CN101421243B - Aryloxyethylamine compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor - Google Patents

Aryloxyethylamine compounds suitable for treating disorders that respond to modulation of the dopamine D3 receptor Download PDF

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CN101421243B
CN101421243B CN2007800134447A CN200780013444A CN101421243B CN 101421243 B CN101421243 B CN 101421243B CN 2007800134447 A CN2007800134447 A CN 2007800134447A CN 200780013444 A CN200780013444 A CN 200780013444A CN 101421243 B CN101421243 B CN 101421243B
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phenyl
base
fluoro
methyl
ethyl
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CN101421243A (en
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R·格兰德尔
W·M·布拉杰
A·豪普特
S·C·特纳
U·兰格
K·德雷谢尔
L·昂格
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AbbVie Deutschland GmbH and Co KG
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Abert & Co KG GmbH
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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

Be applicable to that treatment is to dopamine D < > 3 <> Acceptor is regulated the Aryloxyethylamine compounds of the illness that responds
< > Background of invention <>
The present invention relates to new Aryloxyethylamine compounds.These compounds have valuable therapeutic property, are applicable to that more specifically treatment is to dopamine D < > 3 <> Acceptor is regulated the disease that responds.
Neurone especially obtains their information through G albumen-coupled receptor.Big quantity of material is through these their effects of acceptor performance.Wherein a kind of material is a Dopamine HCL.Existing attested about Dopamine HCL existence and as the discovery of the physiological function of neurotransmitter.The disorder of dopaminergic mediator system causes central nervous system disease, comprises for example schizophrenia, depression and Parkinson's disease.These diseases and other diseases can be with treating with the interactional medicine of Dopamine Receptors.
Up to nineteen ninety, two kinds of hypotypes of Dopamine Receptors are just clearly defined on pharmacology, i.e. D < > 1 <> And D < > 2 <> Acceptor.Recently, found the third hypotype, i.e. D < > 3 <> Acceptor, its as if mediate some effect (J.C.Schwartz etc. of antipsychotic and anti-parkinson, The Dopamine D < > 3 <> Receptor as a Target for Antipsychotics, in Novel Antipsychotic rugs, H.Y.Meltzer, Ed.Raven ress, New York1992,135-144 page or leaf; M.Dooley etc., Drugs and Aging 1998,12,495-514, J.N.Joyce, Pharmacology andTherapeutics 2001,90,231-59 page or leaf " The Dopamine D < > 3 <> Receptor as aTherapeutic Target for Antipsychotic and Antiparkinsonian rugs ").
Hereafter, Dopamine Receptors has been divided into two families.Be D on the one hand < > 2 <> Family is by D < > 2 <> , D < > 3 <> And D < > 4 <> Acceptor is formed and is D on the other hand < > 1 <> Family is by D < > 1 <> And D < > 5 <> Acceptor is formed.D < > 1 <> And D < > 2 <> Acceptor is extensively to distribute, and D < > 3 <> Acceptor regioselectivity expression seemingly.Therefore, the outburst area of preferential system on the edge of of these acceptors and middle limbic brain dopamine system is especially found in the volt nuclear, but for example in the amygdala discovery is arranged also in other zone.Since this opposed area selective expression, D < > 3 <> Acceptor is regarded as side effect target seldom, and supposition, works as selective d < > 3 <> When part has the character of known antipsychotics, it will can not have their dopamine D < > 2 <> Receptor-mediated neurological side effects (P.Sokoloff etc., Localization and Function of theD < > 3 <> Dopamine Receptor, < > Arzneim.Forsch./Drug Res.42 <> (1), 224(1992); .Molecular Cloning and Characterization of a Novel DopamineReceptor(D3)as a Target for Neuroleptics such as P.Sokoloff, < > Nature <> , < > 347 <> , 146(1990)).
< > Summary of the invention <>
The present invention is based on provides as the highly selective dopamine D < > 3 <> The compound of receptors ligand is a purpose.The acid salt that this purpose can tolerate on the physiology of through type I Aryloxyethylamine compounds and these compounds surprisingly is achieved
Wherein
Ar is the heteroaryl of phenyl or aromatics 5-or the C-of 6-unit connection, and wherein Ar can carry 1 R < > a <> Group and wherein Ar can also carry 1 or 2 R < > b <> Group;
R < > a <> Be selected from C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 1 <>-C < > 6 <>-alkyl, C < > 2 <>-C < > 6 <>-thiazolinyl, fluoro C < > 2 <>-C < > 6 <>-thiazolinyl, C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkoxyl group, COOH, NR < > 4 <> R < > 5 <> , CH < > 2 <> NR < > 4 <> R < > 5 <> , ONR < > 4 <> R < > 5 <> , NHC(O) NR < > 4 <> R < > 5 <> , C(O) NR < > 4 <> R < > 5 <> , SO < > 2 <> NR < > 4 <> R < > 5 <> , C < > 1 <>-C < > 6 <>-alkyl-carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphonyl, phenyl sulfonyl, phenyl, phenoxy group, benzyloxy, pyridine-2-base oxygen base and 3-to 7-unit heterocyclic radical mention that phenyl, pyridyl and heterocyclic radical in the group can carry 1,2,3 or 4 and be selected from halogen, cyanic acid, OH, oxo base, CN and radicals R for wherein last 6 < > Aa <> Group, wherein
R < > Aa <> Be selected from C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 1 <>-C < > 6 <>-alkyl, C < > 2 <>-C < > 6 <>-thiazolinyl, fluoro C < > 2 <>-C < > 6 <>-thiazolinyl, C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 6 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkoxyl group, COOH, NR < > 4 <> R < > 5 <> , CH < > 2 <> NR < > 4 <> R < > 5 <> , ONR < > 4 <> R < > 5 <> , NHC(O) NR < > 4 <> R < > 5 <> , C(O) NR < > 4 <> R < > 5 <> , SO < > 2 <> NR < > 4 <> R < > 5 <> , C < > 1 <>-C < > 6 <>-alkyl-carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphonyl,
Each R < > b <> Be selected from halogen, cyanic acid, nitro, OH, methyl, methoxyl group, fluoro methyl, difluoromethyl, trifluoromethyl, fluoro methoxyl group, difluoro-methoxy and trifluoromethoxy, or
Radicals R < > a <> With a radicals R < > b <> If, exist and they are connected on two adjacent carbon atoms of phenyl, can form 5-or 6-unit's heterocycle or carbocyclic ring, said heterocycle or carbocyclic ring and phenyl ring condense, and are unsubstitutedly maybe can carry 1,2 or 3 and be selected from following group: halogen, NO < > 2 <> , NH < > 2 <> , OH, CN, C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 1 <>-C < > 6 <>-alkyl, C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-alkyl-carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkylamino, two-C < > 1 <>-C < > 6 <>-alkylamino, C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, two-C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl and fluoro C < > 1 <>-C < > 6 <>-alkyl sulphonyl,
X is N or CH;
R < > 1 <> Be H, C < > 1 <>-C < > 4 <>-alkyl, C < > 3 <>-C < > 4 <>-cycloalkyl, C < > 3 <>-C < > 4 <>-methyl cycloalkyl, C < > 3 <>-C < > 4 <>-thiazolinyl, fluoro C < > 1 <>-C < > 4 <>-alkyl, fluoro C < > 3 <>-C < > 4 <>-cycloalkyl, fluoro C < > 3 <>-C < > 4 <>-methyl cycloalkyl, fluoro C < > 3 <>-C < > 4 <>-thiazolinyl, formyl radical or C < > 1 <>-C < > 3 <>-alkyl-carbonyl;
R < > 1a <> Be H, C < > 1 <>-C < > 4 <>-alkyl, C < > 3 <>-C < > 4 <>-cycloalkyl, C < > 3 <>-C < > 4 <>-methyl cycloalkyl, C < > 3 <>-C < > 4 <>-thiazolinyl, fluoro C < > 1 <>-C < > 4 <>-alkyl, fluoro C < > 3 <>-C < > 4 <>-cycloalkyl, fluoro C < > 3 <>-C < > 4 <>-methyl cycloalkyl or fluoro C < > 3 <>-C < > 4 <>-thiazolinyl; Or
R < > 1 <> And R < > 1a <> Be that wherein r is 3,4 or 5 (CR together < > 6 <> R < > 7 <> ) r;
R < > 2 <> And R < > 2a <> Independently of one another is H, fluorine, C < > 1 <>-C < > 4 <>-alkyl or fluoro C < > 1 <>-C < > 4 <>-alkyl, or R < > 2 <> And R < > 2a <> Can form m wherein together and be 2,3,4 or 5 ring members (CR < > 6 <> R < > 7 <> ) < > m <> Or
R < > 1a <> And R < > 2a <> Be that wherein n is 2,3 or 4 (CR together < > 6 <> R < > 7 <> ) < > n <> ,
R < > 3 <> Be H or C < > 1 <>-C < > 4 <>-alkyl;
R < > 4 <> , R < > 5 <> Independently of one another and they occur independently of one another, be selected from H, C < > 1 <>-C < > 3 <>-alkyl, C < > 1 <>-C < > 3 <>-alkoxyl group and fluoro C < > 1 <>-C < > 3 <>-alkyl;
R < > 6 <> , R < > 7 <> Independently of one another and they occur independently of one another, be selected from H, fluorine, C < > 1 <>-C < > 4 <>-alkyl and fluoro C < > 1 <>-C < > 4 <>-alkyl;
R < > 8 <> , R < > 8a <> Independently of one another is H, fluorine, C < > 1 <>-C < > 4 <>-alkyl or fluoro C < > 1 <>-C < > 4 <>-alkyl, or R < > 8a <> And R < > 8 <> Can form q wherein together and be 2,3,4 or 5 ring members (CR < > 6 <> R < > 7 <> ) < > q <> Or
R < > 1a <> And R < > 8a <> Be that wherein s is 2 or 3 (CR together < > 6 <> R < > 7 <> ) < > s <> With
R < > 9 <> Be H, C < > 1 <>-C < > 4 <>-alkyl, fluoro C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 4 <>-alkoxyl group or fluoro C < > 1 <>-C < > 4 <>-alkoxyl group.
Therefore The compounds of this invention relates to the acid salt that can tolerate on Aryloxyethylamine compounds and the physiology thereof of general formula I.
The invention still further relates to pharmaceutical composition, said pharmaceutical composition comprise when suitable and physiology on the acid salt that can tolerate on the physiology of Aryloxyethylamine compounds and/or at least a formula I of acceptable carrier and/or auxiliary substance at least a formula I together.
The invention still further relates to dopamine D < > 3 <> Receptor antagonist or dopamine D < > 3 <> The treatment of conditions method that the influence of agonist reacts, said method comprise to the experimenter that these needs are arranged uses the acid salt that can tolerate on the physiology of Aryloxyethylamine compounds and/or at least a formula I of at least a formula I of significant quantity.
< > Detailed Description Of The Invention <>
To dopamine D < > 3 <> The disease that the influence of receptor antagonist or agonist responds especially comprises the obstacle and the disease of central nervous system; Especially be affective disorder, neurological disorder, stress disorders, somatic form (somatoform) obstacle and psychosis; Especially be schizophrenia and depression; And other renal tubal dysfunction, especially be renal tubal dysfunction (referring to WO00/67847) by diabetes caused.
According to the present invention, at least a compound with general formula I of the said implication of beginning is used to treat above-mentioned indication.If can have different spatial disposition for the formula I compound of fixed structure; For example; If they have one or more asymmetric centers, polysubstituted ring or two key; Perhaps as different tautomers; Then also can use mixture of enantiomers, particularly racemic modification, non-enantiomer mixture and tautomers mixture; Yet, pure basically various enantiomorphs, diastereomer and tautomer and/or its salt of advantageous applications formula I compound.
Can use the salt that can tolerate on the physiology of formula I compound equally, especially use the formed acid salt of physiological tolerance acid.Suitable physiological tolerance organic with representative examples of mineral pigments be hydrochloric acid, Hydrogen bromide, phosphoric acid, sulfuric acid, C < > 1 <>-C < > 4 <>-alkylsulphonic acid such as methylsulfonic acid, aromatic sulfonic acid such as Phenylsulfonic acid and toluenesulphonic acids, oxalic acid, toxilic acid, fumaric acid, lactic acid, tartrate, hexanodioic acid and phenylformic acid.Other useful acids are described in Fortschritte Der Arzneimittelforschung [Advances In Drug Research], Volume10, pages224 Ff.,
Figure G2007800134447D0005110014QIETU
Verlag, Basel and Stuttgart, 1966 in.
The concomitant term that the organic moiety of in the definition of above-mentioned variable, mentioning (like term halogen) is listed separately for individual group member.Prefix n-Cm representes the possible number of carbon atom in the group under each situation.
Term halogen is represented fluorine, bromine, chlorine or iodine, especially fluorine and chlorine under each situation.
C < > 1 <>-C < > 4 <> Alkyl is (and equally at C < > 1 <>-C < > 4 <> Hydroxyalkyl, C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 4 <>-alkyl-carbonyl, C < > 1 <>-C < > 4 <> Alkyl-carbonyl-amino, C < > 1 <>-C < > 4 <> Alkyl-carbonyl oxygen base, C < > 1 <>-C < > 4 <> Alkyl sulfenyl, C < > 1 <>-C < > 4 <> Alkyl sulphinyl, C < > 1 <>-C < > 4 <> In the alkyl sulphonyl etc.) for having 1-4 carbon atom straight chain or branched-chain alkyl.The instance of alkyl is methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, 2-butyl, isobutyl-or the tertiary butyl.
C < > 1 <>-C < > 6 <> Alkyl is (and equally at C < > 1 <>-C < > 6 <> Hydroxyalkyl, C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <> Alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <> Alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <> Alkyl sulfenyl, C < > 1 <>-C < > 6 <> Alkyl sulphinyl, C < > 1 <>-C < > 6 <> In the alkyl sulphonyl etc.) for having 1-6 carbon atom straight chain or branched-chain alkyl.Instance comprises aforesaid C < > 1 <>-C < > 4 <> Alkyl and amyl group; The 1-methyl butyl; The 2-methyl butyl; The 3-methyl butyl; 2; The 2-dimethyl propyl; The 1-ethyl propyl; Hexyl; 1; The 1-dimethyl propyl; 1; The 2-dimethyl propyl; The 1-methyl amyl; The 2-methyl amyl; The 3-methyl amyl; The 4-methyl amyl; 1; The 1-dimethylbutyl; 1; The 2-dimethylbutyl; 1; The 3-dimethylbutyl; 2; 2-dimethylbutyl, 3-dimethylbutyl, 3-dimethylbutyl; The 1-ethyl-butyl; 2-ethyl-butyl; 1; 2-trimethylammonium propyl group, 2,2-trimethylammonium propyl group; 1-ethyl-1-methyl-propyl and 1-ethyl-2-methyl-propyl;
Fluoro C < > 1 <>-C < > 6 <> Alkyl is (and equally at fluoro C < > 1 <>-C < > 6 <> Alkyl-carbonyl, fluoro C < > 1 <>-C < > 6 <> Alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <> Alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <> Alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <> Alkyl sulphinyl, fluoro C < > 1 <>-C < > 6 <> In the alkyl sulphonyl etc.) for having 1-6; Especially 1-4 carbon atom; The more preferably straight or branched alkyl of 1-3 carbon atom; Wherein at least one for example 1 or all hydrogen atoms replaced by fluorine atom; For example at methyl fluoride; Difluoromethyl; Trifluoromethyl)-1-fluoro ethyl)-1-fluoro ethyl; The 2-fluoro ethyl; 1; 1-two fluoro ethyls; 2; 2-two fluoro ethyl; 2; 2-trifluoroethyl)-1-fluoropropyl)-1-fluoropropyl; The 2-fluoropropyl; The 3-fluoropropyl; 1; 1-two fluoropropyls; 2; 2-two fluoropropyls; 3; 3-two fluoropropyl; 3; 3-trifluoro propyl)-2-fluoro-1-methylethyl)-2-fluoro-1-methylethyl; 2-two fluoro-1-methylethyl)-2; 2-two fluoro-1-methylethyl)-1; 2-two fluoro-1-methylethyl)-1; 2-two fluoro-1-methylethyl)-2; 2; 2-three fluoro-1-methylethyl)-2; 2; 2-three fluoro-1-methylethyls; 2-fluorine-1-(methyl fluoride) ethyl difluoromethyl)-2; 2-two fluoro ethyl)-1-fluorine butyl)-1-fluorine butyl; 2-fluorine butyl; 3-fluorine butyl; 4-fluorine butyl; 1; 1-difluoro butyl; 2; 2-difluoro butyl, 3-difluoro butyl, 4-difluoro butyl is in the 4-trifluoro butyl etc.;
Side chain C < > 3 <>-C < > 6 <> Alkyl is to have 3-6 carbon atom and at least one alkyl for the second month in a season or tertiary carbon atom.Instance is sec.-propyl, the tertiary butyl, 2-butyl, isobutyl-, 2-amyl group, 2-hexyl, 3-methyl amyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1-methyl-1-ethyl propyl.
C < > 1 <>-C < > 6 <> Alkoxyl group is (and equally at C < > 1 <>-C < > 6 <> Alkoxy carbonyl, C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <> Alkyl, C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <> Alkoxyl group and C < > 1 <>-C < > 6 <> The hydroxy alkoxy base) for having 1-6, the straight or branched alkyl of 1-4 carbon atom especially, it is connected the remainder of molecule via Sauerstoffatom.Instance comprises methoxyl group; Oxyethyl group; Positive propoxy; Isopropoxy; N-butoxy; The 2-butoxy; Different-butoxy; Tert.-butoxy; Pentyloxy; 1-methyl butoxy; 2-methyl butoxy; 3-methyl butoxy; 2; 2-dimethyl propoxy-; 1-ethyl propoxy-; Hexyloxy; 1; 1-dimethyl propoxy-; 1; 2-dimethyl propoxy-; 1-methyl pentyloxy; 2-methyl pentyloxy; 3-methyl pentyloxy; 4-methyl pentyloxy; 1; 1-dimethyl butoxy; 1; 2-dimethyl butoxy; 1; 3-dimethyl butoxy; 2; 2-dimethyl butoxy; 2; 3-dimethyl butoxy; 3; 3-dimethyl butoxy; 1-ethyl butoxy; 2-ethyl butoxy; 1; 2-trimethylammonium propoxy-, 2,2-trimethylammonium propoxy-; 1-ethyl-1-methyl propoxy-and 1-ethyl-2-methyl propoxy-;
Fluoro C < > 1 <>-C < > 6 <> Alkoxyl group is (and equally at fluoro C < > 1 <>-C < > 6 <> Alkoxy carbonyl) for having 1-6; Especially the straight or branched alkoxyl group of 1-4 carbon atom; Wherein at least one for example 1 or all hydrogen atoms replaced by fluorine atom; For example at the fluorine methoxyl group; Difluoro-methoxy; Trifluoromethoxy)-1-fluorine oxyethyl group)-1-fluorine oxyethyl group; 2-fluorine oxyethyl group; 1; The 1-difluoroethoxy; 2; 2-difluoroethoxy; 2; 2-trifluoro ethoxy)-1-fluorine propoxy-)-1-fluorine propoxy-; 2-fluorine propoxy-; 3-fluorine propoxy-; 1; 1-difluoro propoxy-; 2; 2-difluoro propoxy-; 3; 3-difluoro propoxy-; 3; 3-trifluoro propoxy-)-2-fluoro-1-methyl ethoxy)-2-fluoro-1-methyl ethoxy)-2; 2-two fluoro-1-methyl ethoxy)-2; 2-two fluoro-1-methyl ethoxy)-1; 2-two fluoro-1-methyl ethoxy)-1; 2-two fluoro-1-methyl ethoxy)-2; 2; 2-three fluoro-1-methyl ethoxy)-2; 2; 2-three fluoro-1-methyl ethoxies; 2-fluorine-1-(methyl fluoride) oxyethyl group difluoromethyl)-2; 2-difluoroethoxy)-1-fluorine butoxy)-1-fluorine butoxy; 2-fluorine butoxy; 3-fluorine butoxy; 4-fluorine butoxy; 1; 1-difluoro butoxy; 2; 2-difluoro butoxy, 3-difluoro butoxy, 4-difluoro butoxy is in the 4-trifluoro butoxy etc.;
C < > 3 <>-C < > 6 <> Cycloalkyl is the cycloaliphatic group with 3-6 carbon atom, for example cyclopropyl, cyclobutyl and cyclopentyl.Cycloalkyl can be unsubstituted or can carry 1,2,3 and 4 C < > 1 <>-C < > 4 <> The alkyl preferable methyl.An alkyl is preferably placed on the 1-position of cycloalkyl, for example 1-methyl cyclopropyl and 1-methyl cyclobutyl.
Fluoro C < > 3 <>-C < > 6 <> Cycloalkyl is the cycloaliphatic group with 3-6 carbon atom; Cyclopropyl for example; Cyclobutyl and cyclopentyl; Wherein at least one for example 1 or all hydrogen atoms replaced by fluorine atom; For example in 1-fluorine cyclopropyl; 2-fluorine cyclopropyl; 2; 2-difluoro cyclopropyl; 1; 2-difluoro cyclopropyl; 2; 3-difluoro cyclopropyl; Five fluorine cyclopropyl; 1-fluorine cyclobutyl; 2-fluorine cyclobutyl; 3-fluorine cyclobutyl, 2-difluoro cyclobutyl, 3-difluoro cyclobutyl; 1; 2-difluoro cyclobutyl; 1; 3-difluoro cyclobutyl, 3-difluoro cyclobutyl, 4-difluoro cyclobutyl; Or 1, in the 2-trifluoro cyclobutyl.
C < > 3 <>-C < > 6 <> Methyl cycloalkyl is the methyl that carries the cycloaliphatic group that has 3-6 carbon atom as mentioned above.
Fluoro C < > 3 <>-C < > 6 <> Methyl cycloalkyl is to carry cycloaliphatic group with 3-6 carbon atom, wherein at least one for example 1,2,3,4 or all hydrogen atom by the substituted methyl of fluorine atom.
C < > 2 <>-C < > 6 <>-thiazolinyl is the indivedual undersaturated alkyl with 2,3,4,5 or 6 carbon atoms, for example vinyl, allyl group (2-propylene-1-yl), 1-propylene-1-base, 2-propylene-2-base and methylallyl (2-methyl-prop-2-alkene-1-yl) etc.C < > 3 <>-C < > 4 <>-thiazolinyl especially is allyl group, 1-methyl-prop-2-alkene-1-base, 2-butylene-1-base, 3-butylene-1-base, methylallyl, 2-amylene-1-base, 3-amylene-1-base, 4-amylene-1-base, 1-methyl but-2-ene-1-base or 2-ethyl third-2-alkene-1-base.
Fluoro C < > 2 <>-C < > 6 <>-thiazolinyl is the indivedual undersaturated alkyl with 2,3,4,5 or 6 carbon atoms; Wherein at least one for example 1,2,3,4 or all hydrogen atom replaced by fluorine atom; For example fluoride-based at 1-, 2-is fluoride-based, 2; 2-is fluoride-based, 3; 3; 3-fluorine propenyl, 1,1-two fluoro-2-propenyl and 1-fluoro-2-propenyl etc.
C < > 1 <>-C < > 6 <> The alkyl with 1-6 carbon atom of hydroxyalkyl for as above defining, one of them hydrogen atom is replaced by hydroxyl.Instance comprises hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2-hydroxypropyl, 1-methyl-1-hydroxyethyl etc.
C < > 1 <>-C < > 6 <> The hydroxy alkoxy base is replaced by hydroxyl for one of them hydrogen atom of alkoxyl group with 1-6 preferred 2-4 carbon atom of as above definition.Instance comprises 2-hydroxyl-oxethyl, 3-hydroxyl propoxy-, 2-hydroxyl propoxy-, 1-methyl-2-hydroxyl-oxethyl etc.
C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <> The alkyl with 1-4 carbon atom of-alkyl for as above defining, one of them hydrogen atom is by C < > 1 <>-C < > 6 <> Alkoxyl group replaces.Instance comprises methoxymethyl, 2-methoxy ethyl, 1-methoxy ethyl, 3-methoxy-propyl, 2-methoxy-propyl, 1-methyl-1-methoxy ethyl, ethoxyl methyl, 2-ethoxyethyl group, 1-ethoxyethyl group, 3-ethoxycarbonyl propyl, 2-ethoxycarbonyl propyl, 1-methyl-1-ethoxyethyl group etc.
C < > 1 <>-C < > 6 <> Alkoxy-C < > 1 <>-C < > 4 <> The alkoxyl group with 1-4 carbon atom of-alkoxyl group for as above defining, one of them hydrogen atom is by C < > 1 <>-C < > 6 <> Alkoxyl group replaces.Instance comprises methoxymethoxy, 2-methoxy ethoxy, 1-methoxy ethoxy, 3-methoxy propoxy, 2-methoxy propoxy, 1-methyl-1-methoxy ethoxy, oxyethyl group methoxy base, 2-ethoxy ethoxy, 1-ethoxy ethoxy, 3-oxyethyl group propoxy-, 2-oxyethyl group propoxy-, 1-methyl-1-ethoxy ethoxy etc.
C < > 1 <>-C < > 6 <> Alkyl-carbonyl is a formula R-C(O)-group, wherein the alkyl with 1-6 carbon atom of R for as above defining.Instance comprises ethanoyl, propionyl, positive butyryl radicals, 2-methylpropionyl, valeryl etc.
C < > 1 <>-C < > 6 <> Alkyl-carbonyl-amino is formula R-C(O) the-NH-group, wherein R is the alkyl with 1-6 carbon atom that above defines.Instance comprises acetamido, propionamido-, positive butyramide, 2-methyl propanamide base, 2,2-dimethyl propylene amide group etc.
C < > 1 <>-C < > 6 <> The alkyl-carbonyl oxygen base is a formula R-C(O)-O-group, and wherein R is the alkyl with 1-6 carbon atom that above defines.Instance comprises ethanoyl oxygen base, propionyl oxygen base, positive butyryl radicals oxygen base, 2-methylpropionyl oxygen base, 2,2-dimethyl propylene acyloxy etc.
C < > 1 <>-C < > 6 <> The alkyl sulfenyl is a formula R-S-group, and wherein R is the alkyl with 1-6 carbon atom that above defines.Instance comprises methylthio group; Ethylmercapto group; The rosickyite base; Butylthio; Penta sulfenyl; 1-methyl butylthio; 2-methyl butylthio; 3-methyl butylthio; 2; 2-dimethyl propylene sulfenyl; 1-ethyl rosickyite base; Own sulfenyl; 1; 1-dimethyl propylene sulfenyl; 1; 2-dimethyl propylene sulfenyl; 1-methylpent sulfenyl; 2-methylpent sulfenyl; 3-methylpent sulfenyl; 4-methylpent sulfenyl; 1; 1-dimethyl butyrate sulfenyl; 1; 2-dimethyl butyrate sulfenyl; 1; 3-dimethyl butyrate sulfenyl; 2; 2-dimethyl butyrate sulfenyl; 2; 3-dimethyl butyrate sulfenyl; 3; 3-dimethyl butyrate sulfenyl; 1-ethyl butylthio; 2-ethyl butylthio; 1; 2-trimethylammonium rosickyite base, 2,2-trimethylammonium rosickyite base; 1-ethyl-1-methyl-propyl and 1-ethyl-2-methyl-propyl;
C < > 1 <>-C < > 6 <> Alkyl sulphinyl is a formula R-S(O)-group, and wherein R is the alkyl with 1-6 carbon atom that above defines.Instance comprises methylsulfinyl; The ethyl sulfinyl; The propyl group sulfinyl; The butyl sulfinyl; The amyl group sulfinyl; 1-methyl butyl sulfinyl; 2-methyl butyl sulfinyl; 3-methyl butyl sulfinyl; 2; 2-dimethyl propyl sulfinyl; 1-ethyl propyl sulfinyl; The hexyl sulfinyl; 1; 1-dimethyl propyl sulfinyl; 1; 2-dimethyl propyl sulfinyl; 1-methyl amyl sulfinyl; 2-methyl amyl sulfinyl; 3-methyl amyl sulfinyl; 4-methyl amyl sulfinyl; 1; 1-dimethylbutyl sulfinyl; 1; 2-dimethylbutyl sulfinyl; 1; 3-dimethylbutyl sulfinyl; 2; 2-dimethylbutyl sulfinyl; 2; 3-dimethylbutyl sulfinyl; 3; 3-dimethylbutyl sulfinyl; 1-ethyl-butyl sulfinyl; 2-ethyl-butyl sulfinyl; 1; 2-trimethylammonium propyl group sulfinyl, 2-trimethylammonium propyl group sulfinyl; 1-ethyl-1-methyl-propyl and 1-ethyl-2-methyl-propyl;
C < > 1 <>-C < > 6 <> Alkyl sulphonyl is formula R-S(O) < > 2 <>-group, wherein R is the alkyl with 1-6 carbon atom that above defines.Instance comprises methyl sulphonyl; Ethylsulfonyl; The sulfonyl propyl base; The butyl alkylsulfonyl; The amyl group alkylsulfonyl; 1-methyl butyl alkylsulfonyl; 2-methyl butyl alkylsulfonyl; 3-methyl butyl alkylsulfonyl; 2; 2-dimethyl propyl alkylsulfonyl; 1-ethyl propyl alkylsulfonyl; The hexyl alkylsulfonyl; 1; 1-dimethyl propyl alkylsulfonyl; 1; 2-dimethyl propyl alkylsulfonyl; 1-methyl amyl alkylsulfonyl; 2-methyl amyl alkylsulfonyl; 3-methyl amyl alkylsulfonyl; 4-methyl amyl alkylsulfonyl; 1; 1-dimethylbutyl alkylsulfonyl; 1; 2-dimethylbutyl alkylsulfonyl; 1; 3-dimethylbutyl alkylsulfonyl; 2; 2-dimethylbutyl alkylsulfonyl; 2; 3-dimethylbutyl alkylsulfonyl; 3; 3-dimethylbutyl alkylsulfonyl; 1-ethyl-butyl alkylsulfonyl; 2-ethyl-butyl alkylsulfonyl; 1; 2-trimethylammonium sulfonyl propyl base, 2-trimethylammonium sulfonyl propyl base; 1-ethyl-1-methyl-propyl and 1-ethyl-2-methyl-propyl;
Fluoro C < > 1 <>-C < > 6 <> Alkyl-carbonyl is a formula R-C(O)-group, wherein the fluoro-alkyl with 1-6 carbon atom of R for as above defining.Instance comprises the acetyl fluoride base; The difluoro ethanoyl; Trifluoroacetyl group)-1-fluoro ethyl carbonyl)-1-fluoro ethyl carbonyl; 2-fluoro ethyl carbonyl; 1; 1-two fluoro ethyl carbonyls; 2; 2-two fluoro ethyl carbonyl; 2; 2-trifluoroethyl carbonyl)-1-fluoropropyl carbonyl)-1-fluoropropyl carbonyl; 2-fluoropropyl carbonyl; 3-fluoropropyl carbonyl; 1; 1-difluoro propyl group carbonyl; 2; 2-difluoro propyl group carbonyl; 3; 3-difluoro propyl group carbonyl; 3; 3-trifluoro propyl carbonyl)-2-fluoro-1-methylethyl carbonyl)-2-fluoro-1-methylethyl carbonyl)-2; 2-two fluoro-1-methylethyl carbonyl)-2; 2-two fluoro-1-methylethyl carbonyl)-1; 2-two fluoro-1-methylethyl carbonyl)-1; 2-two fluoro-1-methylethyl carbonyl)-2; 2; 2-three fluoro-1-methylethyl carbonyl)-2; 2; 2-three fluoro-1-methylethyl carbonyls; 2-fluorine-1-(methyl fluoride) ethyl carbonyl difluoromethyl)-2; 2-two fluoro ethyl carbonyl)-1-fluorine butyl carbonyl)-1-fluorine butyl carbonyls; 2-fluorine butyl carbonyl; 3-fluorine butyl carbonyl; 4-fluorine butyl carbonyl; 1; 1-difluoro butyl carbonyl; 2; 2-difluoro butyl carbonyl; 3; 3-difluoro butyl carbonyl; 4; 4-difluoro butyl carbonyl, 4-trifluoro butyl carbonyl etc.;
Fluoro C < > 1 <>-C < > 6 <> Alkyl-carbonyl-amino is formula R-C(O) the-NH-group, wherein R is the fluoro-alkyl with 1-6 carbon atom that above defines.Instance comprises the acetyl fluoride amido; The difluoro acetamido; Trifluoroacetyl amido)-1-fluoro ethyl carbonylamino)-1-fluoro ethyl carbonylamino; 2-fluoro ethyl carbonylamino; 1; 1-two fluoro ethyl carbonylaminos; 2; 2-two fluoro ethyl carbonylamino; 2; 2-trifluoroethyl carbonylamino)-1-fluoropropyl carbonylamino)-1-fluoropropyl carbonylamino; 2-fluoropropyl carbonylamino; 3-fluoropropyl carbonylamino; 1; 1-difluoro propyl group carbonylamino; 2; 2-difluoro propyl group carbonylamino; 3; 3-difluoro propyl group carbonylamino; 3; 3-trifluoro propyl carbonylamino)-2-fluoro-1-methylethyl carbonylamino)-2-fluoro-1-methylethyl carbonylamino)-2; 2-two fluoro-1-methylethyl carbonylamino)-2; 2-two fluoro-1-methylethyl carbonylamino)-1; 2-two fluoro-1-methylethyl carbonylamino)-1; 2-two fluoro-1-methylethyl carbonylamino)-2; 2; 2-three fluoro-1-methylethyl carbonylamino)-2; 2; 2-three fluoro-1-methylethyl carbonylaminos; 2-fluorine-1-(methyl fluoride) ethyl carbonylamino difluoromethyl)-2; 2-two fluoro ethyl carbonylamino)-1-fluorine butyl carbonylamino)-1-fluorine butyl carbonylaminos; 2-fluorine butyl carbonylamino; 3-fluorine butyl carbonylamino; 4-fluorine butyl carbonylamino; 1; 1-difluoro butyl carbonylamino; 2; 2-difluoro butyl carbonylamino; 3; 3-difluoro butyl carbonylamino; 4; 4-difluoro butyl carbonylamino; 4; 4-trifluoro butyl carbonylamino etc.
Fluoro C < > 1 <>-C < > 6 <> The alkyl-carbonyl oxygen base is a formula R-C(O)-O-group, and wherein R is the fluoro-alkyl with 1-6 carbon atom that above defines.Instance comprises the acetyl fluoride base; The difluoro ethanoyl; Trifluoroacetyl group)-1-fluoro ethyl ketonic oxygen base)-1-fluoro ethyl ketonic oxygen base; 2-fluoro ethyl ketonic oxygen base; 1; 1-two fluoro ethyl ketonic oxygen bases; 2; 2-two fluoro ethyl ketonic oxygen base; 2; 2-trifluoroethyl ketonic oxygen base)-1-fluoropropyl ketonic oxygen base)-1-fluoropropyl-ketonic oxygen base; 2-fluoropropyl ketonic oxygen base; 3-fluoropropyl ketonic oxygen base; 1; 1-difluoro propyl group ketonic oxygen base; 2; 2-difluoro propyl group ketonic oxygen base; 3; 3-difluoro propyl group ketonic oxygen base; 3; 3-trifluoro propyl ketonic oxygen base)-2-fluoro-1-methylethyl ketonic oxygen base)-2-fluoro-1-methylethyl ketonic oxygen base)-2; 2-two fluoro-1-methylethyl ketonic oxygen base)-2; 2-two fluoro-1-methylethyl ketonic oxygen base)-1; 2-two fluoro-1-methylethyl ketonic oxygen base)-1; 2-two fluoro-1-methylethyl ketonic oxygen base)-2; 2; 2-three fluoro-1-methylethyl ketonic oxygen base)-2; 2; 2-three fluoro-1-methylethyl ketonic oxygen bases; 2-fluorine-1-(methyl fluoride) ethyl ketonic oxygen base difluoromethyl)-2; 2-two fluoro ethyl ketonic oxygen base)-1-fluorine butyl ketonic oxygen base)-1-fluorine butyl ketonic oxygen bases; 2-fluorine butyl ketonic oxygen base; 3-fluorine butyl ketonic oxygen base; 4-fluorine butyl ketonic oxygen base; 1; 1-difluoro butyl ketonic oxygen base; 2; 2-difluoro butyl ketonic oxygen base; 3; 3-difluoro butyl ketonic oxygen base; 4; 4-difluoro butyl ketonic oxygen base, 4-trifluoro butyl ketonic oxygen base etc.;
Fluoro C < > 1 <>-C < > 6 <> The alkyl sulfenyl is a formula R-S-group, and wherein R is the fluoro-alkyl with 1-6 carbon atom that above defines.Instance comprises the fluorine methylthio group; The difluoro methylthio group; Trifluoromethylthio)-1-fluorine ethylmercapto group)-1-fluorine ethylmercapto group; 2-fluorine ethylmercapto group; 1; 1-difluoro ethylmercapto group; 2; 2-difluoro ethylmercapto group; 2; 2-trifluoro ethylmercapto group)-1-fluorine rosickyite base)-1-fluorine rosickyite base; 2-fluorine rosickyite base; 3-fluorine rosickyite base; 1; 1-difluoro rosickyite base; 2; 2-difluoro rosickyite base; 3; 3-difluoro rosickyite base; 3; 3-trifluoropropyl sulfenyl)-2-fluoro-1-methyl ethylmercapto group)-2-fluoro-1-methyl ethylmercapto group)-2; 2-two fluoro-1-methyl ethylmercapto group)-2; 2-two fluoro-1-methyl ethylmercapto group)-1; 2-two fluoro-1-methyl ethylmercapto group)-1; 2-two fluoro-1-methyl ethylmercapto group)-2; 2; 2-three fluoro-1-methyl ethylmercapto group)-2,2-three fluoro-1-methyl ethylmercapto groups; 2-fluorine-1-(methyl fluoride) ethylmercapto group difluoromethyl)-2,2-difluoro ethylmercapto group)-1-fluorine butylthio)-1-fluorine butylthio; 2-fluorine butylthio; 3-fluorine butylthio; 4-fluorine butylthio; 1; 1-difluoro butylthio; 2; 2-difluoro butylthio, 3-difluoro butylthio, 4-difluoro butylthio, 4-trifluoro butylthio etc.;
Fluoro C < > 1 <>-C < > 6 <> Alkyl sulphinyl is a formula R-S(O)-group, and wherein R is the fluoro-alkyl with 1-6 carbon atom that above defines.Instance comprises the methyl fluoride sulfinyl; The difluoromethyl sulfinyl; Trifluoromethyl sulphinyl base)-1-fluoro ethyl sulfinyl)-1-fluoro ethyl sulfinyl; 2-fluoro ethyl sulfinyl; 1; 1-two fluoro ethyl sulfinyls; 2; 2-two fluoro ethyl sulfinyl; 2; 2-trifluoroethyl sulfinyl)-1-fluoropropyl sulfinyl)-1-fluoropropyl sulfinyl; 2-fluoropropyl sulfinyl; 3-fluoropropyl sulfinyl; 1; 1-two fluoropropyl sulfinyls; 2; 2-two fluoropropyl sulfinyls; 3; 3-two fluoropropyl sulfinyl; 3; 3-trifluoro propyl sulfinyl)-2-fluoro-1-methylethyl sulfinyl)-2-fluoro-1-methylethyl sulfinyl)-2; 2-two fluoro-1-methylethyl sulfinyl)-2; 2-two fluoro-1-methylethyl sulfinyl)-1; 2-two fluoro-1-methylethyl sulfinyl)-1; 2-two fluoro-1-methylethyl sulfinyl)-2; 2; 2-three fluoro-1-methylethyl sulfinyl)-2; 2; 2-three fluoro-1-methylethyl sulfinyls; 2-fluorine-1-(methyl fluoride) ethyl sulfinyl difluoromethyl)-2; 2-two fluoro ethyl sulfinyl)-1-fluorine butyl sulfinyl)-1-fluorine butyl sulfinyls; 2-fluorine butyl sulfinyl; 3-fluorine butyl sulfinyl; 4-fluorine butyl sulfinyl; 1; 1-difluoro butyl sulfinyl; 2; 2-difluoro butyl sulfinyl; 3; 3-difluoro butyl sulfinyl; 4; 4-difluoro butyl sulfinyl, 4-trifluoro butyl sulfinyl etc.;
Fluoro C < > 1 <>-C < > 6 <> Alkyl sulphonyl is formula R-S(O) < > 2 <>-group, wherein R is the fluoro-alkyl with 1-6 carbon atom that above defines.Instance comprises the methyl fluoride alkylsulfonyl; The difluoromethyl alkylsulfonyl; Trifluoromethyl sulfonyl)-1-fluoro ethyl alkylsulfonyl)-1-fluoro ethyl alkylsulfonyl; 2-fluoro ethyl alkylsulfonyl; 1; 1-difluoro ethylsulfonyl; 2; 2-difluoro ethylsulfonyl; 2; 2-trifluoroethyl alkylsulfonyl)-1-fluoropropyl alkylsulfonyl)-1-fluoropropyl alkylsulfonyl; 2-fluoropropyl alkylsulfonyl; 3-fluoropropyl alkylsulfonyl; 1; 1-difluoro sulfonyl propyl base; 2; 2-difluoro sulfonyl propyl base; 3; 3-difluoro sulfonyl propyl base; 3; 3-trifluoro propyl alkylsulfonyl)-2-fluoro-1-methylethyl alkylsulfonyl)-2-fluoro-1-methylethyl alkylsulfonyl)-2; 2-two fluoro-1-methylethyl alkylsulfonyl)-2; 2-two fluoro-1-methylethyl alkylsulfonyl)-1; 2-two fluoro-1-methylethyl alkylsulfonyl)-1; 2-two fluoro-1-methylethyl alkylsulfonyl)-2; 2; 2-three fluoro-1-methylethyl alkylsulfonyl)-2; 2; 2-three fluoro-1-methylethyl alkylsulfonyls; 2-fluorine-1-(methyl fluoride) ethylsulfonyl difluoromethyl)-2; 2-difluoro ethylsulfonyl)-1-fluorine butyl alkylsulfonyl)-1-fluorine butyl alkylsulfonyl; 2-fluorine butyl alkylsulfonyl; 3-fluorine butyl alkylsulfonyl; 4-fluorine butyl alkylsulfonyl; 1; 1-difluoro butyl alkylsulfonyl; 2; 2-difluoro butyl alkylsulfonyl; 3; 3-difluoro butyl alkylsulfonyl; 4; 4-difluoro butyl alkylsulfonyl, 4-trifluoro butyl alkylsulfonyl etc.
3-7 unit heterocyclic radical comprise have 3-usually, 4-, 5-, 6-or 7 saturated heterocyclyls that become annular atomses (ring members), have 5-, 6-or 7 unsaturated non-aromatic heterocycles that become annular atomses usually, and have 5-, 6 or 7 heteroaryls that become annular atoms usually.Heterocyclic radical can connect via carbon atom (C) or nitrogen-atoms (N connection) connect.Preferred heterocyclic radical comprises a nitrogen-atoms and optional 1,2 or 3 heteroatoms that is selected from O, S and N in addition independently of one another as ring members as ring members.Same preferred heterocyclic radical comprises 1 heteroatoms that is selected from O, S and N and optional 1,2 or 3 other nitrogen-atoms as ring members as ring members.
The instance of 3-7 unit saturated heterocyclyl comprises 1-or 2-aziridinyl; 2-or 3-azetidinyl; 2-or 3-pyrrolidyl; 3-or 4-piperidyl; 2-or morpholinyl; 2-or 3-thio-morpholinyl, 1-; 2-or 3-piperazinyl, 1-; 2-or-oxazolidinyl; 3-or-isoxazole alkyls; The 2-Oxyranyle, 2-or 3-oxetanyl, 2-or 3-tetrahydrofuran base; 3-or 4-cyclohexene oxide groups (oxanyl), 3-dioxolane-2-or 4-base etc., it can be unsubstituted or it can carry 1 or 3 aforementioned radicals R < > a <> And/or R < > b <>
Unsaturated non-aromatic heterocycle is to have 5-, 6-or 7 heterocyclic radicals that become annular atoms and have 1 or 2 two key that can not form aromatics towering (p) electronic system usually.Instance is 2,3-pyrrolin base, 3,4-pyrrolin base, 2; 3-dihydrofuran base, 3,4-dihydrofuran base, 2,3-dihydro-thiophene base, 3; 4-dihydro-thiophene base, 1,2-dihydropyridine base, 2,3-dihydropyridine base, 3; 4-dihydropyridine base, 1,2,3; 4-tetrahydro pyridyl, 2,4,5-2 tetrahydro pyridyl etc.
5-or 6-unit heteroaryl is the heteroaromatic cyclic group, and wherein said cyclic group has 5 or 6 atoms (ring members) that form ring, and wherein common 1,2,3 or 4 annular atoms is selected from and is O, S and N, and other annular atoms is a carbon atom.More accurately, heteroaryl comprises 1 heteroatoms that is selected from O, S and N and optional 1,2 or 3 other nitrogen-atoms as ring members as ring members.Heteroaryl can connect through carbon atom (C) or nitrogen-atoms (N connection) connect.Preferred heterocyclic radical comprises a nitrogen-atoms and optional 1,2 or 3 heteroatoms that is selected from O, S and N in addition independently of one another as ring members as ring members.Naturally, other heteroatomic ring member has only one can and have only 5-unit heterocyclic aryl can comprise that O or S are as ring members for O or S.Same preferred heterocyclic radical comprises 1 heteroatoms that is selected from O, S and N and optional 1,2 or 3 other nitrogen-atoms as ring members as ring members.The instance of 5-or 6-unit heteroaryl comprises 2-; Or the 4-pyridyl, 2-; 4-or 5-pyrimidyl, pyrazinyl, 3-or 4-pyridazinyl; 2-or 3-thienyl, 2-or the 3-base of muttering, 2-or 3-pyrryl, 1-; 2-or 4-imidazolyl; 3-or 4-pyrazolyl, 1-or 3-[1,2,4 triazolyls; 1-or 4-[1,2,3 triazolyls, 1-; 2-or 5-tetrazyl; 3-or 5-tetrazyl, 3-; 4-or-isoxazolyls, 2-; 3-or 5-thiazolyl, 3-; 4-or 5-isothiazolyl; 4-or 5-[1,2,3]-oxadiazole bases, [1,5]-oxadiazole base (=furazan bases), 3-or 5-[1,2; 4]-oxadiazole bases, [1,3,4]-oxadiazole bases; 4-or 5-[1,2,3 thiadiazolyl groups, [1,5 thiadiazolyl groups, 3-or 5-[1,4 thiadiazolyl groups, or [1,4 thiadiazolyl groups, it can be unsubstituted or it can carry 1 aforementioned radicals R < > a <> With optional 1 or 2 aforementioned radicals R < > b <>
The technician will be understood that, radicals R < > 9 <> Can be connected on any carbon atom of formula I pyridine or pyrimidine part, thereby replace hydrogen atom.Preferably, R < > 9 <> With regard to 1-position theheterocyclic nitrogen atom and 3-position NR < > 3 <>-SO < > 2 <>-Ar group and opinion is connected the 2-position.
Preferably; Ar is the heteroaryl of phenyl or aromatics 5-or the C of 6-unit connection; Said heteroaryl comprises 1 nitrogen-atoms and 0,1,2 or 3 heteroatoms that is selected from O, S and N in addition independently of one another as ring members as ring members, and it can be unsubstituted or it can carry 1,2 or 3 aforementioned radicals R < > a <> And/or R < > b <> In these heteroaryls, preferably comprise 1,2 or 3 nitrogen-atoms and do not have other heteroatoms, perhaps 1 or 2 nitrogen-atoms and 1 heteroaryl that is selected from the atom of O and S as ring members as ring members.Yet thienyl and furyl are preferred equally.Particularly preferred heteroaryl Ar is 2-or 3-thienyl, 2-, 3-or 4-pyridyl, 2-, 4-or 5-pyrimidyl; 2-, 3-or 5-thiazolyl, 1,2; 4-triazole-3-base, 1,2; 3-triazole-4-base, 1,3; 4-thiadiazoles-2-base, particularly 2-thienyl, the 2-pyrimidyl; 5-pyrimidyl and 2-pyridyl, it can be unsubstituted or it can carry 1 aforementioned radicals R < > a <> With optional 1 or 2 aforementioned radicals R < > b <> More preferably, Ar is a phenyl, and it can be unsubstituted or it can carry 1 aforementioned radicals R < > a <> With optional 1 or 2 aforementioned radicals R < > b <>
Preferably, aryl Ar carries 1 above-mentioned radicals R < > a <> With optional 1 or 2 other above-mentioned radicals R < > b <> R < > b <> Be selected from methyl, fluoro methyl, halogen especially, more preferably be selected from fluorine or chlorine.
Aforementioned 5 yuan of heteroaryl Ar preferably in the 3-position (with respect to SO < > 2 <> The position of-group) carries a radicals R on < > a <> With and optional one or two other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Phenyl and aforementioned 6 yuan of heteroaryl Ar preferably in the 4-position (with respect to SO < > 2 <> The position of-group) carries a radicals R on < > a <> With optional one or two other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Ar is a phenyl in highly preferred embodiment of the present invention, and said phenyl carries a R on the 4-position of benzyl ring < > a <> With optional 1 or 2 other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Ar is the 2-pyrimidyl in another embodiment preferred of the present invention, and said pyrimidyl carries radicals R on the 5-position of pyrimidine ring < > a <> With optional 1 or 2 other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Ar is the 5-pyrimidyl in another embodiment preferred of the present invention, and said pyrimidyl carries radicals R on the 2-position of pyrimidine ring < > a <> With optional 1 or 2 other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Ar is the 2-thienyl in another embodiment preferred of the present invention, and said thienyl carries radicals R on the 3-position of thiphene ring < > a <> With optional 1 or 2 other radicals R < > b <> , said radicals R < > b <> Be preferably halogen, particularly fluorine or chlorine.
Ar carries 1 radicals R in preferred embodiments < > a <> , said radicals R < > a <> Be selected from C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 1 <>-C < > 6 <>-alkyl, C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, NR < > 4 <> R < > 5 <> , 1-aziridinyl, azetidine-1-base, tetramethyleneimine-1-base or piperidines-1-base (last four said groups can fluoro), phenyl and aromatics 5 or 6 yuan of heteroaryls that C is connected; Said heteroaryl comprises 1 as ring members nitrogen-atoms and 0,1,2 or 3 other heteroatoms that is selected from O, S and N independently of one another, and wherein latter two group of mentioning can carry 1,2,3 or 4 and be selected from halogen, C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 1 <>-C < > 6 <>-alkyl, C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group and NR < > 4 <> R < > 5 <> Group; And wherein Ar can carry 1 or 2 other radicals R < > b <> , it is selected from halogen, cyanic acid, methyl, methyl fluoride, difluoromethyl, trifluoromethyl, difluoro-methoxy and trifluoromethoxy independently of one another.R in this embodiment < > 4 <> And R < > 5 <> H, the C of preferably being selected from independently of one another < > 1 <>-C < > 2 <>-alkyl and fluoro C < > 1 <>-C < > 2 <>-alkyl.Preferably, radicals R < > 4 <> Or R < > 5 <> In a group be different from hydrogen.Radicals R < > 4 <> Or R < > 5 <> In a group also can be C1-C < > 2 <>-alkoxyl group.
In highly preferred embodiment, group Ar preferably carries a radicals R < > a <> , it has formula R < > A ' <> Structure
Figure G2007800134447D00141
Wherein
Y is N, CH or CF,
R < > A1 <> And R < > A2 <> Be independently from each other C < > 1 <>-C < > 2 <>-alkyl, C < > 1 <>-C < > 2 <>-alkoxyl group, fluoro C < > 1 <>-C < > 2 <>-alkyl, condition are Y when being CH or CF, radicals R < > A1 <> Or R < > A2 <> One of also can be hydrogen or fluorine, or
R < > A1 <> And R < > A2 <> Form group (CH together < > 2 <> ) < > k <> , wherein 1 or 2 hydrogen atom can be by fluorine, hydroxyl, oxo base, C < > 1 <>-C < > 2 <>-alkyl or C1-C < > 2 <>-alkoxyl group replaces, one of them CH < > 2 <> Part can be by O, S, S=O, SO < > 2 <> Or N-R < > c <> Replace R < > c <> Be hydrogen or C < > 1 <>-C < > 2 <>-alkyl, and wherein k is 2,3,4,5 or 6.
Especially
R < > A1 <> And R < > A2 <> Be independently from each other C < > 1 <>-C < > 2 <>-alkyl, fluoro C < > 1 <>-C < > 2 <>-alkyl especially is methyl fluoride, difluoromethyl or trifluoromethyl, and condition is that Y is CH or CF, radicals R < > A1 <> Or R < > A2 <> One of also can be hydrogen or fluorine, or
R < > A1 <> And R < > A2 <> Form group (CH together < > 2 <> ) < > k <> , wherein 1 or 2 hydrogen atom can be replaced by fluorine, and wherein k is 2,3 or 4, especially is CH < > 2 <>-CH < > 2 <> , CHF-CH < > 2 <> CF < > 2 <>-CH < > 2 <> , CH < > 2 <>-CH < > 2 <>-CH < > 2 <> , CHF-CH < > 2 <>-CH < > 2 <> , CF < > 2 <>-CH < > 2 <>-CH < > 2 <> , CH < > 2 <>-CHF-CH < > 2 <> , CH < > 2 <>-CF < > 2 <>-CH < > 2 <>
At R < > A1 <> And R < > A2 <> Under the situation about differing from one another, aforementioned formula R < > A ' <> Group partly can have (R)-or (S)-configuration with respect to Y-.
Radicals R < > A ' <> Preferred examples comprises sec.-propyl)-1-fluoro ethyl)-1-fluoro ethyl; The 2-fluoro ethyl; 1; 1-two fluoro ethyls; 2; 2-two fluoro ethyl; 2; 2-trifluoroethyl)-1-fluoropropyl)-1-fluoropropyl; The 2-fluoropropyl; The 3-fluoropropyl; 1; 1-two fluoropropyls; 2; 2-two fluoropropyl, 3-two fluoropropyl, 3; 3-trifluoro propyl)-2-fluoro-1-methylethyl)-2-fluoro-1-methylethyl)-2; 2-two fluoro-1-methylethyl)-2,2-two fluoro-1-methylethyl)-1,2-two fluoro-1-methylethyl)-1; 2-two fluoro-1-methylethyl)-2,2-three fluoro-1-methylethyl)-2,2; 2-three fluoro-1-methylethyls; 2-fluorine-1-(methyl fluoride) ethyl difluoromethyl)-2,2-two fluoro ethyls; Cyclopropyl; Cyclobutyl; 1-fluorine cyclopropyl; With 2-fluorine cyclopropyl.
Also preferred radicals R < > A ' <> Be R wherein < > A1 <> Or R < > A2 <> In one be C < > 1 <>-C < > 2 <>-alkoxyl group and R < > A1 <> Or R < > A2 <> In another be selected from H, C < > 1 <>-C < > 2 <>-alkyl especially is a methyl, fluoro C < > 1 <>-C < > 2 <>-alkyl especially is methyl fluoride, difluoromethyl or trifluoromethyl.Instance comprises that N-methoxyl group-N-methylamino, N-methoxyl group amino and N-oxyethyl group are amino.
Preferred formula R < > A ' <> Group comprises also that wherein Y is nitrogen and R wherein < > A1 <> And R < > A2 <> Form group (CH < > 2 <> ) < > t <> Formula R < > A ' <> Group, wherein 1 or 2 hydrogen atom can be replaced by fluorine, methyl, trifluoromethyl, methoxyl group or oxo base, and wherein t is 2,3,4 or 5.Instance comprises azetidine-1-base; 2-methyl azetidine-1-base)-2-methyl azetidine-1-base)-2-methyl azetidine-1-base; 3-fluorine azetidine-1-base; 3-methoxyl group azetidine-1-base; 3-hydroxy azetidine-1-base oxazole-5-base; Tetramethyleneimine-1-base)-2-fluoropyrrolidine-1-base)-2-fluoropyrrolidine-1-base; 3-fluoropyrrolidine-1-base)-3-fluoropyrrolidine-1-base)-3-fluoropyrrolidine-1-base; 2; 2-two fluoropyrrolidines-1-base; 3; 3-two fluoropyrrolidines-1-base; 2-crassitude-1-base)-2-crassitude-1-base)-2-crassitude-1-base; 3-crassitude-1-base)-3-crassitude-1-base)-3-crassitude-1-base; 2; 2-dimethyl pyrrolidine-1-base, 3-dimethyl pyrrolidine-1-base; 2-trifluoromethyl pyrpole alkane-1-base)-2-trifluoromethyl pyrpole alkane-1-base)-2-trifluoromethyl pyrpole alkane-1-base; 3-trifluoromethyl pyrpole alkane-1-base)-3-trifluoromethyl pyrpole alkane-1-base)-3-trifluoromethyl pyrpole alkane-1-base; 2-oxo-pyrrolidine-1-base; Piperidines-1-base; Pipecoline-1-base)-2-methyl piperidine-1-base and (R)-2-methyl piperidine-1-base.
Same preferred formula R < > A ' <> Group is R wherein < > A1 <> And R < > A2 <> Form group (CH together < > 2 <> ) < > u <> , wherein 1 or 2 hydrogen atom can be by fluorine, hydroxyl, oxo base, C < > 1 <>-C < > 2 <>-alkyl or C < > 1 <>-C < > 2 <>-alkoxyl group replaces, one of them CH < > 2 <> Part is by O, S, S=O, SOx and N-R < > c <> Substitute R < > c <> Be hydrogen or C < > 1 <>-C < > 2 <>-alkyl, and u is 2,3,4,5 or 6 radicals R < > A ' <> Preferred formula R < > A ' <> Examples of groups also comprises the 4-morpholinyl; The 4-thio-morpholinyl; 4-(1, the 1-dioxo) thio-morpholinyl; Piperazine-1-base; 4-methylpiperazine-1-base; 2-oxo-oxazolidines-3-base; Tetramethyleneimine-2-base; (S)-tetramethyleneimine-2-base; (R)-tetramethyleneimine-2-base; Tetramethyleneimine-3-base; (S)-tetramethyleneimine-3-base; (R)-tetramethyleneimine-3-base; 2-fluoropyrrolidine-1-base; 1-crassitude-2-base)-1-crassitude-2-base)-1-crassitude-2-base; 1-crassitude-3-base)-1-crassitude-3-base and (R)-1-crassitude-3-base.
At formula R < > A ' <> In the group, preferably carry 1,2,3 or 4, particularly the formula R of 1,2 or 3 fluorine atom < > A ' <> Group.
In other embodiment preferred, Ar carries a radicals R < > a <> It is selected from 5-or 6-unit heteroaryl; Said heteroaryl has 1 as the heteroatoms that is selected from O, S and N of ring members with can have other 1,2 or 3 nitrogen-atoms as ring members, and wherein said 5-or 6-unit heteroaryl can carry 1,2 or 3 and be selected from following substituting group: halogen, NO < > 2 <> , NH < > 2 <> , OH, CN, C < > 1 <>-C < > 6 <>-alkyl, C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkylamino, two-C < > 1 <>-C < > 6 <>-alkylamino, C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, two-C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl and fluoro C < > 1 <>-C < > 6 <>-alkyl sulphonyl.In these radicals R < > a <> In, the preferred following group that provides: 2-, 3-; Or 4-pyridyl; 2-, 4-or 5-pyrimidyl; Pyrazinyl; 3-or 4-pyridazinyl; 2-or 3-thienyl; 2-or 3-furyl; 1-, 2-or 3-pyrryl; 2-, 4-or 5-imidazolyl; 1-, 3-; 4-or 5-pyrazolyl; 1-, 3-or 5-[1,2 triazolyls; 1-, 4-or 5-[1,2 triazolyls; 1-or 5-(1H)-tetrazyl; 2-or 5-(2H)-tetrazyl; 2-, 4-or-oxazolyls; 3-, 4-or-isoxazolyl; 4-or 5-thiazolyl; 4-or 5-isothiazolyl; 4-or 5-[1,2,3]-oxadiazole bases; 3-or 4-[1; 5]-oxadiazole base (=furazan base); 3-or 5-[1,2,4]-oxadiazole bases; 2-or 5-[1; 4]-oxadiazole bases; 4-or 5-[1,2,3 thiadiazolyl groups; 3-or 4-[1 thiadiazolyl group; 3-or 5-[1,2,4 thiadiazolyl groups or 2-or 5-[1 thiadiazolyl group especially are selected from: 2-or 3-furyl; 2-or 3-thienyl; 1-, 2-or 3-pyrryl; 4-or 5-pyrazolyl; 1-, 2-, 4-or 5-imidazolyl; 4-or-oxazolyls; 3-, 4-or-isoxazolyls; 2-or 5-[1,3 thiadiazolyl group; 3-or 5-[1,2,4 triazolyl; 4-or 5-[1,3 triazolyls; 1-or 5-(1H)-tetrazyl and 2-or 5-(2H)-tetrazyl and be selected from 1-especially; 4-or 5-pyrazolyl be the 1-pyrazolyl especially, and 2-, and 4-or-oxazolyls are 4-or-oxazolyls especially.These heteroaryls can be unsubstituted or can carry 1-3 above specified substituting group.Heteroaryl R < > a <> On preferred substituted be selected from halogen, C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 4 <>-alkoxyl group, fluoro C < > 1 <>-C < > 4 <>-alkyl and fluoro C < > 1 <>-C < > 4 <>-alkoxyl group.
In other embodiment preferred, Ar carries 1 radicals R that is selected from following groups < > a <> :(CH < > 2 <> ) < > V <> CF < > 3 <> , (CH < > 2 <> ) < > V <> CHF < > 2 <> , (CH < > 2 <> ) < > V <> CH < > 2 <> F, O(CH < > 2 <> ) < > V <> CF < > 3 <> , O(CH < > 2 <> ) < > V <> CHF < > 2 <> , O(CH < > 2 <> ) < > V <> CH < > 2 <> F, wherein v is 0,1,2 or 3.In this embodiment, Ar can also carry 1 or 2 other radicals R < > b <> , it is independently from each other halogen, cyanic acid, methyl, methyl fluoride, difluoromethyl, trifluoromethyl, difluoro-methoxy and trifluoromethoxy.Preferably, Ar does not carry other radicals R < > b <> In this embodiment, Ar preferably carries 1 radicals R < > a <> Phenyl, said radicals R < > a <> Be selected from (CH < > 2 <> ) < > V <> CF < > 3 <> , (CH < > 2 <> ) < > V <> CHF < > 2 <> , (CH < > 2 <> ) < > V <> CH < > 2 <> F, O(CH < > 2 <> ) < > V <> CF < > 3 <> , O(CH < > 2 <> ) < > V <> CHF < > 2 <> , O(CH < > 2 <> ) < > V <> CH < > 2 <> F, wherein V is 0,1,2 or 3.In this embodiment, Ar is phenyl preferably, and said phenyl is with respect to SO < > 2 <> Carry R on 4 of-group < > a <>
In the other embodiment of the present invention, Ar carries 1 radicals R < > a <> , said R < > a <> Be selected from C < > 2 <>-C < > 6 <>-thiazolinyl, fluoro C < > 2 <>-C < > 6 <>-thiazolinyl, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 6 <>-alkoxy-C < > 1 <>-C < > 4 <>-alkoxyl group, COOH, CH < > 2 <> NR < > 4 <> R < > 5 <> , ONR < > 4 <> R < > 5 <> , NHC(O) NR < > 4 <> R < > 5 <> , C(O) NR < > 4 <> R < > 5 <> , SO < > 2 <> NR < > 4 <> R < > 5 <> , C < > 1 <>-C < > 6 <>-alkyl-carbonyl, fluoro C < > 2 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl, fluoro C < > 1 <>-C < > 6 <> The N-of-alkyl sulphonyl, benzenesulfonyl, phenoxy group, benzyloxy, pyridine-2-base oxygen base and 5-or 6-unit is connected heteroaryl, and wherein last six said groups can carry 1,2,3 or 4 and be selected from following group: halogen, NO < > 2 <> , NH < > 2 <> , OH, CN, C < > 1 <>-C < > 6 <>-alkyl, C < > 3 <>-C < > 6 <>-cycloalkyl, C < > 1 <>-C < > 6 <>-alkoxyl group, fluoro C < > 1 <>-C < > 6 <>-alkyl, fluoro C < > 3 <>-C < > 6 <>-cycloalkyl, fluoro C < > 1 <>-C < > 6 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-hydroxyalkyl, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 6 <>-hydroxy alkoxy base, C < > 1 <>-C < > 4 <>-alkoxy-C < > 2 <>-C < > 4 <>-alkoxyl group, C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkylamino, two-C < > 1 <>-C < > 6 <>-alkylamino, C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, two-C < > 1 <>-C < > 6 <>-alkyl amino-carbonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl, C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl-amino, C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, fluoro C < > 1 <>-C < > 6 <>-alkyl-carbonyl oxygen base, C < > 1 <>-C < > 6 <>-alkoxy carbonyl, C < > 1 <>-C < > 6 <>-alkyl sulfenyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulfenyl, C < > 1 <>-C < > 6 <>-alkyl sulphinyl, C < > 1 <>-C < > 6 <>-alkyl sulphonyl, fluoro C < > 1 <>-C < > 6 <>-alkyl sulphinyl and fluoro C < > 1 <>-C < > 6 <>-alkyl sulphonyl.
In the other embodiment of the present invention, Ar is a phenyl, and said phenyl carries 1 R < > a <> With at least one radicals R < > b <> , and R wherein < > a <> With a R < > b <> Be connected on two adjacent carbonss of phenyl and formation and benzyl ring condensed 5-or 6-unit's heterocycle or carbocyclic ring, said heterocycle or carbocyclic ring are unsubstituted or can carry 1,2 or 3 above specified group.Comprise indenyl, indanyl, naphthyl, tetrahydronaphthalene, benzofuranyl, 2 with the instance of saturated or unsaturated 5-or 6-unit's carbocyclic ring or heterocyclic fused benzyl ring; 3-dihydro benzo furyl, benzothienyl, indyl, indazolyl, benzimidazolyl, benzo are disliked thiazolyl, benzo oxadiazoles base, diazosulfide base, benzoxazinyl-, dihydrobenzo oxazines base, quinolyl (chinolinyl), isoquinolyl, tetrahydro isoquinolyl, chromene base, chromanyl etc., and it can be unsubstituted or it can carry 1,2 or 3 aforementioned group.Be selected from halogen, C with the saturated or unsaturated 5-of benzyl ring condensed or 6-unit's carbocyclic ring or heterocyclic preferred substituted < > 1 <>-C < > 4 <>-alkyl, C < > 1 <>-C < > 4 <>-alkoxyl group, fluoro C < > 1 <>-C < > 4 <>-alkyl and fluoro C < > 1 <>-C < > 4 <>-alkoxyl group.
Especially, R < > a <> Be selected from C < > 1 <>-C < > 4 <>-alkyl, fluoro C < > 1 <>-C < > 4 <>-alkyl especially is (CH < > 2 <> ) < > V <> CF < > 3 <> , (CH < > 2 <> ) < > V <> CHF < > 2 <> (CH < > 2 <> )VCH < > 2 <> F, C < > 1 <>-C < > 4 <>-alkoxyl group and fluoro C < > 1 <>-C < > 4 <>-alkoxyl group especially is O(CH < > 2 <> )VCF < > 3 <> , O(CH < > 2 <> ) VCHF < > 2 <> And O(CH < > 2 <> )VCH < > 2 <> F.
Alternative ground, R < > a <> Be selected from especially and have 1 as the heteroatoms that is selected from O, S and N of ring members with can have other 1,2 or 3 5-or 6-heteroaryl, and wherein said 5-or 6-unit heteroaryl can replace as mentioned above as the nitrogen-atoms of ring members.Preferred 5-or 6-heteroaryl R < > a <> And preferred substituted as mentioned above.
More specifically, Ar is a phenyl, and said phenyl is preferably carrying a R with respect on 4 of 1-position alkylsulfonyl < > a <> , said R < > a <> Be selected from C < > 1 <>-C < > 4 <>-alkyl, fluoro C < > 1 <>-C < > 4 <>-alkyl, especially (CH < > 2 <> ) < > V <> CF < > 3 <> , (CH < > 2 <> ) < > V <> CHF < > 2 <> (CH < > 2 <> ) < > V <> CH < > 2 <> F, C < > 1 <>-C < > 4 <>-alkoxyl group, fluoro C < > 1 <>-C < > 4 <>-alkoxyl group, especially O(CH < > 2 <> ) < > V <> CF < > 3 <> , O(CH < > 2 <> ) < > V <> CHF < > 2 <> And O(CH < > 2 <> ) < > V <> CH < > 2 <> F and aforesaid 5-or 6-heteroaryl.
Radicals R < > 1 <> Preferred H, C < > 1 <>-C < > 4 <>-alkyl, C < > 3 <>-C < > 4 <>-cycloalkyl, C < > 3 <>-C < > 4 <>-methyl cycloalkyl, C < > 3 <>-C < > 4 <>-thiazolinyl, fluoro C < > 2 <>-C < > 4 <>-alkyl, fluoro C < > 3 <>-C < > 4 <>-cycloalkyl, fluoro C < > 3 <>-C < > 4 <>-methyl cycloalkyl, fluoro C < > 3 <>-C < > 4 <>-thiazolinyl, formyl radical or C < > 1 <>-C < > 3 <>-alkyl-carbonyl especially is H, C < > 1 <>-C < > 4 <>-alkyl, C < > 3 <>-C < > 4 <>-thiazolinyl, fluoro C < > 2 <>-C < > 4 <>-alkyl, fluoro C < > 3 <>-C < > 4 <>-thiazolinyl, more preferably H, methyl, ethyl, n-propyl, fluoro C < > 2 <>-C < > 3 <>-alkyl or 1-propylene-3-base (allyl group) is in particular H, methyl or n-propyl, especially is n-propyl.
An embodiment preferred of the present invention relates to compound, wherein R < > 1a <> Be hydrogen.R in these compounds < > 1 <> Have above given implication, and preferably be not hydrogen.R in particular < > 1 <> Be n-propyl.In this embodiment, R < > 2a <> Preferably hydrogen and R < > 2 <> Preferably hydrogen, methyl or fluoro methyl.Especially, R < > 2a <> And R < > 2 <> All be hydrogen or radicals R < > 2a <> And R < > 2 <> One for hydrogen another is a methyl.In this embodiment, preferred R < > 8a <> And R < > 8 <> All be hydrogen.
In a further preferred embodiment, R < > 1a <> Not hydrogen and be preferably C < > 1 <>-C < > 4 <>-alkyl, C < > 3 <>-C < > 4 <>-thiazolinyl, fluoro C < > 2 <>-C < > 4 <>-alkyl, fluoro C < > 3 <>-C < > 4 <>-thiazolinyl, more preferably methyl, n-propyl, fluoro C < > 2 <>-C < > 3 <>-alkyl or 1-propylene-3-base especially is a n-propyl.R in these compounds < > 1 <> Has above given implication.Especially, R < > 1 <> Be H, methyl or n-propyl.In this embodiment, R < > 1 <> And R < > 1a <> Have identical implication and especially be methyl or n-propyl.In this embodiment, R < > 2a <> Preferably hydrogen and R < > 2 <> Preferably hydrogen, methyl or fluoro methyl.Especially, R < > 2a <> And R < > 2 <> All be hydrogen or radicals R < > 2a <> And R < > 2 <> One for hydrogen another is a methyl.In this embodiment, preferred R < > 8a <> And R < > 8 <> All be hydrogen.
In a further preferred embodiment, R < > 2a <> And R < > 1a <> Be (CR together < > 6 <> R < > 7 <> ) < > n <> , wherein n is 2,3 or 4 and be in particular 3.R < > 6 <> And R < > 7 <> Be preferably H.R < > 2 <> Be preferably hydrogen.R in these compounds < > 1 <> Has above given implication.Especially, R < > 1 <> Be H, n-propyl or 1-propylene-3-base.In this embodiment, preferred R < > 8a <> And R < > 8 <> All be hydrogen.
In a further preferred embodiment, R < > 8a <> And R < > 1a <> Be (CR together < > 6 <> R < > 7 <> ) < > s <> , wherein s is 2 or 3 and be in particular 2.R < > 6 <> And R < > 7 <> Be preferably H.R < > 2 <> And R < > 2a <> Be preferably H.R < > 8 <> Be preferably H.R in these compounds < > 1 <> Has above given implication.Especially, R < > 1 <> Be H, n-propyl or 1-propylene-3-base, and especially be H or n-propyl.
In going back embodiment preferred, R < > 1 <> And R < > 1a <> Be (CR together < > 6 <> R < > 7 <> ) < > r <> , wherein r is 3,4 or 5 and be in particular 4.R < > 6 <> And R < > 7 <> Be preferably H.In this embodiment, R < > 2a <> And R < > 2 <> And R < > 8a <> And R < > 8 <> All be preferably hydrogen.
An embodiment preferred of the present invention relates to formula I compound, and wherein X is CH.
Another embodiment preferred of the present invention relates to formula I compound, and wherein X is N.
Preferably, R < > 3 <> Be H or methyl and H more preferably.
An embodiment preferred of the present invention relates to formula I compound, wherein R < > 9 <> Be selected from C < > 1 <>-C < > 4 <>-alkyl is methyl, C especially < > 1 <>-C < > 4 <>-alkoxyl group is methoxyl group and hydrogen especially.
In a further preferred embodiment, be close to pyridine and pyrimidine ring nitrogen partly and be connected R < > 9 <> , and R < > 9 <> Be preferably C < > 1 <>-C < > 4 <>-alkoxyl group, especially methoxyl group.
In a further preferred embodiment, be close to pyridine and pyrimidine ring nitrogen partly respectively and be connected R < > 9 <> , and R < > 9 <> Be preferably C < > 1 <>-C < > 4 <>-alkyl, especially methyl.
Another embodiment preferred relates to wherein that X is the compound of CH, and R < > 1a <> , R < > 2 <> , R < > 2a <> , R < > 8 <> And R < > 8a <> Be H, R < > 9 <> Be methoxyl group and R < > a <> Define as above with Ar.
Another embodiment preferred relates to wherein that X is the compound of N, and R < > 1a <> , R < > 2 <> , R < > 2a <> , R < > 8 <> And R < > 8a <> Be H, R < > 9 <> Be methoxyl group and R < > a <> Define as above with Ar.
In a preferred embodiment, Ar(and R < > a <> Together) has one of implication that following table B provides.
The preferred embodiment of the invention is the acid salt that can tolerate on compound and the physiology thereof of following formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, lo, Ip, Iq, Ir, Is, It, Iu, Iv, Iw, Ix, Iy and Iz.Owing to carry four not isoplastic carbon atoms, can there be for example racemic mixture of R-enantiomer or S-enantiomer and enantiomeric mixture in the compound of formula Ii, Ij, Ik, Il, Im, In, lo, Ip, Iq, Ir, Is and It.Embodiment preferred comprises R-and S-enantiomer and the enantiomeric mixture of formula Ii, Ij, Ik, Il, Im, In, lo, Ip, Iq, Ir, Is and It.
In the compound of formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih, Ii, Ij, Ik, Il, Im, In, lo, Ip, Iq, Ir, Is and It, R < > 1 <> , Ar and R < > 1a <> Define as above, and the specified wherein R of preferential especially selection < > 1 <> , Ar and R < > 1a <> Those compounds with a kind of preferred meaning.
Figure G2007800134447D00211
Figure G2007800134447D00221
At the compound of formula Iu, Iv, Iw, Ix, Iy and Iz, the Ar definition as above and especially with reference to those specified compounds, wherein Ar has a kind of preferred implication.
Figure G2007800134447D00222
The instance of general formula I preferred compound is provided among following table A-1, A-2, A-3, A-4, A5, A-6, A-7, A-8, A-9, A-10, A-11, A-12, A-13, A-14, A-15, A-16, A-17, A-18, A-19, A-20, B-1, B-2, B-3, B-4, B-5 and the B-6.
The compound of table A-1: formula Ia, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-2: formula Ib, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-3: formula Ic, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-4: formula Id, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-5: formula Ie, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-6: formula If, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-7: formula Ig, wherein R < > 1a <> Be H and Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-8: formula Ih, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-9: formula Ii comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-10: formula Ij comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-11: formula Ik comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-12: formula Il comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-13: formula Im comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-14: formula In comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-15: formula Io comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-16: formula Ip comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-17: formula Iq comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-18: formula Ir comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-19: formula Is comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
The compound of table A-20: formula It comprises pure S-isomers, pure R-isomers and racemic mixture, wherein Ar and R < > 1 <> Has the given implication of delegation in the Table A.
Table A
NO. R 1 Ar
1. Methyl 4-(trifluoromethoxy)-phenyl
2. Methyl 3-(trifluoromethoxy)-phenyl
3. Methyl The 4-cyano-phenyl
4. Methyl The 4-aminomethyl phenyl
5. Methyl The 4-ethylphenyl
6. Methyl 4-propyl group phenyl
7. Methyl The 4-p-methoxy-phenyl
8. Methyl The 4-fluorophenyl
9. Methyl The 4-chloro-phenyl-
10. Methyl The 4-bromophenyl
11. Methyl The 3-(trifluoromethyl) phenyl
12. Methyl The 4-(trifluoromethyl) phenyl
13. Methyl The 2-(trifluoromethyl) phenyl
14. Methyl 3, the 4-difluorophenyl
15. Methyl 4-bromo-3-fluorophenyl
16. Methyl 4-bromo-2-fluorophenyl
17. Methyl 4-bromine-2, the 5-difluorophenyl
18. Methyl 2-fluoro-4-isopropyl phenyl
19. Methyl The 4-hydroxy phenyl
20. Methyl The 4-isopropyl phenyl
21. Methyl The 4-secondary butyl phenenyl
22. Methyl The 4-isobutyl phenenyl
23. Methyl 4-(1,1-dimethyl propyl)-phenyl
24. Methyl The 4-ethenylphenyl
25. Methyl 4-pseudoallyl phenyl
26. Methyl The 4-(methyl fluoride) phenyl
27. Methyl The 3-(methyl fluoride) phenyl
28. Methyl The 2-(methyl fluoride) phenyl
29. Methyl The 4-(difluoromethyl) phenyl
30. Methyl The 3-(difluoromethyl) phenyl
31. Methyl The 2-(difluoromethyl) phenyl
32. Methyl 4-(1-fluoro ethyl)-phenyl
33. Methyl 4-((S)-1-fluoro ethyl)-phenyl
34. Methyl 4-((R)-1-fluoro ethyl)-phenyl
35. Methyl 4-(2-fluoro ethyl)-phenyl
36. Methyl 4-(1,1-two fluoro ethyl)-phenyl
37. Methyl 4-(2,2-two fluoro ethyl)-phenyl
38. Methyl 4-(2,2,2-trifluoroethyl)-phenyl
39. Methyl 4-(3-fluoropropyl)-phenyl
40. Methyl 4-(2-fluoropropyl)-phenyl
41. Methyl 4-((S)-2-fluoropropyl)-phenyl
42. Methyl 4-((R)-2-fluoropropyl)-phenyl
43. Methyl 4-(3,3-two fluoropropyl)-phenyl
44. Methyl 4-(3,3,3-trifluoro propyl)-phenyl
45. Methyl 4-(1-fluoro-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-two fluoro-1-methylethyl)-phenyl
50. Methyl 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
51. Methyl 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
52. Methyl 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
53. Methyl 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
54. Methyl 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
55. Methyl 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
56. Methyl 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
57. Methyl 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
58. Methyl The 4-ethoxyl phenenyl
59. Methyl 4-propoxy-phenyl
60. Methyl The 4-isopropyl phenyl
61. Methyl The 4-butoxy phenyl
62. Methyl 4-(fluorine methoxyl group)-phenyl
63. Methyl 4-(difluoro-methoxy)-phenyl
64. Methyl 4-(2-fluorine oxyethyl group)-phenyl
65. Methyl 4-(2,2-difluoroethoxy)-phenyl
66. Methyl 4-(2,2,2-trifluoro ethoxy)-phenyl
67. Methyl 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
68. Methyl 4-cyclopropyl phenyl
69. Methyl 4-cyclobutyl phenyl
70. Methyl 4-cyclopentyl phenyl
71. Methyl 4-(2,2-difluoro cyclopropyl)-phenyl
72. Methyl 3-fluoro-4-isopropyl phenyl
73. Methyl 4-(1-hydroxyl-1-methylethyl)-phenyl
74. Methyl 4-(2-hydroxy-2-methyl propyl group)-phenyl
75. Methyl The 4-acetylphenyl
76. Methyl The 4-carboxyl phenyl
77. Methyl 4-(O-benzyl)-phenyl
78. Methyl 4-(2-methoxy ethoxy)-phenyl
79. Methyl 4-(CH 2-N(CH 3) 2)-phenyl
80. Methyl 4-(NH-CO-NH 2)-phenyl
81. Methyl 4-(methyl sulfane base)-phenyl
82. Methyl 4-(methyl fluoride sulfane base)-phenyl
83. Methyl 4-(difluoromethyl sulfane base)-phenyl
84. Methyl 4-(trifluoromethyl sulfane base)-phenyl
85. Methyl 4-(methyl sulphonyl)-phenyl
86. Methyl 4-(N-methoxyl group-N-methyl-amino)-phenyl
87. Methyl The amino)-phenyl of 4-(methoxyl group
88. Methyl The amino)-phenyl of 4-(oxyethyl group
89. Methyl 4-(N-methylamino oxygen base)-phenyl
90. Methyl 4-(N, N-dimethylamino oxygen base)-phenyl
91. Methyl 4-(azetidine-1-base)-phenyl
92. Methyl 4-(2-methyl azetidine-1-base)-phenyl
93. Methyl 4-((S)-2-methyl azetidine-1-base)-phenyl
94. Methyl 4-((R)-2-methyl azetidine-1-base)-phenyl
95. Methyl 4-(3-fluorine azetidine-1-base)-phenyl
96. Methyl 4-(3-methoxyl group azetidine-1-base)-phenyl
97. Methyl 4-(3-hydroxy azetidine-1-base)-phenyl
98. Methyl 4-(tetramethyleneimine-1-base)-phenyl
99. Methyl 4-(tetramethyleneimine-2-base)-phenyl
100. Methyl 4-((S)-tetramethyleneimine-2-base)-phenyl
101. Methyl 4-((R)-tetramethyleneimine-2-base)-phenyl
102. Methyl 4-(tetramethyleneimine-3-base)-phenyl
103. Methyl 4-((S)-tetramethyleneimine-3-base)-phenyl
104. Methyl 4-((R)-tetramethyleneimine-3-base)-phenyl
105. Methyl 4-(2-fluoropyrrolidine-1-base)-phenyl
106. Methyl 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
107. Methyl 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
108. Methyl 4-(3-fluoropyrrolidine-1-base)-phenyl
109. Methyl 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
110. Methyl 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
111. Methyl 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
112. Methyl 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
113. Methyl 4-(2-crassitude-1-base)-phenyl
114. Methyl 4-((S)-2-crassitude-1-base)-phenyl
115. Methyl 4-((R)-2-crassitude-1-base)-phenyl
116. Methyl 4-(3-crassitude-1-base)-phenyl
117. Methyl 4-((S)-3-crassitude-1-base)-phenyl
118. Methyl 4-((R)-3-crassitude-1-base)-phenyl
119. Methyl 4-(1-crassitude-2-base)-phenyl
120. Methyl 4-((S)-1-crassitude-2-base)-phenyl
121. Methyl 4-((R)-1-crassitude-2-base)-phenyl
122. Methyl 4-(1-crassitude-3-base)-phenyl
123. Methyl 4-((S)-1-crassitude-3-base)-phenyl
124. Methyl 4-((R)-1-crassitude-3-base)-phenyl
125. Methyl 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
126. Methyl 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
127. Methyl 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
128. Methyl 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
129. Methyl 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
130. Methyl 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
131. Methyl 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
132. Methyl 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
133. Methyl 4-(2-oxo-pyrrolidine-1-base)-phenyl
134. Methyl 4-(2-oxo-oxazolidines-3-base)-phenyl
135. Methyl 4-(piperidines-1-base)-phenyl
136. Methyl 4-(2-methyl piperidine-1-base)-phenyl
137. Methyl 4-((S)-2-methyl piperidine-1-base)-phenyl
138. Methyl 4-((R)-2-methyl piperidine-1-base)-phenyl
139. Methyl 4-(piperazine-1-base)-phenyl
140. Methyl 4-(4-methylpiperazine-1-base)-phenyl
141. Methyl 4-(morpholine-4-base)-phenyl
142. Methyl 4-(thiomorpholine-4-base)-phenyl
143. Methyl 4-(1-oxo-thiomorpholine-4-base)-phenyl
144. Methyl 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
145. Methyl 4-(pyrroles-1-base)-phenyl
146. Methyl 4-(pyrroles-2-base)-phenyl
147. Methyl 4-(pyrroles-3-base)-phenyl
148. Methyl 4-(1-methylpyrrole-2-base)-phenyl
149. Methyl 44-(1-methylpyrrole-3-base)-phenyl
150. Methyl 4-(furans-2-base)-phenyl
151. Methyl 4-(furans-3-base)-phenyl
152. Methyl 4-(thiophene-2-base)-phenyl
153. Methyl 4-(thiene-3-yl-)-phenyl
154. Methyl 4-(5-propyl group thiophene-2-base)-phenyl
155. Methyl 4-(pyrazol-1-yl)-phenyl
156. Methyl 4-(pyrazole-3-yl)-phenyl
157. Methyl 4-(pyrazoles-4-base)-phenyl
158. Methyl 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
159. Methyl 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
160. Methyl 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
161. Methyl 4-(1H-imidazoles-2-base)-phenyl
162. Methyl 4-(imidazoles-1-base)-phenyl
163. Methyl 4-(1-Methylimidazole-2-base)-phenyl
164. Methyl 4-(oxazole-2-base)-phenyl
165. Methyl 4-((oxazole-4-base)-phenyl
166. Methyl 4-(oxazole-5-base)-phenyl
167. Methyl 4-(isoxazole-3-base)-phenyl
168. Methyl 4-(isoxazole-4-base)-phenyl
169. Methyl 4-(isoxazole-5-base)-phenyl
170. Methyl 4-([1,2,3 triazol-1-yl)-phenyl
171. Methyl 4-([1,2,4 triazol-1-yl)-phenyl
172. Methyl 4-([1,2,3 triazole-2-base)-phenyl
173. Methyl 4-(4H-[1,2,4 triazole-3-base)-phenyl
174. Methyl 4-([1,2,4 triazole-4-base)-phenyl
175. Methyl 4-(2H-[1,2,3 triazole-4-base)-phenyl
176. Methyl 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
177. Methyl 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
178. Methyl 4-([1,3,4]-oxadiazoles-2-base)-phenyl
179. Methyl 4-([1,2,4]-oxadiazoles-3-base)-phenyl
180. Methyl 4-([1,2,4]-oxadiazoles-5-base)-phenyl
181. Methyl 4-([1,2,3]-oxadiazoles-4-base)-phenyl
182. Methyl 4-([1,2,3]-oxadiazoles-5-base)-phenyl
183. Methyl 4-([1,2,3 thiadiazoles-4-base)-phenyl
184. Methyl 4-(1H-tetrazolium-5-base)-phenyl
185. Methyl 4-(tetrazolium-1-base)-phenyl
186. Methyl 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
187. Methyl 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
188. Methyl 4-furazan-3-base-phenyl
189. Methyl 4-(pyridine-2-base)-phenyl
190. Methyl 4-(pyridin-3-yl)-phenyl
191. Methyl 4-(pyridin-4-yl)-phenyl
192. Methyl 4-(pyrimidine-2-base)-phenyl
193. Methyl 4-(pyrimidine-4-base)-phenyl
194. Methyl 4-(pyrimidine-5-base)-phenyl
195. Methyl 5-sec.-propyl thiophene-2-base
196. Methyl 2-chlorothiophene-5-base
197. Methyl 2,5-dichloro-thiophene-4-base
198. Methyl 2,3-dichloro-thiophene-5-base
199. Methyl 2-chloro-3-nitrothiophene-5-base
200. Methyl 2-(phenyl sulfonyl)-thiophene-5-base
201. Methyl 2-(pyridine-2-base)-thiophene-5-base
202. Methyl 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
203. Methyl 2-(2-(methylthiazol-4-base)-thiophene-5-base
204. Methyl 1-methyl-1H-imidazol-4 yl
205. Methyl 1,2-dimethyl-1H-imidazol-4 yl
206. Methyl 3,5-dimethyl isoxazole-4-base
207. Methyl Thiazol-2-yl
208. Methyl 4-methylthiazol-2-base
209. Methyl 4-sec.-propyl thiazol-2-yl
210. Methyl 4-trifluoromethyl thiazole-2-base
211. Methyl 5-methylthiazol-2-base
212. Methyl 5-sec.-propyl thiazol-2-yl
213. Methyl 5-trifluoromethyl thiazole-2-base
214. Methyl 2,4-dimethylthiazole-5-base
215. Methyl 2-acetamido-4-methylthiazol-5-base
216. Methyl H-[1,2,4] triazole-3-base
217. Methyl 5-methyl-4H-[1,2,4] triazole-3-base
218. Methyl 4-methyl-4H-[1,2,4] triazole-3-base
219. Methyl 5-sec.-propyl-4H-[1,2,4] triazole-3-base
220. Methyl 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
221. Methyl 4,5-dimethyl-4H-[1,2,4] triazole-3-base
222. Methyl 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
223. Methyl 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
224. Methyl [1,3,4 thiadiazoles-2-base
225. Methyl 5-methyl-[1,3,4 thiadiazoles-2-base
226. Methyl 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
227. Methyl 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
228. Methyl 3-bromo-2-chloropyridine-5-base
229. Methyl 2-(4-morpholino)-pyridine-5-base
230. Methyl 2-phenoxypyridines-5-base
231. Methyl (2-sec.-propyl)-pyrimidine-5-base
232. Methyl (5-sec.-propyl)-pyrimidine-2-base
233. Methyl The 8-quinolyl
234. Methyl The 5-isoquinolyl
235. Methyl The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
236. Methyl 5-chloro-3-methylbenzene thiophthene-2-base
237. Methyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
238. Methyl Benzothiazole-6-base
239. Methyl Benzo [2,1,3] oxadiazole-4-base
240. Methyl 5-chlorobenzene and [2,1,3] oxadiazole-4-base
241. Methyl 7-chlorobenzene and [2,1,3] oxadiazole-4-base
242. Methyl Benzo [2,1,3] thiadiazoles-4-base
243. Methyl 6-chlorine imidazoles [2,1-b] thiazolyl
244. Ethyl 4-(trifluoromethoxy)-phenyl
245. Ethyl 3-(trifluoromethoxy)-phenyl
246. Ethyl The 4-cyano-phenyl
247. Ethyl The 4-aminomethyl phenyl
248. Ethyl The 4-ethylphenyl
249. Ethyl 4-propyl group phenyl
250. Ethyl The 4-p-methoxy-phenyl
251. Ethyl The 4-fluorophenyl
252. Ethyl The 4-chloro-phenyl-
253. Ethyl The 4-bromophenyl
254. Ethyl The 3-(trifluoromethyl) phenyl
255. Ethyl The 4-(trifluoromethyl) phenyl
256. Ethyl The 2-(trifluoromethyl) phenyl
257. Ethyl 3, the 4-difluorophenyl
258. Ethyl 4-bromo-3-fluorophenyl
259. Ethyl 4-bromo-2-fluorophenyl
260. Ethyl 4-bromine-2, the 5-difluorophenyl
261. Ethyl 2-fluoro-4-isopropyl phenyl
262. Ethyl The 4-hydroxy phenyl
263. Ethyl The 4-isopropyl phenyl
264. Ethyl The 4-secondary butyl phenenyl
265. Ethyl The 4-isobutyl phenenyl
266. Ethyl 4-(1,1-dimethyl propyl)-phenyl
267. Ethyl The 4-ethenylphenyl
268. Ethyl 4-pseudoallyl phenyl
269. Ethyl The 4-(methyl fluoride) phenyl
270. Ethyl The 3-(methyl fluoride) phenyl
271. Ethyl The 2-(methyl fluoride) phenyl
272. Ethyl The 4-(difluoromethyl) phenyl
273. Ethyl The 3-(difluoromethyl) phenyl
274. Ethyl The 2-(difluoromethyl) phenyl
275. Ethyl 4-(1-fluoro ethyl)-phenyl
276. Ethyl 4-((S)-1-fluoro ethyl)-phenyl
277. Ethyl 4-((R)-1-fluoro ethyl)-phenyl
278. Ethyl 4-(2-fluoro ethyl)-phenyl
279. Ethyl 4-(1,1-two fluoro ethyl)-phenyl
280. Ethyl 4-(2,2-two fluoro ethyl)-phenyl
281. Ethyl 4-(2,2,2-trifluoroethyl)-phenyl
282. Ethyl 4-(3-fluoropropyl)-phenyl
283. Ethyl 4-(2-fluoropropyl)-phenyl
284. Ethyl 4-((S)-2-fluoropropyl)-phenyl
285. Ethyl 4-((R)-2-fluoropropyl)-phenyl
286. Ethyl 4-(3,3-two fluoropropyl)-phenyl
287. Ethyl 4-(3,3,3-trifluoro propyl)-phenyl
288. Ethyl 4-(1-fluoro-1-methylethyl)-phenyl
289. Ethyl 4-(2-fluoro-1-methylethyl)-phenyl
290. Ethyl 4-((S)-2-fluoro-1-methylethyl)-phenyl
291. Ethyl 4-((R)-2-fluoro-1-methylethyl)-phenyl
292. Ethyl 4-(2,2-two fluoro-1-methylethyl)-phenyl
293. Ethyl 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
294. Ethyl 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
295. Ethyl 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
296. Ethyl 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
297. Ethyl 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
298. Ethyl 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
299. Ethyl 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
300. Ethyl 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
301. Ethyl The 4-ethoxyl phenenyl
302. Ethyl 4-propoxy-phenyl
303. Ethyl The 4-isopropyl phenyl
304. Ethyl The 4-butoxy phenyl
305. Ethyl 4-(fluorine methoxyl group)-phenyl
306. Ethyl 4-(difluoro-methoxy)-phenyl
307. Ethyl 4-(2-fluorine oxyethyl group)-phenyl
308. Ethyl 4-(2,2-difluoroethoxy)-phenyl
309. Ethyl 4-(2,2,2-trifluoro ethoxy)-phenyl
310. Ethyl 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
311. Ethyl 4-cyclopropyl phenyl
312. Ethyl 4-cyclobutyl phenyl
313. Ethyl 4-cyclopentyl phenyl
314. Ethyl 4-(2,2-difluoro cyclopropyl)-phenyl
315. Ethyl 3-fluoro-4-isopropyl phenyl
316. Ethyl 4-(1-hydroxyl-1-methylethyl)-phenyl
317. Ethyl 4-(2-hydroxy-2-methyl propyl group)-phenyl
318. Ethyl The 4-acetylphenyl
319. Ethyl The 4-carboxyl phenyl
320. Ethyl 4-(O-benzyl)-phenyl
321. Ethyl 4-(2-methoxy ethoxy)-phenyl
322. Ethyl 4-(CH 2-N(CH 3) 2)-phenyl
323. Ethyl 4-(NH-CO-NH 2)-phenyl
324. Ethyl 4-(methyl sulfane base)-phenyl
325. Ethyl 4-(methyl fluoride sulfane base)-phenyl
326. Ethyl 4-(difluoromethyl sulfane base)-phenyl
327. Ethyl 4-(trifluoromethyl sulfane base)-phenyl
328. Ethyl 4-(methyl sulphonyl)-phenyl
329. Ethyl 4-(N-methoxyl group-N-methyl-amino)-phenyl
330. Ethyl The amino)-phenyl of 4-(methoxyl group
331. Ethyl The amino)-phenyl of 4-(oxyethyl group
332. Ethyl 4-(N-methylamino oxygen base)-phenyl
333. Ethyl 4-(N, N-dimethylamino oxygen base)-phenyl
334. Ethyl 4-(azetidine-1-base)-phenyl
335. Ethyl 4-(2-methyl azetidine-1-base)-phenyl
336. Ethyl 4-((S)-2-methyl azetidine-1-base)-phenyl
337. Ethyl 4-((R)-2-methyl azetidine-1-base)-phenyl
338. Ethyl 4-(3-fluorine azetidine-1-base)-phenyl
339. Ethyl 4-(3-methoxyl group azetidine-1-base)-phenyl
340. Ethyl 4-(3-hydroxy azetidine-1-base)-phenyl
341. Ethyl 4-(tetramethyleneimine-1-base)-phenyl
342. Ethyl 4-(tetramethyleneimine-2-base)-phenyl
343. Ethyl 4-((S)-tetramethyleneimine-2-base)-phenyl
344. Ethyl 4-((R)-tetramethyleneimine-2-base)-phenyl
345. Ethyl 4-(tetramethyleneimine-3-base)-phenyl
346. Ethyl 4-((S)-tetramethyleneimine-3-base)-phenyl
347. Ethyl 4-((R)-tetramethyleneimine-3-base)-phenyl
348. Ethyl 4-(2-fluoropyrrolidine-1-base)-phenyl
349. Ethyl 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
350. Ethyl 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
351. Ethyl 4-(3-fluoropyrrolidine-1-base)-phenyl
352. Ethyl 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
353. Ethyl 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
354. Ethyl 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
355. Ethyl 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
356. Ethyl 4-(2-crassitude-1-base)-phenyl
357. Ethyl 4-((S)-2-crassitude-1-base)-phenyl
358. Ethyl 4-((R)-2-crassitude-1-base)-phenyl
359. Ethyl 4-(3-crassitude-1-base)-phenyl
360. Ethyl 4-((S)-3-crassitude-1-base)-phenyl
361. Ethyl 4-((R)-3-crassitude-1-base)-phenyl
362. Ethyl 4-(1-crassitude-2-base)-phenyl
363. Ethyl 4-((S)-1-crassitude-2-base)-phenyl
364. Ethyl 4-((R)-1-crassitude-2-base)-phenyl
365. Ethyl 4-(1-crassitude-3-base)-phenyl
366. Ethyl 4-((S)-1-crassitude-3-base)-phenyl
367. Ethyl 4-((R)-1-crassitude-3-base)-phenyl
368. Ethyl 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
369. Ethyl 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
370. Ethyl 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
371. Ethyl 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
372. Ethyl 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
373. Ethyl 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
374. Ethyl 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
375. Ethyl 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
376. Ethyl 4-(2-oxo-pyrrolidine-1-base)-phenyl
377. Ethyl 4-(2-oxo-oxazolidines-3-base)-phenyl
378. Ethyl 4-(piperidines-1-base)-phenyl
379. Ethyl 4-(2-methyl piperidine-1-base)-phenyl
380. Ethyl 4-((S)-2-methyl piperidine-1-base)-phenyl
381. Ethyl 4-((R)-2-methyl piperidine-1-base)-phenyl
382. Ethyl 4-(piperazine-1-base)-phenyl
383. Ethyl 4-(4-methylpiperazine-1-base)-phenyl
384. Ethyl 4-(morpholine-4-base)-phenyl
385. Ethyl 4-(thiomorpholine-4-base)-phenyl
386. Ethyl 4-(1-oxo-thiomorpholine-4-base)-phenyl
387. Ethyl 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
388. Ethyl 4-(pyrroles-1-base)-phenyl
389. Ethyl 4-(pyrroles-2-base)-phenyl
390. Ethyl 4-(pyrroles-3-base)-phenyl
391. Ethyl 4-(1-methylpyrrole-2-base)-phenyl
392. Ethyl 4-(1-methylpyrrole-3-base)-phenyl
393. Ethyl 4-(furans-2-base)-phenyl
394. Ethyl 4-(furans-3-base)-phenyl
395. Ethyl 4-(thiophene-2-base)-phenyl
396. Ethyl 4-(thiene-3-yl-)-phenyl
397. Ethyl 4-(5-propyl group thiophene-2-base)-phenyl
398. Ethyl 4-(pyrazol-1-yl)-phenyl
399. Ethyl 4-(pyrazole-3-yl)-phenyl
400. Ethyl 4-(pyrazoles-4-base)-phenyl
401. Ethyl 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
402. Ethyl 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
403. Ethyl 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
404. Ethyl 4-(1H-imidazoles-2-base)-phenyl
405. Ethyl 4-(imidazoles-1-base)-phenyl
406. Ethyl 4-(1-Methylimidazole-2-base)-phenyl
407. Ethyl 4-(oxazole-2-base)-phenyl
408. Ethyl 4-(oxazole-4-base)-phenyl
409. Ethyl 4-(oxazole-5-base)-phenyl
410. Ethyl 4-(isoxazole-3-base)-phenyl
411. Ethyl 4-(isoxazole-4-base)-phenyl
412. Ethyl 4-(isoxazole-5-base)-phenyl
413. Ethyl 4-([1,2,3 triazol-1-yl)-phenyl
414. Ethyl 4-([1,2,4 triazol-1-yl)-phenyl
415. Ethyl 4-([1,2,3 triazole-2-base)-phenyl
416. Ethyl 4-(4H-[1,2,4 triazole-3-base)-phenyl
417. Ethyl 4-([1,2,4 triazole-4-base)-phenyl
418. Ethyl 4-(2H-[1,2,3 triazole-4-base)-phenyl
419. Ethyl 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
420. Ethyl 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
421. Ethyl 4-([1,3,4]-oxadiazoles-2-base)-phenyl
422. Ethyl 4-([1,2,4]-oxadiazoles-3-base)-phenyl
423. Ethyl 4-([1,2,4]-oxadiazoles-5-base)-phenyl
424. Ethyl 4-([1,2,3]-oxadiazoles-4-base)-phenyl
425. Ethyl 4-([1,2,3]-oxadiazoles-5-base)-phenyl
426. Ethyl 4-([1,2,3 thiadiazoles-4-base)-phenyl
427. Ethyl 4-(1H-tetrazolium-5-base)-phenyl
428. Ethyl 4-(tetrazolium-1-base)-phenyl
429. Ethyl 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
430. Ethyl 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
431. Ethyl 4 furazans-3-base-phenyl
432. Ethyl 4-(pyridine-2-base)-phenyl
433. Ethyl 4-(pyridin-3-yl)-phenyl
434. Ethyl 4-(pyridin-4-yl)-phenyl
435. Ethyl 4-(pyrimidine-2-base)-phenyl
436. Ethyl 4-(pyrimidine-4-base)-phenyl
437. Ethyl 4-(pyrimidine-5-base)-phenyl
438. Ethyl 5-sec.-propyl thiophene-2-base
439. Ethyl 2-chlorothiophene-5-base
440. Ethyl 2,5-dichloro-thiophene-4-base
441. Ethyl 2,3-dichloro-thiophene-5-base
442. Ethyl 2-chloro-3-nitrothiophene-5-base
443. Ethyl 2-(phenyl sulfonyl)-thiophene-5-base
444. Ethyl 2-(pyridine-2-base)-thiophene-5-base
445. Ethyl 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
446. Ethyl 2-(2-(methylthiazol-4-base)-thiophene-5-base
447. Ethyl 1-methyl-1H-imidazol-4 yl
448. Ethyl 1,2-dimethyl-1H-imidazol-4 yl
449. Ethyl 3,5-dimethyl isoxazole-4-base
450. Ethyl Thiazol-2-yl
451. Ethyl 4-methylthiazol-2-base
452. Ethyl 4-sec.-propyl thiazol-2-yl
453. Ethyl 4-trifluoromethyl thiazole-2-base
454. Ethyl 5-methylthiazol-2-base
455. Ethyl 5-sec.-propyl thiazol-2-yl
456. Ethyl 5-trifluoromethyl thiazole-2-base
457. Ethyl 2,4-dimethylthiazole-5-base
458. Ethyl 2-acetamido-4-methylthiazol-5-base
459. Ethyl H-[1,2,4] triazole-3-base
460. Ethyl 5-methyl-4H-[1,2,4] triazole-3-base
461. Ethyl 4-methyl-4H-[1,2,4] triazole-3-base
462. Ethyl 5-sec.-propyl-4H-[1,2,4] triazole-3-base
463. Ethyl 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
464. Ethyl 4,5-dimethyl-4H-[1,2,4] triazole-3-base
465. Ethyl 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
466. Ethyl 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
467. Ethyl [1,3,4 thiadiazoles-2-base
468. Ethyl 5-methyl-[1,3,4 thiadiazoles-2-base
469. Ethyl 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
470. Ethyl 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
471. Ethyl 3-bromo-2-chloropyridine-5-base
472. Ethyl 2-(4-morpholino)-pyridine-5-base
473. Ethyl 2-phenoxypyridines-5-base
474. Ethyl (2-sec.-propyl)-pyrimidine-5-base
475. Ethyl (5-sec.-propyl)-pyrimidine-2-base
476. Ethyl The 8-quinolyl
477. Ethyl The 5-isoquinolyl
478. Ethyl The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
479. Ethyl 5-chloro-3-methylbenzene thiophthene-2-base
480. Ethyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
481. Ethyl Benzothiazole-6-base
482. Ethyl Benzo [2,1,3] oxadiazole-4-base
483. Ethyl 5-chlorobenzene and [2,1,3] oxadiazole-4-base
484. Ethyl 7-chlorobenzene and [2,1,3] oxadiazole-4-base
485. Ethyl Benzo [2,1,3] thiadiazoles-4-base
486. Ethyl 6-chlorine imidazoles [2,1-b] thiazolyl
487. Propyl group 4-(trifluoromethoxy)-phenyl
488. Propyl group 3-(trifluoromethoxy)-phenyl
489. Propyl group The 4-cyano-phenyl
490. Propyl group The 4-aminomethyl phenyl
491. Propyl group The 4-ethylphenyl
492. Propyl group 4-propyl group phenyl
493. Propyl group The 4-p-methoxy-phenyl
494. Propyl group The 4-fluorophenyl
495. Propyl group The 4-chloro-phenyl-
496. Propyl group The 4-bromophenyl
497. Propyl group The 3-(trifluoromethyl) phenyl
498. Propyl group The 4-(trifluoromethyl) phenyl
499. Propyl group The 2-(trifluoromethyl) phenyl
500. Propyl group 3, the 4-difluorophenyl
501. Propyl group 4-bromo-3-fluorophenyl
502. Propyl group 4-bromo-2-fluorophenyl
503. Propyl group 4-bromine-2, the 5-difluorophenyl
504. Propyl group 2-fluoro-4-isopropyl phenyl
505. Propyl group The 4-hydroxy phenyl
506. Propyl group The 4-isopropyl phenyl
507. Propyl group The 4-secondary butyl phenenyl
508. Propyl group The 4-isobutyl phenenyl
509. Propyl group 4-(1,1-dimethyl propyl)-phenyl
510. Propyl group The 4-ethenylphenyl
511. Propyl group 4-pseudoallyl phenyl
512. Propyl group The 4-(methyl fluoride) phenyl
513. Propyl group The 3-(methyl fluoride) phenyl
514. Propyl group The 2-(methyl fluoride) phenyl
515. Propyl group The 4-(difluoromethyl) phenyl
516. Propyl group The 3-(difluoromethyl) phenyl
517. Propyl group The 2-(difluoromethyl) phenyl
518. Propyl group 4-(1-fluoro ethyl)-phenyl
519. Propyl group 4-((S)-1-fluoro ethyl)-phenyl
520. Propyl group 4-((R)-1-fluoro ethyl)-phenyl
521. Propyl group 4-(2-fluoro ethyl)-phenyl
522. Propyl group 4-(1,1-two fluoro ethyl)-phenyl
523. Propyl group 4-(2,2-two fluoro ethyl)-phenyl
524. Propyl group 4-(2,2,2-trifluoroethyl)-phenyl
525. Propyl group 4-(3-fluoropropyl)-phenyl
526. Propyl group 4-(2-fluoropropyl)-phenyl
527. Propyl group 4-((S)-2-fluoropropyl)-phenyl
528. Propyl group 4-((R)-2-fluoropropyl)-phenyl
529. Propyl group 4-(3,3-two fluoropropyl)-phenyl
530. Propyl group 4-(3,3,3-trifluoro propyl)-phenyl
531. Propyl group 4-(1-fluoro-1-methylethyl)-phenyl
532. Propyl group 4-(2-fluoro-1-methylethyl)-phenyl
533. Propyl group 4-((S)-2-fluoro-1-methylethyl)-phenyl
534. Propyl group 4-((R)-2-fluoro-1-methylethyl)-phenyl
535. Propyl group 4-(2,2-two fluoro-1-methylethyl)-phenyl
536. Propyl group 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
537. Propyl group 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
538. Propyl group 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
539. Propyl group 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
540. Propyl group 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
541. Propyl group 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
542. Propyl group 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
543. Propyl group 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
544. Propyl group The 4-ethoxyl phenenyl
545. Propyl group 4-propoxy-phenyl
546. Propyl group The 4-isopropyl phenyl
547. Propyl group The 4-butoxy phenyl
548. Propyl group 4-(fluorine methoxyl group)-phenyl
549. Propyl group 4-(difluoro-methoxy)-phenyl
550. Propyl group 4-(2-fluorine oxyethyl group)-phenyl
551. Propyl group 4-(2,2-difluoroethoxy)-phenyl
552. Propyl group 4-(2,2,2-trifluoro ethoxy)-phenyl
553. Propyl group 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
554. Propyl group 4-cyclopropyl phenyl
555. Propyl group 4-cyclobutyl phenyl
556. Propyl group 4-cyclopentyl phenyl
557. Propyl group 4-(2,2-difluoro cyclopropyl)-phenyl
558. Propyl group 3-fluoro-4-isopropyl phenyl
559. Propyl group 4-(1-hydroxyl-1-methylethyl)-phenyl
560. Propyl group 4-(2-hydroxy-2-methyl propyl group)-phenyl
561. Propyl group The 4-acetylphenyl
562. Propyl group The 4-carboxyl phenyl
563. Propyl group 4-(O-benzyl)-phenyl
564. Propyl group 4-(2-methoxy ethoxy)-phenyl
565. Propyl group 4-(CH 2-N(CH 3) 2)-phenyl
566. Propyl group 4-(NH-CO-NH 2)-phenyl
567. Propyl group 4-(methyl sulfane base)-phenyl
568. Propyl group 4-(methyl fluoride sulfane base)-phenyl
569. Propyl group 4-(difluoromethyl sulfane base)-phenyl
570. Propyl group 4-(trifluoromethyl sulfane base)-phenyl
571. Propyl group 4-(methyl sulphonyl)-phenyl
572. Propyl group 4-(N-methoxyl group-N-methyl-amino)-phenyl
573. Propyl group The amino)-phenyl of 4-(methoxyl group
574. Propyl group The amino)-phenyl of 4-(oxyethyl group
575. Propyl group 4-(N-methylamino oxygen base)-phenyl
576. Propyl group 4-(N, N-dimethylamino oxygen base)-phenyl
577. Propyl group 4-(azetidine-1-base)-phenyl
578. Propyl group 4-(2-methyl azetidine-1-base)-phenyl
579. Propyl group 4-((S)-2-methyl azetidine-1-base)-phenyl
580. Propyl group 4-((R)-2-methyl azetidine-1-base)-phenyl
581. Propyl group 4-(3-fluorine azetidine-1-base)-phenyl
582. Propyl group 4-(3-methoxyl group azetidine-1-base)-phenyl
583. Propyl group 4-(3-hydroxy azetidine-1-base)-phenyl
584. Propyl group 4-(tetramethyleneimine-1-base)-phenyl
585. Propyl group 4-(tetramethyleneimine-2-base)-phenyl
586. Propyl group 4-((S)-tetramethyleneimine-2-base)-phenyl
587. Propyl group 4-((R)-tetramethyleneimine-2-base)-phenyl
588. Propyl group 4-(tetramethyleneimine-3-base)-phenyl
589. Propyl group 4-((S)-tetramethyleneimine-3-base)-phenyl
590. Propyl group 4-((R)-tetramethyleneimine-3-base)-phenyl
591. Propyl group 4-(2-fluoropyrrolidine-1-base)-phenyl
592. Propyl group 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
593. Propyl group 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
594. Propyl group 4-(3-fluoropyrrolidine-1-base)-phenyl
595. Propyl group 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
596. Propyl group 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
597. Propyl group 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
598. Propyl group 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
599. Propyl group 4-(2-crassitude-1-base)-phenyl
600. Propyl group 4-((S)-2-crassitude-1-base)-phenyl
601. Propyl group 4-(((R)-2-crassitude-1-base)-phenyl
602. Propyl group 4-(3-crassitude-1-base)-phenyl
603. Propyl group 4-((S)-3-crassitude-1-base)-phenyl
604. Propyl group 4-((R)-3-crassitude-1-base)-phenyl
605. Propyl group 4-(1-crassitude-2-base)-phenyl
606. Propyl group 4-((S)-1-crassitude-2-base)-phenyl
607. Propyl group 4-((R)-1-crassitude-2-base)-phenyl
608. Propyl group 4-(1-crassitude-3-base)-phenyl
609. Propyl group 4-((S)-1-crassitude-3-base)-phenyl
610. Propyl group 4-((R)-1-crassitude-3-base)-phenyl
611. Propyl group 4-(2,2-crassitude-1-base)-phenyl
612. Propyl group 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
613. Propyl group 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
614. Propyl group 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
615. Propyl group 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
616. Propyl group 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
617. Propyl group 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
618. Propyl group 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
619. Propyl group 4-(2-oxo-pyrrolidine-1-base)-phenyl
620. Propyl group 4-(2-oxo-oxazolidines-3-base)-phenyl
621. Propyl group 4-(piperidines-1-base)-phenyl
622. Propyl group 4-(2-methyl piperidine-1-base)-phenyl
623. Propyl group 4-((S)-2-methyl piperidine-1-base)-phenyl
624. Propyl group 4-((R)-2-methyl piperidine-1-base)-phenyl
625. Propyl group 4-(piperazine-1-base)-phenyl
626. Propyl group 4-(4-methylpiperazine-1-base)-phenyl
627. Propyl group 4-(morpholine-4-base)-phenyl
628. Propyl group 4-(thiomorpholine-4-base)-phenyl
629. Propyl group 4-(1-oxo-thiomorpholine-4-base)-phenyl
630. Propyl group 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
631. Propyl group 4-(pyrroles-1-base)-phenyl
632. Propyl group 4-(pyrroles-2-base)-phenyl
633. Propyl group 4-(pyrroles-3-base)-phenyl
634. Propyl group 4-(1-methylpyrrole-2-base)-phenyl
635. Propyl group 4-(1-methylpyrrole-3-base)-phenyl
636. Propyl group 4-(furans-2-base)-phenyl
637. Propyl group 4-(furans-3-base)-phenyl
638. Propyl group 4-(thiophene-2-base)-phenyl
639. Propyl group 4-(thiene-3-yl-)-phenyl
640. Propyl group 4-(5-propyl group thiophene-2-base)-phenyl
641. Propyl group 4-(pyrazol-1-yl)-phenyl
642. Propyl group 4-(pyrazole-3-yl)-phenyl
643. Propyl group 4-(pyrazoles-4-base)-phenyl
644. Propyl group 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
645. Propyl group 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
646. Propyl group 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
647. Propyl group 4-(1H-imidazoles-2-base)-phenyl
648. Propyl group 4-(imidazoles-1-base)-phenyl
649. Propyl group 4-(1-Methylimidazole-2-base)-phenyl
650. Propyl group 4-(oxazole-2-base)-phenyl
651. Propyl group 4-((oxazole-4-base)-phenyl
652. Propyl group 4-(oxazole-5-base)-phenyl
653. Propyl group 4-(isoxazole-3-base)-phenyl
654. Propyl group 4-(isoxazole-4-base)-phenyl
655. Propyl group 4-(isoxazole-5-base)-phenyl
656. Propyl group 4-([1,2,3 triazol-1-yl)-phenyl
657. Propyl group 4-([1,2,4 triazol-1-yl)-phenyl
658. Propyl group 4-([1,2,3 triazole-2-base)-phenyl
659. Propyl group 4-(4H-[1,2,4 triazole-3-base)-phenyl
660. Propyl group 4-([1,2,4 triazole-4-base)-phenyl
661. Propyl group 4-(2H-[1,2,3 triazole-4-base)-phenyl
662. Propyl group 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
663. Propyl group 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
664. Propyl group 4-([1,3,4]-oxadiazoles-2-base)-phenyl
665. Propyl group 4-([1,2,4]-oxadiazoles-3-base)-phenyl
666. Propyl group 4-([1,2,4]-oxadiazoles-5-base)-phenyl
667. Propyl group 4-([1,2,3]-oxadiazoles-4-base)-phenyl
668. Propyl group 4-([1,2,3]-oxadiazoles-5-base)-phenyl
669. Propyl group 4-([1,2,3 thiadiazoles-4-base)-phenyl
670. Propyl group 4-(1H-tetrazolium-5-base)-phenyl
671. Propyl group 4-(tetrazolium-1-base)-phenyl
672. Propyl group 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
673. Propyl group 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
674. Propyl group 4-furazan-3-base-phenyl
675. Propyl group 4-(pyridine-2-base)-phenyl
676. Propyl group 4-(pyridin-3-yl)-phenyl
677. Propyl group 4-(pyridin-4-yl)-phenyl
678. Propyl group 4-(pyrimidine-2-base)-phenyl
679. Propyl group 4-(pyrimidine-4-base)-phenyl
680. Propyl group 4-(pyrimidine-5-base)-phenyl
681. Propyl group 5-sec.-propyl thiophene-2-base
682. Propyl group 2-chlorothiophene-5-base
683. Propyl group 2,5-dichloro-thiophene-4-base
684. Propyl group 2,3-dichloro-thiophene-5-base
685. Propyl group 2-chloro-3-nitrothiophene-5-base
686. Propyl group 2-(phenyl sulfonyl)-thiophene-5-base
687. Propyl group 2-(pyridine-2-base)-thiophene-5-base
688. Propyl group 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
689. Propyl group 2-(2-(methylthiazol-4-base)-thiophene-5-base
690. Propyl group 1-methyl-1H-imidazol-4 yl
691. Propyl group 1,2-dimethyl-1H-imidazol-4 yl
692. Propyl group 3,5-dimethyl isoxazole-4-base
693. Propyl group Thiazol-2-yl
694. Propyl group 4-methylthiazol-2-base
695. Propyl group 4-sec.-propyl thiazol-2-yl
696. Propyl group 4-trifluoromethyl thiazole-2-base
697. Propyl group 5-methylthiazol-2-base
698. Propyl group 5-sec.-propyl thiazol-2-yl
699. Propyl group 5-trifluoromethyl thiazole-2-base
700. Propyl group 2,4-dimethylthiazole-5-base
701. Propyl group 2-acetamido-4-methylthiazol-5-base
702. Propyl group H-[1,2,4] triazole-3-base
703. Propyl group 5-methyl-4H-[1,2,4] triazole-3-base
704. Propyl group 4-methyl-4H-[1,2,4] triazole-3-base
705. Propyl group 5-sec.-propyl-4H-[1,2,4] triazole-3-base
706. Propyl group 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
707. Propyl group 4,5-dimethyl-4H-[1,2,4] triazole-3-base
708. Propyl group 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
709. Propyl group 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
710. Propyl group [1,3,4 thiadiazoles-2-base
711 Propyl group 5-methyl-[1,3,4 thiadiazoles-2-base
712. Propyl group 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
713. Propyl group 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
714. Propyl group 3-bromo-2-chloropyridine-5-base
715. Propyl group 2-(4-morpholino)-pyridine-5-base
716. Propyl group 2-phenoxypyridines-5-base
717. Propyl group (2-sec.-propyl)-pyrimidine-5-base
718. Propyl group (5-sec.-propyl)-pyrimidine-2-base
719. Propyl group The 8-quinolyl
720. Propyl group The 5-isoquinolyl
721. Propyl group The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
722. Propyl group 5-chloro-3-methylbenzene thiophthene-2-base
723. Propyl group 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
724. Propyl group Benzothiazole-6-base
725. Propyl group Benzo [2,1,3] oxadiazole-4-base
726. Propyl group 5-chlorobenzene and [2,1,3] oxadiazole-4-base
727. Propyl group 7-chlorobenzene and [2,1,3] oxadiazole-4-base
728. Propyl group Benzo [2,1,3] thiadiazoles-4-base
729. Propyl group 6-chlorine imidazoles [2,1-b] thiazolyl
730. The 3-fluoropropyl The 4-aminomethyl phenyl
731. The 3-fluoropropyl The 4-ethylphenyl
732. The 3-fluoropropyl 4-propyl group phenyl
733. The 3-fluoropropyl The 4-isopropyl phenyl
734. The 3-fluoropropyl The 4-secondary butyl phenenyl
735. The 3-fluoropropyl The 4-isobutyl phenenyl
736. The 3-fluoropropyl 4-(1,1-dimethyl propyl)-phenyl
737. The 3-fluoropropyl The 4-ethenylphenyl
738. The 3-fluoropropyl 4-pseudoallyl phenyl
739. The 3-fluoropropyl The 4-fluorophenyl
740. The 3-fluoropropyl The 4-chloro-phenyl-
741. The 3-fluoropropyl The 4-bromophenyl
742. The 3-fluoropropyl The 4-(methyl fluoride) phenyl
743. The 3-fluoropropyl The 3-(methyl fluoride) phenyl
744. The 3-fluoropropyl The 2-(methyl fluoride) phenyl
745. The 3-fluoropropyl The 4-(difluoromethyl) phenyl
746. The 3-fluoropropyl The 3-(difluoromethyl) phenyl
747. The 3-fluoropropyl The 2-(difluoromethyl) phenyl
748. The 3-fluoropropyl The 4-(trifluoromethyl) phenyl
749. The 3-fluoropropyl The 3-(trifluoromethyl) phenyl
750. The 3-fluoropropyl The 2-(trifluoromethyl) phenyl
751. The 3-fluoropropyl 4-(1-fluoro ethyl)-phenyl
752. The 3-fluoropropyl 4-((S)-1-fluoro ethyl)-phenyl
753. The 3-fluoropropyl 4-((R)-1-fluoro ethyl)-phenyl
754. The 3-fluoropropyl 4-(2-fluoro ethyl)-phenyl
755. The 3-fluoropropyl 4-(1,1-two fluoro ethyl)-phenyl
756. The 3-fluoropropyl 4-(2,2-two fluoro ethyl)-phenyl
757. The 3-fluoropropyl 4-(2,2,2-trifluoroethyl)-phenyl
758. The 3-fluoropropyl 4-(3-fluoropropyl)-phenyl
759. The 3-fluoropropyl 4-(2-fluoropropyl)-phenyl
760. The 3-fluoropropyl 4-((S)-2-fluoropropyl)-phenyl
761. The 3-fluoropropyl 4-((R)-2-fluoropropyl)-phenyl
762. The 3-fluoropropyl 4-(3,3-two fluoropropyl)-phenyl
763. The 3-fluoropropyl 4-(3,3,3-trifluoro propyl)-phenyl
764. The 3-fluoropropyl 4-(1-fluoro-1-methylethyl)-phenyl
765. The 3-fluoropropyl 4-(2-fluoro-1-methylethyl)-phenyl
766. The 3-fluoropropyl 4-((S)-2-fluoro-1-methylethyl)-phenyl
767. The 3-fluoropropyl 4-((R)-2-fluoro-1-methylethyl)-phenyl
768. The 3-fluoropropyl 4-(2,2-two fluoro-1-methylethyl)-phenyl
769. The 3-fluoropropyl 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
770. The 3-fluoropropyl 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
771. The 3-fluoropropyl 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
772. The 3-fluoropropyl 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
773. The 3-fluoropropyl 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
774. The 3-fluoropropyl 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
775. The 3-fluoropropyl 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
776. The 3-fluoropropyl 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
777. The 3-fluoropropyl The 4-p-methoxy-phenyl
778. The 3-fluoropropyl The 4-ethoxyl phenenyl
779. The 3-fluoropropyl 4-propoxy-phenyl
780. The 3-fluoropropyl The 4-isopropyl phenyl
781. The 3-fluoropropyl The 4-butoxy phenyl
782. The 3-fluoropropyl 4-(fluorine methoxyl group)-phenyl
783. The 3-fluoropropyl 4-(difluoro-methoxy)-phenyl
784. The 3-fluoropropyl 4-(trifluoromethoxy)-phenyl
785. The 3-fluoropropyl 3-(trifluoromethoxy)-phenyl
786. The 3-fluoropropyl 4-(2-fluorine oxyethyl group)-phenyl
787. The 3-fluoropropyl 4-(2,2-difluoroethoxy)-phenyl
788. The 3-fluoropropyl 4-(2,2,2-trifluoro ethoxy)-phenyl
789. The 3-fluoropropyl 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
790. The 3-fluoropropyl 4-cyclopropyl phenyl
791. The 3-fluoropropyl 4-cyclobutyl phenyl
792. The 3-fluoropropyl 4-cyclopentyl phenyl
793. The 3-fluoropropyl 4-(2,2-difluoro cyclopropyl)-phenyl
794. The 3-fluoropropyl 3, the 4-difluorophenyl
795. The 3-fluoropropyl 4-bromo-3-fluorophenyl
796. The 3-fluoropropyl 4-bromo-2-fluorophenyl
797. The 3-fluoropropyl 4-bromine-2, the 5-difluorophenyl
798. The 3-fluoropropyl 2-fluoro-4-isopropyl phenyl
799. The 3-fluoropropyl 3-fluoro-4-isopropyl phenyl
800. The 3-fluoropropyl 4-(1-hydroxyl-1-methylethyl)-phenyl
801. The 3-fluoropropyl 4-(2-hydroxy-2-methyl propyl group)-phenyl
802. The 3-fluoropropyl The 4-acetylphenyl
803. The 3-fluoropropyl The 4-carboxyl phenyl
804. The 3-fluoropropyl The 4-cyano-phenyl
805. The 3-fluoropropyl The 4-hydroxy phenyl
806. The 3-fluoropropyl 4-(O-benzyl)-phenyl
807. The 3-fluoropropyl 4-(2-methoxy ethoxy)-phenyl
808. The 3-fluoropropyl 4-(CH 2-N(CH 3) 2)-phenyl
809. The 3-fluoropropyl 4-(NH-CO-NH 2)-phenyl
810. The 3-fluoropropyl 4-(methyl sulfane base)-phenyl
811. The 3-fluoropropyl 4-(methyl fluoride sulfane base)-phenyl
812. The 3-fluoropropyl 4-(difluoromethyl sulfane base)-phenyl
813. The 3-fluoropropyl 4-(trifluoromethyl sulfane base)-phenyl
814. The 3-fluoropropyl 4-(methyl sulphonyl)-phenyl
815. The 3-fluoropropyl 4-(N-methoxyl group-N-methyl-amino)-phenyl
816. The 3-fluoropropyl The amino)-phenyl of 4-(methoxyl group
817. The 3-fluoropropyl The amino)-phenyl of 4-(oxyethyl group
818. The 3-fluoropropyl 4-(N-methylamino oxygen base)-phenyl
819. The 3-fluoropropyl 4-(N, N-dimethylamino oxygen base)-phenyl
820. The 3-fluoropropyl 4-(azetidine-1-base)-phenyl
821. The 3-fluoropropyl 4-(2-methyl azetidine-1-base)-phenyl
822. The 3-fluoropropyl 4-((S)-2-methyl azetidine-1-base)-phenyl
823. The 3-fluoropropyl 4-((R)-2-methyl azetidine-1-base)-phenyl
824. The 3-fluoropropyl 4-(3-fluorine azetidine-1-base)-phenyl
825. The 3-fluoropropyl 4-(3-methoxyl group azetidine-1-base)-phenyl
826. The 3-fluoropropyl 4-(3-hydroxy azetidine-1-base)-phenyl
827. The 3-fluoropropyl 4-(tetramethyleneimine-1-base)-phenyl
828. The 3-fluoropropyl 4-(tetramethyleneimine-2-base)-phenyl
829. The 3-fluoropropyl 4-((S)-tetramethyleneimine-2-base)-phenyl
830. The 3-fluoropropyl 4-((R)-tetramethyleneimine-2-base)-phenyl
831. The 3-fluoropropyl 4-(tetramethyleneimine-3-base)-phenyl
832. The 3-fluoropropyl 4-((S)-tetramethyleneimine-3-base)-phenyl
833. The 3-fluoropropyl 4-((R)-tetramethyleneimine-3-base)-phenyl
834. The 3-fluoropropyl 4-(2-fluoropyrrolidine-1-base)-phenyl
835. The 3-fluoropropyl 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
836. The 3-fluoropropyl 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
837. The 3-fluoropropyl 4-(3-fluoropyrrolidine-1-base)-phenyl
838. The 3-fluoropropyl 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
839. The 3-fluoropropyl 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
840. The 3-fluoropropyl 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
841. The 3-fluoropropyl 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
842. The 3-fluoropropyl 4-(2-crassitude-1-base)-phenyl
843. The 3-fluoropropyl 4-((S)-2-crassitude-1-base)-phenyl
844. The 3-fluoropropyl 4-((R)-2-crassitude-1-base)-phenyl
845. The 3-fluoropropyl 4-(3-crassitude-1-base)-phenyl
846. The 3-fluoropropyl 4-((S)-3-crassitude-1-base)-phenyl
847. The 3-fluoropropyl 4-((R)-3-crassitude-1-base)-phenyl
848. The 3-fluoropropyl 4-(1-crassitude-2-base)-phenyl
849. The 3-fluoropropyl 4-((S)-1-crassitude-2-base)-phenyl
850. The 3-fluoropropyl 4-((R)-1-crassitude-2-base)-phenyl
851. The 3-fluoropropyl 4-(1-crassitude-3-base)-phenyl
852. The 3-fluoropropyl 4-((S)-1-crassitude-3-base)-phenyl
853. The 3-fluoropropyl 4-((R)-1-crassitude-3-base)-phenyl
854. The 3-fluoropropyl 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
855. The 3-fluoropropyl 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
856. The 3-fluoropropyl 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
857. The 3-fluoropropyl 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
858. The 3-fluoropropyl 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
859. The 3-fluoropropyl 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
860. The 3-fluoropropyl 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
861. The 3-fluoropropyl 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
862. The 3-fluoropropyl 4-(2-oxo-pyrrolidine-1-base)-phenyl
863. The 3-fluoropropyl 4-(2-oxo-oxazolidines-3-base)-phenyl
864. The 3-fluoropropyl 4-(piperidines-1-base)-phenyl
865. The 3-fluoropropyl 4-(2-methyl piperidine-1-base)-phenyl
866. The 3-fluoropropyl 4-((S)-2-methyl piperidine-1-base)-phenyl
867. The 3-fluoropropyl 4-((R)-2-methyl piperidine-1-base)-phenyl
868. The 3-fluoropropyl 4-(piperazine-1-base)-phenyl
869. The 3-fluoropropyl 4-(4-methylpiperazine-1-base)-phenyl
870. The 3-fluoropropyl 4-(morpholine-4-base)-phenyl
871. The 3-fluoropropyl 4-(thiomorpholine-4-base)-phenyl
872. The 3-fluoropropyl 4-(1-oxo-thiomorpholine-4-base)-phenyl
873. The 3-fluoropropyl 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
874. The 3-fluoropropyl 4-(pyrroles-1-base)-phenyl
875. The 3-fluoropropyl 4-(pyrroles-2-base)-phenyl
876. The 3-fluoropropyl 4-(pyrroles-3-base)-phenyl
877. The 3-fluoropropyl 4-(1-methylpyrrole-2-base)-phenyl
878. The 3-fluoropropyl 4-(1-methylpyrrole-3-base)-phenyl
879. The 3-fluoropropyl 4-(furans-2-base)-phenyl
880. The 3-fluoropropyl 4-(furans-3-base)-phenyl
881. The 3-fluoropropyl 4-(thiophene-2-base)-phenyl
882. The 3-fluoropropyl 4-(thiene-3-yl-)-phenyl
883. The 3-fluoropropyl 4-(5-propyl group thiophene-2-base)-phenyl
884. The 3-fluoropropyl 4-(pyrazol-1-yl)-phenyl
885. The 3-fluoropropyl 4-(pyrazole-3-yl)-phenyl
886. The 3-fluoropropyl 4-(pyrazoles-4-base)-phenyl
887. The 3-fluoropropyl 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
888. The 3-fluoropropyl 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
889. The 3-fluoropropyl 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
890. The 3-fluoropropyl 4-(1H-imidazoles-2-base)-phenyl
891. The 3-fluoropropyl 4-(imidazoles-1-base)-phenyl
892. The 3-fluoropropyl 4-(1-Methylimidazole-2-base)-phenyl
893. The 3-fluoropropyl 4-(oxazole-2-base)-phenyl
894. The 3-fluoropropyl 4-(oxazole-4-base)-phenyl
895. The 3-fluoropropyl 4-(oxazole-5-base)-phenyl
896. The 3-fluoropropyl 4-(isoxazole-3-base)-phenyl
897. The 3-fluoropropyl 4-(isoxazole-4-base)-phenyl
898. The 3-fluoropropyl 4-(isoxazole-5-base)-phenyl
899. The 3-fluoropropyl 4-([1,2,3 triazol-1-yl)-phenyl
900. The 3-fluoropropyl 4-([1,2,4 triazol-1-yl)-phenyl
901. The 3-fluoropropyl 4-([1,2,3 triazole-2-base)-phenyl
902. The 3-fluoropropyl 4-(4H-[1,2,4 triazole-3-base)-phenyl
903. The 3-fluoropropyl 4-([1,2,4 triazole-4-base)-phenyl
904. The 3-fluoropropyl 4-(2H-[1,2,3 triazole-4-base)-phenyl
905. The 3-fluoropropyl 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
906. The 3-fluoropropyl 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
907. The 3-fluoropropyl 4-([1,3,4]-oxadiazoles-2-base)-phenyl
908. The 3-fluoropropyl 4-([1,2,4]-oxadiazoles-3-base)-phenyl
909. The 3-fluoropropyl 4-([1,2,4]-oxadiazoles-5-base)-phenyl
910. The 3-fluoropropyl 4-([1,2,3]-oxadiazoles-4-base)-phenyl
911. The 3-fluoropropyl 4-([1,2,3]-oxadiazoles-5-base)-phenyl
912. The 3-fluoropropyl 4-([1,2,3 thiadiazoles-4-base)-phenyl
913. The 3-fluoropropyl 4-(1H-tetrazolium-5-base)-phenyl
914. The 3-fluoropropyl 4-(tetrazolium-1-base)-phenyl
915. The 3-fluoropropyl 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
916. The 3-fluoropropyl 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
917. The 3-fluoropropyl 4-furazan-3-base-phenyl
918. The 3-fluoropropyl 4-(pyridine-2-base)-phenyl
919. The 3-fluoropropyl 4-(pyridin-3-yl)-phenyl
920. The 3-fluoropropyl 4-(pyridin-4-yl)-phenyl
921. The 3-fluoropropyl 4-(pyrimidine-2-base)-phenyl
922. The 3-fluoropropyl 4-(pyrimidine-4-base)-phenyl
923. The 3-fluoropropyl 4-(pyrimidine-5-base)-phenyl
924. The 3-fluoropropyl 5-sec.-propyl thiophene-2-base
925. The 3-fluoropropyl 2-chlorothiophene-5-base
926. The 3-fluoropropyl 2,5-dichloro-thiophene-4-base
927. The 3-fluoropropyl 2,3-dichloro-thiophene-5-base
928. The 3-fluoropropyl 2-chloro-3-nitrothiophene-5-base
929. The 3-fluoropropyl 2-(phenyl sulfonyl)-thiophene-5-base
930. The 3-fluoropropyl 2-(pyridine-2-base)-thiophene-5-base
931. The 3-fluoropropyl 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
932. The 3-fluoropropyl 2-(2-(methylthiazol-4-base)-thiophene-5-base
933. The 3-fluoropropyl 1-methyl-1H-imidazol-4 yl
934. The 3-fluoropropyl 1,2-dimethyl-1H-imidazol-4 yl
935. The 3-fluoropropyl 3,5-dimethyl isoxazole-4-base
936. The 3-fluoropropyl Thiazol-2-yl
937. The 3-fluoropropyl 4-methylthiazol-2-base
938. The 3-fluoropropyl 4-sec.-propyl thiazol-2-yl
939. The 3-fluoropropyl 4-trifluoromethyl thiazole-2-base
940. The 3-fluoropropyl 5-methylthiazol-2-base
941. The 3-fluoropropyl 5-sec.-propyl thiazol-2-yl
942. The 3-fluoropropyl 5-trifluoromethyl thiazole-2-base
943. The 3-fluoropropyl 2,4-dimethylthiazole-5-base
944. The 3-fluoropropyl 2-acetamido-4-methylthiazol-5-base
945. The 3-fluoropropyl H-[1,2,4] triazole-3-base
946. The 3-fluoropropyl 5-methyl-4H-[1,2,4] triazole-3-base
947. The 3-fluoropropyl 4-methyl-4H-[1,2,4] triazole-3-base
948. The 3-fluoropropyl 5-sec.-propyl-4H-[1,2,4] triazole-3-base
949. The 3-fluoropropyl 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
950. The 3-fluoropropyl 4,5-dimethyl-4H-[1,2,4] triazole-3-base
951. The 3-fluoropropyl 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
952. The 3-fluoropropyl 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
953. The 3-fluoropropyl [1,3,4 thiadiazoles-2-base
954. The 3-fluoropropyl 5-methyl-[1,3,4 thiadiazoles-2-base
955. The 3-fluoropropyl 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
956. The 3-fluoropropyl 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
957. The 3-fluoropropyl 3-bromo-2-chloropyridine-5-base
958. The 3-fluoropropyl 2-(4-morpholino)-pyridine-5-base
959. The 3-fluoropropyl 2-phenoxypyridines-5-base
960. The 3-fluoropropyl (2-sec.-propyl)-pyrimidine-5-base
961. The 3-fluoropropyl (5-sec.-propyl)-pyrimidine-2-base
962. The 3-fluoropropyl The 8-quinolyl
963. The 3-fluoropropyl The 5-isoquinolyl
964. The 3-fluoropropyl The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
965. The 3-fluoropropyl 5-chloro-3-methylbenzene thiophthene-2-base
966. The 3-fluoropropyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
967. The 3-fluoropropyl Benzothiazole-6-base
968. The 3-fluoropropyl Benzo [2,1,3] oxadiazole-4-base
969. The 3-fluoropropyl 5-chlorobenzene and [2,1,3] oxadiazole-4-base
970. The 3-fluoropropyl 7-chlorobenzene and [2,1,3] oxadiazole-4-base
971. The 3-fluoropropyl Benzo [2,1,3] thiadiazoles-4-base
972. The 3-fluoropropyl 6-chlorine imidazoles [2,1-b] thiazolyl
973. The 2-fluoro ethyl The 4-aminomethyl phenyl
974. The 2-fluoro ethyl The 4-ethylphenyl
975. The 2-fluoro ethyl 4-propyl group phenyl
976. The 2-fluoro ethyl The 4-isopropyl phenyl
977. The 2-fluoro ethyl The 4-secondary butyl phenenyl
978. The 2-fluoro ethyl The 4-isobutyl phenenyl
979. The 2-fluoro ethyl 4-(1,1-dimethyl propyl)-phenyl
980. The 2-fluoro ethyl The 4-ethenylphenyl
981. The 2-fluoro ethyl 4-pseudoallyl phenyl
982. The 2-fluoro ethyl The 4-fluorophenyl
983. The 2-fluoro ethyl The 4-chloro-phenyl-
984. The 2-fluoro ethyl The 4-bromophenyl
985. The 2-fluoro ethyl The 4-(methyl fluoride) phenyl
986. The 2-fluoro ethyl The 3-(methyl fluoride) phenyl
987. The 2-fluoro ethyl The 2-(methyl fluoride) phenyl
988. The 2-fluoro ethyl The 4-(difluoromethyl) phenyl
989. The 2-fluoro ethyl The 3-(difluoromethyl) phenyl
990. The 2-fluoro ethyl The 2-(difluoromethyl) phenyl
991. The 2-fluoro ethyl The 4-(trifluoromethyl) phenyl
992. The 2-fluoro ethyl The 3-(trifluoromethyl) phenyl
993. The 2-fluoro ethyl The 2-(trifluoromethyl) phenyl
994. The 2-fluoro ethyl 4-(1-fluoro ethyl)-phenyl
995. The 2-fluoro ethyl 4-((S)-1-fluoro ethyl)-phenyl
996. The 2-fluoro ethyl 4-((R)-1-fluoro ethyl)-phenyl
997. The 2-fluoro ethyl 4-(2-fluoro ethyl)-phenyl
998. The 2-fluoro ethyl 4-(1,1-two fluoro ethyl)-phenyl
999. The 2-fluoro ethyl 4-(2,2-two fluoro ethyl)-phenyl
1000. The 2-fluoro ethyl 4-(2,2,2-trifluoroethyl)-phenyl
1001. The 2-fluoro ethyl 4-(3-fluoropropyl)-phenyl
1002. The 2-fluoro ethyl 4-(2-fluoropropyl)-phenyl
1003. The 2-fluoro ethyl 4-((S)-2-fluoropropyl)-phenyl
1004. The 2-fluoro ethyl 4-((R)-2-fluoropropyl)-phenyl
1005. The 2-fluoro ethyl 4-(3,3-two fluoropropyl)-phenyl
1006. The 2-fluoro ethyl 4-(3,3,3-trifluoro propyl)-phenyl
1007. The 2-fluoro ethyl 4-(1-fluoro-1-methylethyl)-phenyl
1008. The 2-fluoro ethyl 4-(2-fluoro-1-methylethyl)-phenyl
1009. The 2-fluoro ethyl 4-((S)-2-fluoro-1-methylethyl)-phenyl
1010. The 2-fluoro ethyl 4-((R)-2-fluoro-1-methylethyl)-phenyl
1011. The 2-fluoro ethyl 4-(2,2-two fluoro-1-methylethyl)-phenyl
1012. The 2-fluoro ethyl 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
1013. The 2-fluoro ethyl 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
1014. The 2-fluoro ethyl 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
1015. The 2-fluoro ethyl 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
1016. The 2-fluoro ethyl 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
1017. The 2-fluoro ethyl 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
1018. The 2-fluoro ethyl 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
1019. The 2-fluoro ethyl 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
1020. The 2-fluoro ethyl The 4-p-methoxy-phenyl
1021. The 2-fluoro ethyl The 4-ethoxyl phenenyl
1022. The 2-fluoro ethyl 4-propoxy-phenyl
1023. The 2-fluoro ethyl The 4-isopropyl phenyl
1024. The 2-fluoro ethyl The 4-butoxy phenyl
1025. The 2-fluoro ethyl 4-(fluorine methoxyl group)-phenyl
1026. The 2-fluoro ethyl 4-(difluoro-methoxy)-phenyl
1027. The 2-fluoro ethyl 4-(trifluoromethoxy)-phenyl
1028. The 2-fluoro ethyl 3-(trifluoromethoxy)-phenyl
1029. The 2-fluoro ethyl 4-(2-fluorine oxyethyl group)-phenyl
1030. The 2-fluoro ethyl 4-(2,2-difluoroethoxy)-phenyl
1031. The 2-fluoro ethyl 4-(2,2,2-trifluoro ethoxy)-phenyl
1032. The 2-fluoro ethyl 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
1033. The 2-fluoro ethyl 4-cyclopropyl phenyl
1034. The 2-fluoro ethyl 4-cyclobutyl phenyl
1035. The 2-fluoro ethyl 4-cyclopentyl phenyl
1036. The 2-fluoro ethyl 4-(2,2-difluoro cyclopropyl)-phenyl
1037. The 2-fluoro ethyl 3, the 4-difluorophenyl
1038. The 2-fluoro ethyl 4-bromo-3-fluorophenyl
1039. The 2-fluoro ethyl 4-bromo-2-fluorophenyl
1040. The 2-fluoro ethyl 4-bromine-2, the 5-difluorophenyl
1041. The 2-fluoro ethyl 2-fluoro-4-isopropyl phenyl
1042. The 2-fluoro ethyl 3-fluoro-4-isopropyl phenyl
1043. The 2-fluoro ethyl 4-(1-hydroxyl-1-methylethyl)-phenyl
1044. The 2-fluoro ethyl 4-(2-hydroxy-2-methyl propyl group)-phenyl
1045. The 2-fluoro ethyl The 4-acetylphenyl
1046. The 2-fluoro ethyl The 4-carboxyl phenyl
1047. The 2-fluoro ethyl The 4-cyano-phenyl
1048. The 2-fluoro ethyl The 4-hydroxy phenyl
1049. The 2-fluoro ethyl 4-(O-benzyl)-phenyl
1050. The 2-fluoro ethyl 4-(2-methoxy ethoxy)-phenyl
1051. The 2-fluoro ethyl 4-(CH 2-N(CH 3) 2)-phenyl
1052. The 2-fluoro ethyl 4-(NH-CO-NH 2)-phenyl
1053. The 2-fluoro ethyl 4-(methyl sulfane base)-phenyl
1054. The 2-fluoro ethyl 4-(methyl fluoride sulfane base)-phenyl
1055. The 2-fluoro ethyl 4-(difluoromethyl sulfane base)-phenyl
1056. The 2-fluoro ethyl 4-(trifluoromethyl sulfane base)-phenyl
1057. The 2-fluoro ethyl 4-(methyl sulphonyl)-phenyl
1058. The 2-fluoro ethyl 4-(N-methoxyl group-N-methyl-amino)-phenyl
1059. The 2-fluoro ethyl The amino)-phenyl of 4-(methoxyl group
1060. The 2-fluoro ethyl The amino)-phenyl of 4-(oxyethyl group
1061. The 2-fluoro ethyl 4-(N-methylamino oxygen base)-phenyl
1062. The 2-fluoro ethyl 4-(N, N-dimethylamino oxygen base)-phenyl
1063. The 2-fluoro ethyl 4-(azetidine-1-base)-phenyl
1064. The 2-fluoro ethyl 4-(2-methyl azetidine-1-base)-phenyl
1065. The 2-fluoro ethyl 4-(((S)-2-methyl azetidine-1-base)-phenyl
1066. The 2-fluoro ethyl 4-((R)-2-methyl azetidine-1-base)-phenyl
1067. The 2-fluoro ethyl 4-(3-fluorine azetidine-1-base)-phenyl
1068. The 2-fluoro ethyl 4-(3-methoxyl group azetidine-1-base)-phenyl
1069. The 2-fluoro ethyl 4-(3-hydroxy azetidine-1-base)-phenyl
1070. The 2-fluoro ethyl 4-(tetramethyleneimine-1-base)-phenyl
1071. The 2-fluoro ethyl 4-(tetramethyleneimine-2-base)-phenyl
1072. The 2-fluoro ethyl 4-((S)-tetramethyleneimine-2-base)-phenyl
1073. The 2-fluoro ethyl 4-((R)-tetramethyleneimine-2-base)-phenyl
1074. The 2-fluoro ethyl 4-(tetramethyleneimine-3-base)-phenyl
1075. The 2-fluoro ethyl 4-((S)-tetramethyleneimine-3-base)-phenyl
1076. The 2-fluoro ethyl 4-((R)-tetramethyleneimine-3-base)-phenyl
1077. The 2-fluoro ethyl 4-(2-fluoropyrrolidine-1-base)-phenyl
1078. The 2-fluoro ethyl 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
1079. The 2-fluoro ethyl 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
1080. The 2-fluoro ethyl 4-(3-fluoropyrrolidine-1-base)-phenyl
1081. The 2-fluoro ethyl 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
1082. The 2-fluoro ethyl 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
1083. The 2-fluoro ethyl 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
1084. The 2-fluoro ethyl 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
1085. The 2-fluoro ethyl 4-(2-crassitude-1-base)-phenyl
1086. The 2-fluoro ethyl 4-((S)-2-crassitude-1-base)-phenyl
1087. The 2-fluoro ethyl 4-((R)-2-crassitude-1-base)-phenyl
1088. The 2-fluoro ethyl 4-(3-crassitude-1-base)-phenyl
1089. The 2-fluoro ethyl 4-((S)-3-crassitude-1-base)-phenyl
1090. The 2-fluoro ethyl 4-((R)-3-crassitude-1-base)-phenyl
1091. The 2-fluoro ethyl 4-(1-crassitude-2-base)-phenyl
1092. The 2-fluoro ethyl 4-((S)-1-crassitude-2-base)-phenyl
1093. The 2-fluoro ethyl 4-((R)-1-crassitude-2-base)-phenyl
1094. The 2-fluoro ethyl 4-(1-crassitude-3-base)-phenyl
1095. The 2-fluoro ethyl 4-((S)-1-crassitude-3-base)-phenyl
1096. The 2-fluoro ethyl 4-((R)-1-crassitude-3-base)-phenyl
1097. The 2-fluoro ethyl 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
1098. The 2-fluoro ethyl 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
1099. The 2-fluoro ethyl 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1100. The 2-fluoro ethyl 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1101. The 2-fluoro ethyl 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1102. The 2-fluoro ethyl 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1103. The 2-fluoro ethyl 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1104. The 2-fluoro ethyl 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1105. The 2-fluoro ethyl 4-(2-oxo-pyrrolidine-1-base)-phenyl
1106. The 2-fluoro ethyl 4-(2-oxo-oxazolidines-3-base)-phenyl
1107. The 2-fluoro ethyl 4-(piperidines-1-base)-phenyl
1108. The 2-fluoro ethyl 4-(2-methyl piperidine-1-base)-phenyl
1109. The 2-fluoro ethyl 4-((S)-2-methyl piperidine-1-base)-phenyl
1110. The 2-fluoro ethyl 4-((R)-2-methyl piperidine-1-base)-phenyl
1111. The 2-fluoro ethyl 4-(piperazine-1-base)-phenyl
1112. The 2-fluoro ethyl 4-(4-methylpiperazine-1-base)-phenyl
1113. The 2-fluoro ethyl 4-(morpholine-4-base)-phenyl
1114. The 2-fluoro ethyl 4-(thiomorpholine-4-base)-phenyl
1115. The 2-fluoro ethyl 4-(1-oxo-thiomorpholine-4-base)-phenyl
1116. The 2-fluoro ethyl 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
1117. The 2-fluoro ethyl 4-(pyrroles-1-base)-phenyl
1118. The 2-fluoro ethyl 4-(pyrroles-2-base)-phenyl
1119. The 2-fluoro ethyl 4-(pyrroles-3-base)-phenyl
1120. The 2-fluoro ethyl 4-(1-methylpyrrole-2-base)-phenyl
1121. The 2-fluoro ethyl 4-(1-methylpyrrole-3-base)-phenyl
1122. The 2-fluoro ethyl 4-(furans-2-base)-phenyl
1123. The 2-fluoro ethyl 4-(furans-3-base)-phenyl
1124. The 2-fluoro ethyl 4-(thiophene-2-base)-phenyl
1125. The 2-fluoro ethyl 4-(thiene-3-yl-)-phenyl
1126. The 2-fluoro ethyl 4-(5-propyl group thiophene-2-base)-phenyl
1127. The 2-fluoro ethyl 4-(pyrazol-1-yl)-phenyl
1128. The 2-fluoro ethyl 4-(pyrazole-3-yl)-phenyl
1129. The 2-fluoro ethyl 4-(pyrazoles-4-base)-phenyl
1130. The 2-fluoro ethyl 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
1131. The 2-fluoro ethyl 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
1132. The 2-fluoro ethyl 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
1133. The 2-fluoro ethyl 4-(1H-imidazoles-2-base)-phenyl
1134. The 2-fluoro ethyl 4-(imidazoles-1-base)-phenyl
1135. The 2-fluoro ethyl 4-(1-Methylimidazole-2-base)-phenyl
1136. The 2-fluoro ethyl 4-(oxazole-2-base)-phenyl
1137. The 2-fluoro ethyl 4-(oxazole-4-base)-phenyl
1138. The 2-fluoro ethyl 4-(oxazole-5-base)-phenyl
1139. The 2-fluoro ethyl 4-(isoxazole-3-base)-phenyl
1140. The 2-fluoro ethyl 4-(isoxazole-4-base)-phenyl
1141. The 2-fluoro ethyl 4-(isoxazole-5-base)-phenyl
1142. The 2-fluoro ethyl 4-([1,2,3 triazol-1-yl)-phenyl
1143. The 2-fluoro ethyl 4-([1,2,4 triazol-1-yl)-phenyl
1144. The 2-fluoro ethyl 4-([1,2,3 triazole-2-base)-phenyl
1145. The 2-fluoro ethyl 4-(4H-[1,2,4 triazole-3-base)-phenyl
1146. The 2-fluoro ethyl 4-([1,2,4 triazole-4-base)-phenyl
1147. The 2-fluoro ethyl 4-(2H-[1,2,3 triazole-4-base)-phenyl
1148. The 2-fluoro ethyl 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
1149. The 2-fluoro ethyl 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
1150. The 2-fluoro ethyl 4-([1,3,4]-oxadiazoles-2-base)-phenyl
1151. The 2-fluoro ethyl 4-([1,2,4]-oxadiazoles-3-base)-phenyl
1152. The 2-fluoro ethyl 4-([1,2,4]-oxadiazoles-5-base)-phenyl
1153. The 2-fluoro ethyl 4-([1,2,3]-oxadiazoles-4-base)-phenyl
1154. The 2-fluoro ethyl 4-([1,2,3]-oxadiazoles-5-base)-phenyl
1155. The 2-fluoro ethyl 4-([1,2,3 thiadiazoles-4-base)-phenyl
1156. The 2-fluoro ethyl 4-(1H-tetrazolium-5-base)-phenyl
1157. The 2-fluoro ethyl 4-(tetrazolium-1-base)-phenyl
1158. The 2-fluoro ethyl 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
1159. The 2-fluoro ethyl 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
1160. The 2-fluoro ethyl 4-furazan-3-base-phenyl
1161. The 2-fluoro ethyl 4-(pyridine-2-base)-phenyl
1162. The 2-fluoro ethyl 4-(pyridin-3-yl)-phenyl
1163. The 2-fluoro ethyl 4-(pyridin-4-yl)-phenyl
1164. The 2-fluoro ethyl 4-(pyrimidine-2-base)-phenyl
1165. The 2-fluoro ethyl 4-(pyrimidine-4-base)-phenyl
1166. The 2-fluoro ethyl 4-(pyrimidine-5-base)-phenyl
1167. The 2-fluoro ethyl 5-sec.-propyl thiophene-2-base
1168. The 2-fluoro ethyl 2-chlorothiophene-5-base
1169. The 2-fluoro ethyl 2,5-dichloro-thiophene-4-base
1170. The 2-fluoro ethyl 2,3-dichloro-thiophene-5-base
1171. The 2-fluoro ethyl 2-chloro-3-nitrothiophene-5-base
1172. The 2-fluoro ethyl 2-(phenyl sulfonyl)-thiophene-5-base
1173. The 2-fluoro ethyl 2-(pyridine-2-base)-thiophene-5-base
1174. The 2-fluoro ethyl 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
1175. The 2-fluoro ethyl 2-(2-(methylthiazol-4-base)-thiophene-5-base
1176. The 2-fluoro ethyl 1-methyl-1H-imidazol-4 yl
1177. The 2-fluoro ethyl 1,2-dimethyl-1H-imidazol-4 yl
1178. The 2-fluoro ethyl 3,5-dimethyl isoxazole-4-base
1179. The 2-fluoro ethyl Thiazol-2-yl
1180. The 2-fluoro ethyl 4-methylthiazol-2-base
1181. The 2-fluoro ethyl 4-sec.-propyl thiazol-2-yl
1182. The 2-fluoro ethyl 4-trifluoromethyl thiazole-2-base
1183. The 2-fluoro ethyl 5-methylthiazol-2-base
1184. The 2-fluoro ethyl 5-sec.-propyl thiazol-2-yl
1185. The 2-fluoro ethyl 5-trifluoromethyl thiazole-2-base
1186. The 2-fluoro ethyl 2,4-dimethylthiazole-5-base
1187. The 2-fluoro ethyl 2-acetamido-4-methylthiazol-5-base
1188. The 2-fluoro ethyl H-[1,2,4] triazole-3-base
1189. The 2-fluoro ethyl 5-methyl-4H-[1,2,4] triazole-3-base
1190. The 2-fluoro ethyl 4-methyl-4H-[1,2,4] triazole-3-base
1191. The 2-fluoro ethyl 5-sec.-propyl-4H-[1,2,4] triazole-3-base
1192. The 2-fluoro ethyl 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
1193. The 2-fluoro ethyl 4,5-dimethyl-4H-[1,2,4] triazole-3-base
1194. The 2-fluoro ethyl 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
1195. The 2-fluoro ethyl 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
1196. The 2-fluoro ethyl [1,3,4 thiadiazoles-2-base
1197. The 2-fluoro ethyl 5-methyl-[1,3,4 thiadiazoles-2-base
1198. The 2-fluoro ethyl 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
1199. The 2-fluoro ethyl 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
1200. The 2-fluoro ethyl 3-bromo-2-chloropyridine-5-base
1201. The 2-fluoro ethyl 2-(4-morpholino)-pyridine-5-base
1202. The 2-fluoro ethyl 2-phenoxypyridines-5-base
1203. The 2-fluoro ethyl (2-sec.-propyl)-pyrimidine-5-base
1204. The 2-fluoro ethyl (5-sec.-propyl)-pyrimidine-2-base
1205. The 2-fluoro ethyl The 8-quinolyl
1206. The 2-fluoro ethyl The 5-isoquinolyl
1207. The 2-fluoro ethyl The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
1208. The 2-fluoro ethyl 5-chloro-3-methylbenzene thiophthene-2-base
1209. The 2-fluoro ethyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
1210. The 2-fluoro ethyl Benzothiazole-6-base
1211. The 2-fluoro ethyl Benzo [2,1,3] oxadiazole-4-base
1212. The 2-fluoro ethyl 5-chlorobenzene and [2,1,3] oxadiazole-4-base
1213. The 2-fluoro ethyl 7-chlorobenzene and [2,1,3] oxadiazole-4-base
1214. The 2-fluoro ethyl Benzo [2,1,3] thiadiazoles-4-base
1215. The 2-fluoro ethyl 6-chlorine imidazoles [2,1-b] thiazolyl
1216. The cyclopropyl methyl The 4-aminomethyl phenyl
1217. The cyclopropyl methyl The 4-ethylphenyl
1218. The cyclopropyl methyl 4-propyl group phenyl
1219. The cyclopropyl methyl The 4-isopropyl phenyl
1220. The cyclopropyl methyl The 4-secondary butyl phenenyl
1221. The cyclopropyl methyl The 4-isobutyl phenenyl
1222. The cyclopropyl methyl 4-(1,1-dimethyl propyl)-phenyl
1223. The cyclopropyl methyl The 4-ethenylphenyl
1224. The cyclopropyl methyl 4-pseudoallyl phenyl
1225. The cyclopropyl methyl The 4-fluorophenyl
1226. The cyclopropyl methyl The 4-chloro-phenyl-
1227. The cyclopropyl methyl The 4-bromophenyl
1228. The cyclopropyl methyl The 4-(methyl fluoride) phenyl
1229. The cyclopropyl methyl The 3-(methyl fluoride) phenyl
1230. The cyclopropyl methyl The 2-(methyl fluoride) phenyl
1231. The cyclopropyl methyl The 4-(difluoromethyl) phenyl
1232. The cyclopropyl methyl The 3-(difluoromethyl) phenyl
1233. The cyclopropyl methyl The 2-(difluoromethyl) phenyl
1234. The cyclopropyl methyl The 4-(trifluoromethyl) phenyl
1235. The cyclopropyl methyl The 3-(trifluoromethyl) phenyl
1236. The cyclopropyl methyl The 2-(trifluoromethyl) phenyl
1237. The cyclopropyl methyl 4-(1-fluoro ethyl)-phenyl
1238. The cyclopropyl methyl 4-((S)-1-fluoro ethyl)-phenyl
1239. The cyclopropyl methyl 4-((R)-1-fluoro ethyl)-phenyl
1240. The cyclopropyl methyl 4-(2-fluoro ethyl)-phenyl
1241. The cyclopropyl methyl 4-(1,1-two fluoro ethyl)-phenyl
1242. The cyclopropyl methyl 4-(2,2-two fluoro ethyl)-phenyl
1243. The cyclopropyl methyl 4-(2,2,2-trifluoroethyl)-phenyl
1244. The cyclopropyl methyl 4-(3-fluoropropyl)-phenyl
1245. The cyclopropyl methyl 4-(2-fluoropropyl)-phenyl
1246. The cyclopropyl methyl 4-((S)-2-fluoropropyl)-phenyl
1247. The cyclopropyl methyl 4-((R)-2-fluoropropyl)-phenyl
1248. The cyclopropyl methyl 4-(3,3-two fluoropropyl)-phenyl
1249. The cyclopropyl methyl 4-(3,3,3-trifluoro propyl)-phenyl
1250. The cyclopropyl methyl 4-(1-fluoro-1-methylethyl)-phenyl
1251. The cyclopropyl methyl 4-(2-fluoro-1-methylethyl)-phenyl
1252. The cyclopropyl methyl 4-((S)-2-fluoro-1-methylethyl)-phenyl
1253. The cyclopropyl methyl 4-((R)-2-fluoro-1-methylethyl)-phenyl
1254. The cyclopropyl methyl 4-(2,2-two fluoro-1-methylethyl)-phenyl
1255. The cyclopropyl methyl 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
1256. The cyclopropyl methyl 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
1257. The cyclopropyl methyl 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
1258. The cyclopropyl methyl 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
1259. The cyclopropyl methyl 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
1260. The cyclopropyl methyl 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
1261. The cyclopropyl methyl 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
1262. The cyclopropyl methyl 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
1263. The cyclopropyl methyl The 4-p-methoxy-phenyl
1264. The cyclopropyl methyl The 4-ethoxyl phenenyl
1265. The cyclopropyl methyl 4-propoxy-phenyl
1266. The cyclopropyl methyl The 4-isopropyl phenyl
1267. The cyclopropyl methyl The 4-butoxy phenyl
1268. The cyclopropyl methyl 4-(fluorine methoxyl group)-phenyl
1269. The cyclopropyl methyl 4-(difluoro-methoxy)-phenyl
1270. The cyclopropyl methyl 4-(trifluoromethoxy)-phenyl
1271. The cyclopropyl methyl 3-(trifluoromethoxy)-phenyl
1272. The cyclopropyl methyl 4-(2-fluorine oxyethyl group)-phenyl
1273. The cyclopropyl methyl 4-(2,2-difluoroethoxy)-phenyl
1274. The cyclopropyl methyl 4-(2,2,2-trifluoro ethoxy)-phenyl
1275. The cyclopropyl methyl 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
1276. The cyclopropyl methyl 4-cyclopropyl phenyl
1277. The cyclopropyl methyl 4-cyclobutyl phenyl
1278. The cyclopropyl methyl 4-cyclopentyl phenyl
1279. The cyclopropyl methyl 4-(2,2-difluoro cyclopropyl)-phenyl
1280. The cyclopropyl methyl 3, the 4-difluorophenyl
1281. The cyclopropyl methyl 4-bromo-3-fluorophenyl
1282. The cyclopropyl methyl 4-bromo-2-fluorophenyl
1283. The cyclopropyl methyl 4-bromine-2, the 5-difluorophenyl
1284. The cyclopropyl methyl 2-fluoro-4-isopropyl phenyl
1285. The cyclopropyl methyl 3-fluoro-4-isopropyl phenyl
1286. The cyclopropyl methyl 4-(1-hydroxyl-1-methylethyl)-phenyl
1287. The cyclopropyl methyl 4-(2-hydroxy-2-methyl propyl group)-phenyl
1288. The cyclopropyl methyl The 4-acetylphenyl
1289. The cyclopropyl methyl The 4-carboxyl phenyl
1290. The cyclopropyl methyl The 4-cyano-phenyl
1291. The cyclopropyl methyl The 4-hydroxy phenyl
1292. The cyclopropyl methyl 4-(O-benzyl)-phenyl
1293. The cyclopropyl methyl 4-(2-methoxy ethoxy)-phenyl
1294. The cyclopropyl methyl 4-(CH 2-N(CH 3) 2)-phenyl
1295. The cyclopropyl methyl 4-(NH-CO-NH 2)-phenyl
1296. The cyclopropyl methyl 4-(methyl sulfane base)-phenyl
1297. The cyclopropyl methyl 4-(methyl fluoride sulfane base)-phenyl
1298. The cyclopropyl methyl 4-(difluoromethyl sulfane base)-phenyl
1299. The cyclopropyl methyl 4-(trifluoromethyl sulfane base)-phenyl
1300. The cyclopropyl methyl 4-(methyl sulphonyl)-phenyl
1301. The cyclopropyl methyl 4-(N-methoxyl group-N-methyl-amino)-phenyl
1302. The cyclopropyl methyl The amino)-phenyl of 4-(methoxyl group
1303. The cyclopropyl methyl The amino)-phenyl of 4-(oxyethyl group
1304. The cyclopropyl methyl 4-(N-methylamino oxygen base)-phenyl
1305. The cyclopropyl methyl 4-(N, N-dimethylamino oxygen base)-phenyl
1306. The cyclopropyl methyl 4-(azetidine-1-base)-phenyl
1307. The cyclopropyl methyl 4-(2-methyl azetidine-1-base)-phenyl
1308. The cyclopropyl methyl 4-((S)-2-methyl azetidine-1-base)-phenyl
1309. The cyclopropyl methyl 4-((R)-2-methyl azetidine-1-base)-phenyl
1310. The cyclopropyl methyl 4-(3-fluorine azetidine-1-base)-phenyl
1311. The cyclopropyl methyl 4-(3-methoxyl group azetidine-1-base)-phenyl
1312. The cyclopropyl methyl 4-(3-hydroxy azetidine-1-base)-phenyl
1313. The cyclopropyl methyl 4-(tetramethyleneimine-1-base)-phenyl
1314. The cyclopropyl methyl 4-(tetramethyleneimine-2-base)-phenyl
1315. The cyclopropyl methyl 4-((S)-tetramethyleneimine-2-base)-phenyl
1316. The cyclopropyl methyl 4-((R)-tetramethyleneimine-2-base)-phenyl
1317. The cyclopropyl methyl 4-(tetramethyleneimine-3-base)-phenyl
1318. The cyclopropyl methyl 4-((S)-tetramethyleneimine-3-base)-phenyl
1319. The cyclopropyl methyl 4-((R)-tetramethyleneimine-3-base)-phenyl
1320. The cyclopropyl methyl 4-(2-fluoropyrrolidine-1-base)-phenyl
1321. The cyclopropyl methyl 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
1322. The cyclopropyl methyl 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
1323. The cyclopropyl methyl 4-(3-fluoropyrrolidine-1-base)-phenyl
1324. The cyclopropyl methyl 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
1325. The cyclopropyl methyl 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
1326. The cyclopropyl methyl 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
1327. The cyclopropyl methyl 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
1328. The cyclopropyl methyl 4-(2-crassitude-1-base)-phenyl
1329. The cyclopropyl methyl 4-((S)-2-crassitude-1-base)-phenyl
1330. The cyclopropyl methyl 4-((R)-2-crassitude-1-base)-phenyl
1331. The cyclopropyl methyl 4-(3-crassitude-1-base)-phenyl
1332. The cyclopropyl methyl 4-((S)-3-crassitude-1-base)-phenyl
1333. The cyclopropyl methyl 4-((R)-3-crassitude-1-base)-phenyl
1334. The cyclopropyl methyl 4-(1-crassitude-2-base)-phenyl
1335. The cyclopropyl methyl 4-((S)-1-crassitude-2-base)-phenyl
1336. The cyclopropyl methyl 4-((R)-1-crassitude-2-base)-phenyl
1337. The cyclopropyl methyl 4-(1-crassitude-3-base)-phenyl
1338. The cyclopropyl methyl 4-((S)-1-crassitude-3-base)-phenyl
1339. The cyclopropyl methyl 4-((R)-1-crassitude-3-base)-phenyl
1340. The cyclopropyl methyl 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
1341. The cyclopropyl methyl 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
1342. The cyclopropyl methyl 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1343. The cyclopropyl methyl 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1344. The cyclopropyl methyl 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1345. The cyclopropyl methyl 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1346. The cyclopropyl methyl 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1347. The cyclopropyl methyl 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1348. The cyclopropyl methyl 4-(2-oxo-pyrrolidine-1-base)-phenyl
1349. The cyclopropyl methyl 4-(2-oxo-oxazolidines-3-base)-phenyl
1350. The cyclopropyl methyl 4-(piperidines-1-base)-phenyl
1351. The cyclopropyl methyl 4-(2-methyl piperidine-1-base)-phenyl
1352. The cyclopropyl methyl 4-((S)-2-methyl piperidine-1-base)-phenyl
1353. The cyclopropyl methyl 4-((R)-2-methyl piperidine-1-base)-phenyl
1354. The cyclopropyl methyl 4-(piperazine-1-base)-phenyl
1355. The cyclopropyl methyl 4-(4-methylpiperazine-1-base)-phenyl
1356. The cyclopropyl methyl 4-(morpholine-4-base)-phenyl
1357. The cyclopropyl methyl 4-(thiomorpholine-4-base)-phenyl
1358. The cyclopropyl methyl 4-(1-oxo-thiomorpholine-4-base)-phenyl
1359. The cyclopropyl methyl 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
1360. The cyclopropyl methyl 4-(pyrroles-1-base)-phenyl
1361. The cyclopropyl methyl 4-(pyrroles-2-base)-phenyl
1362. The cyclopropyl methyl 4-(pyrroles-3-base)-phenyl
1363. The cyclopropyl methyl 4-(1-methylpyrrole-2-base)-phenyl
1364. The cyclopropyl methyl 4-(1-methylpyrrole-3-base)-phenyl
1365. The cyclopropyl methyl 4-(furans-2-base)-phenyl
1366. The cyclopropyl methyl 4-(furans-3-base)-phenyl
1367. The cyclopropyl methyl 4-(thiophene-2-base)-phenyl
1368. The cyclopropyl methyl 4-(thiene-3-yl-)-phenyl
1369. The cyclopropyl methyl 4-(5-propyl group thiophene-2-base)-phenyl
1370. The cyclopropyl methyl 4-(pyrazol-1-yl)-phenyl
1371. The cyclopropyl methyl 4-(pyrazole-3-yl)-phenyl
1372. The cyclopropyl methyl 4-(pyrazoles-4-base)-phenyl
1373. The cyclopropyl methyl 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
1374. The cyclopropyl methyl 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
1375. The cyclopropyl methyl 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
1376. The cyclopropyl methyl 4-(1H-imidazoles-2-base)-phenyl
1377. The cyclopropyl methyl 4-(imidazoles-1-base)-phenyl
1378. The cyclopropyl methyl 4-(1-Methylimidazole-2-base)-phenyl
1379. The cyclopropyl methyl 4-(oxazole-2-base)-phenyl
1380. The cyclopropyl methyl 4-(oxazole-4-base)-phenyl
1381. The cyclopropyl methyl 4-(oxazole-5-base)-phenyl
1382. The cyclopropyl methyl 4-(isoxazole-3-base)-phenyl
1383. The cyclopropyl methyl 4-(isoxazole-4-base)-phenyl
1384. The cyclopropyl methyl 4-(isoxazole-5-base)-phenyl
1385. The cyclopropyl methyl 4-([1,2,3 triazol-1-yl)-phenyl
1386. The cyclopropyl methyl 4-([1,2,4 triazol-1-yl)-phenyl
1387. The cyclopropyl methyl 4-([1,2,3 triazole-2-base)-phenyl
1388. The cyclopropyl methyl 4-(4H-[1,2,4 triazole-3-base)-phenyl
1389. The cyclopropyl methyl 4-([1,2,4 triazole-4-base)-phenyl
1390. The cyclopropyl methyl 4-(2H-[1,2,3 triazole-4-base)-phenyl
1391. The cyclopropyl methyl 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
1392. The cyclopropyl methyl 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
1393. The cyclopropyl methyl 4-([1,3,4]-oxadiazoles-2-base)-phenyl
1394. The cyclopropyl methyl 4-([1,2,4]-oxadiazoles-3-base)-phenyl
1395. The cyclopropyl methyl 4-([1,2,4]-oxadiazoles-5-base)-phenyl
1396. The cyclopropyl methyl 4-([1,2,3]-oxadiazoles-4-base)-phenyl
1397. The cyclopropyl methyl 4-([1,2,3]-oxadiazoles-5-base)-phenyl
1398. The cyclopropyl methyl 4-([1,2,3 thiadiazoles-4-base)-phenyl
1399. The cyclopropyl methyl 4-(1H-tetrazolium-5-base)-phenyl
1400. The cyclopropyl methyl 4-(tetrazolium-1-base)-phenyl
1401. The cyclopropyl methyl 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
1402. The cyclopropyl methyl 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
1403. The cyclopropyl methyl 4-furazan-3-base-phenyl
1404. The cyclopropyl methyl 4-(pyridine-2-base)-phenyl
1405. The cyclopropyl methyl 4-(pyridin-3-yl)-phenyl
1406. The cyclopropyl methyl 4-(pyridin-4-yl)-phenyl
1407. The cyclopropyl methyl 4-(pyrimidine-2-base)-phenyl
1408. The cyclopropyl methyl 4-(pyrimidine-4-base)-phenyl
1409. The cyclopropyl methyl 4-(pyrimidine-5-base)-phenyl
1410. The cyclopropyl methyl 5-sec.-propyl thiophene-2-base
1411. The cyclopropyl methyl 2-chlorothiophene-5-base
1412. The cyclopropyl methyl 2,5-dichloro-thiophene-4-base
1413. The cyclopropyl methyl 2,3-dichloro-thiophene-5-base
1414. The cyclopropyl methyl 2-chloro-3-nitrothiophene-5-base
1415. The cyclopropyl methyl 2-(phenyl sulfonyl)-thiophene-5-base
1416. The cyclopropyl methyl 2-(pyridine-2-base)-thiophene-5-base
1417. The cyclopropyl methyl 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
1418. The cyclopropyl methyl 2-(2-(methylthiazol-4-base)-thiophene-5-base
1419. The cyclopropyl methyl 1-methyl-1H-imidazol-4 yl
1420. The cyclopropyl methyl 1,2-dimethyl-1H-imidazol-4 yl
1421. The cyclopropyl methyl 3,5-dimethyl isoxazole-4-base
1422. The cyclopropyl methyl Thiazol-2-yl
1423. The cyclopropyl methyl 4-methylthiazol-2-base
1424. The cyclopropyl methyl 4-sec.-propyl thiazol-2-yl
1425. The cyclopropyl methyl 4-trifluoromethyl thiazole-2-base
1426. The cyclopropyl methyl 5-methylthiazol-2-base
1427. The cyclopropyl methyl 5-sec.-propyl thiazol-2-yl
1428. The cyclopropyl methyl 5-trifluoromethyl thiazole-2-base
1429. The cyclopropyl methyl 2,4-dimethylthiazole-5-base
1430. The cyclopropyl methyl 2-acetamido-4-methylthiazol-5-base
1431. The cyclopropyl methyl H-[1,2,4] triazole-3-base
1432. The cyclopropyl methyl 5-methyl-4H-[1,2,4] triazole-3-base
1433. The cyclopropyl methyl 4-methyl-4H-[1,2,4] triazole-3-base
1434. The cyclopropyl methyl 5-sec.-propyl-4H-[1,2,4] triazole-3-base
1435. The cyclopropyl methyl 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
1436. The cyclopropyl methyl 4,5-dimethyl-4H-[1,2,4] triazole-3-base
1437. The cyclopropyl methyl 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
1438. The cyclopropyl methyl 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
1439. The cyclopropyl methyl [1,3,4 thiadiazoles-2-base
1440. The cyclopropyl methyl 5-methyl-[1,3,4 thiadiazoles-2-base
1441. The cyclopropyl methyl 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
1442. The cyclopropyl methyl 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
1443. The cyclopropyl methyl 3-bromo-2-chloropyridine-5-base
1444. The cyclopropyl methyl 2-(4-morpholino)-pyridine-5-base
1445. The cyclopropyl methyl 2-phenoxypyridines-5-base
1446. The cyclopropyl methyl (2-sec.-propyl)-pyrimidine-5-base
1447. The cyclopropyl methyl (5-sec.-propyl)-pyrimidine-2-base
1448. The cyclopropyl methyl The 8-quinolyl
1449. The cyclopropyl methyl The 5-isoquinolyl
1450. The cyclopropyl methyl The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
1451. The cyclopropyl methyl 5-chloro-3-methylbenzene thiophthene-2-base
1452. The cyclopropyl methyl 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
1453. The cyclopropyl methyl Benzothiazole-6-base
1454. The cyclopropyl methyl Benzo [2,1,3] oxadiazole-4-base
1455. The cyclopropyl methyl 5-chlorobenzene and [2,1,3] oxadiazole-4-base
1456. The cyclopropyl methyl 7-chlorobenzene and [2,1,3] oxadiazole-4-base
1457. The cyclopropyl methyl Benzo [2,1,3] thiadiazoles-4-base
1458. The cyclopropyl methyl 6-chlorine imidazoles [2,1-b] thiazolyl
1459. Allyl group The 4-aminomethyl phenyl
1460. Allyl group The 4-ethylphenyl
1461. Allyl group 4-propyl group phenyl
1462. Allyl group The 4-isopropyl phenyl
1463. Allyl group The 4-secondary butyl phenenyl
1464. Allyl group The 4-isobutyl phenenyl
1465. Allyl group 4-(1,1-dimethyl propyl)-phenyl
1466. Allyl group The 4-ethenylphenyl
1467. Allyl group 4-pseudoallyl phenyl
1468. Allyl group The 4-fluorophenyl
1469. Allyl group The 4-chloro-phenyl-
1470. Allyl group The 4-bromophenyl
1471. Allyl group The 4-(methyl fluoride) phenyl
1472. Allyl group The 3-(methyl fluoride) phenyl
1473. Allyl group The 2-(methyl fluoride) phenyl
1474. Allyl group The 4-(difluoromethyl) phenyl
1475. Allyl group The 3-(difluoromethyl) phenyl
1476. Allyl group The 2-(difluoromethyl) phenyl
1477. Allyl group The 4-(trifluoromethyl) phenyl
1478. Allyl group The 3-(trifluoromethyl) phenyl
1479. Allyl group The 2-(trifluoromethyl) phenyl
1480. Allyl group 4-(1-fluoro ethyl)-phenyl
1481. Allyl group 4-((S)-1-fluoro ethyl)-phenyl
1482. Allyl group 4-((R)-1-fluoro ethyl)-phenyl
1483. Allyl group 4-(2-fluoro ethyl)-phenyl
1484. Allyl group 4-(1,1-two fluoro ethyl)-phenyl
1485. Allyl group 4-(2,2-two fluoro ethyl)-phenyl
1486. Allyl group 4-(2,2,2-trifluoroethyl)-phenyl
1487. Allyl group 4-(3-fluoropropyl)-phenyl
1488. Allyl group 4-(2-fluoropropyl)-phenyl
1489. Allyl group 4-((S)-2-fluoropropyl)-phenyl
1490. Allyl group 4-((R)-2-fluoropropyl)-phenyl
1491. Allyl group 4-(3,3-two fluoropropyl)-phenyl
1492. Allyl group 4-(3,3,3-trifluoro propyl)-phenyl
1493. Allyl group 4-(1-fluoro-1-methylethyl)-phenyl
1494. Allyl group 4-(2-fluoro-1-methylethyl)-phenyl
1495. Allyl group 4-((S)-2-fluoro-1-methylethyl)-phenyl
1496. Allyl group 4-((R)-2-fluoro-1-methylethyl)-phenyl
1497. Allyl group 4-(2,2-fluoro-1-methylethyl)-phenyl
1498. Allyl group 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
1499. Allyl group 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
1500. Allyl group 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
1501. Allyl group 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
1502. Allyl group 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
1503. Allyl group 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
1504. Allyl group 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
1505. Allyl group 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
1506. Allyl group The 4-p-methoxy-phenyl
1507. Allyl group The 4-ethoxyl phenenyl
1508. Allyl group 4-propoxy-phenyl
1509. Allyl group The 4-isopropyl phenyl
1510. Allyl group The 4-butoxy phenyl
1511. Allyl group 4-(fluorine methoxyl group)-phenyl
1512. Allyl group 4-(difluoro-methoxy)-phenyl
1513. Allyl group 4-(trifluoromethoxy)-phenyl
1514. Allyl group 3-(trifluoromethoxy)-phenyl
1515. Allyl group 4-(2-fluorine oxyethyl group)-phenyl
1516. Allyl group 4-(2,2-difluoroethoxy)-phenyl
1517. Allyl group 4-(2,2,2-trifluoro ethoxy)-phenyl
1518. Allyl group 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
1519. Allyl group 4-cyclopropyl phenyl
1520. Allyl group 4-cyclobutyl phenyl
1521. Allyl group 4-cyclopentyl phenyl
1522. Allyl group 4-(2,2-difluoro cyclopropyl)-phenyl
1523. Allyl group 3, the 4-difluorophenyl
1524. Allyl group 4-bromo-3-fluorophenyl
1525. Allyl group 4-bromo-2-fluorophenyl
1526. Allyl group 4-bromine-2, the 5-difluorophenyl
1527. Allyl group 2-fluoro-4-isopropyl phenyl
1528. Allyl group 3-fluoro-4-isopropyl phenyl
1529. Allyl group 4-(1-hydroxyl-1-methylethyl)-phenyl
1530. Allyl group 4-(2-hydroxy-2-methyl propyl group)-phenyl
1531. Allyl group The 4-acetylphenyl
1532. Allyl group The 4-carboxyl phenyl
1533. Allyl group The 4-cyano-phenyl
1534. Allyl group The 4-hydroxy phenyl
1535. Allyl group 4-(O-benzyl)-phenyl
1536. Allyl group 4-(2-methoxy ethoxy)-phenyl
1537. Allyl group 4-(CH 2-N(CH 3) 2)-phenyl
1538. Allyl group 4-(NH-CO-NH 2)-phenyl
1539. Allyl group 4-(methyl sulfane base)-phenyl
1540. Allyl group 4-(methyl fluoride sulfane base)-phenyl
1541. Allyl group 4-(difluoromethyl sulfane base)-phenyl
1542. Allyl group 4-(trifluoromethyl sulfane base)-phenyl
1543. Allyl group 4-(methyl sulphonyl)-phenyl
1544. Allyl group 4-(N-methoxyl group-N-methyl-amino)-phenyl
1545. Allyl group The amino)-phenyl of 4-(methoxyl group
1546. Allyl group The amino)-phenyl of 4-(oxyethyl group
1547. Allyl group 4-(N-methylamino oxygen base)-phenyl
1548. Allyl group 4-(N, N-dimethylamino oxygen base)-phenyl
1549. Allyl group 4-(azetidine-1-base)-phenyl
1550. Allyl group 4-(2-methyl azetidine-1-base)-phenyl
1551. Allyl group 4-((S)-2-methyl azetidine-1-base)-phenyl
1552. Allyl group 4-((R)-2-methyl azetidine-1-base)-phenyl
1553. Allyl group 4-(3-fluorine azetidine-1-base)-phenyl
1554. Allyl group 4-(3-methoxyl group azetidine-1-base)-phenyl
1555. Allyl group 4-(3-hydroxy azetidine-1-base)-phenyl
1556. Allyl group 4-(tetramethyleneimine-1-base)-phenyl
1557. Allyl group 4-(tetramethyleneimine-2-base)-phenyl
1558. Allyl group 4-((S)-tetramethyleneimine-2-base)-phenyl
1559. Allyl group 4-((R)-tetramethyleneimine-2-base)-phenyl
1560. Allyl group 4-(tetramethyleneimine-3-base)-phenyl
1561. Allyl group 4-((S)-tetramethyleneimine-3-base)-phenyl
1562. Allyl group 4-((R)-tetramethyleneimine-3-base)-phenyl
1563. Allyl group 4-(2-fluoropyrrolidine-1-base)-phenyl
1564. Allyl group 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
1565. Allyl group 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
1566. Allyl group 4-(3-fluoropyrrolidine-1-base)-phenyl
1567. Allyl group 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
1568. Allyl group 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
1569. Allyl group 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
1570. Allyl group 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
1571. Allyl group 4-(2-crassitude-1-base)-phenyl
1572. Allyl group 4-((S)-2-crassitude-1-base)-phenyl
1573. Allyl group 4-((R)-2-crassitude-1-base)-phenyl
1574. Allyl group 4-(3-crassitude-1-base)-phenyl
1575. Allyl group 4-((S)-3-crassitude-1-base)-phenyl
1576. Allyl group 4-((R)-3-crassitude-1-base)-phenyl
1577. Allyl group 4-(1-crassitude-2-base)-phenyl
1578. Allyl group 4-((S)-1-crassitude-2-base)-phenyl
1579. Allyl group 4-((R)-1-crassitude-2-base)-phenyl
1580. Allyl group 4-(1-crassitude-3-base)-phenyl
1581. Allyl group 4-((S)-1-crassitude-3-base)-phenyl
1582. Allyl group 4-((R)-1-crassitude-3-base)-phenyl
1583. Allyl group 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
1584. Allyl group 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
1585. Allyl group 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1586. Allyl group 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1587. Allyl group 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1588. Allyl group 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1589. Allyl group 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1590. Allyl group 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1591. Allyl group 4-(2-oxo-pyrrolidine-1-base)-phenyl
1592. Allyl group 4-(2-oxo-oxazolidines-3-base)-phenyl
1593. Allyl group 4-(piperidines-1-base)-phenyl
1594. Allyl group 4-(2-methyl piperidine-1-base)-phenyl
1595. Allyl group 4-((S)-2-methyl piperidine-1-base)-phenyl
1596. Allyl group 4-((R)-2-methyl piperidine-1-base)-phenyl
1597. Allyl group 4-(piperazine-1-base)-phenyl
1598. Allyl group 4-(4-methylpiperazine-1-base)-phenyl
1599. Allyl group 4-(morpholine-4-base)-phenyl
1600. Allyl group 4-(thiomorpholine-4-base)-phenyl
1601. Allyl group 4-(1-oxo-thiomorpholine-4-base)-phenyl
1602. Allyl group 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
1603. Allyl group 4-(pyrroles-1-base)-phenyl
1604. Allyl group 4-(pyrroles-2-base)-phenyl
1605. Allyl group 4-(pyrroles-3-base)-phenyl
1606. Allyl group 4-(1-methylpyrrole-2-base)-phenyl
1607. Allyl group 4-(1-methylpyrrole-3-base)-phenyl
1608. Allyl group 4-(furans-2-base)-phenyl
1609. Allyl group 4-(furans-3-base)-phenyl
1610. Allyl group 4-(thiophene-2-base)-phenyl
1611. Allyl group 4-(thiene-3-yl-)-phenyl
1612. Allyl group 4-(5-propyl group thiophene-2-base)-phenyl
1613. Allyl group 4-(pyrazol-1-yl)-phenyl
1614. Allyl group 4-(pyrazole-3-yl)-phenyl
1615. Allyl group 4-(pyrazoles-4-base)-phenyl
1616. Allyl group 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
1617. Allyl group 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
1618. Allyl group 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
1619. Allyl group 4-(1H-imidazoles-2-base)-phenyl
1620. Allyl group 4-(imidazoles-1-base)-phenyl
1621. Allyl group 4-(1-Methylimidazole-2-base)-phenyl
1622. Allyl group 4-(oxazole-2-base)-phenyl
1623. Allyl group 4-(oxazole-4-base)-phenyl
1624. Allyl group 4-(oxazole-5-base)-phenyl
1625. Allyl group 4-(isoxazole-3-base)-phenyl
1626. Allyl group 4-(isoxazole-4-base)-phenyl
1627. Allyl group 4-(isoxazole-5-base)-phenyl
1628. Allyl group 4-([1,2,3 triazol-1-yl)-phenyl
1629. Allyl group 44-([1,2,4 triazol-1-yl)-phenyl
1630. Allyl group 44-([1,2,3 triazole-2-base)-phenyl
1631. Allyl group 4-(4H-[1,2,4 triazole-3-base)-phenyl
1632. Allyl group 44-([1,2,4 triazole-4-base)-phenyl
1633. Allyl group 4-(2H-[1,2,3 triazole-4-base)-phenyl
1634. Allyl group 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
1635. Allyl group 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
1636. Allyl group 4-([1,3,4]-oxadiazoles-2-base)-phenyl
1637. Allyl group 4-([1,2,4]-oxadiazoles-3-base)-phenyl
1638. Allyl group 4-([1,2,4]-oxadiazoles-5-base)-phenyl
1639. Allyl group 4-([1,2,3]-oxadiazoles-4-base)-phenyl
1640. Allyl group 4-([1,2,3]-oxadiazoles-5-base)-phenyl
1641. Allyl group 4-([1,2,3 thiadiazoles-4-base)-phenyl
1642. Allyl group 4-(1H-tetrazolium-5-base)-phenyl
1643. Allyl group 4-(tetrazolium-1-base)-phenyl
1644. Allyl group 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
1645. Allyl group 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
1646. Allyl group 4-furazan-3-base-phenyl
1647. Allyl group 4-(pyridine-2-base)-phenyl
1648. Allyl group 4-(pyridin-3-yl)-phenyl
1649. Allyl group 4-(pyridin-4-yl)-phenyl
1650. Allyl group 4-(pyrimidine-2-base)-phenyl
1651. Allyl group 4-(pyrimidine-4-base)-phenyl
1652. Allyl group 4-(pyrimidine-5-base)-phenyl
1653. Allyl group 5-sec.-propyl thiophene-2-base
1654. Allyl group 2-chlorothiophene-5-base
1655. Allyl group 2,5-dichloro-thiophene-4-base
1656. Allyl group 2,3-dichloro-thiophene-5-base
1657. Allyl group 2-chloro-3-nitrothiophene-5-base
1658. Allyl group 2-(phenyl sulfonyl)-thiophene-5-base
1659. Allyl group 2-(pyridine-2-base)-thiophene-5-base
1660. Allyl group 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
1661. Allyl group 2-(2-(methylthiazol-4-base)-thiophene-5-base
1662. Allyl group 1-methyl-1H-imidazol-4 yl
1663. Allyl group 1,2-methyl-1H-imidazol-4 yl
1664. Allyl group 3,5-dimethyl isoxazole-4-base
1665. Allyl group Thiazol-2-yl
1666. Allyl group 4-methylthiazol-2-base
1667. Allyl group 4-sec.-propyl thiazol-2-yl
1668. Allyl group 4-trifluoromethyl thiazole-2-base
1669. Allyl group 5-methylthiazol-2-base
1670. Allyl group 5-sec.-propyl thiazol-2-yl
1671. Allyl group 5-trifluoromethyl thiazole-2-base
1672. Allyl group 2,4-dimethylthiazole-5-base
1673. Allyl group 2-acetamido-4-methylthiazol-5-base
1674. Allyl group H-[1,2,4] triazole-3-base
1675. Allyl group 5-methyl-4H-[1,2,4] triazole-3-base
1676. Allyl group 4-methyl-4H-[1,2,4] triazole-3-base
1677. Allyl group 5-sec.-propyl-4H-[1,2,4] triazole-3-base
1678. Allyl group 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
1679. Allyl group 4,5-dimethyl-4H-[1,2,4] triazole-3-base
1680. Allyl group 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
1681. Allyl group 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
1682. Allyl group [1,3,4 thiadiazoles-2-base
1683. Allyl group 5-methyl-[1,3,4 thiadiazoles-2-base
1684. Allyl group 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
1685. Allyl group 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
1686. Allyl group 3-bromo-2-chloropyridine-5-base
1687. Allyl group 2-(4-morpholino)-pyridine-5-base
1688. Allyl group 2-phenoxypyridines-5-base
1689. Allyl group (2-sec.-propyl)-pyrimidine-5-base
1690. Allyl group (5-sec.-propyl)-pyrimidine-2-base
1691. Allyl group The 8-quinolyl
1692. Allyl group The 5-isoquinolyl
1693. Allyl group The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
1694. Allyl group 5-chloro-3-methylbenzene thiophthene-2-base
1695. Allyl group 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
1696. Allyl group Benzothiazole-6-base
1697. Allyl group Benzo [2,1,3] oxadiazole-4-base
1698. Allyl group 5-chlorobenzene and [2,1,3] oxadiazole-4-base
1699. Allyl group 7-chlorobenzene and [2,1,3] oxadiazole-4-base
1700. Allyl group Benzo [2,1,3] thiadiazoles-4-base
1701. Allyl group 6-chlorine imidazoles [2,1-b] thiazolyl
1702. H 4-(trifluoromethoxy)-phenyl
1703. H 3-(trifluoromethoxy)-phenyl
1704. H The 4-cyano-phenyl
1705. H The 4-aminomethyl phenyl
1706. H The 4-ethylphenyl
1707. H 4-propyl group phenyl
1708. H The 4-p-methoxy-phenyl
1709. H The 4-fluorophenyl
1710. H The 4-chloro-phenyl-
1711 H The 4-bromophenyl
1712. H The 3-(trifluoromethyl) phenyl
1713. H The 4-(trifluoromethyl) phenyl
1714. H The 2-(trifluoromethyl) phenyl
1715. H 3, the 4-difluorophenyl
1716. H 4-bromo-3-fluorophenyl
1717. H 4-bromo-2-fluorophenyl
1718. H 4-bromine-2, the 5-difluorophenyl
1719. H 2-fluoro-4-isopropyl phenyl
1720. H The 4-hydroxy phenyl
1721. H The 4-isopropyl phenyl
1722. H The 4-secondary butyl phenenyl
1723. H The 4-isobutyl phenenyl
1724. H 4-(1,1-dimethyl propyl)-phenyl
1725. H The 4-ethenylphenyl
1726. H 4-pseudoallyl phenyl
1727. H The 4-(methyl fluoride) phenyl
1728. H The 3-(methyl fluoride) phenyl
1729. H The 2-(methyl fluoride) phenyl
1730. H The 4-(difluoromethyl) phenyl
1731. H The 3-(difluoromethyl) phenyl
1732. H The 2-(difluoromethyl) phenyl
1733. H 4-(1-fluoro ethyl)-phenyl
1734. H 4-((S)-1-fluoro ethyl)-phenyl
1735. H 4-((R)-1-fluoro ethyl)-phenyl
1736. H 4-(2-fluoro ethyl)-phenyl
1737. H 4-(1,1-two fluoro ethyl)-phenyl
1738. H 4-(2,2-two fluoro ethyl)-phenyl
1739. H 4-(2,2,2-trifluoroethyl)-phenyl
1740. H 4-(3-fluoropropyl)-phenyl
1741. H 4-(2-fluoropropyl)-phenyl
1742. H 4-((S)-2-fluoropropyl)-phenyl
1743. H 4-((R)-2-fluoropropyl)-phenyl
1744. H 4-(3,3-two fluoropropyl)-phenyl
1745. H 4-(3,3,3-trifluoro propyl)-phenyl
1746. H 4-(1-fluoro-1-methylethyl)-phenyl
1747. H 4-(2-fluoro-1-methylethyl)-phenyl
1748. H 4-((S)-2-fluoro-1-methylethyl)-phenyl
1749. H 4-((R)-2-fluoro-1-methylethyl)-phenyl
1750. H 4-(2,2-two fluoro-1-methylethyl)-phenyl
1751. H 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
1752. H 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
1753. H 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
1754. H 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
1755. H 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
1756. H 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
1757. H 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
1758. H 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
1759. H The 4-ethoxyl phenenyl
1760. H 4-propoxy-phenyl
1761. H The 4-isopropyl phenyl
1762. H The 4-butoxy phenyl
1763. H 4-(fluorine methoxyl group)-phenyl
1764. H 4-(difluoro-methoxy)-phenyl
1765. H 4-(2-fluorine oxyethyl group)-phenyl
1766. H 4-(2,2-difluoroethoxy)-phenyl
1767. H 4-(2,2,2-trifluoro ethoxy)-phenyl
1768. H 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
1769. H 4-cyclopropyl phenyl
1770. H 4-cyclobutyl phenyl
1771. H 4-cyclopentyl phenyl
1772. H 4-(2,2-difluoro cyclopropyl)-phenyl
1773. H 3-fluoro-4-isopropyl phenyl
1774. H 4-(1-hydroxyl-1-methylethyl)-phenyl
1775. H 4-(2-hydroxy-2-methyl propyl group)-phenyl
1776. H The 4-acetylphenyl
1777. H The 4-carboxyl phenyl
1778. H 4-(O-benzyl)-phenyl
1779. H 4-(2-methoxy ethoxy)-phenyl
1780. H 4-(CH 2-N(CH 3) 2)-phenyl
1781. H 4-(NH-CO-NH 2)-phenyl
1782. H 4-(methyl sulfane base)-phenyl
1783. H 4-(methyl fluoride sulfane base)-phenyl
1784. H 4-(difluoromethyl sulfane base)-phenyl
1785. H 4-(trifluoromethyl sulfane base)-phenyl
1786. H 4-(methyl sulphonyl)-phenyl
1787. H 4-(N-methoxyl group-N-methyl-amino)-phenyl
1788. H The amino)-phenyl of 4-(methoxyl group
1789. H The amino)-phenyl of 4-(oxyethyl group
1790. H 4-(N-methylamino oxygen base)-phenyl
1791. H 4-(N, N-dimethylamino oxygen base)-phenyl
1792. H 4-(azetidine-1-base)-phenyl
1793. H 4-(2-methyl azetidine-1-base)-phenyl
1794. H 4-((S)-2-methyl azetidine-1-base)-phenyl
1795. H 4-((R)-2-methyl azetidine-1-base)-phenyl
1796. H 4-(3-fluorine azetidine-1-base)-phenyl
1797. H 4-(3-methoxyl group azetidine-1-base)-phenyl
1798. H 4-(3-hydroxy azetidine-1-base)-phenyl
1799. H 4-(tetramethyleneimine-1-base)-phenyl
1800. H 4-(tetramethyleneimine-2-base)-phenyl
1801. H 4-((S)-tetramethyleneimine-2-base)-phenyl
1802. H 4-((R)-tetramethyleneimine-2-base)-phenyl
1803. H 4-(tetramethyleneimine-3-base)-phenyl
1804. H 4-((S)-tetramethyleneimine-3-base)-phenyl
1805. H 4-((R)-tetramethyleneimine-3-base)-phenyl
1806. H 4-(2-fluoropyrrolidine-1-base)-phenyl
1807. H 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
1808. H 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
1809. H 4-(3-fluoropyrrolidine-1-base)-phenyl
1810. H 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
1811. H 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
1812. H 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
1813. H 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
1814. H 4-(2-crassitude-1-base)-phenyl
1815. H 4-((S)-2-crassitude-1-base)-phenyl
1816. H 4-((R)-2-crassitude-1-base)-phenyl
1817. H 4-(3-crassitude-1-base)-phenyl
1818. H 4-((S)-3-crassitude-1-base)-phenyl
1819. H 4-((R)-3-crassitude-1-base)-phenyl
1820. H 4-(1-crassitude-2-base)-phenyl
1821. H 4-((S)-1-crassitude-2-base)-phenyl
1822. H 4-((R)-1-crassitude-2-base)-phenyl
1823. H 4-(1-crassitude-3-base)-phenyl
1824. H 4-((S)-1-crassitude-3-base)-phenyl
1825. H 4-((R)-1-crassitude-3-base)-phenyl
1826. H 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
1827. H 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
1828. H 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1829. H 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1830. H 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
1831. H 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1832. H 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1833. H 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
1834. H 4-(2-oxo-pyrrolidine-1-base)-phenyl
1835. H 4-(2-oxo-oxazolidines-3-base)-phenyl
1836. H 4-(piperidines-1-base)-phenyl
1837. H 4-(2-methyl piperidine-1-base)-phenyl
1838. H 4-((S)-2-methyl piperidine-1-base)-phenyl
1839. H 4-((R)-2-methyl piperidine-1-base)-phenyl
1840. H 4-(piperazine-1-base)-phenyl
1841. H 4-(4-methylpiperazine-1-base)-phenyl
1842. H 4-(morpholine-4-base)-phenyl
1843. H 4-(thiomorpholine-4-base)-phenyl
1844. H 4-(1-oxo-thiomorpholine-4-base)-phenyl
1845. H 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
1846. H 4-(pyrroles-1-base)-phenyl
1847. H 4-(pyrroles-2-base)-phenyl
1848. H 4-(pyrroles-3-base)-phenyl
1849. H 4-(1-methylpyrrole-2-base)-phenyl
1850. H 4-(1-methylpyrrole-3-base)-phenyl
1851. H 4-(furans-2-base)-phenyl
1852. H 4-(furans-3-base)-phenyl
1853. H 4-(thiophene-2-base)-phenyl
1854. H 4-(thiene-3-yl-)-phenyl
1855. H 4-(5-propyl group thiophene-2-base)-phenyl
1856. H 4-(pyrazol-1-yl)-phenyl
1857. H 4-(pyrazole-3-yl)-phenyl
1858. H 4-(pyrazoles-4-base)-phenyl
1859. H 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
1860. H 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
1861. H 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
1862. H 4-(1H-imidazoles-2-base)-phenyl
1863. H 4-(imidazoles-1-base)-phenyl
1864. H 4-(1-Methylimidazole-2-base)-phenyl
1865. H 4-(oxazole-2-base)-phenyl
1866. H 4-(oxazole-4-base)-phenyl
1867. H 4-(oxazole-5-base)-phenyl
1868. H 4-(isoxazole-3-base)-phenyl
1869. H 4-(isoxazole-4-base)-phenyl
1870. H 4-(isoxazole-5-base)-phenyl
1871. H 4-([1,2,3 triazol-1-yl)-phenyl
1872. H 4-([1,2,4 triazol-1-yl)-phenyl
1873. H 4-([1,2,3 triazole-2-base)-phenyl
1874. H 4-(4H-[1,2,4 triazole-3-base)-phenyl
1875. H 4-([1,2,4 triazole-4-base)-phenyl
1876. H 4-(2H-[1,2,3 triazole-4-base)-phenyl
1877. H 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
1878. H 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
1879. H 4-([1,3,4]-oxadiazoles-2-base)-phenyl
1880. H 4-([1,2,4]-oxadiazoles-3-base)-phenyl
1881. H 4-([1,2,4]-oxadiazoles-5-base)-phenyl
1882. H 4-([1,2,3]-oxadiazoles-4-base)-phenyl
1883. H 4-([1,2,3]-oxadiazoles-5-base)-phenyl
1884. H 4-([1,2,3 thiadiazoles-4-base)-phenyl
1885. H 4-(1H-tetrazolium-5-base)-phenyl
1886. H 4-(tetrazolium-1-base)-phenyl
1887. H 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
1888. H 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
1889. H 4-furazan-3-base-phenyl
1890. H 4-(pyridine-2-base)-phenyl
1891. H 4-(pyridin-3-yl)-phenyl
1892. H 4-(pyridin-4-yl)-phenyl
1893. H 4-(pyrimidine-2-base)-phenyl
1894. H 4-(pyrimidine-4-base)-phenyl
1895. H 4-(pyrimidine-5-base)-phenyl
1896. H 5-sec.-propyl thiophene-2-base
1897. H 2-chlorothiophene-5-base
1898. H 2,5-dichloro-thiophene-4-base
1899. H 2,3-dichloro-thiophene-5-base
1900. H 2-chloro-3-nitrothiophene-5-base
1901. H 2-(phenyl sulfonyl)-thiophene-5-base
1902. H 2-(pyridine-2-base)-thiophene-5-base
1903. H 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
1904. H 2-(2-(methylthiazol-4-base)-thiophene-5-base
1905. H 1-methyl-1H-imidazol-4 yl
1906. H 1,2-dimethyl-1H-imidazol-4 yl
1907. H 3,5-dimethyl isoxazole-4-base
1908. H Thiazol-2-yl
1909. H 4-methylthiazol-2-base
1910. H 4-sec.-propyl thiazol-2-yl
1911. H 4-trifluoromethyl thiazole-2-base
1912. H 5-methylthiazol-2-base
1913. H 5-sec.-propyl thiazol-2-yl
1914. H 5-trifluoromethyl thiazole-2-base
1915. H 2,4-dimethylthiazole-5-base
1916. H 2-acetamido-4-methylthiazol-5-base
1917. H H-[1,2,4] triazole-3-base
1918. H 5-methyl-4H-[1,2,4] triazole-3-base
1919. H 4-methyl-4H-[1,2,4] triazole-3-base
1920. H 5-sec.-propyl-4H-[1,2,4] triazole-3-base
1921. H 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
1922. H 4,5-dimethyl-4H-[1,2,4] triazole-3-base
1923. H 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
1924. H 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
1925. H [1,3,4 thiadiazoles-2-base
1926. H 5-methyl-[1,3,4 thiadiazoles-2-base
1927. H 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
1928. H 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
1929. H 3-bromo-2-chloropyridine-5-base
1930. H 2-(4-morpholino)-pyridine-5-base
1931. H 2-phenoxypyridines-5-base
1932. H (2-sec.-propyl)-pyrimidine-5-base
1933. H (5-sec.-propyl)-pyrimidine-2-base
1934. H The 8-quinolyl
1935. H The 5-isoquinolyl
1936. H The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
1937. H 5-chloro-3-methylbenzene thiophthene-2-base
1938. H 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
1939. H Benzothiazole-6-base
1940. H Benzo [2,1,3] oxadiazole-4-base
1941. H 5-chlorobenzene and [2,1,3] oxadiazole-4-base
1942. H 7-chlorobenzene and [2,1,3] oxadiazole-4-base
1943. H Benzo [2,1,3] thiadiazoles-4-base
1944. H 6-chlorine imidazoles [2,1-b] thiazolyl
The compound of table B-1: formula Iu, wherein Ar has the given implication of delegation among the table B.
The compound of table B-2: formula Iv, wherein Ar has the given implication of delegation among the table B.
The compound of table B-3: formula 1w, wherein Ar has the given implication of delegation among the table B.
The compound of table B-4: formula Ix, wherein Ar has the given implication of delegation among the table B.
The compound of table B-5: formula Iy, wherein Ar has the given implication of delegation among the table B.
The compound of table B-6: formula Iz, wherein Ar has the given implication of delegation among the table B.
Table B
NO. Ar
1945. 4-(trifluoromethoxy)-phenyl
1946. 3-(trifluoromethoxy)-phenyl
1947. The 4-cyano-phenyl
1948. The 4-aminomethyl phenyl
1949. The 4-ethylphenyl
1950. 4-propyl group phenyl
1951. The 4-p-methoxy-phenyl
1952. The 4-fluorophenyl
1953. The 4-chloro-phenyl-
1954. The 4-bromophenyl
1955. The 3-(trifluoromethyl) phenyl
1956. The 4-(trifluoromethyl) phenyl
1957. The 2-(trifluoromethyl) phenyl
1958. 3, the 4-difluorophenyl
1959. 4-bromo-3-fluorophenyl
1960. 4-bromo-2-fluorophenyl
1961. 4-bromine-2, the 5-difluorophenyl
1962. 2-fluoro-4-isopropyl phenyl
1963. The 4-hydroxy phenyl
1964. The 4-isopropyl phenyl
1965. The 4-secondary butyl phenenyl
1966. The 4-isobutyl phenenyl
1967. 4-(1,1-dimethyl propyl)-phenyl
1968. The 4-ethenylphenyl
1969. 4-pseudoallyl phenyl
1970. The 4-(methyl fluoride) phenyl
1971. The 3-(methyl fluoride) phenyl
1972. The 2-(methyl fluoride) phenyl
1973. The 4-(difluoromethyl) phenyl
1974. The 3-(difluoromethyl) phenyl
1975. The 2-(difluoromethyl) phenyl
1976. 4-(1-fluoro ethyl)-phenyl
1977. 4-((S)-1-fluoro ethyl)-phenyl
1978. 4-((R)-1-fluoro ethyl)-phenyl
1979. 4-(2-fluoro ethyl)-phenyl
1980. 4-(1,1-two fluoro ethyl)-phenyl
1981. 4-(2,2-two fluoro ethyl)-phenyl
1982. 4-(2,2,2-trifluoroethyl)-phenyl
1983. 4-(3-fluoropropyl)-phenyl
1984. 4-(2-fluoropropyl)-phenyl
1985. 4-((S)-2-fluoropropyl)-phenyl
1986. 4-((R)-2-fluoropropyl)-phenyl
1987. 4-(3,3-two fluoropropyl)-phenyl
1988. 4-(3,3,3-trifluoro propyl)-phenyl
1989. 4-(1-fluoro-1-methylethyl)-phenyl
1990. 4-(2-fluoro-1-methylethyl)-phenyl
1991. 4-((S)-2-fluoro-1-methylethyl)-phenyl
1992. 4-((R)-2-fluoro-1-methylethyl)-phenyl
1993. 4-(2,2-two fluoro-1-methylethyl)-phenyl
1994. 4-((S)-2,2-two fluoro-1-methylethyl)-phenyl
1995. 4-((R)-2,2-two fluoro-1-methylethyl)-phenyl
1996. 4-(2,2,2-three fluoro-1-methylethyl)-phenyl
1997. 4-((S)-2,2,2-three fluoro-1-methylethyl)-phenyl
1998. 4-((R)-2,2,2-three fluoro-1-methylethyl)-phenyl
1999. 4-(2-fluoro-1-methyl fluoride ethyl)-phenyl
2000. 4-(1-difluoromethyl-2,2-two fluoro ethyl)-phenyl
2001. 4-(1,1-dimethyl-2-fluoro ethyl)-phenyl
2002. The 4-ethoxyl phenenyl
2003. 4-propoxy-phenyl
2004. The 4-isopropyl phenyl
2005. The 4-butoxy phenyl
2006. 4-(fluorine methoxyl group)-phenyl
2007. 4-(difluoro-methoxy)-phenyl
2008. 4-(2-fluorine oxyethyl group)-phenyl
2009. 4-(2,2-difluoroethoxy)-phenyl
2010. 4-(2,2,2-trifluoro ethoxy)-phenyl
2011. 4-(1,1,2,2-tetrafluoro oxyethyl group)-phenyl
2012. 4-cyclopropyl phenyl
2013. 4-cyclobutyl phenyl
2014. 4-cyclopentyl phenyl
2015. 4-(2,2-difluoro cyclopropyl)-phenyl
2016. 3-fluoro-4-isopropyl phenyl
2017. 4-(1-hydroxyl-1-methylethyl)-phenyl
2018. 4-(2-hydroxy-2-methyl propyl group)-phenyl
2019. The 4-acetylphenyl
2020. The 4-carboxyl phenyl
2021. 4-(O-benzyl)-phenyl
2022. 4-(2-methoxy ethoxy)-phenyl
2023. 4-(CH 2-N(CH 3) 2)-phenyl
2024. 4-(NH-CO-NH 2)-phenyl
2025. 4-(methyl sulfane base)-phenyl
2026. 4-(methyl fluoride sulfane base)-phenyl
2027. 4-(difluoromethyl sulfane base)-phenyl
2028. 4-(trifluoromethyl sulfane base)-phenyl
2029. 4-(methyl sulphonyl)-phenyl
2030. 4-(N-methoxyl group-N-methyl-amino)-phenyl
2031. The amino)-phenyl of 4-(methoxyl group
2032. The amino)-phenyl of 4-(oxyethyl group
2033. 4-(N-methylamino oxygen base)-phenyl
2034. 4-(N, N-dimethylamino oxygen base)-phenyl
2035. 4-(azetidine-1-base)-phenyl
2036. 4-(2-methyl azetidine-1-base)-phenyl
2037. 4-((S)-2-methyl azetidine-1-base)-phenyl
2038. 4-((R)-2-methyl azetidine-1-base)-phenyl
2039. 4-(3-fluorine azetidine-1-base)-phenyl
2040. 4-(3-methoxyl group azetidine-1-base)-phenyl
2041. 4-(3-hydroxy azetidine-1-base)-phenyl
2042. 4-(tetramethyleneimine-1-base)-phenyl
2043. 4-(tetramethyleneimine-2-base)-phenyl
2044. 4-((S)-tetramethyleneimine-2-base)-phenyl
2045. 4-((R)-tetramethyleneimine-2-base)-phenyl
2046. 4-(tetramethyleneimine-3-base)-phenyl
2047. 4-((S)-tetramethyleneimine-3-base)-phenyl
2048. 4-((R)-tetramethyleneimine-3-base)-phenyl
2049. 4-(2-fluoropyrrolidine-1-base)-phenyl
2050. 4-((S)-2-fluoropyrrolidine-1-base)-phenyl
2051. 4-((R)-2-fluoropyrrolidine-1-base)-phenyl
2052. 4-(3-fluoropyrrolidine-1-base)-phenyl
2053. 4-((S)-3-fluoropyrrolidine-1-base)-phenyl
2054. 4-((R)-3-fluoropyrrolidine-1-base)-phenyl
2055. 4-(2,2-two fluoropyrrolidines-1-base)-phenyl
2056. 4-(3,3-two fluoropyrrolidines-1-base)-phenyl
2057. 4-(2-crassitude-1-base)-phenyl
2058. 4-((S)-2-crassitude-1-base)-phenyl
2059. 4-((R)-2-crassitude-1-base)-phenyl
2060. 4-(3-crassitude-1-base)-phenyl
2061. 4-((S)-3-crassitude-1-base)-phenyl
2062. 4-((R)-3-crassitude-1-base)-phenyl
2063. 4-(1-crassitude-2-base)-phenyl
2064. 4-((S)-1-crassitude-2-base)-phenyl
2065. 4-((R)-1-crassitude-2-base)-phenyl
2066. 4-(1-crassitude-3-base)-phenyl
2067. 4-((S)-1-crassitude-3-base)-phenyl
2068. 4-((R)-1-crassitude-3-base)-phenyl
2069. 4-(2,2-dimethyl pyrrolidine-1-base)-phenyl
2070. 4-(3,3-dimethyl pyrrolidine-1-base)-phenyl
2071. 4-(2-trifluoromethyl pyrpole alkane-1-base)-phenyl
2072. 4-((S)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
2073. 4-((R)-2-trifluoromethyl pyrpole alkane-1-base)-phenyl
2074. 4-(3-trifluoromethyl pyrpole alkane-1-base)-phenyl
2075. 4-((S)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
2076. 4-((R)-3-trifluoromethyl pyrpole alkane-1-base)-phenyl
2077. 4-(2-oxo-pyrrolidine-1-base)-phenyl
2078. 4-(2-oxo-oxazolidines-3-base)-phenyl
2079. 4-(piperidines-1-base)-phenyl
2080. 4-(2-methyl piperidine-1-base)-phenyl
2081. 4-((S)-2-methyl piperidine-1-base)-phenyl
2082. 4-((R)-2-methyl piperidine-1-base)-phenyl
2083. 4-(piperazine-1-base)-phenyl
2084. 4-(4-methylpiperazine-1-base)-phenyl
2085. 4-(morpholine-4-base)-phenyl
2086. 4-(thiomorpholine-4-base)-phenyl
2087. 4-(1-oxo-thiomorpholine-4-base)-phenyl
2088. 4-(1,1-dioxo-thiomorpholine-4-base)-phenyl
2089. 4-(pyrroles-1-base)-phenyl
2090. 4-(pyrroles-2-base)-phenyl
2091. 4-(pyrroles-3-base)-phenyl
2092. 4-(1-methylpyrrole-2-base)-phenyl
2093. 4-(1-methylpyrrole-3-base)-phenyl
2094. 4-(furans-2-base)-phenyl
2095. 4-(furans-3-base)-phenyl
2096. 4-(thiophene-2-base)-phenyl
2097. 4-(thiene-3-yl-)-phenyl
2098. 4-(5-propyl group thiophene-2-base)-phenyl
2099. 4-(pyrazol-1-yl)-phenyl
2100. 4-(pyrazole-3-yl)-phenyl
2101. 4-(pyrazoles-4-base)-phenyl
2102. 4-(1-methyl-1H-pyrazoles-4-base)-phenyl
2103. 4-(1-ethyl-1H-pyrazoles-4-base)-phenyl
2104. 4-(1-methyl-1H-pyrazoles-5-base)-phenyl
2105. 4-(1H-imidazoles-2-base)-phenyl
2106. 4-(imidazoles-1-base)-phenyl
2107. 4-(1-Methylimidazole-2-base)-phenyl
2108. 4-(oxazole-2-base)-phenyl
2109. 4-(oxazole-4-base)-phenyl
2110. 4-(oxazole-5-base)-phenyl
2111. 4-(isoxazole-3-base)-phenyl
2112. 4-(isoxazole-4-base)-phenyl
2113. 4-(isoxazole-5-base)-phenyl
2114. 4-([1,2,3 triazol-1-yl)-phenyl
2115. 4-([1,2,4 triazol-1-yl)-phenyl
2116. 4-([1,2,3 triazole-2-base)-phenyl
2117. 4-(4H-[1,2,4 triazole-3-base)-phenyl
2118. 4-([1,2,4 triazole-4-base)-phenyl
2119. 4-(2H-[1,2,3 triazole-4-base)-phenyl
2120. 4-(4-methyl-4H-[1,2,4 triazole-3-base)-phenyl
2121. 4-(2-methyl-2H-[1,2,3 triazole-4-base)-phenyl
2122. 4-([1,3,4]-oxadiazoles-2-base)-phenyl
2123. 4-([1,2,4]-oxadiazoles-3-base)-phenyl
2124. 4-([1,2,4]-oxadiazoles-5-base)-phenyl
2125. 4-([1,2,3]-oxadiazoles-4-base)-phenyl
2126. 4-([1,2,3]-oxadiazoles-5-base)-phenyl
2127. 4-([1,2,3 thiadiazoles-4-base)-phenyl
2128. 4-(1H-tetrazolium-5-base)-phenyl
2129. 4-(tetrazolium-1-base)-phenyl
2130. 4-(2-methyl-2H-tetrazolium-5-base)-phenyl
2131. 4-(1-methyl-1H-tetrazolium-5-base)-phenyl
2132. 4-furazan-3-base-phenyl
2133. 4-(pyridine-2-base)-phenyl
2134. 4-(pyridin-3-yl)-phenyl
2135. 4-(pyridin-4-yl)-phenyl
2136. 4-(pyrimidine-2-base)-phenyl
2137. 4-(pyrimidine-4-base)-phenyl
2138. 4-(pyrimidine-5-base)-phenyl
2139. 5-sec.-propyl thiophene-2-base
2140. 2-chlorothiophene-5-base
2141. 2,5-dichloro-thiophene-4-base
2142. 2,3-dichloro-thiophene-5-base
2143. 2-chloro-3-nitrothiophene-5-base
2144. 2-(phenyl sulfonyl)-thiophene-5-base
2145. 2-(pyridine-2-base)-thiophene-5-base
2146. 2-(5-(trifluoromethyl) isoxazole-3-base)-thiophene-5-base
2147. 2-(2-(methylthiazol-4-base)-thiophene-5-base
2148. 1-methyl-1H-imidazol-4 yl
2149. 1,2-dimethyl-1H-imidazol-4 yl
2150. 3,5-dimethyl isoxazole-4-base
2151. Thiazol-2-yl
2152. 4-methylthiazol-2-base
2153. 4-sec.-propyl thiazol-2-yl
2154. 4-trifluoromethyl thiazole-2-base
2155. 5-methylthiazol-2-base
2156. 5-sec.-propyl thiazol-2-yl
2157. 5-trifluoromethyl thiazole-2-base
2158. 2,4-dimethylthiazole-5-base
2159. 2-acetamido-4-methylthiazol-5-base
2160. H-[1,2,4] triazole-3-base
2161. 5-methyl-4H-[1,2,4] triazole-3-base
2162. 4-methyl-4H-[1,2,4] triazole-3-base
2163. 5-sec.-propyl-4H-[1,2,4] triazole-3-base
2164. 5-trifluoromethyl-4H-[1,2,4] triazole-3-base
2165. 4,5-dimethyl-4H-[1,2,4] triazole-3-base
2166. 5-sec.-propyl-4-methyl-4H-[1,2,4] triazole-3-base
2167. 5-trifluoromethyl-4-methyl-4H-[1,2,4] triazole-3-base
2168. [1,3,4 thiadiazoles-2-base
2169. 5-methyl-[1,3,4 thiadiazoles-2-base
2170. 5-sec.-propyl-[1,3,4 thiadiazoles-2-base
2171. 5-trifluoromethyl-[1,3,4 thiadiazoles-2-base
2172. 3-bromo-2-chloropyridine-5-base
2173. 2-(4-morpholino)-pyridine-5-base
2174. 2-phenoxypyridines-5-base
2175. (2-sec.-propyl)-pyrimidine-5-base
2176. (5-sec.-propyl)-pyrimidine-2-base
2177. The 8-quinolyl
2178. The 5-isoquinolyl
2179. The 2-(trifluoroacetyl group)-1,2,3,4-tetrahydroisoquinoline-7-base
2180. 5-chloro-3-methylbenzene thiophthene-2-base
2181. 3,4-dihydro-4-methyl-2H-benzo [b] [1,4] oxazinyl
2182. Benzothiazole-6-base
2183. Benzo [2,1,3] oxadiazole-4-base
2184. 5-chlorobenzene and [2,1,3] oxadiazole-4-base
2185. 7-chlorobenzene and [2,1,3] oxadiazole-4-base
2186. Benzo [2,1,3] thiadiazoles-4-base
2187. 6-chlorine imidazoles [2,1-b] thiazolyl
R wherein < > 3 <> And R < > 1a <> The formula I compound that is hydrogen can make through similar method well-known in the art.Preparation compound I preferable methods is summarized in the scheme 1:
Scheme 1
Figure G2007800134447D00951
R in scheme 1 < > 1 <> , R < > 2 <> , R < > 2a <> , R < > 8 <> , R < > 8a <> , R < > 9 <> , X and Ar have above specified implication.PG is amido protecting group such as tert-butoxycarbonyl or benzyl.The blocking group that is suitable for is disclosed in for example P.Kocienski, Protecting Groups, and Thieme-Verlag, Stuttgart2000 is in the 6th chapter.Hal is a halogen, especially is bromine or chlorine.
According to scheme 1; Standard method according to the nucleophilic aromatic substitution reaction; With compound II in step a) in the presence of alkali such as sodium hydride, sodium alkoxide or the salt of wormwood, with amino alcohol VIII in organic solvent such as dimethyl formamide 、 diox or tetrahydrofuran (THF), react (referring to for example WO2004/000830).
Alternative ground, compound III can be made via the described palladium catalyzed reaction of document by compound II and VIII, J.Am.Chem.Soc.2001 for example, 123, described in the pp.10770-10771.Suitable Pd(O) catalyzer instance is Pd(OAc) < > 2 <> , it is usually at aglucon [1 for example, 1 '] dinaphthyl-2-base-two-tert-butyl-phosphine (phosphane) exist down, at solvent toluene or 1 for example, use in the 2-glycol dimethyl ether.
The nitro-compound III that obtains is like this obtained corresponding aminocompound IV through the usual manner reduction in step b).Needed reaction conditions is corresponding to aromatic nitro reductive normal condition, this extensively be described in document (for example referring to J.March, Advanced Organic Chemistry; The third edition, J.Wiley & Sons, New-York; 1985, p.1183 and citing document that should reference) in.For example realize reduction under the acid-reaction condition, promptly use nascent hydrogen or use complex hydride such as lithium aluminum hydride or sodium borohydride through nitro-compound III and metal such as iron, zinc or tin are reacted, preferably at transistion metal compound nickel or cobalt such as NiCl < > 2 <> (P(phenyl) < > 3 <> ) < > 2 <> Or CoCl < > 2 <> (referring to Ono etc., Chem.Ind.(London), 1983p.480) exist down, or use NaBH < > 2 <> S < > 3 <> (referring to Lalancette etc., Can.J.Chem.49,1971, p.2990) at body or in solvent or thinner and depend on that given reagent can carry out these reduction.Hydrogen is used on alternative ground in the presence of transition-metal catalyst, for example in the presence of based on the catalyzer of platinum, palladium, nickel, ruthenium or rhodium, use hydrogen, can realize that III is reduced to IV.Catalyzer can be element form or the salt of transition metal or the complex chemical compound form of oxide compound that contains transition metal; From revising active purpose; Also might use the part that helps commonly used, for example organic phosphine compound such as triphenyl phosphine, tricyclohexyl phosphine or tri-n-butyl phosphine or phosphite (ester).The common consumption of catalyzer is counted 0.001 to 1 mole/every mole compound III with catalyst metal.In preferred variation, reduction reaction is used tin chloride (II) carry out, be similar to Bioorganic and Medicinal Chemistry Letters; 2002,12(15), 1917-1919 page or leaf and J.Med.Chem.2002), the said method of 4679-4688 page or leaf.III and tin chloride (II) reaction preferably in inert organic solvents, alcohols such as methyl alcohol, ethanol, Virahol or butanols, carry out.
With compound IV and the aryl sulfonyl chlorine Cl-SO that so obtains < > 2 <>-Ar preferably in the presence of alkali, reacts according to the standard method of this area, obtains compound V.The reaction of describing in scheme 1 step c) is respectively under the reaction conditions for preparing arylsulfonamide compounds or aromatic yl sulphonate usually, to carry out; Said condition is described in for example J.March OrganicChemistry; Third edition Wiley & Sons York, 1985P444 and the document of wherein quoting, European J.Org.Chem.2002(13), 57(27)pp.5885-5895, Bioorganic and MedicinalChemistry Letters), pp.835-838 and Synthesis2000(1) and, among the pp.103-108.This reaction is normally carried out in inert solvent; For example at ether for example ether, Di Iso Propyl Ether, methyl tertiary butyl ether or tetrahydrofuran (THF); Halohydrocarbon is methylene dichloride for example; Aliphatic hydrocarbon or cycloalphatic hydrocarbon be pentane, hexane and hexanaphthene for example; Aromatic hydrocarbon is for example in toluene, xylenes, the cumene etc., or in the mixture of above-mentioned solvent.Compound IV and Cl-SO < > 2 <> The reaction of-Ar is normally carried out in the presence of auxiliary alkali.Suitable alkali is: mineral alkali is yellow soda ash or salt of wormwood or sodium hydrogencarbonate or saleratus and organic bases trialkylamine for example pyridine, lutidine etc. of triethylamine or pyridine compounds for example for example for example.Compound can be used as solvent simultaneously.Based on amine compound IV meter, complementary alkali is usually with equimolar amount use at least.
In step d), blocking group PG separates (for example referring to P.Kocienski, Protecting Groups, Thieme-Verlag, Stuttgart2000, the 6th chapter) through usual manner, thereby obtains compound I, wherein R < > 1a <> Be hydrogen.
Scheme 2
In scheme 2, the synthetic of formula I compound described, wherein R < > 1 <> , R < > 1a <> , R < > 2 <> , R < > 2a <> , R < > 8 <> , R < > 8a <> , R < > 9 <> , X and Ar have above specified implication.Hal is a halogen, especially is bromine or chlorine.According to scheme 1 described reactions step a), b) and c) carry out reactions step a), b) and c), obtain the compound I in the scheme 2.
Compound II can be obtained by commercial source.
Scheme 3
Figure G2007800134447D00981
If R < > 9 <> Be alkoxyl group, compound II also can be synthetic according to scheme 3.According to standard method, with commercial available compound XI(wherein Hal be halogen, especially for bromine or chlorine) with the alkali salt (the for example for example sodium or the sylvite of methyl alcohol, ethanol or n-propyl alcohol) of alcohol be to react in the solvent at corresponding alcohol like methyl alcohol, ethanol or n-propyl alcohol.The compound II of so acquisition and the mixture of XII for example can be separated through the method for solvent recrystallize or through chromatography, expected compound II is provided.
Shielded alkamine VIII is a commercial available or according to standard method, through the amino of these compounds of selective protection, by commercial available alkamine obtain (for example referring to P.Kocienski, Protecting Groups, loc.Cit.).
Alkamine IX is that commercial available maybe can make through the well-known similar approach in this area.
The technician also understands easily, and the selective alkylation of sulfoamido can obtain wherein R in through type V or the I compound < > 3 <> The formula I compound that is different from hydrogen.
If the R in the compound I < > 1 <> Or R < > 1a <> Be allyl group, then said allyl group can be separated, obtain R wherein and be the compound I of hydrogen ' or I ".For example in the presence of palladium (O) compound of catalytic amount or under reaction conditions, can form the palladium compound (palladium chloride for example of palladium (0) compound; Tetrakis triphenylphosphine palladium (O) or three (dibenzalacetone) two palladium (0)) exist down; Advantageously (for example triaryl phosphine is (like triphenylphosphine) with the phosphine part; Trialkyl phosphine (like tributylphosphine) and cycloalkyl phosphine (like tricyclohexyl phosphine) combine; Especially with the phosphine chelating ligand (like 2 '-two (diphenylphosphino)-1 ' dinaphthalene or 1; Two (diphenylphosphino) butane of 4-) combine; Use the document currently known methods (about in the presence of Thiosalicylic acid, eliminating the N-allyl group, referring to WO94/24088; About 1, the elimination under the 3-dimethyl barbituric acid exists, referring to J.Am. Chem. Soc. 2001,123(28), 6801-6808 page or leaf and J.Org.Chem.2002,67(11), and the 3718-3723 page or leaf), through I[R < > 1 <>=allyl group] react with allyl group trapping agent (like Thiosalicylic acid or 1, the 3-dimethyl barbituric acid), can realize allylic dissociating.Alternative ground; Close in the presence of the rhodium (I) like three (triphenylphosphine) chlorine at rhodium compound; Application by document (referring to J.Chem.Soc. Transaction I:Organic andBio-Organic Chemistry1999(21); 3089-3104 page or leaf and TetrahedronAsymmetry1997), the 3387-3391 page or leaf) known method, react and can realize also that N-is allylic and dissociate.If the R in the compound I < > 1 <> Or R < > 1a <> Be allyl group, this allyl group also can change into n-propyl through hydrogenization in the presence of catalyzer Pd-C.
If not explanation in addition, in solvent, the temperature between the boiling temperature of room temperature-solvent for use is carried out usually in above-mentioned reaction.Alternative ground; The activation energy that can use microwave will react required is incorporated in the reaction mixture; Wherein microwave has been proved to be valuable, particularly in the situation of transition-metal catalysis (about the reaction of applied microwave, referring to Tetrahedron2001; The 9199th page and following pages, the 9225th page and following pages, and in due form, "Microwaves in Organic Synthesis "; Andr é Loupy(Ed.), Wiley-VCH2002.
SULPHURYL CHLORIDE Cl-SO < > 2 <>-Ar can be purchased acquisition, perhaps can make according to the standard synthesis method.Contain the fluoro radicals R < > a <> SULPHURYL CHLORIDE can make through different route of synthesis, for example through suitable hydroxyl precursor or oxo precursor (are for example carried the compound Cl-SO of hydroxyl or oxo substituted radical < > 2 <>-Ar) with fluorination reagent for example DAST(three fluoridize diethylamino sulphur), morpholine-DAST, deoxidation-fluorizating agent (deoxo-fluor)(three fluoridize the amino sulphur of two (2-methoxy ethyls)), Ishikawa ' s reagent (N, N-diethyl-(1,1,3,3-six-fluoropropyl) amine reacts and makes; Journal ofFluorine Chemistry, 1989,43,371-377).More routinely, the hydroxyl that carries the aromatic substance of substituted hydroxy group rather than chlorosulfonyl is changed into leavings group, then leavings group is replaced (J.Org.Chem. with fluoride ion, 1994,59,2898-22901; TetrahedronLetters, 1998,7305-6; J.Org.Chem., 1998,63,9587-9589, Synthesis, 1987,920-21)).Then, directly carry out chlorosulfonylation (Heterocycles, 2001,55,9,1789-1803 with chlorsulfonic acid; J.Org.Chem., 2000,65) perhaps carry out two step method; At first prepare sulfonic acid, use for example chlorsulfonic acid, phosphorus pentachloride (Eur.J.Med.Chem. then, 2002) convert it into SULPHURYL CHLORIDE etc., obtain required SULPHURYL CHLORIDE (Tetrahedron Letters, 1991; 33,507787-7788).SULPHURYL CHLORIDE can also make like this: under acidic conditions with Sodium Nitrite with suitable amine precursor Ar-NH < > 2 <> Carry out diazotization, in acetate, react (scheme (iii) then with sulfurous gas; J.Org.Chem., 1960,25,1824-26; ); Through with suitable heteroaryl-mercaptan S-Ar or heteroaryl-benzyl-thioether C6Hs-CH2-S-Ar chlorine (Synthesis, 1998,36-38; J.Am.Chem.Soc, 1950,74,4890-92; ) be direct oxidation into corresponding SULPHURYL CHLORIDE.Other SULPHURYL CHLORIDE is known in the art or can makes through standard method.For example, sulfydryl-pyrimidine or pyrimidyl-benzyl thioether precursor can for example make (Chemische Berichte, 1960,1208-11 according to the method in the document; Chemische Berichte, 1960,95,230-235; Collection Czechoslow.Chem.Comm., 1959,24,1667-1671; Austr.J.Chem., 1966,19,2321-30; Chemiker-Zeitung, 101,6,1977,305-7; Tetrahedron, 2002,58,887-890; Synthesis, 1983,641-645).
The technician understands easily, and formula I compound can also transform each other through functional group and made by the compound of similar.Especially, the radicals R of N connection < > a <> Be introduced in the formula I compound, this through in the presence of the alkali also preferably in the presence of palladium catalyst, reacting corresponding halogen compounds according to Buchwald-Hartwig is formula I compound, it replaces R < > a <> Carry particularly bromine or iodine atom of halogen atom, react with primary amine or secondary amine.
In following scheme 4-6, shown several route of synthesis, these schemes are suitable for preparing the benzene sulfonyl chloride that carries the fluoro propyl group.
Scheme 4
Figure G2007800134447D01001
4-(1,1-difluoro third-2-yl) benzene-1-sulfonyl chloride intermediate can be made by commercially available 2-phenylpropionic acid.First step a) in, through at acid catalysis (HCl for example, SO < > 2 <> Cl < > 2 <> ) carry out esterification with alcohol (for example methyl alcohol or ethanol) down, the 2-phenylpropionic acid is changed into alkyl ester.Through reductive agent DIBAL(diisobutylaluminium hydride for example) this ester can be reduced into corresponding 2-phenylpropionaldehyde.Through aldehyde being changed into 1 with suitable fluorination reagent reaction; 1-two fluoro-2-propyl derivatives; Said fluorination reagent is that for example DAST(three fluoridizes diethylamino sulphur), morpholine-DAST, deoxidation-fluorizating agent (three fluoridize the amino sulphur of two (2-methoxy ethyls)), Ishikawa ' s reagent (N; N-diethyl-(1,2,3,3-six-fluoropropyl) amine; Journal of Fluorine Chemistry, 1989,43,371-377)(step b).Thus obtained 1,1-two fluoro-2-phenyl-propanes can change into 4-(1 through following method, 1-two fluoro-2-propyl group) benzene sulfonyl chloride: directly carry out chlorosulfonylation (Heterocycles, 2001,55,9,1789-1803 with chlorsulfonic acid; J.Org.Chem., 2000,65)(step c) are perhaps carried out two step method, and (step d) is used for example chlorsulfonic acid, phosphorus pentachloride (Eur.J.Med.Chem. then at first to prepare sulfonic acid; 2002,36,809-828) convert it into SULPHURYL CHLORIDE (step e); Under acidic conditions, suitable amine precursor is carried out diazotization, in acetate, react (J.Org.Chem. then with sulfurous gas with Sodium Nitrite, 1960,25,1824-26); With suitable heteroaryl-mercaptan or heteroaryl-benzyl-thioether chlorine (Synthesis, 1998,36-38; J.Am.Chem.Soc, 1950,74,4890-92; ) be direct oxidation into corresponding SULPHURYL CHLORIDE.
What show in the reaction scheme 4 syntheticly can also use (R)-2-phenylpropionic acid respectively and (S)-2-phenylpropionic acid carries out, to obtain corresponding chirality 4-(1,1-difluoro third-2-yl) benzene-1-SULPHURYL CHLORIDE.
Scheme 5
Figure G2007800134447D01011
4-(1,1,1-trifluoropropyl-2-yl) benzene-1-sulfonyl chloride intermediate can be through the route of synthesis that shows in the scheme 5 by commercially available 2,2, and 2-three fluoro-1-phenyl ethyl ketones make.Can by the following method this ketone be changed into 3; 3; 3-three fluoro-2-phenyl propylene: with suitable inner salt for example methylene radical-triphenylphosphine (through halogenation methyl triphenyl phosphorus and suitable alkali for example lithium diisopropylamine or potassium tert.-butoxide react make) carry out the Wittig reaction; Perhaps according to Horner-Emmons reaction, allow this ketone and suitable phosphonic acid ester for example methyl-phosphorous acid diethyl ester and suitable alkali for example lithium diisopropylamine or potassium tert.-butoxide react.Then can through catalytic hydrogenation (for example Pd-C) with obtained 3,3,3-three fluoro-2-phenyl propylene are reduced into saturated alkane, convert it into SULPHURYL CHLORIDE through the method for describing in the scheme 4 subsequently.
Reaction scheme 5 synthetic can also be used the chiral catalyst that is used for olefin hydrogenation and carried out, preparing corresponding chirality 4-(1, and 1,1-trifluoropropyl-2-yl) benzene-1-SULPHURYL CHLORIDE.
Scheme 6:
Figure G2007800134447D01021
4-(1,1,1-trifluoropropyl-2-yl) benzene-1-SULPHURYL CHLORIDE can also be made by commercially available 1-phenyl-ethyl ketone through four step procedure shown in scheme 6.Through reacting, this ketone is changed into trifluoromethyl hydroxy intermediate (Journal of Organic Chemistry, 2000,65,8848-8856 with trimethylammonium-trifluoromethyl-silicomethane; Journal of Fluorine Chemistry, 2003,122,243-246), can convert it into trifluoromethyl bromide (Journal of the American ChemicalSociety then, 1987,109,2435-4).(for example Pd-C) carries out dehalogenate through catalytic hydrogenation, converts it into SULPHURYL CHLORIDE through aforesaid method then.
The instance of applicable solvent is an ethers, like ether, Di Iso Propyl Ether, methyl tertiary butyl ether or tetrahydrofuran (THF); Polar aprotic solvent is like dimethyl formamide, dimethyl sulfoxide (DMSO), glycol dimethyl ether and acetonitrile; Aromatic hydrocarbons is like toluene and xylenes; Ketone is like acetone or methylethylketone; Halohydrocarbon is like methylene dichloride, trichloromethane and ethylene dichloride; Ester is like ethyl acetate and methyl-butyrate; Carboxylic acid is like acetate or propionic acid; And alcohol, like methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, isopropylcarbinol, 2-butanols and the trimethyl carbinol.
Like needs, in and the proton that in reaction, discharges can have alkali.Suitable alkali comprises mineral alkali, like yellow soda ash, salt of wormwood, sodium hydrogencarbonate or saleratus; Also has alkoxide, like sodium methylate or sodium ethylate; Alkalimetal hydride is like sodium hydride; And organometallic compound such as butyl lithium compounds or alkyl magnesium compound; Or alkaloid, like triethylamine or pyridine.Compound can be used as solvent simultaneously.
Usual manner obtains separating crude product through for example filtering, distillate solvent or from reaction mixture, extract etc.The gained compound is purifying in a conventional manner, for example through recrystallization from solvent, chromatogram or be converted into the mode purifying of acid salt.
Acid salt is in a conventional manner through mixing free alkali with corresponding acid, for example make in the solution of lower alcohol (like methyl alcohol, ethanol or propyl alcohol), ether (like methyl tertiary butyl ether or Di Iso Propyl Ether), ketone (like acetone or methylethylketone) or ester class (like ethyl acetate) at organic solvent when suitable.
Astoundingly, formula I compound according to the present invention is the highly selective dopamine D < > 3 <> Receptors ligand and since they to other acceptors (like D < > 1 <> Acceptor, D < > 4 <> Acceptor, alpha 1 adrenergic and/or α 2-adrenergic receptor, M-ChR, Histamine Receptors, opiate receptor and particularly dopamine D < > 2 <> Acceptor) low affinity, so they are than typical psychosis (D < > 2 <> Receptor antagonist) generation side effect still less.Compound of the present invention can be the dopamine D that comprises PAA < > 3 <> Receptor stimulant, or comprise the dopamine D of part antagonistic activity < > 3 <> Receptor antagonist.
Compound according to the present invention is to D < > 3 <> The high-affinity of acceptor is reflected in extremely low extracorporeal receptor binding constant (K < > i <> (D < > 3 <> ) value), this binding constant is usually less than 50nM(nmol/l), preferably less than 10nM, especially less than 5nM.[ < > 125 <> 1 iodine Sulpiride (iodosulpride) displacement can for example be used for receptors bind research and measure D < > 3 <> The binding affinity of acceptor.
According to compound selective of the present invention, i.e. the K of receptors bind constant < > i <> (D < > 2 <> ) /K < > i <> (D < > 3 <> ) ratio, be at least 50 usually, be preferably at least 100 even better be at least 150.[ < > 3 <> H, [ < > 125 <> 1 iodine Sulpiride or [ < > 125 <> The displacement of 1 spiperone can for example be used to carry out D < > 1 <> , D < > 2 <> And D < > 4 <> In the receptors bind research of acceptor.
Because their binding characteristic, said compound can be used for treatment to dopamine D < > 3 <> Receptors ligand reacts (or separately to dopamine D < > 3 <> The receptor ligands for treatment sensitivity) disease, promptly they can be effective to treatment wherein to dopamine D < > 3 <> Acceptor exert one's influence (adjusting) cause clinical manifestation to improve or cause those diseases of disease cured.The instance of these diseases has the illness or the disease of central nervous system.
Central nervous system disorders or disease are interpreted as meaning the illness that influences spinal cord and especially brain.In implication of the present invention, term " illness " expression obstacle and/or unusual, said obstacle and/or being regarded as pathologic state or function and itself usually can show as the form of definite sign, symptom and/or dysfunction unusually.Although treatment according to the present invention is unusual with individual illness or pathological state is a target; But for can on the cause of disease, being coupled to each other the pattern of being combined into be syndromic several also be possible target unusually, said syndrome can be treated according to the present invention.
Medicable illness especially is the P&N obstacle according to the present invention.These obstacles especially comprise: organic obstacle, comprise the for example acute external source reactive psychosis of symptom obstacle, and perhaps organ or exogen follow mental case like the psychosis relevant with metabolic disturbance, infection and incretopathy; Endogenous psychosis, for example schizophrenia and schizophrenia type and delusional disorder; Affective disorder, for example dysthymia disorders, mania and/or manic-dysthymia disorders; And the mixed form of above-mentioned obstacle; Neural and body type obstacle and with obstacle that stress be relevant; The divergence type obstacle, the loss of consciousness for example, clouding of consciousness, double consciousness and personality disorder; Attention and awakening/disturbance in sleep behavior; For example start from children and adolescent behavior disorder and emotional handicap; For example children are how moving, amentia, particularly attention disorders (attention deficit sexual dysfunction), dysmnesia and cognitive disorder; For example learning and Memory goes down (recognizing ability goes down), dull-witted, ictal disease and somnopathy, the for example restless leg syndrome of sleeping; Dysplasia; Anxiety state, delirium; Sexual life obstacle, for example impotence; Eating disorder, for example apositia or bulimia; Habituation; With other unspecified psychiatric disturbances.
Medicable illness also comprises Parkinson's disease and epilepsy and particularly relevant with it affective disorder according to the present invention.
Addictive disorders comprises mental illness and behavior disorder and other addictive disorders that spirituality material such as medicine or narcotics abuse cause, (impulse control disorder of NEC) for example is addicted to gambling.The instance of addicted substance is: opioid (for example morphine, heroine and morphine monomethyl ether); Cocaine; Nicotine; Alcohol; With the interactional material of GABA chloride channel mixture, tranquilizer, soporific and tranquilizer (benzodiazepines) for example; LSD; Cannabinoids; Psychomotor stimulant (as 3,4-methylene-dioxy-Corvitin (magic potion); Amphetamine and Amphetamine appearance material (like Ritalin) and other energizers that comprise caffeine.Considerable especially addicted substance is opioid, Cocaine, Amphetamine or Amphetamine appearance material, Nicotine and alcohol.
About the treatment of addictive disorders, particularly preferably give those compounds of formula I of itself no any short spiritual effect according to the present invention.This also can observe in rat test, is using to rat according to the present invention behind the applicable compound, and rat has reduced self uses spirituality material such as Cocaine.
According to a further aspect in the invention, compound according to the present invention be applicable to its reason of treatment at least part owing to dopamine D < > 3 <> The active illness of receptor abnormality.
According to a further aspect in the invention, in favourable pharmacological agent meaning, this treatment is especially to preferred exogenous the using and dopamine D of warp < > 3 <> Those illnesss that the mating partner of receptors bind (part) can influence.
The characteristic of available disease according to compounds for treating of the present invention is generally carries out sexual development, and promptly above-mentioned illness is process and changing in time; Being generally seriousness increases, and illness possibly merge each other, or other illnesss except that already present those illnesss also possibly occur.
Compound according to the present invention can be used for treating a large amount of sign, symptom and/or dysfunctions relevant with central nervous system disorders, especially is above-mentioned illness.These signs; Symptom and/or dysfunction for example comprise the confusion contact to reality; Lack vision and the ability of understanding habitual social regulation or life requirement; Makings changes; Individual prime mover changes as is hungry; Sleep; Thirsty senses etc. change and mood alteration; Observe ability obstacle with associating; Personality change especially is an emotional instability; Illusion; The oneself is disorderly; Unset; Ambivalence; Solitarily; Depersonalization and false consciousness; Delusional idea; Chant speech (chanting speech); Synkinesis lacks; Short and small gait (short-step gait), the crooked position of trunk and four limbs trembles; Facial expression is poor; Speech is dull, and depression is indifferent; Spontaneous and decisive being obstructed; Associative ability is poor, anxiety, nerve fires; Stutter; Social phobia, alarmed obstacle, the withdrawal symptom relevant with dependency; Hand shape syndrome (maniform syndrome); Excitement and tangleweed are had the fidgets, the special (Gilles-de-la-Tourette of dyskinetic syndrome and tic disease such as huntington's chorea and Ji Lesi De La Torre) syndrome; Vertiginous syndrome such as periphery property positional; Rotation and vibratility are dizzy; Melancholy, hysteria and hypochondriasis etc.
In implication of the present invention, the present invention's treatment also comprises prophylactic treatment (prevention), particularly recurrence prevention or stage prevention, and treat acute or chronic sign, illness and/or dysfunction.Said treatment can be to be purpose with the symptom, and for example symptom suppresses.This can be that short-term is effective, is target with the mid-term, perhaps can be long-term treatment, is for example keeping under the situation of treatment.
Therefore, preferably be applicable to the treatment central nervous system disease, especially for the treatment affective disorder according to compound of the present invention; Neurosis disorder, stress disorder, body shape obstacle (somatoform disturbances) and psychosis, and in particular for treatment schizophrenia and dysthymia disorders.Because they are to dopamine D < > 3 <> The highly selective of acceptor also is applicable to the treatment renal tubal dysfunction according to compound I of the present invention, particularly the renal tubal dysfunction that is caused by diabetes (referring to WO00/67847), especially diabetic nephropathy.
Especially, The compounds of this invention is applicable to the following illness of treatment: Parkinson's disease, schizophrenia, cognitive disorder, depression, anxiety, habituation, renal tubal dysfunction, eating disorder and epilepsy.
In the scope of treatment, relate to method according to application of compound according to the invention.In the method, the individuality of being treated is prepared-be applied to one or more compounds-common the practice according to pharmacy and veterinary science of significant quantity, preferred mammal, the particularly mankind, productivity animal or domestic animal.Whether indicate with such treatment and with which kind of form and carry out; Depend on individual situation and suffered medical evaluation thereof (diagnosis); Said medical evaluation is considered existing sign, illness and/or dysfunction; And the risk that develops into specific sign, illness and/or dysfunction, and other factors.
Usually; The present invention's treatment realizes through single or repetition administration every day; Under suitable situation with other active compound or contain the preparation of active compound or alternately administration; So that to the individuality of being treated provide following preferred every day dosage; About 0.1-1000mg/kg body weight under case of oral administration, perhaps about 0.1-100mg/kg body weight under the situation of administered parenterally.
The invention still further relates to preparation of drug combination, said composition is used for treatment individuality, preferred mammal, the particularly mankind, productivity animal or domestic animal.Therefore, these parts give with the form of pharmaceutical composition usually, and these compositions comprise pharmaceutically acceptable vehicle and at least a according to compound of the present invention, and also comprise other active compounds in appropriate circumstances.But these compositions are administered through oral, rectum, transdermal, subcutaneous, intravenously, intramuscular or intranasal administration for example.
The instance of suitable pharmaceutical dosage form is a solid drug forms, like pulvis, granule, tablet (particularly film coated tablet), lozenge, pouch agent (sachets), cachet, coated tablet, capsule (like hard gelatin capsule and soft gelatin capsule), suppository or intravaginal drug form; Semisolid dosage form is like ointment, ointment, hydrogel, paste or plaster; And the liquid medicine form, like solution, emulsion (particularly oil-in-water emulsion), suspensoid such as lotion, injection formulations and infusion preparation and eye drops and nasal drop.The implantation releasing device also can be used for the administration of the suppressor factor according to the present invention.Available in addition liposome or microsphere.
When the preparation composition, can choose wantonly and one or more mixed with excipients or dilution according to The compounds of this invention.Vehicle can be solid, semisolid or the fluent material as media, carrier or the medium of active compound.
The vehicle that is fit to is listed in the professional medical works.In addition, preparation can comprise pharmaceutically acceptable carrier or auxiliary substance commonly used, for example glidant; Wetting agent; Emulsifying agent and suspension agent; Sanitas; Antioxidant; Counter irritant; Sequestrant; The dressing auxiliary material; The emulsion stablizer; Film forming agent; Gel former; Odor masking agent; Correctives; Resin; Hydro-colloid; Solvent; Solubilizing agent; Neutralizing agent; The diffusion accelerator; Pigment; Quaternary ammonium compound; Fatting agent and supe rfatting agent (refattingand overfatting agents); The raw material of ointment, creme or finish; Silicone derivative; Apply auxiliary material; Stablizer; Sterilant; Suppository base; Additive of tablet, for example tackiness agent, weighting agent, glidant, disintegrating agent or dressing material; Propelling agent; Siccative; Opalizer; Thickening material; The wax class; Softening agent; And slab oil.In this; Preparation is based on expertise; For example be described in Fiedler, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik undangrenzende Gebiete[Encyclopedia of auxiliary substances for pharmacy and related fields]; The 4th edition, Aulendorf:ECV-Editio-Kantor-Verlag is in 1996.
The following example is to explain the present invention rather than restriction the present invention.
If not explanation in addition, compound is at d < > 6 <> In-methyl-sulphoxide or the d-chloroform in 400MHz or 500MHz NMR device (Bruker AVANCE) go up and to characterize via proton-NMR; Perhaps characterize through mass spectrum; Mass spectrum generally is to write down (electronics spray-ion (ESI) pattern) with quick gradient via HPLC-MS at the C18-material, or characterizes through fusing point.
NMR (Nuclear Magnetic Resonance) spectrum character (NMR) is meant the chemical shift (δ) with part per million (ppm) expression.The relative area of displacement is corresponding to the number of hydrogen atoms of specific function type in the molecule in the 1H NMR spectrum.With regard to multiplicity, displacement property is expressed as unimodal (s), wide unimodal (s.br.), bimodal (d), wide bimodal (d br.), triplet (t), wide triplet (t br.), quartet (q), quintet (quint.) and multiplet (m).
< > Preparation embodiment: <>
< > I. intermediate <>
< > A.[2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl is at propyl group-carboxylamine tertiary butyl <> < > Ester <>
A.1[2-(6-methoxyl group-5-nitro-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester
With 6-bromo-2-methoxyl group-3-nitropyridine (5g, 21.46mmol), (2-hydroxyl-ethyl)-propyl group-carboxylamine tertiary butyl ester (4.36g, 21.46mmol) and K < > 2 <> CO < > 3 <> (2.97g is 21.46mmol) in dimethyl formamide (DMF)(60ml) in mixture stirring at room 24 hours, and stirred 4 hours in 40 ℃.Behind the vapourisation under reduced pressure solvent, with residuum through silica gel chromatography methylene chloride (10:0; 9:1; 7:3; 0:10) as the eluent purifying, obtain product 2.81g(36.9%).
MS(ESI)m/z：356.25[M+H(-BOC)] +
A.2[2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester
With [2-(6-methoxyl group-5-nitro-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester (1.12g) and 10% palladium/charcoal (0.34g, 0.316mmol) in ethanol (80ml) in mixture hydrogenation under atmospheric pressure accomplish up to hydrogen consumption.After the filtration, decompression is evaporating solvent down, obtains title compound 960mg(93.5%).
MS(ESI)m/z：326.25[M+H] +
< > B.6-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-pyridin-3-yl amine <>
B.16-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-3-nitro-pyridine
With 6-bromo-2-methoxyl group-3-nitropyridine (1.5g, 6.44mmol), 1-benzyl-tetramethyleneimine-3-alcohol (1.14g, 6.44mmol) and K < > 2 <> CO < > 3 <> (0.89g is 6.44mmol) in dimethyl formamide (DMF)(20ml) in mixture stirring at room 24 hours, and stirred 4 hours in 40 ℃.Behind the vapourisation under reduced pressure solvent, with residuum through silica gel chromatography methylene chloride (10:0; 9:1; 7:3; 0:10) as the eluent purifying, obtain product 380mg(18.1%).
MS(ESI)m/z：330.15[M+H] +
B.26-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-pyridin-3-yl amine
At 80 ℃, to 6-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-3-nitro-pyridine (0.38g, 1.15mmol) portioning adds iron (0.32g at leisure in the solution of acetate (4ml), 5.77mmol).At 80 ℃ thermopositive reaction was stirred 3 hours.Behind the vapourisation under reduced pressure solvent, solid residue is dissolved among the 1NNaOH, with dichloromethane extraction 6 times.Organic layer after merging is dry through MgSO4, filter and evaporating solvent, obtain title compound 240mg(68.9%).
MS(ESI)m/z：300.15[M+H] +
< > C.2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine <>
According to being similar to the described synthetic operation of preparation intermediate a, begin by 6-bromo-2-methoxyl group-3-nitropyridine and 2-tetramethyleneimine-1-base-ethanol, make required product.
MS(ESI)m/z：268.15[M+H] +
< > D.[2-(5-amino-4-methoxyl group-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl <> < > Ester <>
D.12-chloro-4-methoxyl group-5-nitro-pyrimidine
At-10 ℃, to 2,4-two chloro-5-nitro-pyrimidine (10g are 51.55mmol) in methyl alcohol (150ml) in solution in, be incorporated in methyl alcohol (150ml in 10 minutes) in potassium methylate (3.62g, 51.55mmol) solution.Allow mixture be warming up to 0 ℃, evaporating solvent under 30 ℃ of decompressions.With residuum through silica gel chromatography with normal heptane/ethyl acetate (3:1) as the eluent purifying, obtain title compound 3.7g(37.9%).Obtain 1.34g(13.7% as byproduct) 4-chloro-2-methoxyl group-5-nitro-pyrimidine.
MS(ESI)m/z：196.15[M+H] +
D.2[2-(4-methoxyl group-5-nitro-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl ester
At 0 ℃, in the solution of (2-hydroxyl-ethyl)-propyl group-carboxylamine tertiary butyl ester (1.07g is 5.28mmol) in THF(40ml), add NaH(0.25g, 5.80mmol).Stir suspension after 30 minutes at 0 ℃, add the solution of 2-chloro-4-methoxyl group-5-nitro-pyrimidine (1g is 5.28mmol) in THF(10ml), with mixture stirring at room 16 hours.Mixture is added in the entry, with dichloromethane extraction 3 times.With the organic layer after merging through MgSO < > 4 <> Drying is filtered, and under reduced pressure concentrates, and obtains title compound.
MS(ESI)m/z：357.15[M+H] +
D.3[2-(5-amino-4-methoxyl group-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl ester
At 80 ℃; To rough [2-(4-methoxyl group-5-nitro-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl ester (1.76g) and 10% palladium/charcoal (200mg) in water (15ml) in mixture in; Slowly add ammonium formiate (3.12g, 49.44mmol) in water (10ml) in solution., after 1 hour mixture is filtered and under reduced pressure concentrates 80 ℃ of stirrings.Water layer is with dichloromethane extraction 3 times.With the organic layer after merging through MgSO < > 4 <> Drying is filtered and the vapourisation under reduced pressure solvent.With residuum through silica gel chromatography toluene /THF/MeOH(4:1:1)/2.5% triethylamine purifying, obtain title compound 720mg(44.7%).
MS(ESI)m/z：327.15[M+H] +
< > E.6-(2-dimethylamino-oxyethyl group)-pyridin-3-yl amine <>
According to being similar to the described synthetic operation of preparation intermediate a, begin by 2-chloro-5-nitropyridine and 2-dimethylaminoethanol, make required product.
MS(ESI)m/z：182.15[M+H] +
< > F.[2-(5-amino-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester <>
According to being similar to preparation intermediate a described synthetic operation, by 2-chloro-5-nitropyridine with (2-hydroxyl-ethyl)-propyl group-carboxylamine tertiary butyl ester begins, and makes required product.
MS(ESI)m/z：326.15[M+H] +
< > G.4-((S)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride <>
G.1 toluene-4-sulfonic acid (S)-2-phenyl-propyl diester
Add 28g Tosyl chloride (146.8mmol to 20g(S)-(-)-2-phenyl-1-propyl alcohol portioning in the solution of 40ml methylene dichloride).,,, filter after 18 hours in stirring at room through dried over mgso with organic phase 100ml water washing, and vapourisation under reduced pressure, the 43g title compound obtained.
1H-NMR(CDCl 3，400MHz)：δ[ppm]7.65(d，2H)，7.15-7.3(m，5H)，7.1(d，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
With 9.62g toluene-4-sulfonic acid (S)-2-phenyl-propyl diester (33.13mmol) be dissolved in the 80ml poly(oxyethylene glycol) 400.Add 9.62g Potassium monofluoride (165.6mmol), reaction mixture was stirred 3 days at 50 ℃, stirred 2 days at 5-70 ℃ again.Reaction is handled with the saturated sodium chloride aqueous solution of 50ml, and with Anaesthetie Ether extraction 3 times, the organic layer after will merging then filters and the vapourisation under reduced pressure solvent through dried over mgso.Raw product through silica gel chromatography with 15% cyclohexane/ethyl acetate as the eluent purifying.Separate obtaining the 2.85g desired product, comprise that 25% eliminates byproduct.
< > 1 <> H-NMR(CDCl < > 3 <> , 400MHz): δ [ppm, 5H), several m of 4.3-4.6(, 2H), 3.15(m, 1H), 1.3(m, 3H).
G.34-((S)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride
With 3.5g((S)-2-fluoro-1-methyl-ethyl)-benzene (25.32mmol) be dissolved in the 80ml methylene dichloride.At 0-5 ℃, point is added dropwise to the 11.81g chlorsulfonic acid (101.31mmol that is dissolved in the 20ml methylene dichloride).Reaction mixture stirring at room 30 minutes, was stirred 2 hours at 30 ℃ then.Evaporating solvent.In residuum, add the 50ml Anaesthetie Ether, with the 50ml water washing once, then with organic layer through dried over mgso, filter also vapourisation under reduced pressure solvent.Raw product through silica gel chromatography with normal heptane-methylene dichloride (6:4) as the eluent purifying, obtain the 1.5g title compound.
1H-NMR(CDCl 3，400MHz)：δ[ppm]8.0(d，2H)，7.5(d，2H)，4.5(dd，2H)，3.25(m，1H)，1.4(d，3H)。
< > H.4-((R)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride <>
H.1 toluene-4-sulfonic acid (R)-2-phenyl-propyl diester
According to being similar to the synthetic used operation of toluene-4-sulfonic acid (S)-2-phenyl-propyl diester, but with (R)-2-phenyl-1 propyl alcohol as initial compounds, make title compound.
H.2((R)-2-fluoro-1-methyl-ethyl)-benzene
Use toluene-4-sulfonic acid (R)-2-phenyl-propyl diester and replace toluene-4-sulfonic acid (S)-2-phenyl-propyl diester, methyl-ethyl)-benzene is said, makes title compound for as above synthetic ((S)-2-fluoro-1-.
< > 1 <> H-NMR(CDCl < > 3 <> , 400MHz): δ [ppm, 5H), several m of 4.3-4.6(, 2H), 3.15(m, 1H), 1.3(m, 3H).
H.34-((R)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride
With 1.3g((R)-2-fluoro-1-methyl-ethyl)-benzene (9.4mmol) be dissolved in the 50ml methylene dichloride.At 0-5 ℃, point is added dropwise to the chlorsulfonic acid (9.4mmol that is dissolved in the 10ml methylene dichloride).Reaction mixture was stirred 20 minutes at 0-5 ℃, add to then in the 2.15g phosphorus pentachloride solution that is dissolved in the 40ml methylene dichloride.Reaction mixture was stirred 30 minutes at 0-5 ℃, again stirring at room 1 hour.Evaporating solvent adds the 100ml Anaesthetie Ether, with 50ml water washing mixture once, then with organic layer through dried over mgso, filter also vapourisation under reduced pressure solvent.Raw product through silica gel chromatography with normal heptane-methylene dichloride (1:1) as the eluent purifying, obtain the 0.261g title compound.
1H-NMR(CDCl 3，400MHz)：δ[ppm]8.0(d，2H)，7.5(d，2H)，4.5(dd，2H)，3.25(m，1H)，1.4(d，3H)。
< > I.4-(2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride <>
Synthesize used operation according to being similar to 4-((S)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride, but g.1 begin, make title compound with 2-phenyl-1-propyl alcohol in step.
Figure G2007800134447D01111
1H-NMR(CDCl 3，400MHz)：δ[ppm]8.0(d，2H)，7.5(d，2H)，4.5(dd，2H)，3.25(m，1H)，1.4(d，3H)。
< > K.4-(3-fluoropropyl)-benzene sulfonyl chloride <>
K.1(3-fluoropropyl)-benzene
15.6g three is fluoridized diethylamino sulphur, and (DAST 96.91mmol) is dissolved in the 18ml methylene dichloride.At 0-5 ℃, dropping is dissolved in the 12g3-phenyl-1-propyl alcohol (88.1mmol in the 30ml methylene dichloride).Reaction mixture was stirred 18 hours, add the 30ml methylene dichloride, incline to the 100ml frozen water.Organic layer is separated,, filter and evaporating solvent through dried over mgso.Raw product is being bathed purifying under 106 ℃ of 20mm of temperature through distillation, obtains the 7.4g title compound.
1H-NMR(CDCl 3，400MHz)：δ[ppm]7.1-7.3(m，5H)，4.4(dt，2H)，2.7(m，2H)，2.0(m，2H)。
K.24-(3-fluoropropyl)-benzene sulfonyl chloride
With 4.1g(3-fluoro-propyl group)-benzene (29.67mmol) be dissolved in the 40ml methylene dichloride.At 0-5 ℃, dropping is dissolved in the 6.91g chlorsulfonic acid (59.34mmol in the 10ml methylene dichloride).Reaction mixture was stirred 45 minutes at 0-5 ℃, adds to the 6.8g phosphorus pentachloride (32.63mmol that is dissolved in the 50ml methylene dichloride then) in the solution.Reaction mixture was stirred 1 hour at 5-10 ℃.Evaporating solvent adds the 50ml Anaesthetie Ether, with 50ml frozen water washing soln once, then with organic layer through dried over mgso, filter also vapourisation under reduced pressure solvent.Raw product through silica gel chromatography with normal heptane-methylene dichloride (11:9) as the eluent purifying, obtain the 5.5g title compound.
1H-NMR(CDCl 3，400MHz)：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-fluoro ethyl)-benzene sulfonyl chloride <>
M.1(2-fluoro ethyl)-benzene
According to (3-fluoropropyl)-benzene synthesizes used operation, obtains the 6.8g title compound by commercial available 2-phenyl-ethanol.
1H-NMR(CDCl 3，400MHz)：δ[ppm]7.1-7.3(m，5H)，4.6(m，1H)，4.45(m，1H)，2.95(m，1H)，2.9(m，1H)。
M.24-(2-fluoro ethyl)-benzene sulfonyl chloride
According to the synthetic used operation of 4-((R)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride, obtain 3.55g.
1H-NMR(CDCl 3，400MHz)：δ[ppm]8.0(d，2H)，7.5(d，2H)，4.7(dt，2H)，3.05-3.2(dt，2H)。
< > N.4-(1,1,1-trifluoro propane-2-yl) benzene sulfonyl chloride and 2-(1,1,1-trifluoro propane-2-yl) benzene sulphur <> < > Acyl chlorides <>
According to the operation of general introduction in the scheme 5, make the product of 14g scale.2-(1,1,1-trifluoro propane-2-yl) by product of benzene sulfonyl chloride for reacting.
4-(1,1,1-trifluoro propane-2-yl) benzene sulfonyl chloride:
MS(ESI)m/z：273.1[M+H] +
1H-NMR(DMSO-d 6)：δ[ppm]7.62(d，2H)，7.33(d，2H)，3.81(m，1H)，1.42(d，3H)。
2-(1,1,1-trifluoro propane-2-yl) benzene sulfonyl chloride:
MS(ESI)m/z：273.1[M+H] +
< > O.4-oxazole-4-base-benzene sulfonyl chloride <>
Will be in formic acid (75ml) in 2-bromo-1-phenyl-ethyl ketone (40g, 201mmol) with ammonium formiate (44.35g, solution reflux 703mmol) 2 hours.The reaction mixture vapourisation under reduced pressure is added to residuum in the water, with dichloromethane extraction 3 times.Raw product is through silica gel chromatography ethyl acetate/heptane (0:10; 1:9) as the eluent purifying.At 0 ℃, in 4-Dui Ben Ji oxazole (3g 20.67mmol) slowly is added to 24.08g chlorsulfonic acid (206.67mmol).Reaction mixture was stirred 20 minutes at 0-5 ℃, heat then, stirred 2 hours at 45 ℃ at last to room temperature.Then with the careful (! of reaction mixture ) add in the frozen water.Throw out is filtered, use water washing, dry in 30 ℃ of vacuum drying ovens, obtain title compound (4.3g, 76.8%).
MS(ESI)m/z:240.15[M+H] < > + <> (4-oxazole-4-base-methyl benzenesulfonate)
< > P.6-[2-(benzyl-propyl group-amino)-oxyethyl group methoxyl group-pyridin-3-yl amine <>
P.1 benzyl-[2-(6-methoxyl group-5-nitro-pyridine-2-base oxygen base)-ethyl propyl group-amine
To in toluene (40ml) in Pd(OAc) < > 2 <> (112mg, 0.5mmol) and [1,1 '] (30mg in mixture 0.75mmol), adds 6-bromo-2-methoxyl group-3-pyridine (2.92g to dinaphthalene-2-base-di-t-butyl-phosphine, 12.54mmol), Cs < > 2 <> CO < > 3 <> (20.4g, 62.68mmol) and 2-(benzyl-propyl group-amino)-ethanol (3.63g, 18.8mmol).In room temperature nitrogen, mixture was stirred 24 hours.Behind the vapourisation under reduced pressure solvent, residuum is soluble in water, with dichloromethane extraction 5 times.With residuum through silica gel chromatography with normal heptane-methylene dichloride (10:0; 7:3; 0:10), obtain 2.92g(67.3% as the eluent purifying) product.
MS(ESI)m/z：346.15[M+H] +
< > P.26-[2-(benzyl-propyl group-amino)-oxyethyl group methoxyl group-pyridin-3-yl amine <>
At 80 ℃, to benzyl-[2-(6-methoxyl group-5-nitro-pyridine-2-base oxygen base)-ethyl propyl group-amine (2.92g, 8.45mmol) in acetate (120ml) solution in, portioning adds iron (2.36g at leisure, 42.27mmol).At 80 ℃ thermopositive reaction was stirred 2 hours.Behind the vapourisation under reduced pressure solvent, solid residue is dissolved in NaHCO < > 3 <> In the aqueous solution, with dichloromethane extraction 6 times.Residuum is through silica gel chromatography methylene chloride (10:0; 8:2; 6.5:3.5; 0:10), obtain 1.4g(52.5% as the eluent purifying) product.
MS(ESI)m/z：316.15[M+H] +
< > Q.(S)-2-(5-amino-6-methoxyl group-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid uncle fourth <> < > The base ester <>
Q.1(S)-2-(6-methoxyl group-5-nitro-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid tertiary butyl ester
To in toluene (10ml) in Pd(OAc) < > 2 <> (0.08g, 0.34mmol) and [1,1 '] dinaphthalene-2-base-di-t-butyl-phosphine (0.14g, in mixture 0.34mmol), add 6-bromo-2-methoxyl group-3-nitropyridine (1.0g, 4.29mmol), Cs < > 2 <> CO < > 3 <> (3.5g, 10.73mmol) and (S)-2-hydroxymethyl-tetramethyleneimine-1-carboxylic acid tertiary butyl ester (1.73g, 8.58mmol).In room temperature nitrogen, mixture was stirred 24 hours.Behind the vapourisation under reduced pressure solvent, with residuum through silica gel chromatography with dichloromethane/ethyl acetate/methyl alcohol (10:0:0; 9:0.5:0.5; 7:1.5:1.5; 0:5:5), obtain 0.11g(7.5% as the eluent purifying) product.
MS(ESI)m/z：354.15[M+H] +
Q.2(S)-2-(5-amino-6-methoxyl group-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid tertiary butyl ester
Application ThalesNano
Figure G2007800134447D01131
hydrogenation reactor, with 10% palladium / carbon catalyst cylinder, the (S) -2 - (6 - methoxy-5 - nitro - pyridin-2 - yloxy methyl) - pyrrolidine-1 - carboxylic acid tert-butyl ester (0.11g , 0.32mmol) in methanol (11ml) was hydrogenated in.Behind decompression concentrated solution, obtain title compound 0.10g(92.6%).
MS(ESI)m/z：324.15[M+H] +
< > R.(R)-2-(5-amino-6-methoxyl group-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid uncle fourth <> < > The base ester <>
According to being similar to the described synthetic operation of preparation intermediate q, begin by 6-bromo-2-methoxyl group-3-nitropyridine and (R)-2-hydroxymethyl-tetramethyleneimine-1-carboxylic acid tertiary butyl ester, make required product.
MS(ESI)m/z：324.15[M+H] +
< > S.(S)-2-(5-amino-6-methyl-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid tertiary butyl ester <>
According to being similar to the described synthetic operation of preparation intermediate q, begin by 6-chloro-2-methyl-3-nitro pyridine and (S)-2-hydroxymethyl-tetramethyleneimine-1-carboxylic acid tertiary butyl ester, make required product.
MS(ESI)m/z：340.15[M+H] +
< > T.(R)-2-(5-amino-6-methyl-pyridine-2-base oxygen ylmethyl)-tetramethyleneimine-1-carboxylic acid tertiary butyl <> < > Ester <>
According to being similar to the described synthetic operation of preparation intermediate q, begin by 6-chloro-2-methyl-3-nitro-pyridine and (R)-2-hydroxymethyl-tetramethyleneimine-1-carboxylic acid tertiary butyl ester, make required product.
MS(ESI)m/z：340.15[M+H] +
< > U.[2-(5-amino-6-methyl-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester <>
U.1[2-(6-methyl-5-nitro-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester
At 90 ℃, with 6-chloro-2-methyl-3-nitro-pyridine (1g, 5.79mmol), (2-hydroxyl-ethyl)-propyl group-carboxylamine tertiary butyl ester (1.18g, 5.79mmol) with lithium hydride (0.05g, 6.37mmol) mixture in toluene (5ml) stirred 4 hours.Behind the vapourisation under reduced pressure solvent, with residuum through silica gel chromatography with heptane/ethyl acetate (10:0; 8:2; 0:10), obtain 1.38g(70.2% as the eluent purifying) product.
MS(ESI)m/z:284.15[M+H(-[terf-butyl])] < > + <>
U.2[2-(5-amino-6-methyl-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester
Application ThalesNano
Figure G2007800134447D01141
hydrogenation reactor, with 10% palladium / carbon catalyst cylinder, the [2 - (6 - methyl-5 - nitro - pyridin-2 - yloxy) - ethyl] - propyl - carbamic acid tert-butyl ester (300mg, 0.88mmol) in methanol (10ml) was hydrogenated in.Behind decompression concentrated solution, obtain title compound 230mg(84.2%).
< > V.6-[2-(benzyl-propyl group-amino)-oxyethyl group methyl-pyridin-3-yl amine <>
According to being similar to the described synthetic operation of preparation intermediate p, begin by 6-chloro-2-methyl-3-nitro pyridine and 2-(benzyl-propyl group-amino)-ethanol, make required product.
MS(ESI)m/z：300.15[M+H] +
< > W.6-[2-(benzyl-propyl group-amino)-oxyethyl group methyl-pyridin-3-yl amine <>
According to being similar to the described synthetic operation of preparation intermediate p, begin by 2-chloro-4-methyl-5-nitro pyridine and 2-(benzyl-propyl group-amino)-ethanol, make required product.
MS(ESI)m/z：300.15[M+H] +
< > X.6-[2-(benzyl-propyl group-amino)-oxyethyl group methyl-pyridin-3-yl amine <>
According to being similar to the described synthetic operation of preparation intermediate p, begin by 2-bromo-3-methyl-5-nitro pyridine and 2-(benzyl-propyl group-amino)-ethanol, make required product.
MS(ESI)m/z：300.15[M+H] +
< > Y.4-(2-fluoro-oxyethyl group)-benzene sulfonyl chloride <>
At 0 ℃, (2-fluoro-oxyethyl group)-benzene (20mmol) slowly is added to chlorsulfonic acid (200mmol) in.Reaction mixture was stirred 20 minutes at 0-5 ℃, heat then, stirred 2 hours at 45 ℃ at last to room temperature.Then with the careful (! of reaction mixture ) add in the frozen water.Throw out is filtered, use water washing, dry in 30 ℃ of vacuum drying ovens, obtain title compound.
1H-NMR(CDCl 3)：δ[ppm]4.21-4.45(m，2H)，4.65-5.00(m，2H)，7.08(d，2H)，8.00(d，2H)。
< > Z.4-(2,2-two fluoro-oxyethyl group)-benzene sulfonyl chlorides <>
According to being similar to the described synthetic operation of preparation intermediate y, obtain required product.
1H-NMR(CDCl 3)：δ[ppm]4.21-4.40(m，2H)，5.82-6.45(m，1H)，7.08(d，2H)，8.02(d，2H)。
< > Zz.4-(2,2,2-three fluoro-oxyethyl group)-benzene sulfonyl chlorides <>
According to being similar to the described synthetic operation of preparation intermediate y, obtain required product.
1H-NMR(CDCl 3)：δ[ppm]4.40-4.55(m，2H)，7.10(d，2H)，8.02(d，2H)。
< > II. prepare compound I <>
< > Embodiment 1 <>
< > 4-(3-fluoro-propyl group)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulphur <> < > Acid amides, hydrochloride (x Cl)0 <>
With [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester (200mg, pyridine 0.62mmol) (3ml) solution after 30 minutes, adds 4-(3-fluoro-propyl group)-benzene sulfonyl chloride (160mg, 0.68mmol) in stirring at room.Stirring at room 16 hours, decompression thereafter is evaporating solvent down with mixture.Residuum absorbs with toluene, once more evaporating solvent.Repeat this operation once.With residuum through silica gel chromatography with n-hexane/ethyl acetate (1:0; 1:1; 0:1)/0.2% triethylamine is as the eluent purifying.Residuum is dissolved in methylene dichloride (5ml).At 0 ℃, in this solution, slowly add HCl Anaesthetie Ether (1ml).With mixture stirring at room 6 hours, after under reduced pressure concentrating, with residuum through chromatography (Chromabond-C18) use H < > 2 <> O/ acetonitrile (95:5; 0:100; 95:5)/0.1% acetate is as the eluent purifying.With the solution of oil in 1NNaOH that obtains like this, use methylene dichloride (45ml) extract 3 times.Organic layer after merging is concentrated into 30ml, adds HCl Anaesthetie Ether (2ml).With the solid filtering that forms, dry in vacuum drying oven, obtain title compound 88.9mg(35.6%).
MS(ESI)m/z：426.25[M+H] +
1H-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)。
< > Embodiment 2 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl trifluoromethoxy-benzene sulphur <> < > Acid amides xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-trifluoromethoxy-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：449.25[M+H] +
1H-NMR(D 6-DMSO)：δ[ppm]7.75(d，2H)，7.56(d，2H)，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)。
< > Embodiment 3 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl, 2,2-three fluoro-1-first <> < > Base-ethyl)-benzsulfamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-(2,2,2-three fluoro-1-methyl-ethyl)-benzene sulfonyl chloride begins, and makes required product.
MS(ESI)m/z：462.15[M+H] +
1H-NMR(CDCl 3)：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，1H)，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)。
< > Embodiment 4 <>
< > 4-sec.-propyl-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzsulfamide <> < > XHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-sec.-propyl-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：408.25[M+H] +
< > Embodiment 5 <>
< > 4-difluoro-methoxy-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-difluoro-methoxy-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：432.15[M+H] +
1H-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)，1.70-1.85(m，2H)，1.05(t，3H)。
< > Embodiment 6 <>
< > 4-(2-fluoro-ethyl)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-(2-fluoro-ethyl)-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：412.25[M+H] +
1H-NMR(D 6-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)，0.90(t，3H)。
< > Embodiment 7 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl]-4-oxazole-5-base-benzene sulfonyl <> < > Amine xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and-oxazoles-5-base-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：433.25[M+H] +
1H-NMR(MeOD)：δ[ppm]8.35(s，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)。
< > Embodiment 8 <>
< > 4-(2-fluoro-oxyethyl group)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene <> < > Sulphonamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-(2-fluoro-oxyethyl group)-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：428.10[M+H] +
1H-NMR(D 6-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 br.，2H)，1.60-1.70(m，2H)，0.90(t，3H)。
< > Embodiment 9 <>
< > 4-(2,2-two fluoro-oxyethyl group)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridine-3-<> < > Base benzsulfamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-(2,2-two fluoro-oxyethyl group)-benzene sulfonyl chlorides begin, and make required product.
MS(ESI)m/z：446.05[M+H] +
1H-NMR(D 6-DMSO)：δ[ppm]9.40(s，1H)，9.15(s br.，2H)，7.60(d，2H)，7.45(d，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)。
< > Embodiment 10 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl, 2,2-three fluoro-ethoxies <> < > Base)-benzsulfamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-(2,2,2-three fluoro-oxyethyl group)-benzene sulfonyl chlorides begin, and make required product.
MS(ESI)m/z：464.05[M+H] +
1H-NMR(D 6-DMSO)：δ[ppm]9.45(s，1H)，9.15(s br.，2H)，7.60(d，2H)，7.45(d，1H)，7.25(d，2H)，6.39(d，1H)，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)。
< > Embodiment 11 <>
< > 4-((R)-2-fluoro-1-methyl-ethyl)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridine <> < >-3-base benzsulfamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-6-methoxyl group-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-((R)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：426.15[M+H] +
1H-NMR(D 6-DMSO)：δ[ppm]9.49(s，1H)，9.15(s br.，2H)，7.60(d，2H)，7.50(d，1H)，7.45(d，2H)，6.40(d，1H)，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)。
< > Embodiment 12 <>
< > 4-((S)-2-fluoro-1-methyl-ethyl)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridine <> < >-3-base benzsulfamide xHCl <>
At 0 ℃, and adding 4-((S)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride in 6-[2-(benzyl-propyl group-amino)-oxyethyl group methoxyl group-pyridin-3-yl amine (60mg, pyridine (0.8ml 0.20mmol)) solution (50mg, 0.20mmol).Stirring at room 16 hours, decompression thereafter is evaporating solvent down with mixture.With residuum through silica gel chromatography n-hexane/ethyl acetate (10:0; 9:1; 0:10)/0.2% triethylamine is as the eluent purifying.Application ThalesNano
Figure G2007800134447D0119122414QIETU
hydrogenation reactor, with 10% palladium / carbon catalyst cylinder, the oil thus obtained was hydrogenated.Filter and decompression concentrated solution after, with residuum through chromatography (Chromabond-C18) use H < > 2 <> O/ acetonitrile (95:5; 0:100; 95:5)/0.1% acetate is as the eluent purifying.In the solution of oil in the 2-propyl alcohol of such acquisition, add the HCl Anaesthetie Ether.With the solid filtering that forms, dry in vacuum drying oven, obtain title compound 10mg(20.3%).
MS(ESI)m/z：426.15[M+H] +
1H-NMR(D 6-DMSO)：δ[ppm]9.49(s，1H)，9.15(s br.，2H)，7.60(d，2H)，7.50(d，1H)，7.45(d，2H)，6.40(d，1H)，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)。
< > Embodiment 13 <>
< > 4-sec.-propyl-N-[2-methoxyl group-6-(tetramethyleneimine-3-base oxygen base)-pyridin-3-yl benzsulfamide x <> < > HCl <>
With 6-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-pyridin-3-yl amine (120mg, pyridine 0.40mmol) (2ml) solution after 30 minutes, adds 4-sec.-propyl-benzene sulfonyl chloride (100mg, 0.44mmol) in stirring at room.Stirring at room 16 hours, decompression thereafter is evaporating solvent down with mixture.Residuum absorbs with toluene, then evaporating solvent.Repeat this operation once.With residuum through silica gel chromatography dichloromethane/ethyl acetate (10:0; 9:1; 0:10)/0.2% as the eluent purifying.The oil of acquisition like this and the mixture hydrogenation under atmospheric pressure in 10% palladium/charcoal (20mg is 0.02mmol) in ethanol (20ml) are accomplished up to hydrogen consumption.Filter and decompression concentrated solution after, with residuum through silica gel chromatography methylene chloride (10:0; 0:10; 10:0) as the eluent purifying.In the solution of oil in methyl alcohol of such acquisition, add the HCl Anaesthetie Ether, decompression is concentrated solution down, obtains title compound 31mg(33.2%).
MS(ESI)m/z：392.35[M+H] +
1H-NMR(MeOD)：δ[ppm]7.65(d，1H)，7.60(d，2H)，7.35(d，2H)，6.35(d，1H)，5.55(s br.，1H)，3.45-3.60(m，4H)，3.55(s，3H)，2.90-3.05(m，1H)，2.30-2.40(m，2H)，1.60-1.70(m，2H)，1.25(d，3H)。
< > Embodiment 14 <>
< > N-[2-methoxyl group-6-(tetramethyleneimine-3-base oxygen base)-pyridin-3-yl trifluoromethoxy-benzene sulfonyl <> < > Amine xHCl <>
According to being similar to preparation embodiment 13 described synthetic operations, begin by 6-(1-benzyl-tetramethyleneimine-3-base oxygen base)-2-methoxyl group-pyridin-3-yl amine and 4-trifluoromethoxy-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：434.35[M+H] +
1H-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)。
< > Embodiment 15 <>
< > 4-(3-fluoro-propyl group)-N-[2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl benzene <> < > Sulphonamide <>
With 2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine (200mg, pyridine 0.84mmol) (3ml) solution after 30 minutes, adds 4-(3-fluoro-propyl group)-benzene sulfonyl chloride (200mg, 0.84mmol) in stirring at room.Stirring at room 16 hours, decompression thereafter is evaporating solvent down with mixture.Residuum absorbs with toluene, then evaporating solvent.Repeat this operation once.With residuum through silica gel chromatography methylene chloride (100:0; 95:5; 0:100) as the eluent purifying, obtain title compound 20mg(5.4%).
MS(ESI)m/z：438.15[M+H] +
1H-NMR(CDCl 3)：δ[ppm]7.72(d，1H)，7.60(d，2H)，7.25(d，2H)，6.60(s，1H)，6.30(d，1H)，4.60-4.65(m，2H)，4.35-4.50(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)。
< > Embodiment 16 <>
< > 4-sec.-propyl-N-[2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl benzene sulfonyl <> < > Amine xHCl <>
According to being similar to preparation embodiment 15 described synthetic operations, begin by 2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine and 4-sec.-propyl-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：420.15[M+H] +
< > Embodiment 17 <>
< > 4-((R)-2-fluoro-1-methyl-ethyl)-N-[2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyrrole <> < > Pyridine-3-base benzsulfamide <>
According to being similar to preparation embodiment 15 described synthetic operations, begin by 2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine and 4-((R)-2-fluoro-1-methyl-ethyl)-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：438.15[M+H] +
1H-NMR(CDCl 3)：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)。
< > Embodiment 18 <>
< > N-[2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl, 2,2-three fluoro-1-<> < > Methyl-ethyl)-benzsulfamide <>
According to being similar to preparation embodiment 15 described synthetic operations, by 2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine and 4-(2,2,2-three fluoro-1-methyl-ethyl)-benzene sulfonyl chloride begins, and makes required product.
MS(ESI)m/z：474.25[M+H] +
1H-NMR(CDCl 3)：δ[ppm]7.70(d，1H)，7.65(d，2H)，7.35(d，2H)，6.35(d，1H)，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)。
< > Embodiment 19 <>
< > N-[2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl]-4-oxazole-5-base-benzene sulphur <> < > Acid amides <>
According to being similar to preparation embodiment 15 described synthetic operations, begin by 2-methoxyl group-6-(2-tetramethyleneimine-1-base-oxyethyl group)-pyridin-3-yl amine and-oxazoles-5-base-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：445.15[M+H] +
1H-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)。
< > Embodiment 20 <>
< > 4-sec.-propyl-N-[4-methoxyl group-2-(2-propyl group amino-oxyethyl group)-pyrimidine-5-base benzsulfamide <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-4-methoxyl group-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-sec.-propyl-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：409.15[M+H] +
1H-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)。
< > Embodiment 21 <>
< > N-[4-methoxyl group-2-(2-propyl group amino-oxyethyl group)-pyrimidine-5-base trifluoromethoxy-benzene sulphur <> < > Acid amides <>
According to being similar to preparation embodiment 1 described synthetic operation, begin by [2-(5-amino-4-methoxyl group-pyrimidine-2-yloxy)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-trifluoromethoxy-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：451.15[M+H] +
1H-NMR(MeOD)：δ[ppm]8.02(s，1H)，7.74(d，2H)，7.28(d，2H)，4.30-4.35(m，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)。
< > Embodiment 22 <>
< > N-[6-(2-dimethylamino-oxyethyl group)-pyridin-3-yl sec.-propyl-benzsulfamide x HCl <>
According to being similar to preparation embodiment 15 described synthetic operations, begin by 6-(2-dimethylamino-oxyethyl group)-pyridin-3-yl amine and 4-sec.-propyl-benzene sulfonyl chloride, make required product.
MS(ESI)m/z：364.15[M+H] +
< > Embodiment 23 <>
< > 4-sec.-propyl-N-[6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzsulfamide xHCl <>
According to being similar to preparation embodiment 1 described synthetic operation, [2-(5-amino-pyridine-2-base oxygen base)-ethyl propyl group-carboxylamine tertiary butyl ester and 4-sec.-propyl-benzene sulfonyl chloride begin, and make required product.
MS(ESI)m/z：378.15[M+H] +
< > Embodiment 24 <>
< > N-[6-(2-dipropyl amino-oxyethyl group)-pyridin-3-yl sec.-propyl-benzsulfamide xHCl <>
To 4-sec.-propyl-N-[6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzsulfamide (81mg), propionic aldehyde (13.71mg) and acetate (0.02ml) in the solution in methylene dichloride (5ml); Add triacetyl oxygen base (trisacetoxy) sodium borohydride (68.22mg, 0.32mmol).With mixture stirring at room 1 hour.Behind the vapourisation under reduced pressure solvent, residuum is dissolved in 1NNaOH, with Anaesthetie Ether extraction 3 times.With the organic layer after merging through MgSO < > 4 <> Drying is filtered, and the vapourisation under reduced pressure solvent.0 ℃ in the diethyl ether solution of residuum, add the HCl Anaesthetie Ether.With the solid filtering that forms, dry in vacuum drying oven, obtain title compound 66mg(67.4%).
MS(ESI)m/z：420.25[M+H] +
1H-NMR(DMSO)：δ[ppm]10.20(s br.，2H)，7.85(s，1H)，7.65(d，2H)，7.50(d，1H)，7.45(d，2H)，6.80(d，1H)，4.50-4.57(m，2H)，3.40-3.50(m，2H)，3.00-3.10(m，4H)，2.90-3.00(m，1H)，1.60-1.70(m，4H)，1.20(d，6H)，0.90(t，6H)。
According to being similar to preparation embodiment 1 described synthetic operation, make following examples.
< > Embodiment 25 <>
< > 4-sec.-propyl-N-[2-methoxyl group-6-((R)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl benzene <> < > Sulphonamide xHCl <>
MS(ESI)m/z：392.1[M+H] +
1H-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)，2.97-2.99(m，1H)，2.05-2.15(m，1H)，1.85-2.05(m，2H)，1.68-1.70(m，1H)，1.23(d，6H)。
< > Embodiment 26 <>
< > 4-(2-fluoro-oxyethyl group)-N-[2-methoxyl group-6-((R)-1-tetramethyleneimine-2-ylmethoxy)-pyridine-3-<> < > Base benzsulfamide xHCl <>
MS(ESI)m/z：426.1[M+H] +
1H-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，1H)，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)。
< > Embodiment 27 <>
< > N-[2-methoxyl group-6-((R)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl]-4-oxazole-5-base-<> < > Benzsulfamide xHCl <>
MS(ESI)m/z：431.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.82-9.92(m，1H)，9.63(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)。
< > Embodiment 28 <>
< > 4-sec.-propyl-N-[2-methoxyl group-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
MS(ESI)m/z：392.1[M+H] +
1H-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)，2.97-2.99(m，1H)，2.05-2.15(m，1H)，1.85-2.05(m，2H)，1.68-1.70(m，1H)，1.23(d，6H)。
< > Embodiment 29 <>
< > 4-sec.-propyl-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzsulfamide x <> < > HCl <>
MS(ESI)m/z：392.1[M+H] +
1H-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(d，6H)，1.07(t，3H)。
< > Embodiment 30 <>
< > N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl trifluoromethoxy-benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：434.1[M+H] +
1H-NMR(MeOD)：δ[ppm]7.81(d，2H)，7.46(d，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)。
< > Embodiment 31 <>
< > 4-difluoro-methoxy-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：416.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.85(s，1H)，9.33(bs，2H)，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)，1.63-1.72(m，2H)，0.90(t，3H)。
< > Embodiment 32 <>
< > 4-(2,2-two fluoro-oxyethyl group)-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl <> < > Benzsulfamide xHCl <>
MS(ESI)m/z：430.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.66(s，1H)，9.34(bs，2H)，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)。
< > Embodiment 33 <>
< > 4-(2-fluoro-oxyethyl group)-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
MS(ESI)m/z：412.1[M+H] +
1H-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)。
< > Embodiment 34 <>
< > 4-((R)-2-fluoro-1-methyl-ethyl)-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridine-3-<> < > Base benzsulfamide xHCl <>
MS(ESI)m/z：410.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.74(s，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)。
< > Embodiment 35 <>
< > 4-((S)-2-fluoro-1-methyl-ethyl)-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridine-3-<> < > Base benzsulfamide xHCl <>
MS(ESI)m/z：410.1[M+H] +
1H-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(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)。
< > Embodiment 36 <>
< > N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl]-4-oxazole-5-base-benzsulfamide <> < > XHCl <>
MS(ESI)m/z：417.1[M+H] +
1H-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)。
< > Embodiment 37 <>
< > N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl]-4-oxazole-4-base-benzsulfamide <> < > XHCl <>
MS(ESI)m/z：417.1[M+H] +
1H-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)。
< > Embodiment 38 <>
< > N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl]-4-oxazole-5-base-benzene <> < > Sulphonamide xHCl <>
MS(ESI)m/z：379.1[M+H] +
1H-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)。
< > Embodiment 39 <>
< > 4-(2,2-two fluoro-oxyethyl group)-N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridine-3-<> < > Base benzsulfamide xHCl <>
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)。
< > Embodiment 40 <>
< > 4-(2-fluoro-oxyethyl group)-N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl <> < > Benzsulfamide xHCl <>
MS(ESI)m/z：410.1[M+H] +
1H-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，1H)，4.71-4.85(m，2H)，4.30-4.50(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)。
< > Embodiment 41 <>
< > N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl trifluoromethoxy-benzene <> < > Sulphonamide xHCl <>
MS(ESI)m/z：432.1[M+H] +
1H-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，1H)，4.31-4.47(m，2H)，3.85-3.95(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)。
< > Embodiment 42 <>
< > 4-((R)-2-fluoro-1-methyl-ethyl-N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyrrole <> < > Pyridine-3-base benzsulfamide 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(d，1H)，6.65(d，1H)，4.48-4.62(m，2H)，4.30-4.47(m，2H)，3.85-3.95(m，1H)，3.20-3.30(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)。
< > Embodiment 43 <>
< > 4-sec.-propyl-N-[2-methyl-6-((S)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：390.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.55-9.65(m，2H)，8.93-9.02(m，1H)，7.57(d，2H)，7.45(d，2H)，7.28(d，1H)，6.65(d，1H)，4.30-4.45(m，4H)，3.85-3.95(m，1H)，3.15-3.25(m，2H)，2.95-3.05(m，1H)，2.08-2.15(m，1H)，2.04(s，3H)，1.85-2.00(m，2H)，1.70-1.80(m，1H)，1.24(d，3H)。
< > Embodiment 44 <>
< > N-[2-methyl-6-((R)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl]-4-oxazole-5-base-benzene <> < > Sulphonamide xHCl <>
MS(ESI)m/z：379.1[M+H] +
1H-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，1H)，6.65(d，1H)，4.26-4.47(m，2H)，3.85-3.94(m，1H)，3.20-3.25(m，2H)，2.07-2.15(m，4H)，1.90-2.10(m，2H)，1.70-1.80(m，1H)。
< > Embodiment 45 <>
< > 4-sec.-propyl-N-[2-methyl-6-((R)-1-tetramethyleneimine-2-ylmethoxy)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
MS(ESI)m/z：354.1[M+H] +
1H-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)，1.70-1.80(m，1H)，1.24(d，3H)。
According to being similar to preparation embodiment 12 described synthetic operations, make following examples.
< > Embodiment 46 <>
< > 4-((R)-2,2-two fluoro-1-methyl-ethyl-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyrrole <> < > Pyridine-3-base benzsulfamide xHCl <>
MS(ESI)m/z：444.1[M+H] +
1H-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，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)。
< > Embodiment 47 <>
< > 4-((S)-2,2-two fluoro-1-methyl-ethyl)-N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-<> < > Pyridin-3-yl benzsulfamide xHCl <>
MS(ESI)m/z：444.1[M+H] +
1H-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，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)。
< > Embodiment 48 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl]-4-oxazole-4-base-benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：433.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.58(s，1H)，9.25(bs，2H)，8.81(s，1H)，8.54(s，1H)，7.96(d，2H)，7.71(d，2H)，7.49(d，1H)，6.40(d，1H)，6.10-6.34(m，1H)，4.48-4.51(m，2H)，3.52(s，3H)，3.25-3.28(m，2H)，2.85-2.90(m，2H)，1.63-1.71(m，2H)，0.90(t，3H)。
< > Embodiment 49 <>
< > N-[2-methoxyl group-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl pyrazol-1-yl-benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：432.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.59(s，1H)，8.94(bs，2H)，8.61(d，1H)，8.01(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，2H)，1.56-1.68(m，2H)，0.89(t，3H)。
< > Embodiment 50 <>
< > 4-(3-fluoro-propyl group)-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：410.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.72(s，1H)，9.36(bs，2H)，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，2H)，1.62-1.71(m，2H)，0.89(t，3H)。
< > Embodiment 51 <>
< > N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl)-2,2,2-three fluoro-1-first <> < > Base-ethyl-benzsulfamide xHCl <>
MS(ESI)m/z：446.1[M+H] +
1H-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)。
< > Embodiment 52 <>
< > 4-((R)-2,2-two fluoro-1-methyl-ethyl-N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridine <> < >-3-base benzsulfamide xHCl <>
MS(ESI)m/z：428.1[M+H] +
1H-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)。
< > Embodiment 53 <>
< > N-[2-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl, 2,2-three fluoro-oxyethyl group)-<> < > Benzsulfamide xHCl <>
MS(ESI)m/z：412.1[M+H] +
1H-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)。
< > Embodiment 54 <>
< > 4-((R)-2,2-two fluoro-1-methyl-ethyl)-N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyrrole <> < > Pyridine-3-base benzsulfamide xHCl <>
MS(ESI)m/z：428.1[M+H] +
1H-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)。
< > Embodiment 55 <>
< > N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl]-4-oxazole-4-base benzsulfamide <> < > XHCl <>
MS(ESI)m/z：381.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.73(s，1H)，8.83(s，1H)，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(m，2H)，2.01(s，3H)，1.60-1.68(m，2H)，0.93(t，3H)。
< > Embodiment 56 <>
< > 4-(2,2-two fluoro-oxyethyl group)-N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl <> < > Benzsulfamide xHCl <>
MS(ESI)m/z：394.1[M+H] +
1H-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)。
< > Embodiment 57 <>
< > 4-((R)-2-fluoro-1-methyl-ethyl)-N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyridine-3-<> < > Base benzsulfamide xHCl <>
MS(ESI)m/z：410.1[M+H] +
1H-NMR(DMSO)：δ[ppm]9.76(s，1H)，9.32(bs，2H)，7.60-7.62(m，3H)，7.50(d，2H)，6.68(s，1H)，4.45-4.59(m，4H)，3.20-3.30(m，3H)，2.84-2.91(m，2H)，1.92(s，3H)，1.63-1.71(m，2H)，1.23(d，3H)，0.89(t，3H)。
< > Embodiment 58 <>
< > N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl trifluoromethoxy-benzene sulfonyl <> < > Amine xHCl <>
MS(ESI)m/z：434.1[M+H] +
1H-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(m，2H)，0.91(t，3H)。
< > Embodiment 59 <>
< > 4-sec.-propyl-N-[4-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzsulfamide x <> < > HCl <>
MS(ESI)m/z：392.1[M+H] +
1H-NMR(MeOD)：δ[ppm]7.73(s，1H)，7.63(d，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)。
< > Embodiment 60 <>
< > 4-(2-fluoro-oxyethyl group)-N-[5-methyl-6-(2-propyl group amino-oxyethyl group)-pyridin-3-yl benzene sulphur <> < > Acid amides xHCl <>
MS(ESI)m/z：376.1[M+H] +
1H-NMR(DMSO)：δ[ppm]10.10(s，1H)，9.30(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)，4.30-4.39(m，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(t，3H)。
< > Embodiment 61 <>
< > 4-sec.-propyl-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl) oxygen base] pyridine-3-} benzsulfamide <> < > (2E)-but-2-ene diacid salt (butenedioate) <>
61.12-pyridine methyl-3-nitro-6-(tetramethyleneimine-3-base oxygen base)
With 6-methyl-5-nitro pyridine-2-phenol (pyridinol) (5g) be dissolved in tetrahydrofuran (THF), add DL-3-pyrrolidinol (pyrrolidinol)(2.83g) and triphenylphosphine (12.76g).Be added dropwise in 15 minutes and be dissolved in tetrahydrofuran (THF) (15mL) (E)-diazene-1,2-dicarboxylic acid di-t-butyl ester (11.21g).With reaction mixture stirring at room 50 hours.Concentrate this reaction mixture in a vacuum.The residuum that keeps is suspended in the methylene dichloride, drips trifluoroacetic acid (7.55mL).With reaction mixture stirring at room 12 hours.Concentrate this reaction mixture in a vacuum, and then be dissolved in the methylene dichloride, for several times with the 1N hcl as extraction agent.Water extract after merging is handled to pH10 with 1N NaOH, is used ethyl acetate (3x then) extraction.With the ethyl acetate extract after merging water and brine wash in succession, dry (sodium sulfate).After concentrating in a vacuum, raw product is through purified by flash chromatography (silica gel, methylene dichloride, 1-10% methyl alcohol gradient).Productive rate :1.5g(18.6%, light yellow oil).
61.2.2-oxygen base methyl-3-nitro-6-[(1-propionyl tetramethyleneimine-3-yl)] pyridine
With 2-methyl-3-nitro-6-(tetramethyleneimine-3-base oxygen base) pyridine (1.3g) be dissolved in methylene dichloride (20ml), add triethylamine (1.57ml).Solution is cooled to 0 ℃, is added dropwise to the propionyl chloride (574mg that is dissolved in methylene dichloride (5ml) in 5 minutes) solution.Allow reaction mixture return to room temperature, restir 5 minutes.Add water (10ml).Stir after 3 minutes, separate layer mutually, the water layer dichloromethane extraction.With the organic layer dry (sodium sulfate) after merging, and concentrate in a vacuum.Raw product is through purified by flash chromatography (silica gel, methylene chloride=98/2).Productive rate :950mg(64.9%, light yellow oil).
61.32-oxygen base methyl-6-[(1-propionyl tetramethyleneimine-3-yl)] pyridine-3-amine
With 2-methyl-3-nitro-6-[(1-propionyl tetramethyleneimine-3-yl) the oxygen base] pyridine (940mg) be dissolved in methyl alcohol (50mL) and hydrogenation (H-cube from ThalesNano, 10%Pd/C, 600C, 50bar, 1mL/min).Remove methyl alcohol in a vacuum.Productive rate :800mg(95%, water white oil).
61.44-oxygen base sec.-propyl-N-{2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl)] pyridin-3-yl }-benzsulfamide
With 2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl) the oxygen base] pyridine-3-amine (340mg) be dissolved in pyridine (3.3mL), slowly add 4-isopropyl benzene SULPHURYL CHLORIDE (358mg in the stirring)., after 19 hours reaction mixture is diluted with methylene dichloride in stirring at room, add the 2M NaOH aqueous solution.After 1 hour, separate layer mutually in stirring at room.With organic phase dry (sodium sulfate), concentrate, raw product is through purified by flash chromatography (silica gel, methylene dichloride, 0.5～5% methyl alcohol gradient).Productive rate :460mg(78%, light yellow oil).
61.54-oxygen base sec.-propyl-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl)] pyridin-3-yl }-benzsulfamide (2E)-but-2-ene diacid salt
With lithium aluminum hydride (88mg) be suspended in the tetrahydrofuran (THF) (1mL), be added dropwise to the 4-sec.-propyl-N-{2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl that is dissolved in tetrahydrofuran (THF) (1ml) in room temperature in 5 minutes) the oxygen base] pyridin-3-yl } benzene-sulphonamide (250mg).After stirring another 30 minutes, reaction with the tetrahydrofuran solution cancellation that contains 1% water, is concentrated.Residuum absorbs with methylene dichloride, uses water washing, with organic phase dry (sodium sulfate), concentrates in a vacuum.Raw product is through purified by flash chromatography (silica gel, methylene chloride=97/3).With product (70mg) be dissolved in the methyl alcohol, add (2E)-butylene-2-diacid (19mg).After 1 hour, remove methyl alcohol 40 ℃ of stirrings in a vacuum.Productive rate :89mg(26%, colorless solid).
MS(ESI)m/z：418.1[M+H] +
< > Embodiment 62 <>
< > 4-(2-fluorine oxyethyl group)-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl) oxygen base] pyridine-3-} benzene <> < > Sulphonamide (2E)-but-2-ene diacid salt <>
Be similar to embodiment 61; By 2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl) the oxygen base] pyridine-3-amine and 4-(2-fluorine oxyethyl group) benzene sulfonyl chloride, make 4-(2-fluorine oxyethyl group)-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl) the oxygen base] pyridin-3-yl }-benzsulfamide (2E)-but-2-ene diacid salt
MS(ESI)m/z：438.1[M+H] +
< > Embodiment 63 <>
< > 4-(2,2-difluoroethoxy)-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl) the oxygen base] pyridine-3-} <> < > Benzsulfamide (2E)-but-2-ene diacid salt <>
Be similar to embodiment 61; By 2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl) the oxygen base] pyridine-3-amine and 4-(2; The 2-difluoroethoxy) benzene sulfonyl chloride; Make 4-(2,2-difluoroethoxy)-N-{2-methyl-6-[(1-propyl pyrrole alkane-3-yl) the oxygen base] pyridin-3-yl }-benzsulfamide (2E)-but-2-ene diacid salt.
MS(ESI)m/z：456.1[M+H] +
< > Embodiment 64 <>
< > 4-[(1S)-2,2-two fluoro-1-methylethyl methyl-6-[(1-propyl pyrrole alkane-3-yls) oxygen <> < > Base] pyridine-3-} benzsulfamide (2E)-but-2-ene diacid salt <>
Be similar to embodiment 61; By 2-methyl-6-[(1-propionyl tetramethyleneimine-3-yl) the oxygen base] pyridine-3-amine and 4-[(1S)-2; 2-two fluoro-1-methylethyls] benzene sulfonyl chloride; Make 4-[(1S)-2,2-two fluoro-1-methylethyl methyl-6-[(1-propyl pyrrole alkane-3-base)-oxygen base] pyridin-3-yl } benzsulfamide (2E)-but-2-ene diacid salt.
MS(ESI)m/z：454.1[M+H] +
< > III. the embodiment of galenic form of medication <>
A) tablet
On tabletting machine, suppress the tablet of following composition according to usual way:
40mg embodiment 8 materials
The 20mg W-Gum
13.5mg gelatin
The 45mg lactose
2.25mg Aerosil
Figure G2007800134447D0135124032QIETU
(chemically pure silicate , the subtle submicroscopic dispersion)
6.75mg yam starch (6% paste)
B) coated tablet
20mg embodiment 8 materials
The 60mg tablet core composition
70mg saccharification composition
Tablet core composition is made up of 9 parts of W-Gums, 3 parts of lactose and 1 part of 60:40 V-Pyrol RC/vinyl acetate copolymer.The saccharification composition is made up of 5 portions of sucrose, 2 parts of W-Gums, 2 parts of lime carbonate and 1 part of talcum.Coated tablet for preparation by this way provides anti-gastric juice dressing subsequently.
< > IV. biological study <>
Receptors bind research:
The test material was dissolved in methanol / Chremophor
Figure 2007800134447100002G2007800134447D0135124032QIETU
( BASF-AG) or in dimethyl sulfoxide and then diluted with water to the desired concentration.
Dopamine D < > 3 <> Acceptor:
Test mixing thing (0.250ml) comprising: from～10 < > 6 <> The individual people's dopamine D that possesses stably express < > 3 <> Film, the 0.1nM[of the HEK-293 cell of acceptor < > 125 <> 1 iodine Sulpiride and cultivation damping fluid (the total combination) perhaps comprise confession examination material (inhibition curve) or 1 μ M spiperone (non-specific binding) in addition.Every kind of test mixing thing repeats three times.
Cultivate damping fluid and contain 50mM tris, 120mM NaCl, 5mM KCl, 2mM CaCl < > 2 <> , 2mM MgCl < > 2 <> With 0.1% bovine serum albumin, 10 μ M quinolones and 0.1% xitix (prepared fresh every day).Regulate damping fluid to pH7.4 with HCl.
Dopamine D < > 2L <> Acceptor:
Test mixing thing (1ml) comprising: from～10 < > 6 <> The individual people's dopamine D that possesses stably express < > 2L <> The film of the HEK-293 cell of acceptor (long shaped body), 0.01nM[ < > 125 <> 1 iodine spiperone and cultivation damping fluid (the total combination) perhaps comprise confession examination material (inhibition curve) or 1 μ M haloperidol (non-specific binding) in addition.Every kind of test mixing thing repeats three times.
Cultivate damping fluid and contain 50mM tris, 120mM NaCl, 5mM KCl, 2Mm CaCl < > 2 <> , 2mM MgCl < > 2 <> With 0.1% bovine serum albumin.Regulate damping fluid to pH7.4 with HCl.
Measure and analyze:
After hatching 60 minutes under 25 ℃, the application cell collector passes through WhatmanGF/B glass fibre filter filter test mixture under vacuum.Use the filter transfer system filter is transferred to the flicker bottle.Add 4ml Ultima
Figure G2007800134447D0136124149QIETU
(Packard) after The sample was shaken for 1 hour and then at Beta-Counter (Packard, Tricarb2000 or 2200CA) radioactivity counted.Application standard quenching series is converted into dpm with the program that belongs to this instrument with the cpm value.
" the statistical analysis system (SAS) that program is similar by the iteration non-linear regression analysis, analyzes and suppresses curve for application and the said "LIGAND of Munson and Rodbard.
The result of receptors bind research is respectively with the receptors bind constant K < > i <> (D < > 2 <> ) and K < > i <> (D < > 3 <> ) expression, as said before this paper, and in table 3, provide.
In these tests, compound exhibits according to the present invention is extraordinary to D < >3 <>The affinity of acceptor (<10nM, often<5nM) with to D < >3 <>The selective binding of acceptor.
Table 1 provides the result who combines test.
Table 1:
Embodiment K i(D 3) * K i(D 2) */K i(D 3) *
1 ++++ ++
2 +++ +
3 +++ ++
4 ++++ ++
5 +++ ++
6 +++ ++
7 ++++ ++++
8 +++ ++++
9 +++ ++++
10 +++ ++++
11 ++++ ++++
13 + +
15 ++ +
16 +++ +
17 +++ ++
18 +++ +
19 ++ +
20 +++ +
21 + ++
22 + n.d.
23 ++ +
24 ++ ++
27 +++ +++
29 ++++ ++++
34 +++ ++++
36 ++ ++++
43 +++ +++
57 ++ ++
61 +++ +
< > * <> According to the receptors bind constant that said mensuration obtained before this paper
Tabulation:
K i(D 3) *
+ 50～150nM
++ 10～50nM
+++ 1～10nM
++++ <;1nM
K i(D 2) */K i(D 3) *
+ 10～50
++ 50～100
+++ 100～150
++++ >;150

Claims (23)

1. formula I Aryloxyethylamine compounds
Figure FSB00000704980700011
Wherein
Ar is a phenyl, and wherein Ar carries 1 R < > a <> Group;
R < >a <>Be selected from C < >1 <>-C < >6 <>-alkyl, fluoro C < >1 <>-C < >6 <>-alkyl, C < >1 <>-C < >6 <>-alkoxyl group, fluoro C < >1 <>-C < >6 <>-alkoxyl group and 2-, 4-or 5-
Figure FSB00000704980700012
The azoles base,
X is N or CH;
R < > 1 <> Be H or C < > 1 <>-C < > 4 <>-alkyl;
R < > 1a <> Be H or C < > 1 <>-C < > 4 <>-alkyl; Or
R < > 1 <> And R < > 1a <> Be that wherein r is 4 (CR together < > 6 <> R < > 7 <> ) < > r <>
R < > 2 <> And R < > 2a <> Independently of one another is H; Or
R < > 1a <> And R < > 2a <> Be that wherein n is 3 (CR together < > 6 <> R < > 7 <> ) < > n <> ,
R < > 3 <> Be H;
R < > 6 <> , R < > 7 <> Independently of one another and they occur independently of one another, be selected from H;
R < > 8 <> , R < > 8a <> Independently of one another is H; Or
R < > 1a <> And R < > 8a <> Be that wherein s is 2 (CR together < > 6 <> R < > 7 <> ) < > S <> With
R < > 9 <> Be H, C < > 1 <>-C < > 4 <>-alkyl or C < > 1 <>-C < > 4 <>-alkoxyl group;
And the acid salt that can tolerate on the physiology of these compounds.
2. compound as claimed in claim 1, wherein Ar carries a formula R < > a <> ' shown in radicals R < > a <>
Figure FSB00000704980700013
Wherein
Y is CH or CF,
R < > A1 <> And R < > A2 <> Be independently from each other C < > 1 <>-C < > 2 <>-alkyl, fluoro C < > 1 <>-C < > 2 <>-alkyl, and radicals R < > A1 <> Or R < > A2 <> In one also can be hydrogen or fluorine.
3. compound as claimed in claim 2, wherein R < > a <> ' be selected from sec.-propyl)-1-fluoro ethyl)-1-fluoro ethyl; The 2-fluoro ethyl; 1; 1-two fluoro ethyls; 2; 2-two fluoro ethyl; 2; 2-trifluoroethyl)-1-fluoropropyl)-1-fluoropropyl; The 2-fluoropropyl; The 3-fluoropropyl; 1; 1-two fluoropropyls; 2; 2-two fluoropropyl, 3-two fluoropropyl, 3; 3-trifluoro propyl)-2-fluoro-1-methylethyl)-2-fluoro-1-methylethyl)-2; 2-two fluoro-1-methylethyl)-2,2-two fluoro-1-methylethyl)-1,2-two fluoro-1-methylethyl)-1; 2-two fluoro-1-methylethyl)-2,2-three fluoro-1-methylethyl)-2,2; 2-three fluoro-1-methylethyls; 2-fluorine-1-(methyl fluoride) ethyl and 1-(difluoromethyl)-2,2-two fluoro ethyls.
4. like claim 2 or 3 described compound, wherein radicals R < > a <> ' carry 1,2,3 or 4 fluorine atom.
5. the described compound of claim 1, wherein Ar carries 1 radicals R that is selected from following groups < > a <> :(CH < > 2 <> ) < > V <> CF < > 3 <> , (CH < > 2 <> ) < > V <> CHF < > 2 <> , (CH < > 2 <> ) < > V <> CH < > 2 <> F, O(CH < > 2 <> ) < > V <> CF < > 3 <> , O(CH < > 2 <> ) < > V <> CHF < > 2 <> And O(CH < > 2 <> ) < > V <> CH < > 2 <> F, wherein v is 0,1,2 or 3.
6. compound as claimed in claim 1, wherein Ar carries 1 R < >a <>, said R < >a <>Be 2-, 4-or 5-
Figure FSB00000704980700021
The azoles base.
7. compound as claimed in claim 1 or 2, wherein Ar carries a R on 4 of benzyl ring < > a <> Group.
8. compound as claimed in claim 1 or 2, wherein X is CH.
9. compound as claimed in claim 1 or 2, wherein R < > 9 <> Be hydrogen, methoxyl group or methyl.
10. compound as claimed in claim 1 or 2, wherein R < > 9 <> Be positioned at relative 1-position theheterocyclic nitrogen atom and 3-position-NR < > 3 <>-SO < > 2 <> The 2-position of-Ar group.
11. compound as claimed in claim 1 or 2, wherein R < > 1 <> Be H, methyl or n-propyl.
12. compound as claimed in claim 1 or 2, wherein R < > 1a <> Be hydrogen or C < > 1 <>-C < > 4 <>-alkyl.
13. compound as claimed in claim 1 or 2, wherein R < > 2a <> Be hydrogen.
14. compound as claimed in claim 1 or 2, wherein R < > 2 <> Be hydrogen.
15. compound as claimed in claim 1 or 2, wherein R < > 8a <> Be hydrogen.
16. compound as claimed in claim 1 or 2, wherein R < > 8 <> Be hydrogen.
17. compound as claimed in claim 1 or 2, wherein R < > 2a <> And R < > 1a <> Form n wherein together and be 3 alkylidene group (CH < > 2 <> ) < > n <>
18. compound as claimed in claim 1 or 2, wherein R < > 8a <> And R < > 1a <> Form s wherein together and be 2 alkylidene group (CH < > 2 <> ) < > S <>
19. compound as claimed in claim 1 or 2, wherein R < > 1 <> And R < > 1a <> Form r wherein together and be 4 alkylidene group (CH < > 2 <> ) < > r <>
20. compound as claimed in claim 1 or 2, wherein R < > 1a <> , R < > 2 <> , R < > 2a <> , R < > 8 <> And R < > 8a <> The H that respectively does for oneself, R < > 1 <> Be propyl group, R < > 9 <> Be methoxyl group, and Ar is the definition in claim 1 or 2.
21. compound as claimed in claim 1 or 2, wherein R < > 1a <> , R < > 2 <> , R < > 2a <> , R < > 8 <> And R < > 8a <> Be H, R < > 1 <> Be propyl group, R < > 9 <> Be methyl, and Ar is the definition in claim 1 or 2.
22. pharmaceutical composition, it comprises acceptable auxiliary substance on any one described formula I compound of at least a aforementioned claim or its pharmacy acceptable salt and the optional physiology.
23. pharmaceutical composition as claimed in claim 22, wherein said auxiliary substance is a carrier.
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