1-(3-AMINOPROPYL) SUBSTITUTED CYCLIC AMINE COMPOUNDS, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

摘要

Provided are 1-(3-aminopropyl) substituted cyclic amine compounds as represented by formula (I), pharmaceutically acceptable salts, enantiomers, diastereoisomers, racemates and mixtures thereof, and a method of synthesizing said 1-(3-aminopropyl) substituted cyclic amine compounds by using aromatic heterocyclic formaldehyde as raw material. Said compounds can be used as CCR 5 antagonist for the treatment of HIV infection.;

主权项

1. A compound of formula I, a pharmaceutically acceptable salt, enantiomer, diastereoisomer, racemate or mixture thereof, wherein, W is absent or —CH2CH2—; X is N or CR6; R1 is selected from a 5 to 7-membered heteroaryl unsubstituted or substituted with 1-3 substituents, wherein said heteroaryl contains 1 to 3 heteroatoms selected from oxygen, sulfur or nitrogen and each of said substituents is independently selected from a halogen, a C1-C4 straight or branched alkyl, a C1-C4 straight or branched haloalkyl, a C1-C4 straight or branched alkyloxy, a C1-C4 straight or branched chain haloalkoxy, —NR10R11, —C(═O)R12, a C1-C4 straight or branched alkanoyloxy, a cyano, a nitro and a hydroxy, or two adjacent substituents together with the attached carbon atom form a 5-7 membered ring; each of R10 and R11 is independently selected from a group consisting of H, a C1-C4 straight or branched alkyl and —C(═O)R13; R12 is selected from a group consisting of a C1-C4 straight or branched alkyl, a C1-C4 straight or branched alkyloxy, a hydroxyl, an amino (NH2) and a C1-C4 straight or branched alkylamino; R13 is selected from a group consisting of H and a C1-C4 straight or branched alkyl; R2 is selected from the following groups unsubstituted or substituted with 1-3 substituents: a C1-C6 straight or branched alkyl, a C3-C7 cycloalkyl, a 4 to 7-membered heterocyclic group, a C6-C12 aryl or a 5-7 membered heteroaryl; wherein, said substituent is selected from a group consisting of a halogen, a hydroxy, a C1-C4 straight or branched alkyl, a C1-C4 straight or branched haloalkyl, a C1-C4 straight or branched alkyloxy, a C1-C4 straight or branched alkyl carbonyl, a C1-C4 straight or branched haloalkoxy, a C1-C4 straight or branched alkylsulfonyl group, a C1-C4 straight or branched alkylsulfonylcarbamoyl, a tetrazolyl, a cyano, a nitro, an amino, a carboxy, a phenyl and a phenoxy; each of R3, R4 and R5 is independently selected from a group consisting of H, a C1-C6 straight or branched alkyl and a C3-C7 cycloalkyl; R6 is selected from a group consisting of H and a C1-C6 straight or branched alkyl; alternatively, R5 and R6 may bind together withto form R7 is selected from a group consisting of H, C(═O)R8, C(═O)OR8, C(═O)NR8R9, SO2R8 and the following groups substituted by 1-3 substituents: a C1-C6 straight or branched alkyl, a C3-C7 cycloalkyl, a 4 to 7-membered heterocyclic group, a benzyl, a C6-C12 aryl and a 5-7 membered heteroaryl; wherein said substituent is selected from a halogen, a hydroxy, a C1-C4 straight or branched alkyloxy, a C1-C4 straight or branched alkyl, a C1-C4 straight or branched haloalkyl, a C1-C4 straight or branched haloalkoxy, a cyano, a nitro, an amino and a carboxyl; each of R8 and R9 is independently selected from a group consisting of a hydrogen and the following groups unsubstituted or substituted with 1-3 substituents: a C1-C6 straight or branched alkyl, a C3-C7 cycloalkyl, a 4-7 membered heterocyclic group, a benzyl, a C6-C12 aryl and a 5-7 membered heteroaryl; wherein said substituent is selected from a group consisting of a halogen, a hydroxy, a C1-C4 straight or branched alkoxy, a C1-C4 straight or branched alkyl, a C1-C4 straight or branched haloalkyl, a C1-C4 straight or branched haloalkoxy, a cyano, a nitro, an amino, and a carboxyl.