -(2-dimethylmethyl 11 piroxicam-1-yl)-phenyl 1343. Cyclopropylmethyl 4-((S)-2-trifluoromethylindenyl-1-yl)_ Phenyl 1344. Cyclopropylmethyl 4-((R)-2-dimethylmethylpyridyl-1-1-yl)-phenyl 1345. Cyclopropylmethyl 4-(3-dimethylmethyl) °Bilozolidine-1-yl)-phenyl 1346. Cyclopropylmethyl 4-((S)_3_trifluoroindolylpyrrolidinyl)-phenyl 1347. Cyclopropylmethyl 4- ((R)-3-Trifluoromethyl-l-rheptan-1-yl)-phenyl 1348. Cyclopropylmethyl 4-(2_ side-milk σ-pyridin-1-yl)phenyl 1349. Cyclopropylmethyl 4-(2-hydroxyl-oxazolidine-3-yl)-phenyl 1350. Cyclopropylmethyl 4·(Budden-1-yl)-phenyl 1351. Cyclopropyl Methyl 4-(2-methyl brigade. Ding-1-yl)-phenyl 119387.doc -84- 200808727 No. R1 Ar 1352. Cyclopropyl decyl 4-((S)-2-methylbendyl-1.yl)-phenyl 1353. Propyl fluorenyl 4-((R)-2-methyl succinyl-1 yl)-phenyl 1354. Cyclopropylmethyl 4-(piperazin-1-yl)-phenyl 1355. Cyclopropyl Methyl 4-(4-indolyl-purine-methyl-1-yl)-phenyl 1356. Cyclopropyl fluorenyl 4_(Merlin-4.yl)-phenyl 1357. Cyclopropyl fluorenyl 4-(sulfur吗 morpholin-4-yl)-phenyl 1358. Cyclopropyl decyl 4-(1-flavoryl-thiomorphin-4-yl)-phenyl 1359. Cyclopropylmethyl 4-( 1 , 1 -di-branched-thio- linyl 4-yl)-phenyl 1360. cyclopropylmethyl 4-(.pyr-l-yl)-phenyl 1361. cyclopropyl fluorenyl 4- (.pyrrol-2-yl)-phenyl 1362. Cyclopropylmethyl 4-(°bi-3-yl)-phenyl 1363. Cyclopropylmethyl 4-(1-methylindole- 2-yl)-phenyl 1364. Cyclopropyl decyl 4-(1-methyl 0-pyridin-3-yl)-phenyl 1365. Cyclopropyl fluorenyl 4-(bate-2-yl)- Phenyl 1366. cyclopropylmethyl 4-(bung-3-yl)-phenyl 1367. cyclopropylmethyl 4-(°cephen-2-yl)-phenyl 1368. cyclopropyl fluorenyl 4-(Thien-3-yl)-phenyl 1369. Cyclopropylmethyl 4-(5- Propyl decenophen-2-yl)-phenyl 1370. Cyclopropylmethyl 4-(indolyl-1 -yl)-phenyl 1371. Cyclopropylmethyl 4 decazol-3-yl) -phenyl 1372. Cyclopropylmethyl 4-(σ ratio -4--4-yl)-phenyl 1373. Cyclopropylmethyl 4_(umethyl-lH-nbiazole-4.yl)-benzene Base 1374. Cyclopropylmethyl 4-(1-ethyl-1Η-indole σ 圭-4-yl)-phenyl 1375. Cyclopropylmethyl 4-(1-methyl-1 Η-carbazole- 5-yl)-phenyl 1376. Cyclopropylmethyl 4-(1Η-imidazol-2-yl)-phenyl 1377. Cyclopropyl fluorenyl 4-(mouth m β-l-yl)-phenyl 1378. Cyclopropylmethyl 4-(1-methyl-n-n-yl-2-yl)-phenyl 1379. Cyclopropylmethyl 4-(oxazol-2-yl)-phenyl 1380. Cyclopropyl A 4-(oxazol-4-yl)-phenyl 1381. Cyclopropylmethyl 4-(oxazol-5-yl)-phenyl 1382. Cyclopropylmethyl 4-(isoxazole-3- ))-phenyl 1383. Cyclopropyl decyl 4-(isoxazole-4-yl)-phenyl 1384. Cyclopropylmethyl 4-(isoxazole-5-yl)-phenyl 119387.doc -85- 200808727 No. R1 Ar 1385. Cyclopropylmethyl 4-([1,2,3]-triazol-1-yl)-phenyl 1386. Cyclopropylmethyl 4-([1,2, 4]-triazol-1-yl)-phenyl 1387. Cyclopropylmethyl 4-([1,2,3 ]-二° sit-2-yl)-phenyl 1388. Cyclopropylmethyl 4-(4Η-[1,2,4]-triazole·3-yl)-phenyl 1389. Cyclopropylmethyl 4·([1,2,4]_triazol-4-yl)-phenyl 1390. Cyclopropylmethyl 4-(2Η-[1,2,3]-triazol-4-yl)-benzene 1391391. Cyclopropylmethyl 4-(4-methyl-4Η-[1,2,4]-triazole-3-yl)-phenyl 1392. Cyclopropylmethyl 4-(2-methyl-2Η [1,2,3]·Triazol-4-yl)-phenyl 1393. Cyclopropylmethyl 4-([1,3,4]-oxadiazol-2-yl)-phenyl 1394. Cyclopropylmethyl 4-([1,2,4]-oxadiazol-3-yl)-phenyl 1395. Cyclopropyl decyl 4-([1,2,4]-oxadiazol-5 -yl)-phenyl 1396. cyclopropylmethyl 4-([1,2,3]-oxadiazol-4-yl)-phenyl 1397. cyclopropylmethyl 4-([1,2, 3]-oxadiazol-5-yl)-phenyl 1398. Cyclopropylmethyl 4-([1,2,3]-thiadiazol-4-yl)-phenyl 1399. Cyclopropylmethyl 4-(1Η-tetrazol-5-yl)-phenyl 1400. Cyclopropylmethyl 4-(tetrazol-1-yl)phenyl 1401. Cyclopropylmethyl 4-(2-methyl-2Η -tetrazol-5-yl)-phenyl 1402. Cyclopropylmethyl 4-(1-methyl-1H-tetrazol-5-yl)-phenyl 1403. Cyclopropylmethyl 4-bito- 3-yl-phenyl 1404. cyclopropylmethyl 4 Bite-2-yl)-phenyl 1405. Cyclopropylmethyl 4-(σ ratio σ--3-yl)-phenyl 1406. Cyclopropylmethyl 4·(σ ϋ定-4_yl) -phenyl 1407. Cyclopropylmethyl 4-(mouth-2-yl)-phenyl 1408. Cyclopropylmethyl 4-(carno-4-yl)-phenyl 1409. Cyclopropylmethyl 4-(mouth bit-5-yl)-phenyl 1410. cyclopropylmethyl 5-isopropyl σ-cephen-2-yl 1411. cyclopropylmethyl 2-chloro sigma-5-yl 1412 Cyclopropylmethyl 2,5-diqithiophen-4-yl 1413. Cyclopropylmethyl 2,3-digas σ-cephen-5-yl 1414. Cyclopropylmethyl 2_gas-3- Nitroexephen-5-yl 1415. Cyclopropylmethyl 2-(phenylsulfonyl)-thiophen-5-yl 1416. Cyclopropylmethyl 2-(π ratio -2-yl) σ Phen-5-yl 1417. Cyclopropylmethyl 2-(5-(trifluoromethyl)isoxazol-3-yl)-thiophen-5-yl 119387.doc •86- 200808727 No. R1 Ar 1418. Ring Propylmethyl 2_(2-mercaptothiazol-4-yl)-thiophen-5-yl 1419. Cyclopropylmethyl 1-methyl-1H-imidazol-4-yl 1420. Cyclopropylmethyl 1, 2-Dimethyl-1H-imidazol-4yl 1421. Cyclopropylmethyl 3,5-dimethylisoxazole carbene 1422. Cyclopropylmethylhydrazine 11 sitting-2-yl 1423. Cyclopropyl Base 4-methylthiazol-2-yl 1424. Cyclopropylmethyl 4-isopropylthiazol-2-yl 1425. Cyclopropylmethyl 4-trifluoromethylthiazol-2-yl 1426. Cyclopropyl Methyl 5-methylindole 11 sit-2-yl 1427. cyclopropylmethyl 5-isopropylthiazol-2-yl 1428. cyclopropylmethyl 5-trifluoromethylthiazol-2-yl 1429. Cyclopropylmethyl 2,4-dimethylthiazol-5-yl 1430. Cyclopropylmethyl 2-acetamido-4-methylthiazole-5-yl 1431. Cyclopropylmethyl 4H-[ 1,2,4]triazol-3-yl 1432. Cyclopropylmethyl 5-methyl-4H-[1,2,4]triazol-3-yl 1433. Cyclopropylmethyl 4-methyl -4H-[1,2,4]triazol-3-yl 1434. Cyclopropylmethyl 5-isopropyl-4H-[1,2,4]triazol-3-yl 1435. cyclopropyl 5-Trifluoromethyl-4Η·[1,2,4]triazol-3-yl 1436. Cyclopropylmethyl 4,5-dimethyl-4-anthracene-[1,2,4]triazole- 3-yl 1437. Cyclopropylmethyl 5·isopropyl-4-methyl-4Η-[1,2,4]triazol-3-yl 1438. Cyclopropylmethyl 5-trifluoromethyl- 4-methyl-4Η-[1,2,4]triazol-3-yl 1439. Cyclopropylmethyl[1,3,4]thiadiazol-2-yl 1440. Cyclopropylmethyl 5- Methyl-[1,3,4]thiadiazol-2-yl 1441. Cyclopropylmethyl 5- Propyl-[1,3,4]thiadiazol-2-yl 1442. Cyclopropylmethyl 5-trifluoromethyl-[1,3,4]thiadiazol-2-yl 1443. Cyclopropyl Mercapto 3-bromo-2·chloroacridin-5-yl 1444. Cyclopropylmethyl 2-(4·morpholinyl)-pyridin-5-yl 1445. Cyclopropylmethyl 2- phenyl thiol 17定-5-基1446. Cyclopropylmethyl(2-isopropyl)-♦ ace-5-yl 1447. Cyclopropyl decyl (5. isopropyl)-pyrimidin-2-yl 1448. Propylmethyl 8-meronyl 1449. Cyclopropylmethyl 5-isoquinolinyl 1450. Cyclopropylmethyl 2-(trifluoroethenyl)-1,2,3,4-tetrahydroiso Quinoline-7-yl 119387.doc -87- 200808727 No. R1 Ar 1451. Cyclopropylmethyl 5-chloro-3-methylbenzoquinone-2-yl 1452. Cyclopropylmethyl 3,4-di氲-4-methyl-2H-benzoquinone [b][l,4]oxazinyl 1453. Cyclopropylmethylbenzoquinone-6-yl 1454. Cyclopropylmethylbenzoquinone [2,1, 3] oxadiazole-4.yl 1455. Cyclopropylmethyl 5-chlorophenylhydrazone [2,1,3]oxadiazole-4.yl 1456. Cyclopropylmethyl 7-gas benzoquinone [2, 1,3]oxadiazol-4-yl 1457. cyclopropylmethylphenylhydrazone [2,1,3]thiadiazole bucketyl 1458. cyclopropylmethyl 6-chloroimidazolium [2,1-7] Thiazolyl 1459 Allyl 4-methylphenyl 1460. Allyl 4-ethylphenyl 1461. Dilyl 4-propylphenyl 1462. Dilyl 4-isopropylphenyl 1463. Allyl 4 - second butyl phenyl 1464. allyl 4-isobutyl phenyl 1465. allyl 4-(1,1-dimethylpropyl)-phenyl 1466. allyl 4-vinyl benzene Base 1467. Allyl 4-isopropenylphenyl 1468. Dilyl 4-fluorophenyl 1469. Allyl 4-phenylphenyl 1470. Allyl 4-diphenyl 1471. (fluoromethyl)phenyl 1472, allyl 3-(fluoromethyl)phenyl 1473. allyl 2-(fluoromethyl)phenyl 1474. allyl 4-(difluoromethyl)phenyl 1475. Indolyl 3-(difluoromethyl)phenyl 1476. Allyl 2-(difluoromethyl)phenyl 1477. Allyl 4_(trifluoromethyl)phenyl 1478. Allyl 3 -(Trifluoromethyl)phenyl 1479. Allyl 2-(trifluoromethyl)phenyl 1480. Allyl 4_(1_fluoroethyl)-phenyl 1481. Dilyl 4-((S )-l·fluoroethyl)-phenyl 1482. allyl 4 —((R)-1-fluoroethyl)-phenyl 1483. allyl 4-(2-fluoroethyl)-phenyl 119387. Doc -88 - 200808727 No. R1 Ar 1484. Allyl 4-(1,1-two Ethyl)-phenyl 1485. Allyl 4-(2,2·difluoroethyl)-phenyl 1486. Allyl 4-(2,2,2-tridityethyl)-phenyl 1487. Allyl 4-(3-fluoropropyl)-phenyl 1488. Allyl 4-(2-fluoropropyl)-phenyl 1489. Allyl 4-((S)-2-fluoropropyl) Phenyl 1490. Allyl 4-((R)-2-fluoropropyl)-phenyl 1491. Allyl 4-(3,3-di-propyl)-phenyl 1492. Allyl 4 -(3,3,3-trifluoropropyl)-phenyl 1493. Allyl 4-(1-fluoro_1.methylethyl)-phenyl 1494. Allyl 4-(2-fluoro- 1-methylethyl)-phenyl 1495. Allyl 4-((S)-2-fluorosuccinylethyl)-phenyl 1496. Dilyl 4-((R)-2-fluoro- 1-methylethyl)-phenyl 1497. Allyl 4-(2,2-dis-l-methylethyl)-phenyl 1498. Allyl 4-((S)-2,2 -difluoro-1-methylethyl)-phenyl 1499. Dilyl 4-((R)-2,2- bis- 1 -methylethyl)phenyl 1500. Allyl 4-(2 , 2,2-trifluoro-1-methylethyl)-phenyl 1501. allyl 4-((S)-2,2,2-trifluoromethylethyl)-phenyl 1502. Propyl 4-((R)-2,2,2-trifluoro-1-methylethyl)-phenyl 1503. Allyl 4-(2-fluoro-1-fluoromethylethyl)-benzene Base 1504. Allyl 4-(1- Fluoromethyl-2,2-difluoroethyl)-phenyl 1505. Dilyl 4·(1,1-dimethyl-2-fluoroethyl)-phenyl 1506. propyl 4-methoxy Phenylphenyl 1507. Allyl 4-ethoxyphenyl 1508. Propylpropyl 4-propoxyphenyl 1509. Allyl 4-isopropoxyphenyl 1510. Allyl 4-butoxy Phenyl 1511. Allyl 4-(fluoromethoxy)-phenyl 1512. Allyl 4-(dimethoxymethoxy)-phenyl 1513. Dilyl 4-(trifluoromethoxy)- Phenyl 1514. 浠propyl 3-(trifluoromethoxy)-phenyl 1515. Dilyl 4-(2-fluoroethoxy)-phenyl 1516. Allyl 4-(2,2-di Fluoroethoxy)-phenyl 119387.doc -89- 200808727 No. R1 Ar 1517. Dilyl 4-(2,2,2-trifluoroethoxy)-phenyl 1518. Allyl 4-(1 ,1,2,2-tetrafluoroethoxy)-phenyl 1519. Allyl 4-cyclopropylphenyl 1520. Allyl 4-cyclobutylphenyl 1521. Dilyl 4-cyclopentyl Phenyl 1522. Allyl 4-(2,2-difluorocyclopropyl)-phenyl 1523. Allyl 3,4-difluorophenyl 1524. Allyl 4-oxa-3-fluorophenyl 1525. Allyl 4-bromo-2-fluorophenyl 1526. 浠propyl 4-di-2,5-difluorophenyl 1527. allyl 2- 4-isopropylphenyl 1528. Dilyl 3-fluoro-4-isopropylphenyl 1529. Allyl 4-(1-hydroxy-1-methylethyl)·phenyl 1530. 4-(2-3⁄4-yl-2-methylpropyl)-phenyl 1531. Allyl 4-ethylhydrinylphenyl 1532. Allyl 4-carboxyphenyl 1533. Allyl 4-cyano Phenyl 1534. allyl 4-hydroxyphenyl 1535. allyl 4-(0-benzyl)-phenyl 1536. allyl 4-(2-methoxyethoxy)-phenyl 1537 Allyl 4-(CHrN(CH3)2)-phenyl 1538. Allyl 4-(NH-CO-NH2)-phenyl 1539. Allyl 4-(methylthio)-phenyl 1540 Allyl 4_(fluoromethylthio)-phenyl 1541. Allyl 4-(difluoromethylsulfanyl)-phenyl 1542. Propylpropyl 4-(trifluoromethylsulfanyl)-benzene Base 1543. Dilyl 4-(methylsulfonyl)-phenyl 1544. Allyl 4-(N-methoxy-N-methyl-amino)-phenyl 1545. Allyl 4- (methoxyamino)-phenyl 1546. allyl 4-(ethoxyamino)-phenyl 1547. 浠propyl 4-(N-methylaminooxy)-phenyl 1548. Propyl 4-(N,N-dimethylaminooxy)-phenyl 1549. Allyl 4-(azetidin-1-yl)-phenyl 119387.doc -90- 20080 8727 No. R1 Ar 1550. Dilyl 4-(2-methyl-butyl succinyl-1-yl)-phenyl 1551. Allyl 4-((S)·2·methyl 丫 σ 定·1·yl)-phenyl 1552. Allyl 4_((尺)-2-methyl °丫. Ding-1-yl)·phenyl 1553. allyl 4-(3-fluoro. decyl 1 dec-1-yl)-phenyl 1554. allyl 4-(3-methoxy butyl σ定-1-yl)-phenyl 1555. Dilyl 4-(3-3⁄4 base 丫丁丁定-1·yl)-phenyl 1556. Allyl 4 decapyridin-1-yl) -phenyl 1557. allyl 4_(σ pyrrole_2-yl)-phenyl 1558. allyl 4-((S)-ntb^^-2-yl)phenyl 1559. Benzene-2-yl)-phenyl 1560. Allyl 4 decapyridin-3-yl)-phenyl 1561. Allyl 4-((8)_°Bilo-3-yl)-benzene Base 1562. Allyl '-((R)-17 is more than 嘻σding-3-yl)-phenyl 1563. Allyl 4-(2-Gaol ratio 嘻°-1-yl)-phenyl Allyl 4-((S)-2-fluoropyrrolidin-1-yl)-phenyl 1565. Allyl 4-((R)-2- gas σ 洛 σ 定 -1 -1 -yl) -Phenyl 1566. Allyl 4-(3-Bido-l-yl)-phenyl 1567. Allyl 4-((S)-3-Gas 0bi 17:-1-yl)- Phenyl 1568. Allyl 4-((R)-3-gas ϋ 洛 σ -1- -1- yl)-phenyl 1569. Dilyl 4-(2,2-digas 13 洛洛 bit-1 · yl)-phenyl 1570. allyl 4-(3,3-dimuropyrazine-1-yl)-phenyl 1571. allyl 4-(2-methylpyrrolidin-1_ Base)-phenyl Allyl 4-((S)_2-methyloxaridin-1-yl)phenyl 1573. Allyl 4-((R)-2-methylindolebine-1_yl) -Phenyl 1574. Allyl 4-(3-methylindoleridin-1-yl)-phenyl 1575. Dilyl 4_((S)-3-methyl 17 洛洛定定_1_基)-phenyl 1576. Allyl 4-((R)-3-methylpyrrolidin-1-yl)-phenyl 1577. Dilyl 4-(1-methyl-ralocidin-2-yl) -phenyl 1578. Allyl 4-((S)-l-methylpyrrolidin-2-yl)-phenyl 1579. Allyl 4_((R)-1-methyl-pyridinidine-2- Base)-phenyl 1580. Allyl 4-(1·methyl.pyrrolidin-3-yl)-phenyl 1581. Allyl 4-((S)-1 -methylpyrrolidine-3- Base)-phenyl 1582. Allyl 4-((R)-l-methyloxaridin-3-yl)-phenyl 119387.doc -91- 200808727 No. R1 Ar 1583. Dilyl 4-( 2,2-Dimethyloxaridin-1-yl)-phenyl 1584. Allyl 4-(3,3-dimethylpyrrolidin-1-yl)-phenyl 1585. Allyl 4_( 2_dimethylmethyl 0 piroxime-1-yl)phenyl 1586. allyl 4-((S)-2-dimethylmethylpyridinium-1-yl)-phenyl 1587. Propyl 4-((R)-2-trifluoromethyloxaridin-1-yl)-phenyl 1588. Dilyl 4-(3-disintegrated methyl 0 洛洛定- 1-yl)-phenyl 1589. Allyl 4-((S)-3-trifluorodecylpyrrolidin-1-yl)-phenyl 1590. 浠propyl 4-((R)-3_ Dimethylmethyl ratio 嘻σ定-1-yl)-phenyl 1591. Allyl 4-(2-flavoryl pi-pyridin-1-yl)-phenyl 1592. Allyl 4-( 2-sided oxy-oxazolidine-3-yl) phenyl 1593. allyl 4-(Big 定-1-yl)-phenyl 1594. Allyl 4-(2-methyl brigade σ Di-1-yl)-phenyl 1595. Allyl 4-((S)-2.methylpiperidin-1-yl)-phenyl 1596. Allyl 4-((R)-2-A Base σ -1- -1-yl)·phenyl 1597. Allyl 4-(11 嗓-1 -yl)-phenyl 1598. Allyl 4-(4-methyl 嘻-1-yl) -Phenyl 1599. Allyl 4-(TM)-4-phenyl)-phenyl 1600. Dilyl 4-(thiomorphin-4-yl)-phenyl 1601. Allyl 4-( 1-sided oxy-thioxoin-4-yl)-phenyl 1602. allyl 4-(1,1-di-oxy-thio-indol-4-yl)-phenyl 1603. Propyl 4-(°Pilo-1 -yl)-phenyl 1604. Dilyl 4 Tetrapyr-2-yl)-phenyl 1605. Dilyl 4 Tetrapyr-3-yl)-phenyl 1606. Dilyl 4-(1-methylindol-2-yl)-phenyl 1607. Allyl 4-(1-methylindol-3-yl)-phenyl 1608. Allyl 4-(bung-2-yl)-phenyl 1609. Dilyl 4-(furan-3-yl)-phenyl 1610. Dilyl 4-(thiophen-2-yl)-phenyl 1611. Allyl 4·(σsecen-3-yl)-phenyl 1612. Dilyl 4-(5-propylthiophen-2-yl)-phenyl 1613. Dilyl 4-tetrazole- 1-yl)-phenyl 1614. Dilyl 4 decathiazole-3.yl)·phenyl 1615. Allyl 4 decapyrazol-4-yl)·phenyl 119387.doc -92- 200808727 No. R1 Ar 1616. Propyl 4-(1-methyl-1H-indazol-4-yl)-phenyl 1617. Allyl 4-(1-ethyl-1H-indazol-4-yl)-phenyl Allyl 4-(1-methyl-lmh-s--5-yl)-phenyl 1619. 浠propyl 4-(1Η-imidazole-2-yl)-phenyl 1620. Allyl 4-( Imidazol-1-yl)-phenyl 1621. Dilyl 4-(1-methylindol-2-yl)-phenyl 1622. Allyl 4-(oxazol-2-yl)-phenyl 1623 Allyl 4-(oxazol-4-yl)-phenyl 1624. Allyl 4-(oxazol-5-yl)-phenyl 1625. Allyl 4-(iso. evil. Sodium-3-yl)-phenyl 1626. Allyl 4-(isoxazol-4-yl)-phenyl 1627. Allyl 4-(isoxazole-5-yl)-phenyl 1628. Propyl 4-([1,2,3]-dioxan-1-yl)-phenyl 1629. Allyl 4-([1,2,4]-triazole small)-phenyl 1630. Allyl 4-([1,2,3]-dioxos-2-yl)-phenyl 1631. Allyl 4-(4Η·[1,2,4]·triazol-3-yl) -phenyl 1632. allyl 4-([1,2,4]-triazol-4-yl)-phenyl 1633. Dilyl 4-(2Η-[1,2,3]-triazole-4 -yl)-phenyl 1634. allyl 4-(4-methyl-4Η-[1,2,4]·triazol-3-yl)-phenyl 1635. allyl 4·(2-A Base-2-indole-[1,2,3]-triazol-4-yl)-phenyl 1636. allyl 4-([1,3,4]-σ oxa guan-2-yl)-phenyl 1637. Allyl 4-([1,2,4]-oxadiazol-3-yl)-phenyl 1638. Allyl 4-([1,2,4]·oxadiazol-5-yl) -phenyl 1639. Allyl 4-([1,2,3]-oxadiazol-4-yl)-phenyl 1640. Allyl 4-([1,2,3]-oxadiazole- 5-yl)-phenyl 1641. Allyl 4-([1,2,3]-thiadiazol-4.yl)-phenyl 1642. Allyl 4-(1Η·tetrazol-5-yl Phenyl 1643. allyl 4-(tetradecyl-1-yl)·phenyl 1644. allyl 4-(2 -mercapto-2-indole-tetrazol-5-yl)-phenyl 1645. allyl 4-(1-methyl-1H-tetrazole-5(yl)-phenyl 1646. allyl 4-furazan -3-yl-phenyl 1647. Allyl 4-(indolyl-2-yl)-phenyl 1648. Allyl 4 decapyridin-3-yl)-phenyl 119387.doc -93- 200808727 No. R1 Ar 1649. Dilyl 4-(σ ratio bite ~4_yl)-phenyl 1650. Allyl 4-(喊σ定-2-yl)-phenyl 1651. Allyl 4·(mouth ϋ -4-yl)-phenyl 1652. Allyl 4-( σ 定 -5 -5-yl)-phenyl 1653. Allyl 5-isopropyl σ cephen-2-yl 1654. Allyl 2- 2-thiophen-5-yl 1655. Allyl 2,5-dichlorothiophen-4-yl 1656. Allyl 2,3-dioxythiophen-5-yl 1657. Allyl 2- _ 3-nitroσ-sent-5-yl 1658. Allyl 2-(phenyl-acyl)-σ-sent-5-yl 1659. Allyl 2-(σ ratio -2- thiophene -5-yl 1660. Allyl 2-(5-(trifluoromethyl)isoxazol-3-yl)-thiophen-5-yl 1661. Allyl 2-(2-methylthiazole-4- ))-thiophene-5-yl 1662. allyl 1-mercapto-1H-imidazol-4-yl 1663. allyl 1,2-dimethyl-1H-imidazol-4-yl 1664. allyl 3,5-Dimethylisoxazole bucket base 1665. Allyl Ruthenium-2-yl 1666. Allyl 4-methylthiazol-2-yl 1667. Allyl 4-isopropylthiazol-2-yl 1668. Allyl 4-trifluoromethylhydrazine- 2-yl 1669. Allyl 5-mercaptothiazol-2-yl 1670. Allyl 5-isopropylthiazol-2-yl 1671. Dilyl 5·trifluoromethylthiazol-2-yl 1672. Dilyl 2,4-dimethylthiazol-5-yl 1673. Dilyl 2-ethylaminoamino_4_mercaptopurine. Sit-5-yl 1674. Allyl 4Η-[1,2,4]triazol-3-yl 1675. Allyl 5-mercapto-4Η-[1,2,4]triazole-3_yl 1676 Allyl 4-mercapto-4Η-[1,2,4]triazol-3-yl 1677. 浠propyl 5-isopropyl-4Η·[1,2,4]triazole _3_yl 1678. Allyl 5-trifluoromethyl-4Η-[1,2,4]triazol-3-yl 1679. Dilyl 4,5-dimethyl-4-anthracene-[1,2,4]triazole -3·yl 1680. Allyl 5-isopropyl-4-methyl-4-indole-[1,2,4]triazol-3-yl 1681. Allyl 5-trifluoromethyl-4-methyl Base-4Η-[1,2,4]triazol-3-yl 119387.doc -94- 200808727 No. R1 Ar 1682. Allyl [1,3,4]thiadiazol-2-yl 1683. 5-yl-yl-[1,3,4]thiadiazole-2-yl 1684. allyl 5-isopropyl-[1,3,4]thiadiazole-2-yl 1685. 5-Trifluoromethyl-[1,3,4]thiadiazol-2-yl 1686. Allyl 3 - > odor-2-chloro^ ratio. Ding-5-yl 1687. allyl 2-(4-morpholinylindolepyridin-5-yl 1688. allyl 2-phenoxyacridin-5yl 1689. fluorenyl (2-iso) Propyl hydrazine - mouth 11 fixed -5-yl 1690. allyl (5-isopropylidene-2-yl 1691. allyl 8-mercapto 1692. allyl 5-isoquinolyl 1693. Allyl 2-(dihydroethylene)-1,2,3,4-tetrazosine-7-yl 1694. Allyl 5-chloro-3-methylbenzoquinone 0 thiophene-2 -yl 1695. allyl 3,4-dihydro-4-methyl-2-indole-benzoquinone [b][l,4]oxazinyl 1696. allylbenzothiazole-6-yl 1697. Benzoquinone [2,1,3]oxadiazol-4-yl 1698. Dilyl 5-chlorobenzoquinone p,l,3]oxadiazol-4-yl 1699. Allyl 7-chlorophenylhydrazine [2,1,3]oxadiazol-4-yl 1700. allylphenylhydrazine [2,1,3]thiadiazole-4-yl 1701. Dilylpropyl 6-chloroimidazolium [2,lb] Thiazolyl 1702. 冬 Winter (trifluoromethoxy)-phenyl 1703, Η 3_(trifluoromethoxy)-phenyl 1704. Η 4-cyanophenyl 1705. Η 4-methylphenyl 1706. Η 4-ethylphenyl 1707. Η 4-propylphenyl 1708. Η 4-methoxyphenyl 1709. Η 4-fluorophenyl 1710. Η 4-chlorophenyl 1711. Η 4- Desert phenyl 17 12. Η 3-(Trifluoromethyl)phenyl 1713. Η 4-(Trifluoromethyl)phenyl 1714. Η 2-(Trifluoromethyl)phenyl 119387.doc -95- 200808727 No. R1 Ar 1715 Η 3,4-Difluorophenyl 1716. Η 4-演-3-敦phenyl 1717. Η 4-Deep-2-Denylphenyl 1718. Η 4->Smelly-2,5-dibenzene Base 1719. Η 2-Gas-4-isopropylphenyl 1720. Η 4-Hydroxyphenyl 1721. Η 4-isopropylphenyl 1722. Η 4-Secondylphenyl 1723. Η 4-Different Butylphenyl 1724. Η 4-(1,1-dimethylpropyl)-phenyl 1725. Η 4·vinylphenyl 1726. Η 4-isopropylphenyl phenyl 1727. Η 4-(fluorine Methyl)phenyl 1728. Η 3-(fluoromethyl)phenyl 1729. Η 2-(fluoromethyl)phenyl 1730. Η 4-(difluoromethyl)phenyl 1731. Η 3-(difluoro Methyl)phenyl 1732. Η 2-(dioxamethyl)phenyl 1733. Η 4-(1-fluoroethyl)phenyl 1734. Η 4-((S)-1 -fluoroethyl)-benzene 1 1735. Η 4-((R)-l-fluoroethyl)phenyl 1736, Η 4-(2-fluoroethyl)-phenyl 1737. Η 4-(1,1-diethylethyl)- Phenyl 1738. Η 4-(2,2-difluoroethyl)-phenyl 1739. Η 4-(2,2,2-trifluoro 1 ethyl)-phenyl 1740. Η 4-(3- gas Propyl)-phenyl 1741. Η 4-(2- Propyl)-phenyl 1742. Η 4-((8)-2-fluoropropyl)-phenyl 1743. Η 4-((R)-2-fluoropropyl)-phenyl 1744. Η 4-(3, 3-difluoropropyl)-phenyl 1745. Η 4-(3,3,3-trifluoropropyl)-phenyl 1746. Η 4-(1·Fluoromethylethyl)-phenyl 1747. Η 4-(2-Fluoro-1·methylethyl)-phenyl 119387.doc -96- 200808727 No. R1 Ar 1748. Η 4-((S)-2-Gas-1 -methylethyl)- Phenyl 1749. Η 4_((R)-2-Fluoromethylethyl)-phenyl 1750. Η 4-(2,2-Dimethyl-1-methylethyl)-phenyl 1751. Η 4 -((S)-2,2-difluoro-1-methylethyl)-phenyl 1752. Η 4-((R)-2,2-dioxa-1-methylethyl)-phenyl 1753. Η 4-(2,2,2-Difluoro-1-methylethyl)-phenyl 1754. Η 4-((S)-2,2,2-Trifluoro-1-methylethyl )-Phenyl 1755. Η 4-((R)-2,2,2-Trifluoro(1-yl)ethyl)-phenyl 1756. Η 4_(2-Ann-1-fluoromethylethyl) -phenyl 1757. Η 4-(1·Difluoromethyl·2,2-difluoroethyl)-phenyl 1758. Η 4-(1,1-Dimethyl-2-1ethyl)-benzene 1 1759. Η 4-ethoxyphenyl 1760. Η 4-propoxyphenyl 1761. Η 4-isopropoxyphenyl 1762. Η 4-butoxyphenyl 1763. Η 4-(fluorocarbon Oxy)-phenyl 1764. Η 4- (Difluorodecyloxy)-phenyl 1765. Η 4-(2-Gasethoxy)-phenyl 1766. Η 4-(2,2-Bismoethoxy)-phenyl 1767. Η 4- (2,2,2-trifluoroethoxy)-phenyl 1768. Η 4-( 1,1,2,2-tetrafluoroethoxy)-phenyl 1769. Η 4-cyclopropylphenyl 1770 Η 4-cyclobutylphenyl 1771. Η 4-cyclopentylphenyl 1772. Η 4-(2,2-difluorocyclopropyl)-phenyl 1773. Η 3-fluoro-4-isopropyl Phenyl 1774. Η 4-(1-^-yl-1-methylethyl)-phenyl 1775. Η 4-(2-(yl)-2-mercaptopropyl)-phenyl 1776. Η 4-B Nonylphenyl 1777. Η 4-carboxyphenyl 1778. Η 4-(0-phenylhydrazino)-phenyl 1779. Η 4-(2-methoxyethoxy)-phenyl 1780. Η 4- (CH2-N(CH3)2)-phenyl 119387.doc -97- 200808727 No. R1 Ar 1781. Η 4-(NH-CO-NH2)-phenyl 1782. Η 4-(methylthio)-benzene 1 1783. Η 4-(fluoromethylthio)-phenyl 1784. Η 4-(difluoromethylsulfanyl)-phenyl 1785. Η 4-(trifluoromethylsulfanyl)-phenyl 1786. Η 4-(Methylsulfonyl)-phenyl 1787. Η 4-(N-Methoxy-N-methyl-amino)-phenyl 1788. Η 4-(methoxyamino)-benzene Base 1789. Η 4-(ethoxyamino)-phenyl 1790. Η 4-(N-A胺aminooxy)-phenyl 1791. Η 4-(N,N-dimethylaminooxy)-phenyl 1792. Η 4-(σ丫丁丁-1-yl)-phenyl 1793. Η 4-(2-methylbutyl. -1--1-yl)-phenyl 1794. Η 4-((S)-2-methylazetidin-1-yl)-phenyl 1795. Η 4-((R)-2-methyloxime ϋ丁定-1-yl)-phenyl 1796. Η 4-(3-Fluoro-butylidene-1-yl)-phenyl 1797. Η 4-(3-methyllate-based ^丁^-1- ))·Phenyl 1798. Η 4-(3-Phenylbutyrate-1-yl)-phenyl 1799. Η 々-(.Bilo bite-1 -yl)-phenyl 1800. Η 4- (°Bilo-2-yl)-phenyl 1801. Η 4-((S)j-pyridin-2-yl)-phenyl 1802, Η 4-((R)-吼-rhrodin-2- )) phenyl 1803. Η 4-(σ 比洛 σ-3-yl)-phenyl 1804. Η 1805. Η 4-((R)-pyrrolidin-3-yl)-phenyl 1806. Η 4-(2-gas 17 is more than -1-yl)-phenyl 1807. Η 4-((S)-2-气11 比洛 bit-1-yl)-phenyl 1808. Η 4-(( R)-2-乱11比洛 bit-1-yl)phenyl 1809. Η 4-(3-gas σ pyrrole-1-yl)-phenyl 1810. Η 4-((S)-3 · gas σ 唆 唆 唆-1-yl)-phenyl 1811. Η 4- (for)-3-gas 11 than 唆 唆-1_ yl)-phenyl 1812. Η 4- (2,2-difluoro Ethrolidin-1-yl)-phenyl 1813. Η 4-(3,3-digas 17 pirin-1-yl)-phenyl 119387.doc -98- 200808727 No. R1 Ar 1814. Η 4- (2-mercapto 11 is more than _-1-yl)-phenyl 1815. Η 4-(( S)-2-methyl σ pirin. 1,4--1-yl)-phenyl 1816. Η 4-((R)-2-methyl 0 piroxime-1-yl)-phenyl 1817. Η 4-(3-Methyl 0, pyridin-1-yl)-phenyl 1818. Η 4-((S)-3-Methyl 0, pyridin-1-yl)-phenyl 1819. Η 4-((R)-3-methyl°Pilo-1-yl)-phenyl 1820. Η 4-(1-indolylpyridin-2-yl)-phenyl 1821. Η 4-( (S) Small methyl oxaridin-2-yl)-phenyl 1822. Η 4-((R)-l-methylpyrrolidin-2-yl)-phenyl 1823. Η 4-(1-A 1717(B)-Phenyl-3-yl)-phenyl 1824. Η 4-((S)-l.methylpyrrolidin-3-yl)phenyl 1825. Η 4-((R)-l-methyl ))-phenyl 1826. Η 4-(2,2-dimethyl-pyrene-1-yl)-phenyl 1827. Η 4-(3,3-dimethyl-l-pyridin-1-yl )-phenyl 1828. Η 4-(2-dimethylmethyl 11 piroxicam-l-yl)-phenyl 1829. Η 4-((S)_2-dimethylmethyl ° piroxime-1 -yl)-phenyl 1830. Η 4-((R)_2-dimethylmethyl 0 pyrrole-1-yl)·phenyl 1831. Η 4-(3-dimethylmethyl 0 洛 咬-1-yl)-phenyl 1832. Η 4-((S)-3-dimethylmethyl^1 pir. -1-1_yl)-phenyl 1833. Η 4-((R)-3-dimethylmethyl 11 piroxime-1-yl)·phenyl 1834. Η 4-(2-flavor based)比 σ 定 -1- -1- yl) phenyl 1835. Η 4- (2-sided milk base " ^ evil 11 sitting bit-3-yl) - phenyl 1836. Η 4_ (Niandian-1_ base)- Phenyl 1837. Η 4-(2_methylbine-1,yl)-phenyl 1838. Η 4-((S)-2-Methylnidinyl-1-yl)-phenyl 1839. Η 4-((R)-2-methylpiperidinyl)-phenyl 1840. Η 4-(旅嘻-1-yl)-phenyl 1841. Η 4-(4_methyl 嘻 嘻-1- ))-phenyl 1842. Η 4-(morpholin-4-yl)-phenyl 1843. Η 4-(thiomorphin-4-yl)-phenyl 1844. Η 4-(1-sideoxy - thiomorphin-4-yl)-phenyl 1845. Η 4-(1,1-di-oxy-thiomorpholin-4-yl)-phenyl 1846. Η 4-(0 洛洛- 1-yl)-phenyl 119387.doc -99- 200808727 No. R1 Ar 1847. Η 4-(°Bilo-2·yl)-phenyl 1848. Η 4 十比咯-3-yl)-phenyl 1849 Η 4-(1-Methyl σ-pyrrol-2-yl)-phenyl 1850. Η 4-(1-methyl-port-haha-3-yl)-phenyl^ 1851. Η 4-(butter -2-yl)-phenyl 1852. Η 4-(σf-amyl-3-yl)-phenyl 1853. Η 4 decepan-2-yl)-phenyl 1854. Η 4-(thiophene-3- Base)-phenyl 1855. Η 4-(5-propyl σ-sec-2-yl)-phenyl 1856. Η 4-(° ratio 0 -1-yl)-phenyl 1857. Η 4 decazole-3-yl)- Phenyl 1858. Η 4-(ϋ ratio σ sit-4-yl)-phenyl 1859. Η 4-(1-methyl-111-11 is 11--4-yl)-phenyl 1860. Η 4- (1-ethyl-1H-port ratio 坐4-yl)-phenyl 1861. Η 4-(1-methylbenza-5-yl)-phenyl 1862. Η 4-(1Η-imidazole· 2-yl)-phenyl 1863. Η 4-(u ϋ -1-1 -yl)-phenyl 1864. Η 4-(1-methylimidazolyl-2-yl)-phenyl 1865. Η 4-( Oxazol-2-yl)-phenyl 1866. Η 4_(oxazol-4-yl)-phenyl 1867. Η 4-(oxazol-5-yl)-phenyl 1868. Η 4-(isoxazole -3-yl)-phenyl 1869. Η 4-(isoxazol-4-yl)-phenyl 1870. Η 4-(isoxazole-5-yl)-phenyl 1871. Η 4_([1, 2,3]_triazol-1-yl)-phenyl 1872. Η 4-([1,2,4]-triazol-1-yl)-phenyl 1873. Η 4-([1,2, 3]-dispan-2-yl)-phenyl 1874. Η 4-(4Η-[1,2,4]-triazol-3-yl)phenyl 1875. Η 4·([1,2,4 ]_Triazol-4-yl)-phenyl 1876. Η 4-(2Η-[1,2,3]-triazol-4-yl)-phenyl 1877. Η 4-(4-methyl-4Η- [1,2,4]-triazol-3-yl)-phenyl 1878. Η 4-(2•methyl-2Η-[1,2,3]-three 4-yl)-phenyl 1879. Η 4-([1,3,4]-oxadiazol-2-yl)-phenyl 119387.doc -100- 200808727 No. R1 Ar 1880. Η 4-([ 1,2,4]-σoxadi-3-yl)-phenyl 1881. Η 4-([1,2,4]-oxadiazol-5-yl)-phenyl 1882. Η 4-( [1,2,3]·^Evil II. -4-yl)-phenyl 1883. Η 4-([1,2,3]-σ oxadisin-5-yl)·phenyl 1884. Η 4-([1,2,3]-°二二°坐-4-yl)-phenyl 1885. Η 4-(1Η-tetrazol-5-yl)-phenyl 1886. Η 4-(tetrazol-1-yl)-phenyl 1887. Η 4 -(2_methyl-211-tetrakisin-5-yl)-phenyl 1888. Η 4-(1_methyl-1H-tetrazol-5-yl)-phenyl 1889. Η 4-furazan -3-yl-phenyl 1890. Η 4 decapyridin-2-yl)·phenyl 1891. Η 4-(σ ratio -3-yl)-phenyl 1892. Η 4 1,4-pyrimidin-4-yl )-phenyl 1893. Η σ 定 -2- -2-yl)-phenyl 1894. Η 4-(mouth σ-4-yl)-phenyl 1895. Η 4-(mouth σ--5-yl)- Phenyl 1896. Η 5-isopropyl σ cephen-2-yl 1897. Η 2-chlorothiophen-5-yl 1898. Η 2,5-di gas σ-cetin-4-yl 1899. Η 2,3 - Dioxothiophene-5-yl 1900. Η 2-Gas-3-nitrosøsin-5-yl 190L Η 2-(Phenyl acyl)-σ sept-5-yl 1902. Η -卜比唆^-基户塞滕^-基1903. Η 2-(5-(Trifluoromethyl)isoxanthyl-3-yl)-porphin-5-yl 1904. Η 2-(2-A 0 1,2-dimethyl-111-imidazol-4-yl, 嗟 1-methyl-1H-imidazol-4-yl 1906. Η 1,2-dimethyl-111-imidazol-4-yl 1907. Η 3,5-dimethyl Isoxazol-4-yl 1908. Η thiazol-2-yl 1909. Η 4-mercaptothiazol-2-yl 1910. Η 4_isopropylthiazol-2-yl 1911. Η 4-trifluoromethylthiazole -2·yl group 1912. Η 5-methylthiazol-2-yl 119387.doc -101 - 200808727 No. R1 Ar 1913. Η 5-isopropylthiazole-2·yl 1914. Η 5-trifluoromethylthiazole- 2·Base 1915. Η 2,4-Dimethylthiazol-5-yl 1916. Η 2-Ethylamino-4-methylthiazole _5-yl 1917. Η 4Η-[1,2,4]3 Zyridin-3-yl 1918. Η 5-methyl-4Η-[1,2,4]triazole_3_yl 1919. Η 4-methyl-4Η_[1,2,4]triazole·3-yl 1920 Η 5_isopropyl-4Η-[1,2,4]triazol-3-yl 1921. Η 5-trifluoromethyl-4Η-[1,2,4]triazol-3-yl 1922. Η 4,5_Dimethyl-4Η·[1,2,4]triazol-3-yl 1923. Η 5-isopropyl-4-methyl-4Η-[1,2,4]triazole-3 - group 1924. Η 5-trifluoromethyl-4-indolyl-4Η_[1,2,4]triazol-3-yl 1925. Η [1,3,4]thiadiazol-2-yl 1926. Η 5-Methyl-[1,3,4]thiadiazole-based 1927. Η 5-isopropyl-[1,3,4]thiadiazol-2-yl 1928. Η 5-trifluoromethyl -[1,3,4]thiadiazol-2-yl 1929. Η 3-> odor-2-gas 11 than bite-5-based 1930. Η 2-(4-吓► base)·σ 唆-5-based 1931. Η 2-phenoxy ° bite -5-based 1932. Η (2-isopropyl)-mouth 唆-5-yl 1933. Η (5- Isopropyl)-σ dense sigma-2-yl 1934. Η 8-喧 lyophilized 1935. Η 5-isoquinolinyl 1936. Η 2-(diqi acetyl)-1,2,3,4 _ tetraaza-wow-7-yl 1937. Η 5-chloro-3-methylphenylhydrazine σ-secen-2-yl 1938. Η 3,4-dihydro-4-methyl-2Η-benzoquinone [ b][l,4]oxazinyl 1939. 幷 benzothiazole-6-yl 1940. Η benzoquinone [2,1,3]oxadiazol-4-yl 1941. Η 5-chlorophenylhydrazine [2, 1,3]oxadiazol-4-yl 1942. Η 7-chlorobenzoquinone [2,1,3]oxadiazole bucket base 1943. Η benzoquinone [2,1,3]thiadiazole-4-yl 1944. Η 6-Chloramimidazolium [2, lb] thiazolyl. Table Bl: Compound of the formula Iu, wherein Ar has the meaning given in the column 119, 119 387. doc - 102 - 200808727. Table B-2: Compound of the formula Iv, wherein Ar has the meaning given in one of the columns of Table B. Table B-3: Compound of the formula Iw, wherein Ar has the meaning given in one of the columns of Table B. Table B-4: Compound of formula lx wherein Ar has the meaning given in one of the columns of Table B. Table B-5: Compound of the formula Iy, wherein Ar has the / meaning given in one of the columns of Table B. Table B-6: Compound of formula Iz wherein Ar has the meaning given in one of the columns of Table B.

Table B No. Ar 1945. 4-(Trifluoromethoxy)-phenyl 1946. 3-(Trifluoromethoxy)-phenyl 1947. 4-Cyanophenyl 1948. 4-Mercaptophenyl 1949. 4-ethylphenyl 1950. 4-propylphenyl 1951. 4-methoxyphenyl 1952. 4-fluorophenyl 1953. 4-chlorophenyl 1954. 4- Desert phenyl 1955. 3- (three Fluoromethyl)phenyl 1956. 4-(Trifluoromethyl)phenyl 1957. 2-(Trifluoromethyl)phenyl 1958. 3,4-Difluorophenyl 1959. 4-Moly-3-fluorobenzene Base 119387.doc -103- 200808727 No. Ar 1960. 4-Bromo-2-fluorophenyl 1961. 4-> Odor-2,5-difluorophenyl 1962. 2-Fluoro-4·isopropylphenyl 1963. 4-Phenylphenyl 1964. 4-isopropylphenyl 1965. 4-Dibutylphenyl 1966. 4-Isobutylphenyl 1967. 4·(1,1-dimethylpropyl -Phenyl 1968. 4-Ethylphenyl 1969. 4-Isopropenylphenyl 1970. 4-(fluoromethyl)phenyl 1971. 3-(fluoromethyl)phenyl 1972. 2-(Fluorine Methyl)phenyl 1973. 4-(Difluoroindolyl)phenyl 1974. 3-(Difluoromethyl)phenyl 1975. 2-(Difluoromethyl)phenyl 1976. 4-(1-Fluoroethyl Base)-phenyl 1977. 4-((S)-1 -fluoroethyl)-phenyl 1978. 4-((R)-l-Denylethyl)-phenyl 1979. 4-(2-Fluorine Base)-phenyl 1980. 4-(1,1-Difluoro*ethyl)-phenyl 1981. 4-(2,2-difluoroethyl)-phenyl 1982. 4-(2,2,2 - tris-ethyl) phenyl 1983. 4-(3-fluoropropyl)-phenyl 1984. 4-(2-fluoropropyl)-phenyl 1985. 4-((S)-2-fluoropropene Base)-phenyl 1986. 4-((R)-2-fluoropropyl)-phenyl 1987. 4-(3,3-di-propyl)-phenyl 1988. 4-(3,3,3 -Trifluoropropyl)-phenyl 1989. 4-(1-Fluoro-1-methylethyl)-phenyl 1990. 4-(2-Ga-1 *methylethyl)-phenyl 1991. 4 -((S)_2-fluoro-1-methylethyl)-phenyl 1992. 4-((R)-2-fluoro-1·methylethyl)-phenyl 119387.doc -104- 200808727 Ar 1993. 4-(2,2-Difluoro-1-methylethyl)-phenyl 1994. 4-((S)-2,2-Difluoro-1-methylethyl)phenyl 1995. 4-((R)-2,2-dioxa-1 -methylethyl)-phenyl 1996. 4·(2,2,2-difluoro_1-methylethyl)·phenyl 1997. 4-((S)-2,2,2·trifluoromethylethyl)-phenyl 1998. 4-((R)-2,2,2-trifluoro-1-methylethyl)- Phenyl 1999. 4-(2-Fluoro-1-cyclodecylethyl)-phenyl 2000. 4-(1-Difluoro^methyl-2,2-difluoroethyl)-phenyl 2001. 4 -(1,1-Dimethyl·2·ethyl)-phenyl 2002. 4-ethoxyphenyl 2003. 4-propoxy Phenyl 2004. 4-isopropoxyphenyl 2005. 4-Butoxyphenyl 2006. 4-(fluorodecyloxy)-phenyl 2007. 4-(dimethoxymethoxy)-phenyl 2008. 4-(2-decyloxy)-phenyl 2009. 4-(2,2-difluoroethoxy)-phenyl 2010. 4-(2,2,2-difluoroethoxy)-phenyl 2011. 4-(1,1,2,2-tetrafluoroethoxy)-phenyl 2012. 4-cyclopropylphenyl 2013. 4-cyclobutylphenyl 2014. 4-cyclopentylphenyl 2015 4-(2,2-Difluorocyclopropyl)-phenyl 2016. 3-Fluoro-4-isopropylphenyl 2017. 4-(1-Phenyl-1-methylethyl)-phenyl 2018. 4-(2-Hydroxy-2-methylpropyl)-phenyl 2019. 4-Ethylphenyl 2020. 4-carboxyphenyl 2021. 4-(0-Benzyl)-phenyl 2022 4-(2-methoxyethoxy)phenyl 2023. 4-(CHrN(CH3)2)-phenyl 2024. 4 - (NH-CO-NH2)-phenyl 2025. 4-(methyl Thio)-phenyl 119387.doc -105- 200808727 No. Ar 2026. 4-(Fluoromethylthio)-phenyl 2027. 4-(Difluoromethylsulfanyl)-phenyl 2028. 4_(Trifluoro Methylthio) phenyl 2029. 4-(decylsulfonyl) phenyl 2030. 4-(N-methyllacyl-N-methyl-amino)-phenyl 2031. 4_(methoxy Amino group)-phenyl 2032. 4-(ethoxyamino group -Phenyl 2033. 4-(N-Methylaminooxy)-phenyl 2034. 4-(N,N-Dimethylaminooxy)-phenyl 2035. 4-(ϋ丫丁唆-1-yl)·phenyl 2036. 4_(2_methyl^丫丁丁_1_yl)-phenyl 2037. 4-((S)_2-methyl 11 丫丁唆-1-yl)- Phenyl 2038. 4-((R)-2-methylazetidin-1 -yl)-phenyl 2039. 4-(3-Gas 丫 丫 σ -1- -1--1-yl)-phenyl 2040. 4 -(3-methyllacyl σ 丫 σ 定 -1 · · · · · 204 204 204 204 204 204 204 204 204 204 204 204 204 204 204 204 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- 4- ^17定-1-yl)-phenyl 2043. 4-(σ 鸣 · · 2-yl)-phenyl 2044. 4-((S)- 吼 吼 -2- -2- -2-yl)-phenyl 2045. 4-((乂吼^^唆-di-kibphenyl 2046. 2047. 4-((S)·吼 吼 -3-)-3-yl)-phenyl 2048. 4-((R)·吼4-(2-)-(2-)-(()-pyrene-pyridin-1-yl)-phenyl 2050. 4-((S)-2- gas^ )-Phenyl 2051. 4-((R)-2-Insulin^pyrazine-l-yl)-phenyl 2052. 4-(3-A gas 11 piroxicam-1-yl)-phenyl 2053. 4-((S)-3-Gas 0 to 嘻σ定-1-yl)-Phenyl 2054. 4-((R)-3-Gas pi-r-indole-1-yl)·Phenyl 2055 4-(2,2-dihydropyrrolidin-1-yl)-phenyl 2056. 4-(3,3-difluoro-palladium -1-yl)-phenyl 2057. 4-(2-Methyloxaridin-1-yl)-phenyl 2058. 4-((S)-2-Methyl 11-Butyl-1-yl) -Phenyl 119387.doc •106- 200808727 No. Ar 2059. 4-(() 2-2-indolylpyrazine-1-yl)-phenyl 2060. 4-(3-methylindole -1-yl)-phenyl 2061. 4-((S)-3-methylpyrrolidin-1-yl)-phenyl 2062. 4-((R)-3-methylpyrrolidin-1-yl )-Phenyl 2063. 4-(1-methyl. Biloxidin-2-yl)-phenyl 2064. 4-((S)-l-methyl-methyl oxetidine-2-yl)-phenyl 2065. 4-((R)-l-methyl 11 Birozide-2-yl)-phenyl 2066. 4-(1-decylpyrrolidin-3-yl)-phenyl 2067. 4-((S)-l-methylpyrrolidin-3- 4-(2,2-dimethylpyrene-pyridin-1-yl) 4-((R)-l-methyl-tolyl-3-yl)-phenyl 2069 )-Phenyl 2070. 4-(3,3-Dimethylpyrazole-1-yl)·Phenyl 2071. 4-(2-Dimethylmethylσpyrrolidine-l-yl)-Benzene 4-((S)-2-dimethylmethyl π pirin-1-yl)-phenyl 2073. 4-((R)-2-dimethylmethyl σ 洛 bits -1- Base) phenyl phenyl 2074. 4-(3-dimethylmethyl 0 bromo-1-yl)-phenyl 2075. 4-((S)-3_di-gas methyl σ 洛洛 bite-l- ))-phenyl 2076. 4-((R)_3-disindolylmethylpyrazine-1-yl)phenyl 2077. 4-(2-Sideoxyl phloate-1-yl)- Phenyl 2078. 4-(2-Sideoxy-oxazolidine-3-yl)-phenyl 2079. 4-(Big bit-1-yl)-phenyl 2080. 4-(2-methylpiperidine -1-yl)-phenyl 2081. 4-((S)-2-indenyl-branched-l-yl)-phenyl 2082. 4-((R)-2-methylpyridine-1- 4-)-phenyl 2083. 4-(Break-1-yl)-phenyl 2084. 4-(4-Mexyl-l-yl)-phenyl 208 5. 4-(morpholin-4-yl)-phenyl 2086. 4_(thiomorphin-4-yl)-phenyl 2087. 4·(1 · oxo-thiomorpholine-4-yl Phenyl 2088. 4·( 1,1 -di- oxy-thiomorpholin-4-yl)-phenyl 2089. 4 decyl-1-yl)-phenyl 2090. 4-(π Bis-2-yl)-phenyl 2091. 4:10-pyrrol-3-yl)-phenyl 119387.doc -107- 200808727 No. Ar 2092. 4-(1-Methyl σ-pyrrol-2-yl) -Phenyl 2093. 4-(1-Methyl σ-pyrrol-3-yl)-phenyl 2094. 4-(.f-am-2-yl)-phenyl 2095. 4-(N--3-yl) -Phenyl 2096. 4-(σ-cephen-2-yl)-phenyl 2097. 4-(Phenyl-3-yl)-phenyl 2098. 4-(5-propyl sigma-2- 4-(pyrazole-1-yl)-phenyl 2100. 4-(pyrazole-3-yl)-phenyl 2101. 4-(σ ϋ -4--4-yl)_ Phenyl 2102. 4-(1-methyl-1Η-pyrazol-4-yl)-phenyl 2103. 4-(1-Ethyl-1Η-η-pyrazol-4-yl)-phenyl 2104. 4 -(1-methyl-1H-oxazol-5-yl)-phenyl 2105. 4-(1Η-imidazole-2-yl)-phenyl 2106. 4-(imidazol-1-yl) phenyl 2107 4-(1-Mercapthylimidin-2-yl)-phenyl 2108. 4-(oxazol-2-yl)-phenyl 2109. 4-(oxazol-4-yl)-phenyl 2110. 4- (oxazol-5-yl)-phenyl 21 11. 4-(isoindole-3-yl)-phenyl 2112. 4-(isoindole-4-yl)·phenyl 2113. 4-(iso 1^ evil 11 sitting-5-yl -Phenyl 2114. 4-([1,2,3]-Diin-1-yl)-phenyl 2115. 4-([1,2,4]-Triazol-1-yl)-phenyl 2116 4-([1,2,3]-2-11--2-yl)-phenyl 2117. 4-(411-[1,2,4]-triazol-3-yl)-phenyl 2118. 4 -([1,2,4]-triazol-4-yl)-phenyl 2119. 4-(2Η-[1,2,3]-triazol-4-yl)·phenyl 2120. 4-( 4-methyl-4Η-[1,2,4]-triazol-3-yl)-phenyl 2121. 4-(2-methyl_2Η-[1,2,3]-triazole-4- 4-([1,3,4]-oxadiazol-2-yl)-phenyl 2123. 4-([1,2,4]-oxadiazol-3-yl) -Phenyl 2124. 4-([1,2,4]-oxadiazol-5-yl)-phenyl 119387.doc -108- 200808727 No. Ar 2125. 4-([1,2,3]-Evil 4-oxazol-4-yl)-phenyl 2126. 4-([1,2,3]-oxadiazol-5-yl)-phenyl 2127. 4-([1,2,3]-thiadiazole -4-yl)-phenyl 2128. 4-(1Η-tetrazol-5-yl) phenyl 2129. 4-(tetradec-1-yl)-phenyl 2130. 4-(2-methyl- 2H-tetrazol-5-yl)·phenyl 2131. 4-(1-methyl-1H-tetrazol-5-yl)-phenyl 2132. 4-Butyl-3-yl-phenyl 2133. -(^ than bite ^-based 丨-phenyl 2134. 4 decapine _3_yl)-phenyl 2135. 4 decapyridin-4-yl)-phenyl 2136. 4-(mouth-2-yl)-phenyl 2137. 4 tens of sigma 4-yl)-phenyl 2138. 4-(ρ-Bite-5-yl)-phenyl 2139. 5-isopropyl porphin-2-yl 2140. 2-A gas 11 phene-5-yl 2141 2,5-dichlorothiophen-4-yl 2142. 2,3-dioxane 11 cephen-5-yl 2143. 2- gas-3-decyl thiophene-5-yl 2144. 2-(benzene 2-sulfonyl)-thiophen-5-yl 2145. 2-(pyridin-2-yl)thiophen-5-yl 2146. 2-(5-(disorganomethyl)iso- 10--3-yl)- σ 塞 phen-5-yl 2147. 2-(2-methyl 0 嗤 嗤-4-yl)-σ cephen-5-yl 2148. 1-methyl-1 Η-imidazol-4-yl 2149. 2-Dimethyl-1Η-imidazol-4-yl 2150. 3,5-Dimethylisoxazole-4-yl 2151. Thiazol-2-yl 2152. 4-methylthiazol-2-yl 2153. 4 _isopropylthiazole-2-yl 2154. 4-trifluoromethyl-2-yl 2155. 5-methylthiazol-2-yl 2156. 5-isopropylthiazol-2-yl 2157. 5· Trifluoromethylthiazol-2-yl 119387.doc -109- 200808727 No. Ar 2158. 2,4-Dimethylthiazol-5-yl 2159. 2-Ethylamino-4-mercapto. Sodium-5-yl 2160. 4H-[1,2,4]triazol-3-yl 2161. 5-methyl-4H-[1,2,4]triazol-3-yl 2162. 4-methyl- 4H-[1,2,4]triazol-3-yl 2163. 5-isopropyl-4H-[1,2,4]triazol-3-yl 2164. 5-trifluoromethyl-4H-[ 1,2,4]triazol-3-yl 2165. 4,5-Dimethyl-4H-[1,2,4]triazol-3-yl 2166. 5-isopropyl-4-indolyl- 4H-[1,2,4]triazol-3-yl 2167. 5-trifluoromethyl-4-methyl-4H-[1,2,4]triazol-3-yl 2168. [1,3 , 4] thiadiazol-2-yl 2169. 5-methyl-[1,3,4]thiadiazol-2-yl 2170. 5-isopropyl-[1,3,4]thiadiazole_ 2_基2171. 5-Trifluoromethyl-[1,3,4]thiadiazol-2-yl 2172. 3-Han-2-gas σ ratio bite-5-yl 2173. 2-(4-?琳基)-° ratio bite-5-yl 2174. 2-Benzyl lactyl ratio bite-5-yl 2175. (2-isopropyl 2176. (5-isopropyl 2177. 8-quinolinyl) 2178. 5-Isoquinolinyl 2179. 2-(Trifluoroethenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl 2180. 5-Gas-3-methylbenzoquinone -2-yl 2181. 3,4-dihydro-4-methyl-2H·benzoquinone [b][l,4]oxazinyl 2182. Benzothiazole-6-yl 2183. Benzoquinone [2,1 , 3] oxadiazole-4·yl 2184. 5-chlorophenylhydrazine P, l, 3] oxadiazol-4-yl 2185. 7_ Chlorobenzoquinone P,l,3]oxadiazol-4-yl 2186. Benzene [2,1,3]thiadiazole-4-yl 2187. 6-azamidazolium [2,lb]thiazolyl wherein R3 Compounds of formula I wherein 111 andamp; both are hydrogen can be prepared by methods analogous to those well known in the art. For the preparation of compound I, 119 387. doc - 110 - 200808727 is preferred in Scheme 1. Overview: Process 1

In the scheme 1, R1, r2, R2a, r8, R8a, R9, and Ar have the meanings given above. PG is an amine protecting group such as a third butoxycarbonyl group or a benzyl group. Suitable protection groups are disclosed, for example, in p. Kocienski, Protecting Groups, Thieme-Verlag, Stuttgart 2000, Chapter 6. Hal is a halogen, especially bromine or chlorine. According to Scheme 1, according to standard methods for nucleophilic aromatic substitution reactions, in the presence of a base such as sodium hydride, sodium alkoxide or potassium carbonate in an organic solvent such as dimethyl decylamine, dioxane or tetrahydrofuran Compound π is reacted with amino alcohol VIII in step a) (see, for example, w〇2004/000830). Alternatively, 'Compound III can be prepared from the compound oxime and the compound VIII via a palladium catalyzed reaction described in the literature ', for example, J. Am. Chem. Soc. 2001, 123, pp. 10770-10771. An example of a suitable Pd(〇) catalyst is Pd(OAc)2, which is typically present in the presence of, for example, a ligand such as [ι,ι'] binaphthyl-2-yl-di-tert-butyl-phosphine. For example, it is used in a solvent such as toluene or hydrazine, 2-dimethoxyethane. 119387.doc -111 - 200808727 The nitro compound III thus obtained is reduced in a conventional manner in step b) to give the corresponding amino compound IV. The desired reaction conditions correspond to the customary conditions used to reduce the aromatic nitro group as detailed in the literature (see, for example,

March, Advanced Organic Chemistry, 3rd edition, J. Wiley & Sons, New-York, 1985, page 1183 and references cited therein. The reduction method is, for example, under acidic reaction conditions, that is, using nascent hydrogen or using a complex hydride such as lithium aluminum hydride or sodium borohydride, preferably such as NiCh (P(phenyl) 〇 2 or C 〇 Cl 2 In the presence of a transition metal compound of nickel or cobalt (see Ono et al., Chem. Ind. (London), 1983, p. 480)' or using NaBH2S3 (see Lalancette et al., Can J. Chem. 49, 1971, Page 2990), by reacting a nitro compound ruthenium with a metal such as iron, rhenium or tin, depending on the given reagent, it is possible to carry out such reduction in the substance or in a solvent or diluent. The reduction of (1) to IV can be carried out using hydrogen in the presence of a transition metal catalyst, for example in the presence of a catalyst which is mainly in the form of a turning, shifting, recording, hydrazine or hydrazine. The catalyst may contain an elemental form or a complex compound, a transition metal Transition metal in the form of a salt or an oxide 'In order to change the activity, it is possible to use a conventional co-ligand such as an organic phosphine compound such as triphenylphosphine, tricyclohexylphosphine or tri-n-butylphosphine or phosphite. Usually used to catalyze Metal, per mole of compound III, 0_001 moles to i moles of catalyst. In a preferred variation, 'using tin (II) chloride, a reduction method similar to that described in the following literature: Bioorganic and Medicinal Chemistry Letters, 2002, 12(15), pp. 1917-1919 and J. Med. Chem. 2002, 45(21), pp. 4679-4688. The reaction of III with vaporized tin (π) is preferably idle. 119387.doc -112- 200808727 The organic solvent is preferably carried out in an alcohol such as methanol, ethanol, isopropanol or butanol. The compound IV thus obtained is compared with the arylsulfonyl group gas Cl-S02-Ar. Preferably, in the presence of a base, the reaction is carried out according to standard procedures of the art to produce compound V. The process is carried out under the reaction conditions conventionally employed in the preparation of arylsulfonamide compounds or aryl sulfonates, for example, as described in the following literature. Reaction described in step c) of 1: J. March, Advanced Organic Chemistry, 3rd edition, John Wiley & Sons, New York, 1985, page 444 and references cited therein, European J. Org. Chem. 2002 (13), 2094 (4) 2108, Tetrahedron 2001, 57 (27), pp. 5885-5895, Bioorganic and Medicinal Chemistry Letters, 2000, 10(8), pp. 835-838 and Synthesis 2000 (1), pp. 103-10. The reaction is usually carried out in an inert solvent such as an ether such as diethyl ether, diisopropyl ether, methyl tert-butyl ether or tetrahydrofuran; a chiral hydrocarbon such as dichloromethane; an aliphatic or cycloaliphatic hydrocarbon such as pentane, Ethylene or cyclohexane; or an aromatic hydrocarbon such as toluene, xylene, cumene or the like or a mixture of the above solvents. The reaction of IV with Cl-S02-Ar is usually carried out in the presence of an auxiliary base. Properly tested as an inorganic test, such as sodium carbonate or carbonic acid or sodium bicarbonate or hydrogencarbonate 'and organic tests, such as 'three alkyl amines' such as triethylamine, or σ ratio bite compounds, such as ° ratio σ, two Methyl π ratio bite and its analogs. The latter compound can be used as a solvent at the same time. An auxiliary base which is at least a molar amount based on the amine compound IV is usually used. In step d), the protecting group PG is cleaved by conventional means (see, for example, Kocienski, Protecting Groups, Thieme-Verlag, Stuttgart 119387. doc-113-200808727 2000, Chapter 6), whereby Rla is produced Hydrogen compound work. Process 2

The synthesis of the compound of formula I is described in Scheme 2, wherein R1, Rla, Han 2, R 2a, R 8 , R 8a, R 9 , X and Ar have the meanings given above. Take 1 as _, especially bromine and gas. The reaction steps a), b) and c) are carried out in Scheme 2 according to the reaction steps a), ... and c) as described in Scheme 1. Compound II is available from commercial sources. Process 3

If R9 is an alkoxy group, Compound II can also be synthesized according to Scheme 3. According to standard methods, a salt of a commercially available compound XI with an alcohol, such as a sodium or potassium salt of methanol, ethanol or n-propanol, in which Hal is a halogen, especially bromine or a gas, is used as the corresponding alcohol in the solvent (for example Reaction in methanol, ethanol or n-propanol). The mixture of the compound II and XH thus obtained can be, for example, recrystallized by means of an autolysing agent or separated by means of chromatography to give the desired compound π. Protected amino alcohols VIII are commercially available or can be obtained according to standard methods (eg 119387.doc -114- 200808727)

Kocienski, Protecting Groups, l〇c. Sexual protection of the amine groups of these compounds is obtained from commercially available amino alcohols. The amino alcohol IX is commercially available or can be prepared by methods analogous to those well known in the art. Those skilled in the art should also understand that R3 is not hydrogen. "The complex can be obtained by selective alkylation of a sulfonamide group in a compound of formula V or I. If R1 or Rla in compound I is With allyl, the allyl group can be cleaved to obtain 4 compounds or oximes wherein R is hydrogen. For example, a catalytic amount of a (p) compound or a palladium compound capable of forming a palladium (ruthenium) compound under the reaction conditions, such as palladium dichloride, ruthenium (triphenylphosphine) palladium (0) or bis(diphenylene) In the presence of methyl palladium) dipalladium (0), advantageously with a phosphine ligand, such as a triarylphosphine such as triphenylphosphine, such as a trialkylphosphine of tributylphosphine, and such as tricyclohexylphosphine a cycloalkylphosphine' and especially a chelating ligand with a phosphine such as 2,2,-bis(diphenylphosphino)-1,1'-binaphthyl or 1,4-bis(diphenylphosphino)butane Alkane combination, using an method known from the following literature, to achieve ally by reacting I [rL allyl] with an allylic collector such as mercaptobenzoic acid or 1,3-dimethylbarbituric acid The cleavage of the base, the above document is for the elimination of N-mercaptopropyl groups in the presence of thiobenzoic acid, see WO 94/24088; for elimination in the presence of 1,3-dimethylbarbituric acid, see J. Am. Chem. Soc. 2001, 123 (28), pp. 6801-6808 and J. Org. Chem 2002, 67(11), pp. 3718-3723. Alternatively, the cleavage of the N-allyl group can also be achieved by a reaction using a method known from the following literature in the presence of a ruthenium compound such as gins(triphenylphosphine) chloroindole (I) (see J. Chem. Soc). · Perkin Transaction I: Organic and Bio-Organic Chemistry 1999 (21), pp. 3089-3104 and 119387.doc -115- 200808727

Tetrahedron Asymmetry 1997, 8(20), pp. 3387-3391). If R1 or 111& in the compound I is an allyl group, the allyl group can also be converted into a n-propyl group by hydrogenation in the presence of Pd-C as a catalyst. Unless otherwise indicated, the above described reaction is usually carried out in a solvent at a temperature between room temperature and the boiling temperature of the solvent used. Alternatively, microwaves can be used, which prove to be valuable especially in the case where the reaction is catalyzed by a transition metal, and the activation energy required for the reaction is introduced into the reaction mixture (for the reaction using microwaves, see Tetrahedron 2001, 57, 9199 ff Page, page 9225 ff. and in a general manner, ''Microwaves in Organic Synthesis'', Andre Loupy (ed.), Wiley-VCH 2002). Sulfonyl chloride Cl-S02-Ar is commercially available or can be prepared according to standard synthesis methods. The sulfonyl group-containing gas containing a fluorinated group Ra can be prepared by various synthetic routes, for example, by using a suitable hydroxy or pendant oxy group precursor (for example, a compound having a group substituted with a hydroxyl group or a pendant oxy group, Cl-S02-) Ar) with, for example, DAST (diethylaminosulfur trifluoride), morpholine-DAST, deoxy-fluoride (bis(2-methoxyethyl)aminosulfur trifluoride), Ishikawa reagent (Ishikawafs) Reagent) (N,N-diethyl(1,1,2,3,3,3-hexapropyl)amine;]〇111*11&1〇€ Fluorine Chemistry,1989, 43 371-377) The fluorinating reagent reacts. More conventionally, the hydroxyl group of an aromatic compound having a hydroxy-substituted group but not a chlorosulfonyl group is converted to a leaving group which is subsequently replaced by a fluoride ion (7). 1^·

Chem., 1994, 59, 2898-22901; Tetrahedron Letters, 1998, 7305-6; J. Org. Chem., 1998, 63, 9587-9589, Synthesis, 1987, 920-21). Subsequently, sulfonate is directly sulfonated with gas sulfonic acid 119387.doc -116- 200808727 (Heterocycles, 2001, 55, 9, 1789-1803; J. Org Chem, 2000, 65, 1399-1406) or first prepared sulfonate An acid derivative which is subsequently converted into a sulfonyl chloride by, for example, chlorosulfonic acid or phosphorus pentoxide (Eur·J. Med. Chem., 2002, 36, 809-828) and the like. The desired sulfonyl chloride is produced (Tetrahedron Letters, 1991, 33, 50 7787. 7788). The reaction of the appropriate amine precursor Ar-NH2& with sulfur dioxide in acetic acid can also be carried out by diazotizing under acidic conditions with sodium nitrite (flow) (j) Org. Chem., I960, 25, 1824-26 ;); by using a gas directly to the appropriate heteroaryl-thiol HS-Ar or heteroaryl-benzyl-thioether C6H5-CH2-S-Ar (Synthesis, 1998, 36-38; J. Am. Chem. Soc., 1950, 74, 4890-92;) Oxidation to the corresponding sulfonyl group gas to prepare sulfonyl chloride. Others are known in the art or can be prepared by standard methods. For example, a mercapto-pyrimidine or pyrimidinyl-benzyl sulfide precursor precursor can be prepared, for example, according to the following literature (Chemische Berichte, 1960, 1208-11; Chemische Berichte, 1960, 95, 230-235; Collection Czechoslow ·

Chem. Comm.. 1959. 245 1667-1671; Austr. J. Chem., 1966, 19, 2321-30; Chemiker-Zeitung, 101, 6, 1977, 305-7; Tetrahedron, 2002, 58, 887-890 Synthesis, 1983, 641-645). Those skilled in the art will readily appreciate that compounds of formula I can also be converted from functionally related compounds by structurally similar compounds. In particular, the corresponding halogen compound, i.e., a compound of formula I (which (but not Ra) has a halogen atom, especially a bromine or iodine atom), and a first or second amine, preferably in the presence of a base, may be preferred. Also in the presence of a catalyst, according to Buchwald-Hartwig, 119, 387. doc • 117, 200808727, the reaction of 'incorporating the N-bonded group Ra into a chelating compound' is shown in the following Schemes 4 to 6 There are several ways to gasify propyl benzoate to prepare hydrazine chloride. ~ Process 4: Η /=\ >=0

The 4-(1,1-difluoropropan-2-yl)benzenesulfonyl gas intermediate can be prepared from commercially available phenyl phenylpropionic acid. In the first step, the 2' phenylpropionic acid is converted to an alkyl ester by acid catalysis (e.g., Hci, S〇2Cl2) by hydration with an alcohol (e.g., methanol or ethanol). The ester can be transported to the corresponding 2-phenylpropyl disk by a reducing agent such as DIBAL (diisobutylaluminum hydride). By with, for example, das T (diethylmelamine disulfide), morphine-DAST, deoxy-fluoride (bis(2-methoxyethyl)aminosulfur trifluoride), Ishikawa reagent ( N,N-Diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine, Journal of Fluorine Chemistry, 1989, 43, 371 · 377) Suitable fluorinating agent reaction, aldehyde Conversion to a difluoro-2-propyl derivative (step b). By direct chlorosulfonation with chlorosulfonic acid (Heter〇cyeles, 2001, 55, 9, 1789-1803; J. 〇rg. Chem., 2000, 65, 1399_ 1406) (step c) or by first preparing A transacid derivative (step d), which is subsequently converted to a decyl chloride by, for example, a gas-acidic, five-gassing reaction (Eur. J. Med. Chem., 2002, 36, 809-828) (Step e) two steps 119387.doc -118- 200808727 method; by diazotizing the appropriate amine precursor under acidic conditions with sodium nitrite and reacting with sulfur dioxide in acetic acid (J. Org Chem., I960, 25, 1824-26); direct introduction of the appropriate heteroaryl-thiol or heteroaryl-benzyl-thioether with chlorine (Synthesis, 1998, 36-38; J. Am. Chem. Soc., 1950) , 74, 4890-92) is oxidized to the corresponding sulfonyl chloride, and the thus obtained l,i-difluoro-2-phenylpropane can be converted into 4-(1,1-difluoro-2-propyl)benzene Sulfonyl chloride. The synthesis shown in Scheme 4 can also be carried out using (R)-2-phenylpropionic acid and (8)-2-phenylpropionic acid, respectively, to produce the corresponding pair of palmitic 4-(1,1-difluoropropane). _2_ base) benzene-1-ylidene chloride. Process 5:

CH2CI2> 0-35〇C Ck 〆 SO

The ciso3h 4 (1,1,1-fluoropropanol-2-yl) benzathine base gas intermediate can be commercially available from 2,2,2_trifluoro-hydrazine by the synthetic route shown in Scheme 5. Preparation of phenyl ethyl ketone. This can be carried out by reacting with a suitable dipole such as anthracenyltriphenylphosphine (by subjecting the halogenated methyltriphenyl scale and the diisopropylamine or the third butanol to an appropriate reaction) • tig reaction, or according to H〇mer_Emm_reverse: by appropriate reaction of hydrazine with a suitable oleic acid vinegar such as methylphosphonic acid diacetate and potassium ethoxide such as ... Conversion of hydrazine to -119-200808727 Phenylpropene can be reduced to a saturated alkane by catalytic hydrogenation (e.g., Pd-C) followed by conversion to the sulfonyl chloride by the method described in Scheme 4. The synthesis of Scheme 5 can also be carried out using a palmitic catalyst for the hydrogenation of alkenes to allow the preparation of the corresponding para-p'(^^trifluoropropenyl)benzene-sulfonyl chloride. Process 6:

(CH3)3SiCF3

Cf3 •OH PBr3 ---^ 〇-{ CR ,3 a Br

4-(l,l,l-difluoropropan-2-yl)benzene-1-inosinyl chloride can also be obtained from commercially available indole-phenyl-ethanone by a four-step procedure as shown in Scheme 6. preparation. The ketone can be converted to a trifluoromethylhydroxyl intermediate by reaction with trimethyl-trifluorodecyl-decane (〇 111:11 &1〇£'〇^&111(:(1;1^) 111181^, 2000, 65, 8848-8856; Journal of Fluorine Chemistry, 2003, 122, 243-246), which can subsequently be converted to tri-methane methyl desert (Journal of the Amerieeiri Chemical Society, 1987, 109, 2435- 4). Subsequently, after dehalogenation by catalytic hydrogenation (for example, Pd-C), it can be converted into aglycolyl chloride by the method discussed above. Examples of solvents which can be used are ethers such as diethyl ether and diisopropyl ether. , methyl tert-butyl ether or tetrahydrofuran; aprotic polar solvents such as dimethylformamide, dimethyl sulfoxide, dimethoxyethane and acetonitrile; aromatic hydrocarbons such as toluene and xylene Ketones such as acetone or methyl ethyl ketone; halogenated hydrocarbons such as dichloromethane, trioxane and dichloroethane; esters such as acetic acid 119387. Doc -120- 200808727 Ethyl vinegar and butyric acid, such as acetic acid or propionic acid; and alcohol, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 2-butanol and Tributanol. If necessary, a base may be present to neutralize the protons released during the reaction. Suitable bases include inorganic bases such as sodium carbonate, potassium carbonate, sodium hydrogencarbonate or potassium hydrogencarbonate, in addition to alkoxides such as sodium or sodium ethoxide, metal hydrides such as hydrogenated steel, and butyl lithium compounds or alkanes such as An organometallic compound of a magnesium-based compound, or an organic nitrogen base such as triethylamine or pyridine. The latter compound can be used as a solvent at the same time. The crude product is isolated in a conventional manner, for example, by filtration, distillation of a solvent or extraction from a reaction mixture. The resulting compound can be purified in a conventional manner, for example, by recrystallization from a solvent, by means of chromatography or by conversion to an acid addition salt. The acid addition salt is prepared in a conventional manner by mixing the free base with the corresponding acid, suitably in the form of, for example, a lower alcohol such as methanol, ethanol or propanol; an ether such as methyl tert-butyl ether or diisopropyl Ether; _, such as acetone or methyl ethyl _; or 6 in a solution such as ethyl acetate in an organic solvent. The formula according to the present invention is a surprisingly highly selective dopamine h receptor ligand due to its toxicity to agents such as Di receptors, D4 receptors, 'adrenalin and/or α2·adrenergic receptors, Receptors, histamine receptors, dentin receptors and especially dopamine D receptors. ^, and the low affinity of other receptors in the sputum to produce a side effect that is less than the traditional sputum of the D2 receptor antagonist. The compound of the present invention may be a dopamine D3 receptor stimulating effect including partial agonistic activity 119387. Doc-121-200808727 Agent or dopamine E>3 receptor antagonist comprising partial antagonistic activity. The high affinity of the compounds for use in the D3 receptor according to the invention is reflected in very low in vitro receptor binding constants (Ki(D3) values of typically less than 50 nM (nmoin), preferably less than 1 〇 nM and especially less than 5 nM. ). [14] The substitution of iohexapride can be used, for example, in the receptor binding assay for determining the binding affinity to the D3 receptor. The selectivity of the compound according to the invention, ie the ratio of the receptor binding constant Ki (D2) /Ki(D3) is usually at least 50, preferably at least 100, and even more preferably at least 〇5 。. The substitution of [3H]SCH2339〇, [14] iohexapride or [(2) spiperone can be used, for example, for receptor binding studies on 匕, 〇2 and 仏 receptors. Due to their binding profile, the compounds are useful in the treatment of diseases which respond to dopamine-receptor ligands (or can be treated with dopamine D3 receptor ligands, respectively), ie, such compounds are useful in the treatment of The dopamine D3 receptor exerts effects (modulations) on medical conditions or diseases that result in improved clinical signs or disease. Examples of such diseases are disorders or diseases of the central nervous system. The disease or disease of the central nervous system is understood to mean a condition that affects the spinal cord and especially the brain. Within the meaning of the present invention, the term "disease" means a disorder and/or abnormality that is generally regarded as a pathological condition or function and which may manifest itself as a specific sign, symptom and/or dysfunction. Although the treatment according to the present invention may be directed to individual conditions, i.e., abnormal or pathological conditions, it may be used in association with each other in a progressive synthesis pattern (a number of abnormalities that may also be treated in accordance with the present invention. Hou Qun) 119387. Doc-122- 200808727 The conditions which can be treated according to the invention are in particular psychiatric and neurological disorders. Such disorders include, inter alia, uterine disorders, including symptomatic disorders such as acute exogenous psychosis or psychosis associated with organ or exogenous causes such as 'psychiatric disorders associated with metabolic disorders, infections and endocrinopathogies, · endogenous psychosis, such as schizophrenia and schizophrenic and delusional disorders; affective disorders such as depression, snoring and/or depression; and a mixture of the above disorders; neurological and lichen-like disorders Mental disorders and stress-related disorders; schizophrenic disorders such as loss of consciousness, confusion, dual consciousness and aversion disorders; barriers to attention and wakefulness/sleeping behaviors such as behavioral disorders and emotions in children and youth Disorders such as child hyperactivity disorder, mental retardation, especially attention deficit disorder (attention deficit disorder), memory impairment and cognitive impairment, such as impaired learning and memory (impaired cognitive function), dementia, narcolepsy and sleep disorders 'eg leg restlessness syndrome; developmental disorders; anxiety state, paranoia; sex Living disorders, such as male impotence; eating disorders such as anorexia or bulimia, addiction; and other unspecified psychiatric disorders. The conditions treated according to the invention also include Parkinson's disease and pain and especially affective disorders associated therewith. Adult diseases include psychiatric disorders and behavioral disorders caused by the abuse of psychotropic substances such as medicines or anesthetics, and other addictive diseases such as gambling = (an impulse control disorder not otherwise classified). Examples of addictive substances are: opioids (eg morphine, heroin and codeine), cocaine _, substances interacting with GABA chloride channel complexes, sleeping pills and Ningshen, such as alum Call; coffee: marijuana test · H9387. Doc • 123- 200808727 Psychomotor stimuli such as 3,4-methylenedioxyglycolylamine (ecstasy); amphetamine and amphetamine-like substances such as methyiphenidate and including caffeine Other irritants. The addictive substances specifically considered are opioids, cocaine, amphetamine or amphetamine-like substances, nicotine and alcohol. Particularly preferred for treatment into m is a hydrazine compound according to the invention which does not itself have any psychotropic effect. It is also possible to reduce the self-administration of psychotropic drugs such as cocaine by using a test towel of a rat after the rat is administered a compound according to the present invention. According to another aspect of the invention, the compounds according to the invention are suitable for the treatment of conditions in which the cause can be at least partially attributed to the abnormal activity of the dopamine quinone 3 receptor. According to another aspect of the invention, the treatment is particularly directed to being affected by the appropriate exogenous administration of a binding partner (ligand) to the dopamine quinone 3 receptor in the sense of appropriate medical treatment. And other illnesses. Diseases which can be treated with a compound according to the invention are characterized by progressive progression (i.e., within the time course, the above-mentioned conditions); often, the severity increases and the conditions may merge with each other or (10) at the other Other conditions may occur in addition to the condition. Like a smuggled goods, -W mouth takes six τ very; ^ A system of symptoms and many signs, symptoms and / or dysfunction associated with the above conditions. Such signs, symptoms, and/or dysfunctions include, for example, dysfunctional relationships with straightness, lack of insight, and changes in the conformity of social norms or life-giving needs, such as hunger, sleep, thirst, etc. Obstacles and personality changes in the ability of personal instincts and emotional changes, observations and combinations, especially 119387. Doc -124- 200808727 Emotional instability, hallucinations, self-disorders, upset IL, emotional contradictions, autism, personality disintegration and false feelings, delusional thoughts, c- speech, lack of joint movement, short step State, body and limb flexion posture, tremor, lack of facial expression, monotonous language (_〇t〇n〇us speech), depression, apathy, spontaneous and decisive obstruction, lack of association ability, ,, nervousness, stuttering, Social phobia, panic disorder, dependence-related withdrawal symptoms, hand-shaped syndrome (_if〇rm), excitement and confusion, restlessness, dyskinesia syndrome, and convulsions, such as Hunter's dance Disease (Η-chorea) and Toray syndrome (GiUes_de_la T〇urette, s ten vertigo syndromes such as peripheral rotation and oscillating dizziness, depression, rickets, suspected and similar signs, symptoms and/or dysfunction. Within the meaning of the present invention, 'treatment also includes prophylactic treatment (prevention), especially acute or chronic signs, symptoms and/or Treatment can be a disorder. The treatment can be symptomatic adjusted, for example, to suppress symptoms. It can be achieved in a short period of time, with a mid-term adjustment or, for example, in the case of maintenance therapy, can be a long-term treatment. The compound is preferably suitable for (four) treatment of central nervous system diseases, especially for the treatment of affective disorders; neurological disorders, stress disorders and somatoform disorders and psychosis, and especially for the treatment of mental and depression. High selectivity of 3 receptors, according to the invention: compounds! Also suitable for the treatment of renal dysfunction, in particular by dysfunction of diabetes (4) (see W〇00/67847) and especially diabetic nephropathy. The compound is suitable for the treatment of the following conditions: Pa Quansen 119387. Doc -125- 200808727 Disease, schizophrenia, cognitive impairment, depression, anxiety, addiction, renal dysfunction, eating disorders and epilepsy. In the case of treatment, the use of a compound according to the invention comprises a method. In this method, an effective amount of one or more compounds, usually formulated according to medical and veterinary specifications, is administered to an individual to be treated, preferably a mammal, especially a human, a productive animal or a domestic animal. Regardless of the treatment indicated, and the form to be taken will depend on the individual's condition and will be considered for the consideration of existing signs, symptoms and/or dysfunctions, the risk of developing specific signs, symptoms and/or dysfunctions and other factors. Evaluation (diagnosis). Usually, by means of a single or repeated daily administration, if appropriate, together with other active compounds or preparations containing the active compound or both, in order to provide a preferred dosage of about 1 mg to 1000 mg per kilogram of body weight to the individual to be treated. (in the case of oral administration), or about 0.1 mg to 100 mg per kg of body weight (in the case of parenteral administration). The invention is also directed to a method of making a pharmaceutical composition for treating an individual, preferably a mammal, particularly a human, a productive animal or a domestic animal. Thus, the ligands are usually administered in the form of a pharmaceutical composition comprising a pharmaceutically acceptable excipient together with at least one compound according to the invention and, where appropriate, other active compounds. Such compositions can be administered, for example, orally, rectally, transdermally, subcutaneously, intravenously, intramuscularly or intranasally. Examples of suitable pharmaceutical formulations are solid pharmaceutical forms such as powders, granules, lozenges (especially film lozenges), buccal agents, sachets, cachets, dragees, capsules (such as hard gelatin capsules and soft gelatin capsules). , suppository or vaginal drug form, semi-solid drug form, such as ointment, cream, hydrogel, paste 119387. Doc-126 - 200808727 or plasters' and liquid pharmaceutical forms such as solutions, especially oil-in-water emulsions, suspensions such as lotions, injectable preparations and infusion preparations, and eye drops and ear drops. A human release device can also be implanted for administration of an inhibitor according to the present invention. In addition, it is also possible to use liposomes or microspheres. When making a composition, the compound according to the invention is optionally mixed with or diluted with one or the other excipients. The excipient can be a solid semi-solid or liquid material which acts as a vehicle, carrier or medium for the active compound. Suitable excipients are listed in the monograph on specialty medicines. In addition, the formulation may comprise a pharmaceutically acceptable carrier or a conventional auxiliary substance such as a slip agent; a wetting agent; an emulsifier and a suspending agent; a preservative; an antioxidant; an anti-irritant; a chelating agent; Emulsion stabilizer; film former; gel forming agent, odor masking agent; taste correcting agent; resin; hydrocolloid; solvent; solubilizer; neutralizer; diffusion promoter; pigment; tetraammonium compound; Refattmg agent and overfatting agent; raw materials for ointments, creams or oils; polyoxyl derivatives; spreading aids; stabilizers, sterilizing agents; suppository bases; Such as binders, fillers, slip agents, disintegrants or coatings; propellants; desiccants; opacifiers; thickeners; waxes; plasticizers and white mineral oils. In this respect, the formulation is based on expertise as described, for example, in Fiedler, Η·Ρ·, Lexikon der Hilfsstoffe fiir Pharmazie, Kosmetik und angrenzende Gebiete [Encyclopedia of auxiliary substances for pharmacy,cosmetics and related fields ], 4th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996. 119387. Doc-127-200808727 The following examples are intended to illustrate the invention and not to limit it. The compound is in df dimethyl sapite or d-chloroform (if not stated otherwise) on a 400 MHz or 500 MHz NMR instrument (Bruker AVANCE) via proton-NMR or by usual HPLC-MS at C18 Materials (electrospray-ionization (ESI) mode) were characterized by mass spectrometry or refining points recorded by fast gradients. Nuclear magnetic resonance spectroscopy (NMR) refers to the chemical shift (δ) expressed in parts per million (ppm). In the 1H NMR spectrum, the relative area of the displacement corresponds to the number of hydrogen atoms of a particular functional type in the molecule. In terms of multiplicity, the / property of the displacement is indicated by a single peak (s), a broad single peak (s· br), a double peak (d), and a broad double peak (d br. ), triplet (1), broad triplet (t br·), quartet (q), quintet (quint·), and multiplet (m). Preparation examples: I.  Intermediate a· [2-(5-Amino-6-methoxy-acridin-2-yloxy)·ethyl]-propyl-aminocarboxylic acid tert-butyl ester a.  1 [2-(6-Methoxy-5-nitro-acridin-2-yloxy)-ethyl]-propyl-aminocarbamic acid tert-butyl ester 6-indol-2-indoleoxy -3-nitroindole 唆 (5 g, 21. 46 mmol), (2-carbo-ethyl)-propyl-carbamic acid tert-butyl _ (4. 36 g, 21. 46 mmol) and K2C03 (2. 97 g, 21. A mixture of 46 mmol) in dimethylformamide (DMF) (60 ml) was stirred at room temperature for 24 h and at 40 ° C for 4 h. After evaporating the solvent under reduced pressure, the residue was purified by silica gel chromatography eluting with di-methane/methanol (10:0; 9:1; 7:3; 0:10) as a solvent. 81 g (36. 9%) product. 119387. Doc -128- 200808727 MS (ESI) m/z: 356. 25 [M+H(-BOC)] + a·2 [2-(5-Amino-6-methoxypyridin-2-yloxy)-ethyl]-propyl-carbamic acid III Butyl ester [2-(6-decyloxy-5-nitro-acridin-2-yloxy)-ethyl]-propyl-amino decanoic acid tert-butyl ester (1. 12 g, 3. 16 mmol) and 10% palladium charcoal (0. A mixture of 34 g, 0-316 mmol) in ethanol (80 ml) was hydrogenated under atmospheric pressure until complete consumption of hydrogen. After filtration and evaporation of the solvent under reduced pressure, 960 mg (93. 5〇/c>) Title compound. MS (ESI) m/z: 326. 25 [M+H] + b· 6-(1-benzyl-pyrrolidin-3-yloxy)-2-methoxy-pyridin-3-ylamine b. l 6-(1-Benzyl-pyrrolidin-3-yloxy)-2-methoxy-3-nitro-pyridine will be 6-indifferent to 2-oxo-oxy-3-zepa Bite (1. 5 g, 6. 44 mmol), 1-benzyl-β-pyrrol-3-ol (1·14 g, 6. 44 mmol) and K2CO3 (0. 89 g, 6. A mixture of 44 mmol) in dimethylformamide (DMF) (20 ml) was stirred at room temperature for 24 h and at 40 ° C for 4 h. After evaporating the solvent under reduced pressure, the residue was purified by chromatography eluting with methylene chloride/methanol (10:0; 9:1; 7:3; 0:10) as a solvent to yield 380 mg. (18. 1%) product. MS (ESI) m/z: 330. 15 [M+H] + b. 2 6-(1-Benzylbipirin-3-yloxy)-2-methoxyl ratio π _3_ylamine At 80 ° C, iron (〇·32 g, 5. 77 mmol) slowly added in portions to 6-(1-benzylmethylpyrrolidin-3-yloxy)-2-methoxy_3_nitro-吼 bite (0. 38 g, 1. 15 mmol) in a solution of acetic acid (4 ml). The exothermic reaction was stirred for 3 h at 8 °C. After evaporating the solvent under reduced pressure, 119,387. Doc -129- 200808727 The solid residue was dissolved in 1 N NaOH and extracted 6 times with di- methane. The combined organic layers were dried over MgS04. 'Filtered and evaporated to give 24 〇mg (68. 9%) title compound. MS (ESI) m/z: 300. 15 [M+H] + c· methoxy·6-(2-pyrrolidin-l-yl-ethoxypyrid-3-ylamine) is described and used to prepare intermediates a. A synthetic procedure similar to that of the synthesis procedure starts from 6-bromo-2-methoxy-3-nitropyridine and 2-pyrrolidin-1-yl-ethanol to give the desired product. MS (ESI) m/z: 268. 15 [M+H] + d· [2·(5_Amino-4-methoxy-pyrimidin-2-yloxy)-ethylpropylpropylaminocarbamic acid tert-butyl ester d. l 2-Chloro-4-methoxy_5_nitro-pyrimidine at -10 ° C, potassium methoxide (3·62 g, 51·55 mmol) in methanol 〇5 over a period of 1 Torr Add the solution in 〇ml) to 2,4_digas-nitrogen (10 g, 51. 5 5 mmol) in a solution of methanol (150 ml). The mixture was allowed to warm to 〇 °c and the solvent was evaporated under reduced pressure at 3 Torr. The residue was purified by chromatography eluting with n-heptane / ethyl acetate (3: EtOAc) as solvent. 7 g (37. 9%) title compound. 134 g (13 7%) of 4-oxo-2-methoxy-5-nitrosozine as a by-product was obtained. MS (ESI) m/z: 196. 15 [M+H] + d. 2 [2-(4-Methoxy-5-nitro-pyrimidin-2-yloxypethyl]-propyl-amino decanoic acid tert-butyl ester under 〇 C will be NaH (0. 25 g, 5. 80 mmol) was added to (2 - by 119387. Doc -130- 200808727 base-ethyl)-propyl-amino decanoic acid tert-butyl ester (1. 07 g, 5. 28 mmol) in THF (40 ml). After stirring the suspension for 3 minutes at 〇 °c, 2 g of chloro-4-methyl-5-nitropyrimidine (1 g, 5. A solution of 28 mmol) in THF (10 ml) and mixture was stirred at room temperature for 16 h. The mixture was added to water and extracted three times with two gas burners. The combined organic layers were dried over MgSCU, filtered and dried under reduced pressure to afford title compound. MS (ESI) m/z: 357. 15 [M+H] + d. 3 [2-(5-Amino-4-methoxy-pyrimidin-2-yloxy)-ethyl]-propyl-amino decanoic acid tert-butyl ester. At 80 C, ammonium formate (3. 12 g, 49. 44 mmol) solution in water (1 〇 ml) was slowly added to the crude [2_(4_methoxy-5.nitro-pyrimidin-2-yloxy)-ethyl]-propyl-carbamic acid Third butyl ester oxime. 76 g, 4. 94 mmol) and 10% of the mixture of charcoal (2 mg) in water (15 ml). After stirring at 80 ° C for 1 h, the mixture was filtered and concentrated under reduced pressure. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried over MgSCU, filtered and evaporated. The residue was chromatographed using toluene/THF/MeOH (4:1:1). Purification with 5% triethylamine to yield 720 mg (44. 7%) title compound. MS (ESI) m/z: 327. 15 [M+H] + e·6_(2-dimethylamino-ethoxy)-pyridine-3-ylamine according to a synthetic procedure similar to that described for the preparation of the intermediate a· 2-Chloro-5-nitropyridine and 2-dimethylaminoethanol were initially obtained to give the desired product. 119387. Doc -131- 200808727 MS (ESI) m/z: 182. 15 [M+H] + f.  [2-(5-Amino-pyridin-2-yloxy)-hexyl]-propyl-amino decanoic acid tert-butyl ester was synthesized in a similar manner to the synthetic procedure described for the preparation of the intermediate a• The procedure was carried out starting from 2-chloro-5-nitropyridine and (2-hydroxy-ethyl)-propyl-aminocarboxylic acid tert-butyl ester to give the desired product. MS (ESI) m/z: 326. 15 [M+H] + g· 4-((S)-2·fluoro-1·methyl-ethylbenzenesulfonyl group gas g.  l toluene-4-sulfonic acid (S)-2-phenyl·propyl ester 28 g p-toluenesulfonyl chloride 〇 46. 8 mmol) was added portionwise to a solution of 20 g of (S)-(-)-2-phenyl-1-propanol in 240 ml of dichloromethane. After stirring at rt for 18 h, EtOAc (EtOAc)EtOAc. 'H-NMR (CDC135 400 MHz): δ [ppm] 7. 65 (d, 2H) 5 7. 15-7. 3 (m,5H),7,1 (d5 2H),4·0-4·1 (m,2H), 3. 1 (m, 1H), 2. 4 (s, 3H), 1. 3 (d, 3H). g. 2 ((S)-2_fluoro-1-methyl-ethyl)·benzene will be 9. 62 g of toluene-4-sulfonic acid (S) 2 -phenyl-propyl ester (33. 13 mmol) was dissolved in 80 ml of polyethylene glycol 400. Add 9. 62 g potassium fluoride (165. 6 mmol) and the reaction mixture was stirred at 50 °C for 3 days and then disturbed for 2 days at 551:-70C. The reaction was quenched with EtOAc (EtOAc)EtOAc. The crude product was passed through a ring 119387. Doc -132- 200808727 The calcined/acetic acid ethyl ester was purified by using a 55% as a dissolving agent. Separation 2. 8 5 g of the desired product, which contains ~25% elimination by-product. ^-NMR (CDC135 400 MHz): δ [ppm] 7. 2-7. 4 (m5 5H)? 4. 3-4. 6 (several m, 2H), 3. 15 (m, 1Η)·1·3 (m, 3H). G-3 4-((S)-2-fluoro-1-methyl-ethyl)·benzenesulfonyl chloride 3. 5 g ((S)-2-fluoro-1-indenyl-ethyl)-benzene (25. 32 mmol) was dissolved in 80 ml of di-methane. Here. At 〇-5 °C, the solution was dissolved in 20 ml of dichloromethane. 81 g gas sulfonic acid (101. 31 mmol). The reaction mixture was stirred at room temperature for 30 min and at 30 ° C for 2 h. Evaporate the solvent. 150 ml of diethyl ether were added to the residue, which was washed with 150 ml of water and dried over magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography eluting with n-heptane-di- methane (6: 4) as solvent. 'H-NMR (CDC13? 400 MHz): δ [ppm] 8. 0 (d, 2H)? 7. 5 (d, 2H), 4, 5 (dd5 2H), 3·25 (m, 1H), 1. 4 (d, 3H). h· 4-((R)-2-fluoro-1-methyl-ethyl)-benzenesulfonyl group gas h. l Toluene_4_sulfonic acid (R)-2-phenyl-propyl ester according to the procedure similar to that used to synthesize toluene-4-sulfonic acid (S)-2-phenyl-propyl ester 'but use ( R) 2-Phenyl-1-propanol was used as the starting compound to give the title compound. H-2 ((R)-2-Ga-1-methyl-ethyl)-This is described above for the synthesis ((S)-2-fluoro-1-methyl-ethyl)- stupid Compound, but using toluene-4-sulfonic acid (R)-2-phenyl-propyl ester 119387. Doc -133- 200808727 Instead of (S)-2-phenyl-propyl toluene-4-sulfonic acid. ^-NMR (CDC135 400 MHz): δ [ppm] 7. 2-7. 4 (m5 5H), 4·3·4·6 (several m, 2H), 3·15 (m, 1Η)·1·3 (m, 3H). h. 3 4-((R)-2-Fluoro-l-methyl-ethylbenzenesulfonyl chloride L3 g ((R)-2-fluoro-1-methylethyl)-benzene (9. 4 mmol) was dissolved in 50 ml of di-methane. At 〇 °C _5. (: Next, add ι·ι g chlorophosphoric acid (9·4 mmol) dissolved in 10 ml of dichlorohydrazine. Dissolve the reaction mixture for 20 min at -5-5 C and then add To 2. 15 g of five-gasified phosphorus is dissolved in 40 ml of di-methane. The reaction mixture was stirred at 〇 ° C - 5 ° C for 30 min and at room temperature for 1 h. The solvent was evaporated, EtOAc (3 mL) was evaporated. The crude product was purified by silica gel chromatography using n-heptane·dichloromethane (1:1) as a solvent. 261 g of title compound. 'H-NMR (CDC135 400 MHz): δ [ppm] 8. 0 (d, 2H)? 7. 5 (d, 2H), 4. 5 (dd, 2H), 3·25 (m, 1H), 1. 4 (d, 3H). Le 4-(2-Fluoro-i-indolyl-ethyl)-benzenesulfonyl chloride is similarly used to prepare 4-((S)-2-fluoro-1_methyl-ethyl)-benzenesulfonate The procedure of the program of the base gas, but in step a. Starting from 2_phenyl-1-propanol in 3gl, the title compound was obtained. W-NMR (CDC13, 400 ΜΗζ)·· δ [ppm] 8·〇 (d, 2H), 7. 5 (d, 2Η), 4·5 (dd, 2Η), 3. 25 (m, 1Η), 1·4 (d, 3Η). k· 4_(3_Fluoropropyl)-benzenesulfonyl group gas 119387. Doc -134- 200808727 k. l (3-Fluoropropyl)-benzene 15·6 g of diethylaminosulfur trifluoride (DAST, 96. 91 mmol) was dissolved in 18 ml of dichloromethane. At 0 ° C - 5 ° C, 12 g of 3-phenyl-1-propanol dissolved in 30 ml of di-methane was added dropwise (88. 1 mmol). The reaction mixture was spoiled for 18 h and after 30 ml of dioxane was added, it was poured onto 100 ml of ice water. The organic layer was separated, dried over magnesium sulfate, filtered and evaporated. The crude product was purified by distillation at 20 mm at a bath temperature of 106 ° C to give 7. 4 g of the title compound. ^-NMR (CDCls, 400 MHz): δ [ppm] 7. 1-7. 3 (m5 5H), 4·4 (dt, 2H), 2·7 (m, 2Η)·2·0 (m5 2H). k. 2 4-(3-Fluoropropyl)-benzenesulfonyl chloride will be 4. 1 g of (3-fluoro-propyl)-benzene (29-67 mmol) was dissolved in 40 ml of dichloromethane. At 〇 ° C -5 ° C, the addition of dissolved in 10 ml of methylene chloride was added dropwise. 918 chlorosulfonic acid (59. 34 111111〇1). At 0. (:-5° (:, the reaction mixture was stirred for 45 min and then added to 6. 8 g of five gasified phosphorus (32. 63 mmol) was dissolved in 50 ml of the solution in methylene chloride. The reaction mixture was stirred at 5 °C - 10 °C for 1 h. The solvent was evaporated, 150 ml of diethyl ether was added, and the solution was washed with 150 ml of ice water, and the organic layer was dried over magnesium sulfate, filtered and evaporated. The crude product was purified by chromatography eluting with hexanes (1:9) as a solvent to afford 5·5 g of the title compound. ^-NMR (CDC135 400 MHz): δ [ppm] 7. 95 (d? 2H), 7. 45 (d, 2H), 4. 5 (dt, 2H), 2. 9 (t, 2H), 2. 05 (m, 2H). m· 4-(2-fluoroethyl)·benzenesulfonyl hydrazine 119387. Doc -135- 200808727 m. l (2-Fluoroethyl)-benzene is used in the synthesis of (3-fluoropropyl)-stupid, from the commercial 孓 基 _ _ ethanol to obtain 6. 8 g of the title compound. h-NMR (CDCl3, 400 MHz): § [ppm] 7 17 3 (called 5H), 4. 6 (m, 1H), 4. 45 (m, 1H), 2 % (four) ih), 2 9 (m 1H). , m. 2 4-(2-Fluoroethyl)-benzenesulfonyl chloride was obtained according to the procedure used for the synthesis of 4·((Κ)_2_fluoro-1-methyl-ethyl)-benzenesulfonyl chloride. 55 g. ^-NMR (CDC13? 400 MHz): δ [ppm] 8. 0 (d5 2H)3 7. 5 (d, 2H), 4. 7 (dt, 2H), 3. 05-3. 2 (dt, 2H). n· 4-(l,l,l-trifluoropropan-2-yl)benzenesulfonyl base gas and trifluoropropane-2-yl)benzenesulfonyl base gas according to the procedure outlined in Scheme 5, 丨4 g scale preparation. 2_(1,1,1-Trifluoropropan-2-yl)benzenesulfonyl chloride is a by-product of the reaction. 4_(1,1,1_Trifluoropropan-2-yl)benzenesulfonyl chloride: MS (ESI) m/z: 273. 1 [M+H] + W-NMR (DMSO-d6)·· δ [ppm] 7·62 (d, 2H), 7. 33 (d, 2H), 3. 81 (m, 1H), 1. 42 (d, 3H). 2-(l,l,l-trifluoropropan-2-yl)benzenesulfonyl group gas: MS (ESI) m/z: 273. 1 [M+H] + 〇· 4-Chewing -4-yl-phenyl- fluorene-based gas 2-in-1-1-phenylethanone (40 g, 201 mmol) and formic acid (44. 35 g, 703 mmol) of the solution in formic acid (75 ^ 1) was heated back to 119387. Doc •136· 200808727 The flow lasts 2 hours. The reaction mixture was evaporated under reduced pressure. The crude product was purified by chromatography using ethyl acetate / heptane (0:10; U) as a solvent. At 0 ° C, 4_p-phenyloxazole (3 g, 20. 67 mmol) was slowly added to 24. 08 g gas is sour (206. 67 mmol). The reaction mixture was stirred at 〇 ° C - 5 ° C for 20 min and then warmed to room temperature and finally stirred at 45 ° C for 2 h. Subsequently, the reaction mixture was carefully added (1) to ice water. The precipitate was filtered, washed with water and dried in a vacuum oven at 30 ° C to give the title compound. 3 g, 76. 8%). MS (ESI) m/z·· 240. 15 [M+H]+(4-oxazol-4-yl-benzenesulfonate methyl ester) ρ·6-[2-(benzyl-propyl-amino)-ethoxy]-2·A Oxy-. Bipyridine-3_ylamine ρ·1 benzyl-[2-(6-methoxy-5-nitro-acridin-2-yloxy)-ethyl]•propyl-amine will be 6- Desert-2-methoxy-3 - bite (2,92 g, 12. 54 mmol), Cs2CO3 (20. 4 g, 62·68 mmol) and 2-(benzyl-propyl-amino)_ethanol (3. 63 g, 18. 8 mmol) was added to Pd(〇Ac) 2 (112 mg, 〇·5 mmol) and [1,1']binaphthyl-di-tert-butyl-phosphine (3〇mg, 〇·75 mmol) In a mixture of toluene (40 ml). The mixture was stirred at room temperature for 24 h under nitrogen. After evaporating the solvent under reduced pressure, the residue was dissolved in water and extracted five times with dichloromethane. The residue was purified by ruthenium chromatography using n-heptane / di- methane (10:0; 7:3; 〇:1 〇) as a dissolving agent to yield 119,387. Doc -137- 200808727 Health 2. 92 g (67. 3%) product. MS (ESI) m/z: 346. 15 [M+H] + p·2 6-[2·(benzyl-propyl-amino)-ethoxy]·2-methoxy- a than 唆-3_ylamine at 80 ° C Next, will iron (2. 36 g, 42. 27 mmol) slowly added in portions to benzyl-[2-(6-methoxy-5-nitro- η than butyl-2-yloxy)-ethyl]-propyl-amine (2. 92 g, 8. 45 mmol) in a solution of acetic acid (120 ml). The exothermic reaction was stirred at 80 ° C for 2 h. After evaporating the solvent under reduced pressure, the solid residue was dissolved in aqueous NaHCO3, and extracted twice with methane. The residue was purified by silica gel chromatography using dichloromethane/methanol (10:0; 8:2; 6_5:3·5; 0:10) as a solvent. 4 g (52. 5%) product. MS (ESI) m/z: 316. 15 [M+H] + q· (s)-2-(5-Amino-6-methoxy-pyridin-2-yloxymethyl)-pyrrolidine·1-carboxylic acid tert-butyl ester q. l (S)-2-(6-Methoxy-5-nitro-acridin-2-yloxymethyl)-indenylpyridine-1-dicarboxylic acid tert-butyl ester 6-bromo-2-methyl Oxy-3 nitropyridine (1. 〇 g, 4. 29 mmol), Cs2C03 (3. 5 g, ΐ〇·73 mmol) &(s)_2_hydroxymethyl-pyrrolidine _ 1-carboxylic acid tert-butyl ester (1·73 g, 8. 58 mmol) added to Pd(〇Ac)2 (〇·〇8 g,0. 34 mmol) and [1,1'] binaphthyl-2-yl-di-tert-butylphosphine (0·14 g, 〇·34 mmol) in a mixture of toluene (10 ml). The mixture was stirred at room temperature for 24 h under nitrogen. After evaporating the solvent under reduced pressure, the residue was obtained from methane/ethyl acetate/methanol (10:0:0; 9:0·5··0_5,·7·1·5:1·5 ; 0··5··5) as a dissolving agent 矽 387 119387. Doc •138- 200808727 Purification by gel chromatography to produce o. Ll g (7. 5%) product. MS (ESI) m/z: 354. 15 [M+H] + q. 2 (S)-2-(5-Amino-6-methoxy-indot-2-yloxyindenyl) η each bite 1-carboxylic acid tert-butyl ester using Thales Nano H-Cube® hydrogenation reactor , using a 1% palladium charcoal catalyst cartridge, (S)_2-(6-methoxy-5-nitro-lalid-2-yloxymethyl)-pyrrolidine_1-carboxylic acid tert-butyl Ester (0. 11 g, 0. A solution of 32 mmol) in methanol (11 ml) was hydrogenated. After the solution was concentrated under reduced pressure, it was obtained. 10 g (92. 6%) title compound. MS (ESI) m/z: 324. 15 [M+H] + r· Amino-6-methoxyl-bito-2_yloxymethyl piroxime _ 1-carboxylic acid tert-butyl ester according to the description used to prepare the intermediate q Synthetic Procedure A similar synthetic procedure was initiated starting from 6-bromo-2-methoxy-3-nitropyridine and (R)-2-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester. MS (ESI) m/z: 324. 15 [M+H] + s· (S)-2-(5-Amino-6-fluorenyl-σ-Bitter-2-yloxymethyl)-e ratio slightly 唆-1_ formic acid tert-butyl ester According to the synthetic procedure similar to that described for the preparation of intermediate q, from 6-gas-2-methyl-3-nitroguanidine and (S)-2-hydroxymethyl-pyrrolidine-1 The third ester of formic acid starts to give the desired product. MS (ESI) m/z: 340. 15 [M+H] + t.  (R)-2-(5-Amino-6-methyl-pyridin-2-yloxymethyl)-pyrrolidinium-hydrazide tert-butyl formate 119387. Doc -139- 200808727 According to a synthetic procedure similar to that described for the preparation of intermediate q, from 6-chloro-2-indolyl-3-nitro-pyridine and (R)-2-hydroxymethyl- Pyrrolidine_1-carboxylic acid tert-butyl ester starts to give the desired product. MS (ESI) m/z: 340. 15 [M+H] + u· [2-(5-Amino-6-methylpyridin-2-yloxy)-ethyl]-propyl-aminocarbamic acid tert-butyl ester u. l [2·(6-Methyl-5-nitro^pyridin-2-yloxy)-ethyl]-propyl-carbamic acid tert-butyl ester at 90C '6-gas-2- Methyl-3-stone Schottky_σ ratio bite (1 g, 5. 79 mmol), (2-hydroxy-ethyl)-propyl-aminocarboxylic acid tert-butyl ester (1. 18 g, 5. 79 mmol) and lithium hydride (0. 05 g, 6. A mixture of 37 mmol) in toluene (5 ml) was stirred for 4 h. After evaporating the solvent under reduced pressure, the residue was purified by EtOAc EtOAc (EtOAc: EtOAc (EtOAc) 38 g (70. 2%) product. MS (ESI) m/z: 284. 15 [M+H(-[Third butyl])]+ u.  2 [2-(5-Amino-6-methyl-0-indol-2-yloxy)-ethyl]-propyl-carbamic acid tert-butyl ester using a Thales Nano H-Cube® hydrogenation reactor, [2-(6-Methyl-5-nitro-pyridin-2-yloxy)-ethyl]-propyl-carbamic acid tert-butyl ester (300) using a 10% palladium charcoal catalyst cartridge Mg,0. A solution of 88 mmol) in methanol (10 ml) was hydrogenated. After the solution was concentrated under reduced pressure, 230 mg (84. 2%) title compound. v.  6-[2-(phenylhydrazino-propyl-amino)-ethoxy]-2-methyl-pyridin-3-ylamine is similar to the synthetic procedure described for the preparation of intermediate P 119387. The synthetic procedure of doc-140-200808727 starts with 6-chloro-2-methyl-3-nitroσ odor and 2-(benzyl-propyl-amino)-ethanol to give the desired product. MS (ESI) m/z: 300. 15 [M+H] + w· 6-[2-(benzyl-propyl-amino)-ethoxy]-4-methyl-t-butylamine as described for the preparation of intermediate p A synthetic procedure similar to that of the synthetic procedure was initiated starting from 2-chloro-4-methyl-5-succinylpyridinium and 2-(benzyl-propyl-amino)-ethanol. MS (ESI) m/z: 300. 15 [M+H] + χ·6-[2-(benzyl-propyl-amino)-ethoxy b 5-methyl ratio _3 • Alkylamine as described for the preparation of intermediates A similar synthetic procedure for the synthesis of P from 2-bromo-3-methyl-5-nitropyridine and 2-(phenylhydrazino-propyl-amino)-ethanol afforded the desired product. MS (ESI) m/z: 300. 15 [M+H] + y.  4-(2-I-ethoxy)-benzene-based base gas (2-D-Ethyloxy)-benzene (20 mmol) was slowly added to gas sulfonic acid (200 mmol). The reaction mixture was stirred at -5 °C for 20 min and then warmed to room temperature and finally stirred at 45 s for 2 h. The reaction mixture was then carefully (!) added to ice water. The precipitate was filtered, washed with water and dried in a vacuum oven at 30 ° C to give the title compound. !H-NMR (CDCls): δ [ppm] 4. 21-4. 45 (m, 2H)? 4. 65- 5. 00 (m, 2H), 7. 08 (d, 2H), 8. 00 (d, 2H). ζ·4·(2,2-Difluoro-ethoxy)-benzenesulfonyl-based gas is similar to the synthetic procedure described for the preparation of intermediate y 119387. Doc 141 · 200808727 The synthesis procedure yields the desired product. ^-NMR (CDCI3): δ [ppm] 4. 21-4. 40 (m, 2H)? 5. 82-6·45 (m, 1H), 7. 08 (d, 2H), 8·02 (d, 2H). Ζζ·4·(2,2,2-trifluoro-ethoxy)-benzenesulfonyl-based gas The desired product was obtained according to a synthetic procedure similar to that described for the preparation of intermediate y. 'H-NMR (CDCI3): δ [ppm] 4. 40-4. 55 (m5 2H)? 7. 10 (d, 2H), 8. 02 (d, 2H). ΪΙ·Preparation of Compound I Example 1 4-(3-propylpropylmethoxypropylamino)-ethoxy p-pyridyl-3-ylbenzinamide xHCl At room temperature, [2-(5 -Amino-6-methoxy-pyridin-2-yloxy)-ethyl]-propyl-aminocarboxylic acid tertidine (2 〇〇 mg, 0·62 mmoljK π 唆 (3 ml) After the solution was stirred for 3 minutes, 4-(3 -1 -propyl)-benzene hydrazinyl chloride (160 mg, 〇·68 mmol) was added. The mixture was stirred at room temperature for 16 h and then decompressed. The solvent was evaporated. The residue was dissolved in toluene and then evaporated again. The procedure was repeated. The residue was taken from n-hexane/ethyl acetate (1:0; 1:1; 0:1)/0. 2% triethylamine was purified as a dissolving agent by gel chromatography. The residue was dissolved in dioxane (5 ml). Here. Under the armpit, HC1 (1 ml) in the scales was slowly added to the solution. The mixture was stirred for 6 h at room temperature. After concentrating under reduced pressure, the residue was purified by H.sub.2/acetonitrile (95:5; 〇:1 〇〇; 95·5)/0·1. Purification of the indole acetic acid as a dissolving agent (Chromabond_C18). The oil thus obtained is in 119387 in i N Na〇H. Doc -142- 200808727 The solution was extracted three times with dichloromethane (45 ml). The combined organic layers were concentrated to 30 ml and added to HCl (2 ml). The formed solid was filtered and dried in a vacuum oven to obtain 88. 9 mg (35. 6%) title compound. MS (ESI) m/z: 426. 25 [M+H] + i-NMR (MeOD): δ [ppm] 7. 70 (m, 1H), 7. 60 (d, 2H), 7. 35 (d, 2H), 6. 45 (d, 1H), 4. 50-4. 60 (m, 2H), 4. 35-4. 50 (m, 2H), 3. 60 (s, 3H), 3. 40-3. 45 (m, 2H), 3. 00-3. 10 (m, 2H), 2. 75-2. 80 (m, 2H), 1. 90-2. 10 (m, 2H), 1·70-1·85 (m, 2H), 1. 05 (t, 3H) 〇 Example 2 N-[2-methoxy·6-(2·propylamino-ethoxy)-indenyl-3-yl]_4_trifluoromethoxy-benzene Sulfonamide xHCl was synthesized from [2-(5-amino-6-methoxy-acridin-2-yloxy)ethyl]-propyl according to a synthetic procedure similar to that described for Example 1. Starting from the butyl-aminocarbamic acid tert-butyl ester and 4-trifluoromethoxy-benzenesulfonyl group to give the desired product 0 MS (ESI) m/z: 449. 25 [M+H] + h-NMR (D6-DMSO): δ [ppm] 7. 75 (d, 2H), 7·56 (d, 2H) 5 7_45 (d, 1H), 6. 30 (d, 1H), 4·15_4·25 (m, 2H), 3. 40 (s, 3H), 2. 80-2. 90 (m, 2H), 2. 50-2. 55 (m, 2H), 1. 35-1. 45 (m, 2H), 0. 85 (t, 3H). Example 3 N-[2-Methoxy-6-(2-propylamino-ethoxy)-pyridin-3-yl]-4-(2,2,2-trifluoro-1-methyl- Ethyl)-benzenesulfonamide xHCl 119387. Doc • 143- 200808727 According to a synthetic procedure similar to that described for Example 1, from [2-(5-amino-6-decyloxypyridin-2-yloxy)-ethyl]-prop The desired product is obtained starting from the butyl-amino decanoic acid tert-butyl ester and the 4·(2,2,2-trifluoro-1-methyl-ethyl)-benzenesulfonyl group. MS (ESI) m/z: 462. 15 [M+H] + h-NMR (CDC13): δ [ppm] 9·90 (s br·, 2H), 7·70 (d, 1H), 7. 65 (d, 2H), 7. 40 (d, 2H), 6. 45 (d, 1H), 4. 60-4. 70 (m, 2H), 3. 55(s, 3H), 3. 35-3. 50 (m, lH), 3. 30-3. 35 (m, 2H), 2. 95-3. 05 (m, 2H), 1. 90-2. 00 (m, 2H), 1·50 (d, 3H), 0·95 (t, 3H). Example 4 4_Isopropyl-N-[2-methoxy-6-(2-propylamino-ethoxy)·"pyridin-3-ylbenzenesulfonamide xHCl as per the example 1 A synthetic procedure similar to the one described in the synthesis procedure from [2-(5-Amino-6-methoxy-n-bi-2-yloxy)-ethyl]-propyl-amino decanoic acid tert-butyl The ester and 4-isopropyl-benzenesulfonyl chloride are initially used to obtain the desired product. MS (ESI) m/z: 408. 25 [M+H] + Example 5 4-Difluoromethoxy-indole-[2-methoxy-6-(2-propylamino-ethoxy)-pyridine-3-ylbufene The amine xHCl was synthesized from [2-(5-amino-6-methoxy-anthracene-2-yl)-ethyl]-propyl- according to a synthetic procedure similar to that described for Example 1. The third butyl carbamate and 4-difluoromethoxy-benzenesulfonyl group gas initially obtain the desired product 0 119387. Doc -144- 200808727 MS (ESI) m/z: 432. 15 [M+H] + h-NMR (MeOD): δ [ppm] 7. 70-7. 80 (m, 3H), 7. 25 (d, 2H), 7. 70 (t, 1H), 6. 45 (d, 1H), 4. 50-4. 55 (m, 2H), 3. 60 (s, 3H), 3·40-3·45 (m, 2H), 3. 00-3. 10 (m, 2H), ι·7〇-ι·85 (m, 2H), 1. 05 (t, 3H). Example 6 4_(2-Fluoro-ethyl)-N-[2-methoxy·6-(2-propylamino-ethoxy) butyl 3-yl]-benzenesulfonamide xHCl A synthetic procedure similar to that described in Example 1 is a similar synthetic procedure from [2-(5-amino-6-methoxy-leptin-2-yloxy)-ethyl]-propyl-aminocarboxylic acid The desired product is obtained starting from butyl ester and 4-(2-fluoro-ethyl)-benzenesulfonyl group. MS (ESI) m/z: 412. 25 [M+H] + W-NMR (D6-DMSO): δ [ppm] 9. 45 (s br·, 3H), 7. 55 (d, 2H), 7. 40-7. 50 (m, 3H), 7·10 (d, 2H), 6. 40 (d, 1H), 4·60· 4·75 (m, 2H), 4. 45-4. 55 (m, 2H), 3. 50 (s, 3H), 3. 20-3. 30 (m? 2H), 3. 00-3. 10 (m, 2H)? 2. 85 (t, 2H), 1. 65-1. 75 (m, 2H) 5 0. 90 (t, 3H). Example 7 N-[2-Methoxy-6-(2-propylamino-ethoxy)pyridin-3-yl]-4-oxazol-5-yl-benzenesulfonamide xHCl A synthetic procedure similar to that described in Example 1 was similar to [2-(5-Amino-6-methoxy-acridin-2-yloxy)-ethyl]-propyl-aminocarboxylic acid Butyl ester and 4-oxazole-5-yl-benzenesulfonyl chloride start to obtain the desired yield of 119387. Doc -145- 200808727 MS (ESI) m/z: 433. 25 [M+H] + i-NMR (MeOD): δ [ppm] 8·35 (s5 1H), 7. 85 (d, 2H), 7·80 (d, 2H), 7. 70-7. 75 (m, 3H), 6. 45 (d, 1H), 4·50-4·55 (m, 2H), 3. 60 (s, 3H), 3. 40-3. 45 (m, 2H), 3. 00-3. 05 (m, 2H), 1. 60- 1. 70 (m, 2H), 1. 05 (t, 3H). Example 8 4-(2-Fluoroethyl)-N-[2-decyloxy-6(2-propylamino-ethoxy)-indole ratio _3-yl]-benzenesulfonamide xHCl According to a synthetic procedure similar to that described for Example 1, from [2-(5-amino-6-methoxy-acridin-2-yloxy)ethyl]-propyl-amino The third product of tert-butyl formate and 4-(2-fluoro-ethoxy)-benzenesulfonyl group were initially obtained to give the desired product: 0 MS (ESI) m/z: 428. 10 [M+H] + W-NMR (D6-DMSO): δ [ppm] 9·40 (s, 1H), 9·25 (s br·, 2H), 7·60 (d, 2H), 7 . 45 (d, 1H), 7·10 (d, 2H), 6. 35 (d, 1H), 4·75 (d, 2H), 4. 50 (m, 2H), 4. 30 (d, 2H), 3. 55 (s, 3H), 3·25 (s br. , 2H), 2. 85 (s bi··, 2H), 1. 60-1. 70 (m, 2H), 0. 90 (t, 3H). Example 9 4-(2,2-Difluoro-hexyloxy)-[2-methoxy-6-(2-propylamino-ethoxy)-pyridin-3-yl]-benzenesulfonamide XHC1 was synthesized according to a synthetic procedure similar to that described for Example 1 from [2-(5-amino methoxyoxypyridin-2-yloxy)-ethyl]-propyl-amino decanoic acid Tributyl ester and 4-(2,2-difluoro-ethoxy)-benzenesulfonyl group gas were initially obtained as 119387. Doc -146- 200808727 To produce. MS (ESI) m/z: 446. 05 [M+H] + 'H-NMR (D6-DMSO): δ [ppm] 9. 40 (s5 1H)? 9. 15 (s br. 5 2H)? 7. 60 (d, 2H), 7. 45 (d5 1H), 7. 15 (d, 2H), 6. 40 (t, 1H), 6. 39 (d, 1H), 4. 47 (m, 2H), 4·40 (t, 2H), 3. 55 (s, 3H), 3·25 (s br·, 2H), 2. 88 (s br·, 2H), 1. 60-1. 70 (m, 2H), 0. 90 (t, 3H). Example 10 N-[2-Methoxy-6-(2-propylamino-ethoxy)-pyridin-3-ylbu 4-(2,2,2-trifluoroethoxy)-benzene Sulfaguanamine xHCl was synthesized from [2-(5-amino-6-methoxy-acridin-2-yloxy)-ethyl]-propyl according to a synthetic procedure analogous to that described for Example 1. The base-amino phthalic acid terpene vinegar and the 4-(2,2,2-trifluoro-ethoxy)-benzophenone base gas are initially used to obtain the desired product. MS (ESI) m/z: 464. 05 [M+H] + iH-NMR (D6-DMSO): δ [ppm] 9. 45 (s, 1H), 9. 15 (s br·, 2H), 7. 60 (d5 2H)5 7. 45 (d3 1H) 5 7. 25 (d5 2H)5 6,39 (d5 1H)5 4. 85-4. 90 (m, 2H), 4. 45-4. 50 (m, 2H), 3. 55 (s, 3H), 3. 25 (s br·, 2H), 2. 88 (s br·, 2H), 1. 60-1. 70 (m, 2H), 0. 90 (t, 3H). Example 11 4-((R)-2-Shen*-1-methyl-ethyl)-N-[2-methoxy-6-(2-propylamino-ethoxy)-pyridine_3 _yl]-benzenesulfonamide xHCl was synthesized from [2-(5-amino-6-methoxy-n-pyridin-2-yloxy) according to a synthetic procedure similar to that described for Example 1. -Ethyl]-propyl-aminocarbamic acid tert-butyl ester and 4-((R)-2-fluoro-1-methyl-ethyl)-benzenesulfonyl chloride starting from 119387. Doc -147- 200808727 Get the desired product. MS (ESI) m/z: 426. 15 [M+H] + iH-NMR (D6-DMSO): δ [ppm] 9. 49 (s, 1H), 9. 15 (s br·, 2H), 7. 60 (d, 2H), 7. 50 (d, lH), 7. 45 (d, 2H), 6. 40 (d, lH), 4. 45-4. 60 (m, 4H), 3. 45 (s, 3H), 3. 20-3. 30 (m, 3H), 2. 90 (s br·, 2H), 1·60_1·70 (m, 2H), 1·22 (d, 3H), 0. 90 (t, 3H). Example 12 4_((S)_2_Fluoro-1-methyl-ethyl)-N-[2_methoxy_6彳2-propylamino-ethoxylated)-pyridin-3-ylbenzene Sulfonamide xHCl 4-((S)-2·fluoro-1_methyl-ethyl)-benzenesulfonyl group gas (5〇mg, 0. 20 mmol) added to 6-[2-(benzylidene-propyl-amino)-ethoxy brom-2-methoxyl-pyridyl-3-amine (6〇mg,〇2〇mtn〇i ) in a solution of pyridine (0 8 ml). After the mixture was stirred at room temperature for i 6 , the solvent was evaporated under reduced pressure. The residue was taken up in dichloromethane / ethyl acetate (10:0; 9:1; 0:10) /. 23⁄4 triethylamine was purified as a dissolving agent by gel chromatography. The mixture of oils thus obtained was hydrogenated using a Thales Nano H-Cube® hydrogenation reactor using a 10% palladium charcoal catalyst. After filtering and evaporating the solvent under reduced pressure, the residue was purified eluting with EtOAc/EtOAc (EtOAc:EtOAc:EtOAc Chromatography of 1% acetic acid as a dissolving agent (Chr〇mab〇nd_ci8m. HC1 in diethyl ether was added to the solution of the oil thus obtained in 2-propanol. The solid formed was filtered and placed in a vacuum oven Dry to produce 1 〇mg (20. 3%) title compound. MS (ESI) m/z: 426. 15 [M+H] + H-NMR (D6-DMSO): δ [ppm] 9. 49 (s, 1H), 9·15 (s br·, 2H), 119387. Doc 200808727 7. 60 (d, 2H), 7. 50 (d, iH), 7. 45 (d, 2H), 6. 40 (d, lH), 4. 45- 4. 60 (m, 4H), 3. 45 (s, 3H), 3·2〇-3·3〇 (m, 3H), 2·90 (s br. 3 2H), 1. 60-1. 70 (m, 2H), 1. 22 (d, 3H), 0. 90 (t, 3H). Example 13 Isopropylmethoxy-6-(pyrrolidin-3-yloxy)-pyridin-3-ylbenzenesulfonamide xHCl

'Benzyl-pyrrolidin-3-yloxy)-2-methoxy-pyridin-3-ylamine (120 mg, 〇·4〇mm〇1) in pyridine (2 ml) at room temperature After stirring the solution for 30 minutes, 4-isopropylbenzenesulfonyl chloride (1 mg, 〇·44 mmol) was added. After the mixture was stirred at room temperature for 16 h, the solvent was evaporated under reduced pressure. The residue was dissolved in toluene and the solvent was evaporated. Repeat this procedure once. The residue was purified by silica gel chromatography eluting with dichloromethane/ethyl acetate (1:::::::::::::::): The oil thus obtained and ίο% palladium charcoal (20 mg, 〇〇 2 mm〇i) are in ethanol (the hydrazine is hydrogenated at atmospheric pressure until the hydrogen is completely consumed. After filtration and evaporation of the solvent under reduced pressure, The residue is purified by gel chromatography using dichloromethane/methanol (10.0, G.1G, 1G.G.) as the eluent. HCl in diethyl ether is added to the solution of the oil thus obtained in methanol. The solution was concentrated under reduced pressure to give the title compound (31). MS (ESI) m/z: 392.35 [M+H] + NMR (MeOD): δ [ppmi ηίΛ LPPm"7·65 (d,1H),7·60 (d,2H),7·35 ( d, 2H), 6.35 (d, 1H), 5.55 3.55 (s, 3H), 2.90-3.05 (m, 1.70 (m, 2H), 1.25 (d, 3H). (s br·, 1H), 3· 45-3·60 (m, 4H), 1H), 2.30-2.40 (m, 2H), 1.6〇- 119387.doc -149- 200808727 Example 14 N-[2-Methoxy-6-(pyrrolidine- 3-Methoxypyridin-3-yl]-4-trifluoromethoxy-benzenesulfonamide xHCl from a 6-(1-benzyl group) according to a synthetic procedure analogous to that described for Example 13 - pyrrrolidin-3-yloxy)-2-methoxy-pyridin-3-ylamine and 4-trifluorodecyloxy-benzenesulfonyl chloride starting to give the desired product. MS (ESI) m/z : 434.35 [M+H] + i-NMR (MeOD): δ [ppm] 7.92 (d, 1H), 7.80 (d, 2H), 7.405 (d, 2H), 6.40 (d, 1H), 5.57 (s Br·,1H), 3.45-3.60 (m, 4H), 3.55 (s, 3H), 2.30-2.40 (m, 2H). Example 15 4 (3-Gas-propyl)methoxy- 6-(2_σ Bilo bite-1 -yl-ethoxy)-ϋ ______ _ _ _ _ _ 醯 醯 在 在 在 在 在 在 在 在 在 在 在 在 在 在 在 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- Ethoxy)-pyridine-3-ylamine (20 After stirring for 30 minutes in a solution of pyridine (3 ml), 4-(3-fluoro-propyl)-benzenesulfonyl (200 mg, 0.84 mmo1) was added. After stirring at room temperature for 16 h, the solvent was evaporated <RTI ID=0.0></RTI>jjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj ; 0:1 〇〇) Purification by chromatography on a solvent to give 2 mg (5.4%) of the title compound. MS (ESI) m/z: 438.15 [M+H] + W-NMR (CDC13): δ [ppm] 7.72 (d,1H), 7.60 (d,2H), 7.25 (d, 2H), 6.60 (Sj 1H)5 6.30 (d, 1H), 4.60-4.65 (m? 2H)5 4.35^ 119387 .doc 200808727 4.50 (m, 2H), 3.85-3.95 (m, 2H), 3.60 (s, 3H), 3.40-3.45 (m, 2H), 2.90-3.00 (m, 2H), 2.05-2.20 (m, 4H), 1.95-2.05 (m, 2H) 〇 Example 16 4_isopropyl-N-[2_methoxy- 6-(2-ff piroxime-l-yl-ethoxy)-3⁄4b bite -3-yl]benzenesulfonamide&gt;&lt;HCl from 2-methoxy-6-(2-pyrrolidin-1-yl-ethoxy)-pyridin-3-ylamine and 4 according to a synthetic procedure analogous to the one described in Example 15 The isopropyl-benzenesulfonyl group gas initially gives the desired product. MS (ESI) m/z: 420.15 [M+H] + &lt;&quot;&&&&&&&&&&&&&&&& -pyrrolidin-1-yl-ethoxy)-° ratio _3·yl]-benzoic amine according to a synthetic procedure similar to that described for Example 15 from 2-decyloxy-6- (2-Pyrrolidin-1-yl-ethoxy)-pyridine-3-ylamine and 4-((R)-2-fluoro-1-methyl-ethyl)phenylphosphonium base gas to obtain the desired product . MS (ESI) m/z: 438.15 [M+H] + W-NMR (CDC13): δ [ppm] 7.65 (d,2H), 7.15-7.30 (m,3H), 6.20-6.35 (d,1H) , 4.35-4.50 (m, 2H), 4.25-4.35 (m, 2H), 3.55 (s, 3H), 3.05-3.20 (m, 1H), 2.70-2.85 (m, 2H), 2·55· 2.60 ( m, 4H), 1.75-1.80 (m, 4H), 1.30 (d, 3H). Example 18 Ν·[2_methoxy-6_(2_pyrrolidineβ1_yl-ethoxypyridine-3-yl]_4_(2,2,2-trifluoro-1-methyl-ethyl)_ Benzene-branched amine 119387.doc • 151 - 200808727 According to a synthetic procedure similar to that described for Example 15, from 2-methoxy-6·(2-indolobi sigma-1-yl-ethoxy The desired product was obtained by the starting of the starting material from the base of the product: MS (ESI) m/z: 474.25. [M+H] + h-NMR (CDC13): δ [ppm] 7.70 (d, 1H), 7.65 (d, 2H), 7.35 (d, 2H), 6.35 (d, lH), 4.35-4.40 (m , 2H), 3.50 (s, 3H), 2.85-2.92 (m, 2H), 2.60-2.73 (m, 4H), 1.80-1.90 (m, 4H), 1.50 (d, 3H). Example 19 N-[ 2-methoxy-6-(2-0-Butyl-1-yl-ethoxy)-|»Bis-3-yl]-4-oxazol-5-yl-benzenesulfonamide A synthetic procedure similar to the one described for the synthesis procedure described in Example 15 from 2-methoxy-6-(2-pyrrolidino-1-yl-ethoxy)-σ butyl-3-amine and 4 - oxazol-5-yl-benzenesulfonyl group gas to give the desired product. MS (ESI) m/z: 445.15 [M+H] + h-NMR (MeOD): δ [ppm] 8.35 (s, 1H ), 7.85 (d, 2H), 7.75 (d, 2H), 7.71 (d, 1H), 7·69 (s, 1H), 6.45 (d, 1H), 4.55-4.60 (m, 2H), 3.65-3.75 (m, 2H), 3.60 (s, 3H), 3·60_3·65 (m, 2H), 3.15-3.25 (m, 2H), 2·00-2_25 (m, 4H). Example 20 4-isopropyl Ν-Ν·[4-Methoxy-2-(2-propylamino-ethoxy)- singly-based] Benzene sulfonamide according to a synthetic procedure similar to that described in Example 1 From [2-(5-Amino-4-methoxy-pyrimidin-2-yloxy)-ethyl]-propyl-aminomethyl 119387.doc -152· 200808727 acid tert-butyl ester and 4- The isopropyl-benzenesulfonyl group was initially obtained to give the desired product. MS (ESI) m/z: 409.15 [M+H] + iH-NMR (DMSO): δ [ppm] 8.00 (s, 1H), 7.55 ( d, 2H), 7·48 (d, 2H), 4.25-4.30 (m, 2H), 3.50 (s, 3H), 2.90-3.00 (m, 1H), 2.85-2.92 (m, 2H), 2.55- 2.60 (m, 2H), 1.37-1.50 (m, 2H), 1.20 (d, 6H), 0.85 (t, 3H). Example 21 N-[4-Methoxy-2-(2-propylamino-ethoxy)-snack--5-yl]-4_trioxanoxy-benzenesulfonamide according to the relevant examples A synthetic procedure similar to that described in the synthesis procedure from [2-(5-Amino-4-methoxy-pyrimidin-2-yloxy)-ethyl]-propyl-carbamic acid tert-butyl ester And 4-trifluoromethoxy-benzenesulfonyl group gas initially to obtain the desired product. MS (ESI) m/z: 451.15 [M+H] + iH-NMR (MeOD): δ [ppm] 8.02 (s, 1H), 7.74 (d, 2H), 7.28 (d5 2H), 4:30, 4e35 (m5 2H), 3·55 (s, 3H), 2.95-3.00 (m, 2H), 2.60-2.67 (m, 2H), 1.48-1.52 (m, 2H), 0.87 (t, 3H). Example 22 N-[6-(2-Didecylamino-ethoxy)-indole ratio thiophene isopropyl benzoic acid xHCl was synthesized according to a synthetic procedure similar to that described for Example 15. 6-(2-(1-Methylamino)-ethoxyindole-indole-11--3-ylamine and 4-isopropyl-behenylxanthene base gas afforded the desired product. MS (ESI) m/z: 364.15 [M+H] + 119387.doc -153- 200808727 Example 23 4-isopropyl-N-[6-(2 • propylamino-ethyl)- ιι 唆-3-ylbenzene Indoleamine XHC1 was synthesized from [2-(5-amino-acridin-2-yloxy)-ethyl]-propyl-amino decanoic acid according to a synthetic procedure similar to that described for Example 1. Starting from tributyl acrylate and 4-isopropyl-benzene- hydrazine gas, the desired product was obtained. MS (ESI) m/z: 378.15 [M+H] + Example 24 Ν·[6-(2-dipropylamine) Base _ ethoxy) _n ratio thiophene 4 isopropyl phenyl hydrazide XHC1 参 醯 醯 侧 侧 ( 68 (68.22 mg, 0.32 mmol) was added to 4 isopropyl-N-[6-( 2-propylamino-ethoxy)_ σ is more than decyl phthalamide (81 mg, 0.21 mmol), propionaldehyde (13.71 mg, 0.24 mmol) and acetic acid (0.22 ml) in dichloropurine Alkane (5 ml) In the solution, the mixture was stirred for 1 h at room temperature. After evaporating the solvent under reduced pressure, the residue was dissolved in 1 n NaOH </ </ RTI> and extracted three times with B. The combined organic layer was dried over MgS 4 The solvent was evaporated under reduced pressure and the HCl was added to diethyl ether in diethyl ether. The solid formed was transferred and dried in vacuo to give 66 mg (67.4%). The title compound. MS (ESI) m/z: 42 </RTI> [M+H] + b-NMR (DMSO): δ [ppm] 10·20 (s br·, 2H), 7.85 (s, 1H), 7.65 ( d, 2H), 7.50 (d, lH), 7.45 (d, 2H), 6.80 (d, lH), 4.50-4·57 (m, 2H), 3.40-3.50 (m, 2H), 3.00-3.10 ( m, 4H), 2.90- 119387.doc -154- 200808727 3.00 (m, 1Η), 1.60-1.70 (m, 4H), 1.20 (d, 6H), 0.90 (t, 6H). The following is an example of a synthetic procedure similar to the one described in the synthesis procedure. Example 25 4_Isopropyl-indole-[2-methoxy-6-((R)_l-pyrrolidin-2-ylmethoxy)-pyridine - 3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 392.1 [M+H] + iH-NMR (DMSO): δ [ppm] 9.20-9.70 (m,2H),7·60 ( d, 2H) 7.50 (d,1H), 7.40 (d,2H), 6.40 (d,1H), 4.38-4.48 (m,2H), 3.85-88 (m,1H),3.52 (s,3H),3.12-3.22 ( m, 2H), 2.97 earned 2.99 (m, 1H), 2.05-2.15 (m, 1H), 1.85-2.05 (m, 2H), 1.68-1.70 (m, 1H), 1.23 (d, 6H). Example 26 4-(2-Arsin-ethoxy)-oxime [2-methoxy-6-((R)-l -11 piroxicam-2-yloxy)-pyridin-3-yl Benzenesulfonamide xHCl MS (ESI) m/z: 426.1 [M+H] + W-NMR (DMSO): δ [ppm] 9.98 (bs, 1H), 9.32-9.38 (m, 2H), 7.58 ( d, 2H), 7.38 (d, 1H), 7.09 (d, 2H), 6.36 (d, 1H), 4.68-4.80 (m, 2H), 4.36-4.45 (m, 2H), 4.27-4.35 (m, 2H), 3.80-3.86 (m, lH), 3.55 (s, 3H), 3.12-3_20 (m, 2H), 2.03-2.10 (m, 1H), 1.83-1.97 (m, 2H), 1.64-1.72 ( m, 1H). Example 27 N-[2-Methoxy-6-((R)-1 _ σ 洛 咬 -2--2-ylmethoxy) ϋ 咬 咬 -3 - _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 087. s,1H), 9.22-9.28 (m,1H),8·53 (s,1H),7.88 (d,2H), 7.87 (s,1H), 7.48 (d,1H),6.38 (d,1H) , 4.32-4.46 (m, 2H), 3.80-88 (m, 1H), 3·49 (s, 3H), 3.12-3.22 (m, 2H), 2.02-2.10 (m, 1H), 1.82-1.98 ( m, 2H), 1·62·1·72 (m, 1H). Example 28 4-isopropyl-N-[2-methoxy-6-((S)-l-pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 392.1 [M+H] + b-NMR (DMSO): δ [ppm] 9.20-9.70 (m, 2H), 7.60 (d, 2H), 7.50 (d, 1H), 7.40 ( d, 2H), 6.40 (d, 1H), 4.38-4.48 (m, 2H), 3.85 face 88 (m, 1H), 3.52 (s, 3H), 3.12-3.22 (m, 2H), 2.97-2.99 ( m, 1H), 2.05-2.15 (m, 1H), 1.85-2.05 (m, 2Η), 1.68·1·70 (m, 1H), 1·23 (d5 6H). Example 29 4 -Isopropyl-N-[2-indolyl-6·(2-propylamino-ethoxy)-11 than acetyl-3-yl]-benzenesulfonamide xHCl MS (ESI) m /z: 392.1 [M+H] + W-NMR (MeOD): δ [ppm] 7·63 (d, 2H), 7·47 (d, 1H), 7·43 (d, 2H), 6.78 ( d, 1H), 4.58-4.62 (m, 2H), 3.45-3.51 (m, 2H), 3.00-3.10 (m, 3H), 2.14 (s, 3H), 1.72-1.85 (m, 2H), 1.30 ( D5 6H), 1.07 (t, 3H). 119387.doc -156- 200808727 Example 30 N -[2-Methyl-6-(2-propylamino-ethoxy)-indole-bine-3-yl]_4_dimethoxy-benzenesulfonate Hydrazine xHCl MS (ESI) m/z: 434.1 [M+H] + NMR (MeOD): δ [ppm] 7.81 (d5 2H)5 7.46 (d5 2H)? 7.40 (d,1H), 6.72 ( d,1H), 4.57-4.59 (m,2H),3.44-3.46 (m,2H), 3.05-3.08 (m,2H),2.14 (s,3H),1.72-1.81 (m,2H),1.05 ( t, 3H). Example 31 4-Difluoromethoxy-indole [2-methyl-6-(2-propylamino)ethoxy)-pyridin-3-yl]-benzenesulfonamide xHCl MS (ESI) m /z: 416.1 [M+H] + !H-NMR (DMSO): δ [ppm] 9.85 (s5 1H)? 9.33 (bs5 2H)5 7.71 (d,2H), 7.42 (t,1H), 7.36 ( d, 2H), 7.22 (d, 1H), 6_63 (d, 1H), 4.47-4.49 (m, 2H), 3.24-3.27 (m, 2H), 2.85-2.91 (m, 2H), 2.10 (s, 3H) 5 1.63-1, 72 (m5 2H), 〇e90 (t, 3H). Example 32 4-(2,2-Difluoro-ethoxy)-N-[2-methyl-6-(2-propylaminobenzene-ethoxy)·acrid-3-yl]-benzenesulfonate Hydrazine xHCl MS (ESI) m/z: 430.1 [M+H] + NMR (DMSO): δ [ppm] 9.66 (s? 1H), 9.34 (bs5 2H)3 7.61 (d,2H), 7.23 (d, 1H), 7.18 (d, 2H), 6.63 (d, 1H), 6.31-6.55 (m, 1H), 4.40-4.50 (m, 4H), 3.24-3.30 (m, 2H), 2.85-2.95 (m, 2H), 2.11 (s, 3H), 1.65-1.75 (m, 2H), 0.90 (t, 3H). 119387.doc -157- 200808727 Example 33 4·(2-Fluoro-ethoxy)-N-[2-mercapto-6-(2-propylamino-ethoxy)-lepidine-3-yl - Benzenesulfonamide xHCl MS (ESI) m/z: 412.1 [M+H] + b-NMR (DMSO): δ [ppm] 9.62 (s, 1H), 9.32 (bs, 2H), 7.60 (d) , 2H), 7.23 (d, 1H), 7.13 (d, 2H), 6.64 (d, 1H), 4.70-4.85 (m, 2H), 4.48-4.50 (m, 2H), 4.30-4.39 (m, 2H) ), 3.24 - 3.32 (m, 2H), 2.85 - 2.95 (m, 2H), 2.11 (s, 3H), 1.65-1.75 (m, 2H), 0.90 (t, 3H). Example 34 4-((R)-2-Fluoro-1-methyl-ethyl)-indole-[2·methyl-6-(2-propylamino-ethoxy)-pyridin-3-yl - Benzenesulfonamide xHCl MS (ESI) m/z: 410.1 [M+H] + NMR (DMSO): δ [ppm] 9.74 (s5 1H)? 9.35 (bs, 2H)? 7.61 (d, 2H), 7.50 (d, 2H), 7.26 (d, 1H), 6.63 (d, 1H), 4.40-4.62 (m, 4H), 3.20-3.30 (m, 2H), 3.05-3.08 (m, 1H) , 2.85-2.95 (m, 2H), 2.04 (s, 3H), 1·65-1·75 (m, 2H), 1.24 (d, 3H), 0.91 (t, 3H). Example 35 4-((S)-2 -Ga-1-methyl-ethyl)-N-[2-mercapto-6-(2-propylamino-ethoxy)pyridin-3-yl - Benzenesulfonamide xHCl MS (ESI) m/z: 410.1 [M+H] + b-NMR (DMSO): δ [ppm] 9·77 (s, 1H), 9.38 (bs, 2H), 7 · 61 (d, 2H), 7.50 (d, 2H), 7.26 (d, 1H), 6.63 (d, 1H), 4.40-4.62 119387.doc • 158- 200808727 (m, 4H), 3.20-3.30 (m , 3H), 2.85-2.95 (m, 2H), 2.04 (s, 3H), 1.65-1.75 (m, 2H), 1.24 (d, 3H), 0.89 (t, 3H). Example 36 N_[2-Methyl-6-(2-propylamino-ethoxy)-0-pyridin-3-yl]_4-11-oxan-5-yl-benzenesulfonamide xHCl MS (ESI) m/z: 417.1 [M+H] + iH-NMR (DMSO): δ [ppm] 9·92 (s, 1H), 9.35 (bs, 2H), 8.57 (s, 1H), 7.93 (d, 2H) ), 7.92 (s, 1H), 7.45 (d, 2H), 7.24 (d, 1H), 6.64 (d, 1H), 4.47-4.50 (m, 2H), 3.24-3.30 (m, 2H), 2.85- 2.92 (m, 2H), 2.11 (s, 3H), 1.64-1.73 (m, 2H), 0.90 (t, 3H). Example 37 N-[2-Methyl-6·(2-propylamino-ethoxy)-111 butyl-3-yl]-4-oxan-4-yl-benzenesulfonamide xHCl MS (ESI m/z: 417.1 [M+H] + !H-NMR (DMSO): δ [ppm] 9.86 (s, 1H)? 9.31 (bs, 2H)? 8.84 (s, 1H), 8.54 (s, 1H) ), 7.99 (d, 2H), 7.72 (d, 2H), 7.25 (d, 1H), 6.65 (d, 1H), 4.47-4.50 (m, 2H), 3.20-3.30 (m, 2H), 2.85- 2.92 (m, 2H), 2.11 (s, 3H), 1.64-1.72 (m, 2H), 0.90 (t, 3H). Example 38 N-[2-Methyl-6-((S)-l-pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-4-oxazol-5-yl-benzenesulfonamide xHCl MS (ESI) m/z: 379.1 [M+H] + 119387.doc -159 - 200808727 W-NMR (DMSO): δ [ppm] 9.60-9.80 (m, 2H), 9.00-9.10 (m, 1H) ), 8.52 (bs, 1H), 7.85-7.90 (m, 3H), 7.69 (d, 2H), 7.21 (d, 1H), 6.60 (d, 1H), 4·28-4·41 (m, 2H) ), 3.80-3.90 (m, 1H), 3.10-3.20 (m, 2H), 2.05-2.10 (m, 4H), 1.80-1.95 (m, 2H), 1.65-1.75 (m, 1H). Example 39 4-(2,2-Difluoro-ethoxy)-N-[2-methyl-6-((S)-l-.pyrrolidin-2-ylmethoxy)-pyridine-3 - phenyl sulfonamide x HCl MS (ESI) m/z: 428.1 [M+H] + 1H-NMR (DMSO): δ [ppm] 9.50-9.60 (m, 2H), 8.90-9.00 (m, 1H), 7.89 (d, 2H), 7.24 (d, 1H), 7.18 (d, 2H), 6.64 (d, 1H), 6.28-6.57 (m, 1H), 4.28-4.48 (m, 4H), 3.80 -3.90 (m, 1H), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H), 1.85-2.00 (m, 2H), 1.70-1.80 (m, 1H). Example 40 4-(2-Gas-Ethoxy)_N-[2-Methyl-6-((S)_1-0 0-Butyl-2-ylmethoxy)-pyridin-3-yl]-benzenesulfonate Indoleamine xHCl MS (ESI) m/z: 410.1 [M+H] + W-NMR (DMSO): δ [ppm] 9.60-9.70 (m,1H), 9.54 (s,1H), 8.95-9.05 (m , 1H), 7.58 (d, 2H), 7.24 (d, 1H), 7.13 (d, 2H), 6.64 (d, lH), 4.71-4.85 (m, 2H), 4.30-4.50 (m, 4H), 3.80-3.90 (m, lH), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H), 1.85. 2.00 (m, 2H), 1.70-1.80 (m, 1H). Example 41 119387.doc -160- 200808727 N- [2-Methyl-6-((S)-l -11 鸣 * _ -2- -2-yloxy)-0 ratio _ -3- yl] _4-dioxamethoxy-benzenesulfonamide xHCl MS (ESI) m/z: 432.1 [M+H] + h-NMR (DMSO): δ [ppm] 9.90 (s, 1H), 9.60-9.70 ( m,1H), 8.95-9.05 (m,1H), 7.79 (d,2H), 7.60 (d,2H), 7.27 (d,1H), 6.66 (d,lH),4.31-4.47 (m,2H) , 3.85-3.95 (m, lH), 3.15-3.25 (m, 2H), 2.05-2.15 (m, 4H), 1.85-2.00 (m, 2H), 1.70-1.80 (m, 1H). Example 42 4-((R)-2_Gas-1 -Methyl-ethyl)-N-[2_methyl-6-((S)-l_ϋ 鸣 鸣 &quot;Bite-2-ylmethoxy)_ Pyridin-3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 408.1 [M+H] + 1H-NMR (DMSO): δ [ppm] 9.65 (s, 1H), 9.45-9.55 (m ,1H), 8.85-8.95 (m,1H),7·60 (d,2H),7.51 (d,2H),7·28 (d5 1H), 6.65(d,lH),4.48-4.62 (m, 2H), 4.30-4.47 (m, 2H), 3.85-3: 95 (m5 1H), 3β20-3·30 (m, 2H), 2.08-2.15 (m, 1H), 2.04 (s, 3H), 1.85 -2.00 (m, 2H), 1.70-1.80 (m, 1H), 1.27 (d, 3H). Example 43 4-isopropyl-N-[2·methyl-6-((S)_l-indole ratio 1^-2_ylmethoxy)-0 ratio bite-3 phenyl sulfonamide xHCl MS (ESI) m/z: 390.1 [M+H] + ^-NMR (DMSO): δ [ppm] 9.55-9.65 (m? 2H)? 8.93-9.02 (m3 1H), 7.57 (d, 2H), 7.45 (d, 2H), 7.28 (d, 1H), 6·65 (d, 1H), 119387.doc • 161- 200808727 4·30_4·45 (m, 4H), 3.85-3.95 (m, 1H), 3.15 -3.25 (m, 2H), 2.95-3.05 (m, lH), 2.08-2.15 (m, lH), 2.04 (s, 3H), 1.85 - 2·00 (m, 2H), 1.70-1.80 (m, 1H), 1.24 (d, 3H). Example 44 N-[2-Methyl-6-((R)-l.pyrrolidin-2-ylmethoxy)-pyridin-3-yl]-4-oxazol-5-yl-benzenesulfonamide xHCl MS (ESI) m/z: 379.1 [M+H] + b-NMR (DMSO): δ [ppm] 9·75 (s,1H), 9.14-9.24 (m,1H), 8.64-8.74 (m , 1H), 8.57 (s, 1H), 7.90-7.95 (m, 3H), 7.73 (d, 2H), 7.27 (d, lH), 6.65 (d, lH), 4.26-4.47 (m, 2H) ), 3.85- 3.94 (m5 1H)? 3.20-3.25 (m5 2H)? 2.07-2.15 (m, 4H), 1.90-2·10 (m, 2H), 1.70-1.80 (m, 1H). Example 45 4_Isopropyl-indole·[2-methyl-6-((R)-l-pyrrolidin-2-yloxy)-indole bite-3· phenyl sulfonamide xHCl MS (ESI) m/z: 354.1 [M+H] + W-NMR (DMSO): δ [ppm] 9.59 (s,1H), 9.36-9.44 (m,1H), 8.78-8.86 (m,1H), 7·57 (d, 2H), 7·45 (d, 2H), 7·28 (d, 1H), 6·65 (d, 1H), 4.28-4.47 (m, 4H), 3.85-3.94 (m , 1H), 3.18-3.25 (m, 2H), 2.95-3.05 (m, 1H), 2.08.2.15 (m, 1H), 2.04 (s, 3H), 1.88-2.00 (m, 2H), 1.H80 (m, 1H), 1·24 (d, 3H). The following examples were obtained according to a synthesis procedure similar to the one described in connection with Example 12. 119387.doc -162- 200808727 Example 46 4-((R)-2,2-Difluoro 4 _1_methyl-ethyl)_N-[2-methoxy- 6_(2-propylamino-B Oxy)-pyridin-3-ylbenzenesulfonamide xHCl MS (ESI) m/z: 444.1 [M+H] + b-NMR (DMSO): δ [ppm] 9.54 (s,1H), 9.44 ( Bs,2H), 7.61- 7.63 (m? 2H)? 7.49-7.52 (m5 3H)5 6.40 (d5 1H), 6.10- 6.34 (m,1H), 4.50-4.52 (m,2H), 3.43 (s, 3H), 3.32-3.40 (m, 1H), 3·25·3_28 (m, 2H), 2.85-2.90 (m, 2H), 1.65-1.73 (m, 2H), 1.31 (d, 3H), 0.89 ( t, 3H). Example 47 4-((S)-2,2-dioxa-1-methyl-ethyl)-N-[2-methoxy-6-(2-propylamino)ethoxylated-pyridine -3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 444.1 [M+H] + iH-NMR (DMSO): δ [ppm] 9.54 (s, 1H), 9.44 (bs, 2H) , 7.61- 7.63 (m, 2H), 7.49-7.52 (m, 3H), 6.40 (d, lH), 6.10- 6.34 (m, 1H), 4·50-4·52 (m, 2H), 3.43 ( s,3H),3·32·3·40 (m,1H), 3.25-3.28 (m,2H),2-85-2.90 (m,2H),1.65-1.73 (m,2H),1.31 (d , 3H), 0_89 (t, 3H). Example 48 N-[2-Methoxy-6-(2-propylamino-ethoxy)-pyridin-3-yl]-4-oxazole-4-yl-benzenesulfonamide xHCl MS (ESI) m /z: 433.1 [M+H] + iH-NMR (DMSO): δ [ppm] 9.58 (s, 1H), 9·25 (bs, 2H), 8.81 (s, 1H), 8.54 (s, 1H), 7.96 (d5 2H), 7.71 (d, 2H), 7·49 (d, 119387.doc -163 - 200808727 1Η), 6·40 (d, 1Η), 6·10-6·34 (m , 1H), 4.48-4.51 (m, 2H), 3.52 (s? 3H)? 3.25-3.28 (m5 2H)5 2.85-2.90 (m? 2H)5 1.63-1.71 (m, 2H), 0.90 (t, 3H). Example 49 N-[2-Methoxy-6-(2-propylamino)ethoxy)-n ratio -3-yl]-4-n than sal-7-yl-benzenesulfonamide xHCl MS (ESI) m/z: 432.1 [M+H] + &lt;RTI ID=0.0&gt;&gt;&gt;&gt; · 01 (d, 2H), 7.82 (s, 1H), 7.75 (d, 2H), 7.50 (d, 1H), 6.61 (bs, 1H), 6.40 (d, 1H), 4.42-4.47 (m, 2H) ), 3.54 (s, 3H), 3.25-3.30 (m, 2H), 2.85-2.95 (m, 2Ή), 1.56-1.68 (m, 2H), 0.89 (t, 3H). Example 50 4_(3-Air-propyl)_Ν·[2-methyl-6-(2-propylamino-ethoxy)-11 ratio bit -3-methyl]• benzenesulfonamide xHCl MS (ESI) m/z: 410,1 [M+H] + ^-NMR (DMSO): δ [ppm] 9.72 (s5 1H)? 9.36 (bs5 2H)5 7.56 (d, 2H), 7.41 (d, 2H), 7.22 (d, 1H), 6.61 (d, 1H), 4.35-4.48 (m, 4H), 3.20-3.30 (m, 2H), 2.83-2.90 (m, 2H), 2.70-2.76 (m, 2H), 2.03 (s, 3H), 1.85-2.00 (m, 2 H), 1.62-1-71 (m, 2H), 0.89 (t, 3H). Example 51 N-[2-Methyl-6-(2-propylamino-ethoxy)-octyl-3-yl]-4-((R)-2,2,2-trifluoro- 1_Methyl-ethyl)-benzenesulfonamide xHCl 119387.doc -164· 200808727 MS (ESI) m/z: 446.1 [M+H] + iH-NMR (DMSO): δ [ppm] 9.86 (s , 1H), 9·36 (bs, 2H), 7.66 (d, 2H), 7.60 (d, 2H), 7.25 (d, 1H), 6.62 (d, 1H), 4.45-4.48 (m, 2H), 3.90-4.02 (m, 1H), 3.20-3.30 (m, 2H), 2.83-2.90 (m, 2H), 1.98 (s, 3H), 1.62-1.71 (m, 2H), 1.44 (d, 3H), 0.89 (t, 3H). Example 52 4-((R)_2,2-Difluoro-1-methyl-ethyl)-N-[2-methyl-6-(2-propylamino-ethoxy)-pyridine-3 - Benzene sulfonamide x HCl MS (ESI) m/z: 428.1 [M+H] + W-NMR (DMSO): δ [ppm] 9.81 (s, 1H), 9.36 (bs, 2H), 7.62 (d, 2H), 7.52 (d, 2H), 7.24 (d, 1H), 6.62 (d, 1H), 6.09-6.32 (m, 1H), 4.45-4.48 (m, 2H), 3.34-3.42 (m , 1H), 3.22-3.27 (m, 2H), 2.83-2.90 (m, 2H), 2.01 (s, 3H), 1.62-1.71 (m, 2H), 1.30 (d, 3H), 0-89 (t , 3H). Example 53 N_[2-Methyl-6·(2-propylamino-ethoxy)_11 butyl-3-yl]-4-(2,2,2-difluoro-ethoxy)-benzene Sulfonamide xHCl MS (ESI) m/z: 412.1 [M+H] + W-NMR (DMSO): δ [ppm] 9.68 (s, 1H), 9.31 (bs, 2H), 7_62 (d, 2H) , 7.22-7.24 (m, 3H), 6.63 (d, 1H), 4.87-4.92 (m, 2H), 4.46-4.51 (m, 2H), 3.24-3.30 (m, 2H), 2.85-2.95 ( m, 2H), 2.11 (s, 3H), 1.65-1.74 (m, 2H), 0.92 (t, 3H). Example 54 119387.doc -165- 200808727 4-((R)-2,2_dioxa-1 -mercapto-ethyl)-N-[4-methyl-6-(2-propylamino)- Ethoxy)-pyridin-3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 428.1 [M+H] + b-NMR (DMSO): δ [ppm] 9·70 (s, 1H ), 8.60-8.66 (m, 2H), 7.64-7.69 (m, 3H), 7.56 (d, 2H), 6.70 (s, 1H), 6.09-6.39 (m, 1H), 4.45-4.48 (m, 2H) ), 3.30-3.45 (m, 3H), 2.90-3.00 (m, 2H), 1.94 (s, 3H), 1.60-1.70 (m, 2H), 1.35 (d, 3H), 0.94 (t, 3H). Example 55 N-[4-Mercapto-6-(2-propylamino-ethoxy)-pyridin-3-yl]-4.oxazol-4-yl-benzenesulfonamide xHCl MS (ESI) m/z: 381.1 [M+H] + ^-NMR (DMSO): δ [ppm] 9.73 (s5 1H)5 8.83 (s? 1H)5 8.56-8.65 (m, 2H), 8.01 (d, 2H) ,7·73 (d,2H), 7.66 (s,1H), 6.71 (s,1H),4.44-4.47 (m,2H), 3.30-3.45 (m,2H), 2.90-3.00 (m5 2H), 2:01 (s5 3H), 1·60-1·68 (m, 2H), 0.93 (t, 3H). Example 56 4-(2,2-Difluoro-ethoxy)-N-[4-methyl-6-(2-propylaminobenzene-ethoxy)·acridin-3-yl]-benzenesulfonate Indoleamine xHCl MS (ESI) m/z: 394.1 [M+H] + h-NMR (DMSO): δ [ppm] 9.70 (s, 1H), 9.35 (bs, 2H), 7.58-7.62 (m, 3H ), 7.17 (d, 1H), 6.69 (s, 1H), 6.29-6.55 (m, 1H), 4.38-4.50 (m, 4H), 3.21-3.28 (m, 2H), 2.82-2.90 (m, 2H) ), 1.99 (s, 3H), 1.62-1.71 (m, 2H), 0.89 (t, 3H). 119387.doc -166- 200808727 Example 57 4-((R)-2-Fluoro-1-indolyl-ethyl)-N-[4-methyl-6-(2-propylamino-ethoxy) )-pyridin-3-yl]-benzenesulfonamide xHCl MS (ESI) m/z: 410.1 [M+H] + h-NMR (DMSO): δ [ppm] 9.76 (s, 1H), 9.32 (bs , 2,,,,, , 2H), 1.92 (s, 3H), 1_63·1.71 (m, 2H), 1.23 (d, 3H), 0.89 (t, 3H). Example 58 N-[4-Methyl-6-(2-propylamino-ethoxy)-0 butyl-3-yl]-4-dimethoxy-benzenesulfonamide xHCl MS (ESI m/z: 434.1 [M+H] + h-NMR (DMSO): δ [ppm] 9·88 (s, 1H), 8_80·8·90 (m, 1H), 7.79 (d, 2H), 7.58-7.63 (m, 3H), 6.70 (s, 1H), 4.43-4.46 (m, 2H), 3_44-3·46 (m, 2H), 3.25-3.35 (m, 2H), 2·85-2 · 95 (m, 2H), 1.95 (s, 3H), 1·58·1·68 (m5 2H) 5 0:91 (t5 3H). Example 59 4-isopropyl-N-[4-methyl-6-(2-propylamino-ethoxy)-nfcb-3-yl]-benzenesulfonamide xHCl MS (ESI) m/z : 392.1 [M+H] + ^-NMR (MeOD): δ [ppm] 7.73 (s? 1H)5 7.63 (d5 2H)? 7.42 (d, 2H), 6.81 (s, 1H), 4.55-4.58 ( m, 2H), 3.44-3.46 (m, 2H), 3.00-3.10 (m, 3H), 2.05 (s, 3H), 1.72-1.80 (m, 2H), 1.29 (d, 6H), 1.05 (t, 3H). 119387.doc -167· 200808727 Example 60 4_(2-Fluoro-ethoxy)-N-[5-methyl-6-(2-propylamino-ethoxy)^bit-3-yl] - Benzenesulfonamide xHCl MS (ESI) m/z: 376.1 [M+H] + h-NMR (DMSO): δ [ppm] 1 〇·10 (s, 1H), 9 3 〇 (bs, 2H) , 7.62-7.66 (m,3H), 7.31 (d,1H), 7.09 (d,2H), 4.70-4.80 (m, 2H)? 4.48-4.50 (m? 2H)5 4.30-4.39 (m5 2H), 3.24-3.30 (m? 2H), 2.85-2.90 (m, 2H), 2.12 (s, 3H), 1.62-1.72 (m, 2H), 0.90 (t5 3H). Example 61 4-Isopropyl-N-{2-methylpropylpyrrolidinyl)oxy]pyridyl}benzenesulfonamide (2E)-but-2-ene disulfonium salt 61·1 2·methyl 3-nitro-6-(pyrrolidinyl-3-yloxy)pyridine 6-methyl-5-nitropyridine-2-alcohol (5 g) was dissolved in tetrahydrofuran and DL-3-pyrrolidine was added Alcohol (2·83 g) and triphenylphosphine (12·76 g). (7) diazoene-1,2-dicarboxylic acid di-t-butyl ester (11·21 g) dissolved in tetrahydrofuran (15 mL) was added dropwise over 15 mm. The reaction mixture was scrambled for 50 h at room temperature. The reaction mixture was concentrated in vacuo. The remaining residue was suspended in methylene chloride and trifluoroacetic acid (7.55 mL) was added dropwise. The reaction mixture was stirred for 12 h at room temperature. The reaction mixture was concentrated in vacuo, redissolved in: methane, and extracted with 1 N hydrochloric acid several times. The combined aqueous extracts were treated with 1 N Na 〇H to pH 10 and the combined ethyl acetate extracts were washed sequentially with water and brine and dried (1 S sodium). After concentrating in vacuo, the crude material was purified by flash chromatography 119 387. Yield: 1.5 g ( 18.6%, pale yellow oil). 61.2. 2-Mercapto-3-nitro-6-[(1-propionylpyrrolidin-3-yl)oxyp is a bit of 2-methyl-3-nitro-6-(pyrrolidine- 3-Methoxy)pyridine (1.3 g) was dissolved in dichloromethane (20 ml) and triethylamine (1.57 ml) was added. The solution was cooled to 〇 ° C and a solution of propyl chlorobenzene (574 mg) in dichloromethane (5 mL) The reaction mixture was allowed to reach room temperature and stirred for additional 5 min. Add water (10 ml). After stirring for 3 min, the phases were separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried (sodium sulfate) and concentrated in vacuo. The crude product was purified by flash chromatography (dichloromethane, methylene chloride / methanol = 98/2). Yield: 95 〇 11 ^ (64.9%, pale yellow oil). 61.3 2-Methyl-6-[(1-propyl aryl), -3-yl)oxy ρ, 唆·3-amine 2-methyl-3-nitro-6-[(l- Propionyl η than pyridyl _3·yl)oxy p-pyridine (940 mg) &gt; glutamic acid in methanol (50 mL) and nitriding (H-cube, from Thales Nano, 10% Pd/C, 60 °C, 50 bar, 1 mL/min). The methanol was removed in vacuo. Yield: 800 mg (95%, colorless oil). 61.4 4-isopropyl-N-{2-mercapto_6_[(1-propenyl σ-pyridin-3-yl)oxy] oxazol-3-yl}benzenesulfonamide 2:A Base-6-[(1-propionyl hydrazine _3_yl)oxy] 吼___amine (3 40 mg) was dissolved in pyridine (3.3 mL) and slowly added with stirring -4 Isopropyl benzene sulfonyl chloride (358 mg). After stirring at room temperature for 19 h, the reaction mixture was diluted with dioxane and aq. After stirring at room temperature for 1 h, the phases were separated. The organic phase was dried (sodium sulphate), concentrated and purified and purified elute Yield: 460 mg (78%, light yellow oil). 6·5 4-isopropyl-N-{2_methyl_6-[(1-propylpyrrolidin-3-yl)oxy] 比 咬 -3 - base} - butyl-2 -dicarboxylic acid salt lithium aluminum hydride (88 mg) was suspended in tetrahydrofuran (丨mL) and added to tetrahydrofuran (丨ml) dropwise at room temperature for 5 min. Propyl_N-{2-mercapto-6-[(l-propionylfluorenyl-3-yl)oxypyridinyl-3-ylsulfonamide (250 mg). After stirring for an additional 30 min, the reaction was quenched with 1% water in tetrahydrofuran. The solution in South Central is stopped and concentrated. The residue was taken up in EtOAc (EtOAc)EtOAc. The crude product was purified by flash chromatography (d.sub.2, EtOAc, m. The product (70 mg) was dissolved in methanol and (2E) u-enediic acid (19 mg) was added. After stirring at 40 ° C for 1 h, the methanol was removed in vacuo. Yield: 89 mg (26%, colorless solid). MS (ESI) m/z: 418.1 [M+H] + </ RTI> </ RTI> </ RTI> 4-(2- ethoxyethoxy) _n_{2_methyl_6-[(l-propylpyrrolidinyl)oxy] 0-pyridine-3-yl}benzenesulfonamide (2E)·but-2-enedionate 4-(2-fluoroethoxy)-N- {2_methyl-6-[(1_- Base 吼嘻3_yl)oxy]pyridine_3_yl}benzenesulfonamide (2E)-but-2-ene dicarboxylate is similar to Example 6 i from 2-methyl-6-[( Preparation of l-propionyl pyrrolidine-3-yloxy]pyridine_3_amine and 4-(2-fluoroethoxy)benzenesulfonyl chloride. MS (ESI) m/z: 438.1 [M+H] + EXAMPLE 63 4 (2'2 · fluoroethoxymethyl-6-[(l-propyl.). .doc -170- 200808727 base]pyridin-3-yl}benzenesulfonamide (2E)-but-2,2-enedionate 4-(2,2-difluoroethoxy)-]^-{ 2-methyl-6-[(1-propyl ° than biting _3-yl) oxy] fluorene-3-yl} phenyl decylamine (2E)-but-2-enedionate is similar Example 61 from 2-methyl-6-[(l-propionylpyrrolidin-3-yl)oxy]acridin-3-amine and 4-(2,2-difluoroethoxy)benzenesulfonate Prepared by hydrazino chloride MS (ESI) m/z: 456.1 [M+H] + Example 64 4-[(lS)-2,2-difluoro-1-methylethyl]·Ν-{2- Base-6·[(1-propyln-pyrrolidin-3-yl)oxy] ° pyridine-3-yl}benzenesulfonamide (2Ε)-but-2-enedionate 4-[( lS)-2,2-difluoro-1-methylethyl]_ν·{2_methyl-6-[(1-propylpyrrolidin-3-yl)oxy]pyridin-3-yl}benzene Sulfonamide (2Ε)-but-2-enedioate is similar to Example 61 from 2-methyl-6-[(1-propionylpyrrolidin-3-yl)oxy]pyridin-3-amine And 4-[(18)-2,2-difluoro-1-methylethyl]benzenesulfonyl group gas. MS (ESI) m/z: 454.1 [M+H] + III·Gallen ) the form of administration A) Lozenges In a conventional manner, tablets of the following compositions are compressed on a tablet machine: 40 mg of material from Example 8 120 mg corn starch 13.5 mg gelatin 45 mg lactose 2.25 mg Aerosil® (submicroscopic fine dispersion) Chemically pure tannic acid) 6.75 mg potato starch (in the form of a 6% paste) B) Sugar-coated tablets 119387.doc • 171 - 200808727 20 mg of the substance from Example 8 60 mg core composition 70 mg saccharification composition core combination The composition consists of 9 parts of corn starch, 3 parts of lactose and bismuth (9): (10) vinylpyrrolidone/vinyl acetate copolymer. The saccharification composition consists of 5 parts sucrose, 2 parts corn starch, 2 parts calcium carbonate and talc talc. The dragee tablet prepared in this manner is then provided with an anti-gastric coating. IV. Biological Studies Receptor binding studies: The substance to be tested is dissolved in methanol/Chrem(R)ph(r) (BASF_AG) or dimethyl sulfoxide and then diluted with water to the desired concentration. Dopamine D3 Receptor: The assay mixture (0.250 ml) consists of a membrane derived from ~1〇6 多·293 cells with stable expression of the human dopamine D3 receptor, 0·1 ηΜ [1251]-A Sulpiride and culture buffer (total binding) or, in addition, test substance (inhibition curve) or 1 μM spiperone (non-specific binding). Each assay mixture was run in triplicate. The culture buffer contains 50 mM tris, 120 mM NaCl, 5 mM KC1, 2 mM CaCl2, 2 mM MgCl2 and 0.1% bovine serum albumin, 10 μ of quinolone (qUin〇i〇ne) and 〇"〇/0 ascorbic acid. (prepared freshly every day). The buffer was adjusted to pH 7.4 with HC1. Dopamine D2L Receptor: The assay mixture (1 ml) consists of ~1〇6 stable human dopamine Da receptors (long isoforms) 119387.doc -172- 200808727 HEK- Membrane of 293 cells and 0.01 nM [125I] oxarone and incubation buffer (total binding) or, in addition, test substance (inhibition curve) or 1 μl of haloperidol (non-specific binding). Each assay mixture was run in triplicate. The culture buffer contained 50 mM tris, 120 mM NaC, 5 mM KC1, 2 mM CaCl2, 2 mM MgCl2, and 0.1% bovine serum albumin. The buffer was adjusted to pH 7.4 with HC1. Measurement and analysis: After incubation at 25 ° C for 60 minutes, the assay mixture was filtered through a Whatman GF/B glass fiber filter using a cell collection device under vacuum. Use a filter transfer system to transfer the filter to the flash bottle. After adding 4 ml of Ultima Gold® (Packard), the sample was shaken for one hour and then radioactivity was counted using a beta counter (Beta-Counter) (Packard, Tricarb 2000 or 2200CA). The cpm value is converted to dpm using the standard quench series and the programs belonging to the instrument. The inhibition curves were analyzed by iterative nonlinear regression analysis using a Statistical Analysis System (SAS) similar to the 'LIGAND' program described by Munson and Rodbard. The results of the receptor binding studies are expressed as The receptor binding constants Ki (D2) and Ki (D3) described above and given in Table 3. In these tests, the compounds according to the invention exhibited excellent affinity for the D3 receptor ( &lt;1〇 nM, often &lt;5 nM) and binds sexually to D3 receptor selection 119387.doc -173- 200808727. The results of the combined test are given in Table 1. Table 1 · Example 1 _ 2 _ 3_ 4__ ^_ _6__2_ s__ 9__ 10 Π_ \3_ 15_ 16_XI_ 18 19 20 21_ 22 23_ 24 27 29 34 36 43_ 57

Kj(D3) ++++ +++ +++ +++ ++++ +++ +++ +++ ++++ +_ ++ +++ +++ ++ +++ + + ++ ++ +++ ++++ +++ ++ +++ ++ Talk 2)*_3)* ++_ +_ ++_ ++_ ++ ++ ++++ ++ ++ ++++ ++++ + + +_ ++ +_ + +_ ++ nd + ++ +++ ++++ ++++ +++ ++ 119387.doc -174- 200808727 Example Ki(D3)* Post 2)*/Post 3)* 61 +++ + *Recipient binding constant annotation obtained according to the test described above:

Ki(D3)^ + between 50 nM and 150 nM ++ between 10 nM and 50 nM +++ between 1 nM and 10 nM ++++ &lt;1ηΜ

Ki(D2)7Ki(D3)* + between 10 and 50 ++ between 50 and 100 +++ between 100 and 150 ++++ &gt; 150 119387.doc 175-

Claims (1)

200808727 X. Patent application scope: 1. An aryloxyethylamine compound of formula I (I) wherein Ar is a phenyl group or an aromatic 5 or 6 member (: a bonded heteroaromatic group, which may have 1 group Ra and wherein Ar may also have i or 2 groups Rb; Free group of the following groups: Cl_C6 alkyl, fluorinated Ci-C6 alkyl, c2-c6 dilute, I-C2-C6 alkenyl, c3-c6 cycloalkyl, fluorinated CVC6 cycloalkyl, CrC : 6 alkoxy, fluorinated alkoxy, CVC6 hydroxyalkyl, Ci-C: 6 alkoxy-CVC4 alkyl, methoxy group, Ci-C6 alkoxy-CVC4 alkoxy, COOH, NR4R5, CH2NR4R5, ONRV, nhc(o)nr4r5, c(o)nr4r5, S02NR4R5, CVC6 alkylcarbonyl, fluorinated CrC6 alkylcarbonyl, CrC: 6 alkylcarbonylamino, fluorinated C^C:6 alkyl Carbonylamino, C^C6 alkylcarbonyloxy, fluorinated fluorene oxime alkylcarbonyloxy, CrQ alkoxycarbonyl, fluorinated Cl-C6 alkoxycarbonyl, CrC6 alkylthio, fluorinated CrCs Thiothio group, CrC6 alkyl sulfinylene group, fluorinated Cj-C: 6 alkyl decyl fluorenyl group, Ci-C6 alkyl group fluorenyl group, fluorinated Ci-C6 alkyl group thiol group, phenyl group Base, phenyl, phenoxy, benzyloxy, η than bite 2 - group 119387.doc 200808727 oxy And a 3 to 7 membered heterocyclic group, wherein the phenyl, pyridyl and heterocyclic groups in the last six groups may have 1, 2, 3 or 4 selected from halogen 'cyano' OH, side a group of an oxy group, CN and a group Raa, wherein Raa is selected from the group consisting of CVC6 alkyl, fluorinated CVC6 alkyl, (: 2-oxime: 6 alkenyl, fluorinated C2-C6 alkenyl, C3-C6 naphthenic , fluorinated C3-C6 cycloalkyl, CVC6 alkoxy, fluorinated oxy, CV C6 alkyl, CrCs alkoxy-CVC4 alkyl, CVC6 hydroxy alkoxy, CVC6 alkoxy-CVC4 alkane Oxygen, COOH, NR4R5, CH2NR4R5, 〇nr4r5, NHC(0)NR4R5, C(0)NR4R5, S02NR4R5, CVC6 alkyl group, fluorinated CVC6 alkylcarbonyl, CVC6 alkylcarbonylamino group, fluorinated CVC6 Alkylcarbonylamino group, 0 wide (: 6 alkylcarbonyloxy group, fluorinated Ci-C: 6 alkylcarbonyloxy group, 〇1_〇6 alkoxycarbonyl group, fluorinated alkoxycarbonyl group, Cl_c6 alkyl sulfide Base, fluorinated Ci-C: 6 alkylthio group, Ci-C6 alkyl sulfinylene group, fluorinated CrC6 alkyl sulfinylene group, ^^(^alkylsulfonyl group, fluorinated alkylsulfonate The base, the parent-R is selected from the group consisting of halogen, cyano, nitro, hydrazine H, methyl, methoxy, fluoromethyl, Fluoromethyl, triditymethyl, methoxy, dimethoxy and trifluoromethoxy, or if a group Ra and a group Rb are bonded to two adjacent carbon atoms of the phenyl group , which may form a 5 or 6 membered heterocyclic ring or a carbocyclic ring which is fused to the phenyl ring and which is unsubstituted or may have i, 2 or 3 groups selected from the following groups of 119387.doc 200808727: halogen, N02, NH2, OH, CN, CKC6:), fluorinated CVC6 alkyl, c3-c6 cycloalkyl, fluorinated c3-c6 cycloalkyl, alkoxy, fluorinated Ci-C^ alkoxy, Cvc6 via a base group, a CrC* alkoxy-C2-C4 alkyl group, a CVC6 hydroxyalkoxy group, a C1-C4 yard-based _C2_C4 succinyl group, a Ci_C6 alkyl group, a fluorinated CVC6 alkylcarbonyl group, VC6 alkylamino group, di-(VC6 alkylamino group, CrC6 alkylaminocarbonyl group, di-CrCs alkylaminocarbonyl group, CrC6 alkylcarbonylamino group, fluorinated Ci-Cs alkylcarbonylamino group, Cr C6 alkylcarbonyloxy, fluorinated C"c6 alkylcarbonyloxy, alkoxycarbonyl, CrCs alkylthio, fluorinated Ci-Cs alkylthio, Ci_C6 alkyl sulphate, gasification Ci-Cs succinyl continuation base, C 1 - C 6 sinter shale base and gasification C 1 - C 6 calcined base, X is N or CH; R is H, C1-C4 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkyl, C; 3-C4 dilute, fluorinated Ci_C4 An alkyl group, a fluorinated C3-C4 cycloalkyl group, a fluorinated C3-C4 cycloalkylmethyl group, a fluorinated C3-C4 alkenyl group, a decyl group or a C1-C3 alkyl group; R is a H, a Ci_C4 alkyl group , C3-C4 cycloalkyl, C3-C4 cycloalkyl, C3-C4 alkenyl, fluorinated alkyl, fluorinated C3-C4 cycloalkyl, fluorinated C3-C4 cycloalkylmethyl or fluorinated C3-C4 alkenyl; or R1 and Rla together are (CR6R7)r, wherein r is 3, 4 or 5; R2 and R2a are each independently H, fluoro, CVC4 alkyl or fluorinated CVC4 alkyl or R2a&amp;R2 Together form a ring member (CR6R7)m, where m is 2, 3, 4 or 5; or 119387.doc 200808727 Heart and R2a together are (CR6R7)n, where n is 2, 3 or 4 and R3 is Η4〇ν 〇: 4 alkyl; R4, R5 are independent of each other and are individually selected from H, alkyl, CrC3 alkoxy, and fluorinated Cl-c3 alkyl; R, R7 are independent of each other and are independently present when individually present It is selected from the group consisting of ruthenium, fluorine, Ci-C4 alkyl and fluorinated alkyl; R8 and R8a are each independently fluorene, fluorine, Cl_C4 alkyl or fluorinated c Or R8a and R8 together form a ring member (CR6R7, wherein q is 2, 3' 4 or 5; or Rla&amp;R8a is (CR6R7)S together, wherein 11 is 2 or 3; R9 is H, cvc4 alkyl, Fluorinated Cl_c4 alkyl, 〇1_〇4 alkoxy or fluorinated Crq alkoxy; and physiologically tolerated acid addition salts of such compounds. 2. The compound of claim 1, wherein Ar is a phenyl group or a aryl group containing one nitrogen atom as a ring member and ruthenium, osmium, 2 or 3 other hetero atoms selected from the group consisting of ruthenium, S and N as a ring member .546MC bonded heteroaromatic group, wherein Ar has a group selected from the group consisting of: alkyl 'fluorinated cvc6 alkyl, C3_C6 cycloalkyl, fluorinated c3_C6 cycloalkyl, cKc6 Alkoxy, fluorinated Ci-C6 alkoxy, nr4r5, 丨_吖 啶 啶 丫 丫 咬 咬 咬 咬 咬 咬 L L 或 或 或 或 或 ( ( ( ( ( ( ( ( ( ( ( a phenyl group and a heteroaromatic group containing a nitrogen atom as a member of the ring and a quinone, fluorene, 2 or 3 other heterocyclic atoms selected from the group consisting of argon, heterocyclic atoms The group (wherein the last two groups may have 2, 3 or 4 groups of 119387.doc 200808727 selected from the group consisting of arginyl and the group Raa, wherein the R group is selected from the group consisting of q-C6 alkyl, fluorinated Ci -Cs alkyl, c3_C6 cycloalkyl, fluorinated C3_c0 cycloalkyl, Cl_C0 alkoxy, fluorinated alkoxy and NR4R5); and wherein the edge may also have 1 or 2 other groups Rb, Equivalent group Rb This is independently selected from the group consisting of halogen, cyano, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy and trifluoromethoxy; and wherein R and R are independent of each other and each Individually occurring, they are independently selected from the group consisting of H, CVC3 alkyl and fluorinated alkyl. 3. The compound of claim 1 or 2, wherein Ar has a group of the formula Ra': Ra1 - Y: Ra · V2 wherein Y is N, CH or CF, and Ral and Ra2 are independently selected from the group consisting of Ci_C2 alkyl, Ci_C2 alkoxy, fluorinated CrCz alkyl, the restriction condition is that γ is CH or CF, one of the groups Ral or Ra2 may also be hydrogen or fluorine, or Ral and Ra2 together form a ring member (CH2)k, Wherein i or 2 hydrogen atoms may be replaced by fluorine, hydroxyl, pendant oxy, Cl_C2 alkyl or Ci-C2 alkoxy, and one of the ch2 moieties may be replaced by 0, s, s=〇, s〇24N_RC, wherein氲 or (:: 1 &lt; 2 alkyl, and wherein] &lt;: is 2, 3, 4, 5 or 6. 4. The compound of claim 3, wherein the group Ra is selected from isopropyl, (r) _ gas ethyl (S)-1-fluoroethyl, 2-fluoroethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl , (R)-i-fluoropropyl, (s)-:ufluoropropyl, 2-fluoropropyl, 3-fluoropropyl, I-difluoropropyl, 2,2-difluoropropyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, (R)_2_a small methyl ethyl 119387.doc 200808727 base, (S)-2-fluoro-1-methylethyl , (R) -2,2-difluoromethylethyl, (S)-2,2-difluoro-1-methylethyl, (R)-1,2-difluoromethylethyl, (S)-l , 2-difluoro_1-methylethyl, (R)-2,2,2-trifluoro-b-methylethyl, (S)-2,2,2-trifluoro_1-methylethyl, 2-fluoro-1·(fluoromethyl)ethyl, 1-(difluoromethyl)-2,2-difluoroethyl, cyclopropyl, cyclobutyl, 1-fluorocyclopropyl and 2- gas 5. A compound according to claim 3, wherein the group Ra is selected from the group consisting of 4-morpholinyl, 4-thiomorphinyl, 4-azepine, di-oxooxy)thiomorpholine Base, piperazine-i-yl, 4, methylpiperazin-1-yl, azetidin-1-yl, 2-methylazetidin-1-yl, (s), 2-methyl Acridine-1·yl, (R)-2-methylazetidin-1-yl, 3-f-butylindole-1-yl, 3-methoxyazetidin-1-yl, 3-hydroxyl Azeidine - Bulu 15 3,.恶ο sitting _ 5 _ base, mouth than 唆 唆 _ 1 - base, mouth bite each bite 2-base, (S) mouth ratio 2, base, (R) _tj ratio σ σ -2- group , π, 唆 唆 -3-yl, (S)-°, piroxicam- 3 flu-soil, (trans)-pyrrolidin-3-yl, 2-fluoropyrrolidine-1-yl, (S)- 2-fluoropyrrole&quot; fluorenyl, (R)-2. fluoropyrrolidin-1-yl, 3-fluoropyrrolidin-1-yl, (S)-3_gasyrrolidine-1-yl, (R --3-fluoropyrrolidine-buyl, 2,2-difluoropyrrole&quot;dine-1, cis, 3,3-difluoropyrrolidin-1-yl, 2-mercaptopyrrolidin-1-yl, (S) methyl η 唆 唆 唆-1-yl, (R)-2-methylindole-1-yl, 3-methyl-pyrene-diyl, 〇3-methylpyrrolidine-work- , methyl pyrrole bite-: U-based, 1-decylpyrrolidin-2-yl, (S)-l-decylpyrrolidin-2-yl, ()1 methyl alpha ratio T7 each sigma-2 - group, 1-methyl σ pirox-3 base, (S)-l-methyl σ ratio 17 beer, 3-yl, (R)-1-methylpyrrolidin-3-yl, 2 ,2-Dimethylpyrrole&quot;疋-1_yl, 3,3-dimercaptopyrrolidin-1·yl, 2-trifluoromethylpyrrolidine-buki' (S), 2-trifluoromethyl (r)pyridin-1-yl, (R)-2-trifluoromethyl fluorene 119387.doc 2008087 27 =1 base, 3-two said methyl 吼嘻 bit · ^ base, (8) three gas methyl 吼 Luo.疋_1·基, (8) Xiao Wang see methyl pyrrolidine small group, 2 _ oxypyrrole bit yl 2 - oxy-oxazolidin-3-yl, piperidin-1-yl, 2-methyl pipe Acridine _ br, (S)-2·methyl brigade bite + base and (8) benzhydrylpiperidine small group. 6. The compound of claim 3, wherein the group Ra has 丨, 2, 3 or 4 chaotic atoms. 7. A compound of the 'substituent' wherein the Ar is unsubstituted or has a group selected from the group consisting of: (CH2)vCF3, (CH2)VCHF2^(CH2)vCH2F &gt; 0(CH2 vCF3 . 〇(ch2)vchf2 and 〇(CH2)vCH2F, where V is 0, 1, 2 or 3. 8. The compound of claim 1, wherein the Ar is unsubstituted or has a group Ra', the group Ra is selected from the group consisting of J hetero atoms selected from the group consisting of 〇, s and N as a ring member and may further have a 5- or 6-membered heteroaromatic group as a ring member, 2 or 3 nitrogen atoms, and wherein the 5 or 6 membered heteroaromatic group may have 1, 2 or 3 groups selected from the group consisting of Substituent halogen, N02, NH2, OH, CN, CVC6 alkyl, fluorinated Ci_C6 alkyl, Cs_C6 cycloalkyl, fluorinated C3_C6 cycloalkyl, CVC6 alkoxy, fluorinated Cl-c6 saponin , CVC6 via ketone, Ci-C4 alkoxy-c2-c4 alkyl, cv C6 hydroxyalkoxy, CVC4 alkoxy-CVC: 4 alkoxy, (VC6 alkyl group, fluorinated alkyl) a few groups, (^-(^alkylamino, dialkylamino, Ci-C: 6 alkylaminocarbonyl, di-CVC6 alkylaminocarbonyl, C!-C6 alkylaminol, Fluorinated CVC6 alkylamino group, Ci-Cs alkylcarbonyloxy group, fluorinated CrC6 alkylcarbonyloxy group, "(Alkoxy group, Ci-C6 alkylthio group, fluorinated alkyl group) Thio group, alkyl group 119387.doc 200808727 sulphate, fluorinated Cl_c6 alkyl sulfinium sulfonate An alkylsulfonyl group and a C1-C6 alkylsulfonyl group. The compound of claim 8, wherein Ar has a heteroaromatic group selected from the group consisting of Ra: furyl, thienyl , pyrrolyl, pyrazolyl, indolyl, anthraquinone, isopropionyl, [1,3,4]-indenyl, [1,2,4]-didecyl, three An azolyl group and a tetrazolyl group, wherein the heteroaromatic group may be unsubstituted or may have 1 to 3 substituents selected from the group consisting of halogen, C^C4 alkyl, c"C4 alkoxy, The fluorinated Ci-C4 alkyl group and the fluorinated Ci-c4 alkoxy group. The compound according to any one of items 1, 2, 7, 8 and 9, wherein Ar is a phenyl group. The compound of Item 10, which has a group Ra at the 4-position of the benzene ring. The compound of any one of items 1, 2, 7, 8, and 9, wherein χ is CH. 13·= The compound of any one of items 1, 2, 7, 8 and 9 wherein R9 is a compound of any one of items 1, 2, 7, 8 and 9. Relative to the 2-position of the nitrogen ring atom and the 3_position _NR3-S〇2_Ar group. 16. The compound of claim 1, 2, 7, H, methyl, n-propyl, such as the claim 1 '2, 7, hydrogen or an alkyl group, wherein Ri is fluorinated ( VC: a compound of any one of 8 and 9, wherein Rla is 119387.doc 200808727 17·If any of items i, 2, 7, 8, and 9 a compound wherein r2 a is hydrogen. The compound of any one of claims 1, 2, 7, 8, and 9, wherein r2a is hydrogen. The compound of any one of claims 1, 2, 7, 8 and 9, wherein r8 a is hydrogen. The compound of any one of claims 1, 2, 7, 8, and 9, wherein the compound 8 is hydrogen. The compound of any one of claims 1, 2, 7, 8, and 9, wherein R2a and Rla together form an alkylene group (CH2)n, wherein n is 2, 3 or 4. 22. The compound of any one of claims 1, 2, 7, 8 and 9, wherein the rule "and Rla together form an alkylene (CH2)S, wherein s is 2 or 3. 23" as requested! 2. A compound according to any one of clauses 2, 8 and 9 wherein, and Rla together form an alkylene group (CHA, wherein r is 3, 4 or 5. 24. as claimed in claims!, 2, 7, 8 and 9 A compound according to any one of the preceding claims, wherein Ria, RR, ruler and ruler are each h'r1 is propyl and r9 is methoxy and is as defined in any one of claims 1 to 11. 25. 2. The compound of any one of clauses 2, 8 and 9 wherein Rla, R2, R2a, R8 and are H, Ri is propyl, r9 is methyl and ^ is as defined in any one of claims 1 to 11. A pharmaceutical composition comprising at least one compound of the formula I as claimed in any one of claims i to pharmaceutically acceptable salts thereof, optionally together with at least one physiologically acceptable carrier or Auxiliary material. 27. A compound according to any one of claims 1 to 25 or a pharmaceutically acceptable salt thereof 119387.doc -9-200808727 for the preparation of a therapeutically detectable dopamine d3 receptor Use of a pharmaceutical composition for a medical condition of a ligand treatment method. 28. The use of claim 27, wherein the medical condition is a central nervous system disease 0 119387.doc -10- 200808727 VII. Designated representative figure: a) The representative representative of the case is: (none) (2) The symbol of the symbol of the representative figure is simple: 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 119387.doc