Substituted tetrahydroisoquinoline compounds as factor XIa inhibitors

摘要

The present invention provides compounds of Formula (I):;
or stereoisomers, pharmaceutically acceptable salts thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of factor XIa and/or plasma kallikrein which may be used as medicaments.

主权项

1. A compound selected from the formulae:RR′R″HPiperazineFPiperazineFPiperazineFPiperazineFPiperazineFPiperazineFPiperazineFPiperazine6-indazole-1-CBzFBoc-piperazine6-indazole-1-tBocFPiperazine6-indazole,RR′2-F2-F4-F6-indazole4-F6-indazole4-F4-FRR′R″F-4-PhCOOHCH3H-4-PhNHCOOCH3CH3F-4-PhCNCH3H-4-PhCOOHH-4-PhCOOHCH3OOC—H-4-PhNHCOOCH3F-4-PhNHCOOCH3CH3OOC—F-4-PhFCH3OOC—F-4-PhCNCH3OOC—F6-indazoleCH3,R′COOEtCOOEtCOOH COOH,RR′R″tetrazole2-FCOOHtetrazole2-FCOOHtetrazole2-FCOOHtetrazole2-FCOOtBu—COMe2-FCOOH—COMe2-FCOOH—COMe2-FCOOHtetrazole4-FCOOHtetrazole4-FCOOHtetrazole2-FCOOEttetrazole2-FCOOEttetrazole2-F COOEt,RR′-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOtBu-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOtBu-4-PhCOOEt-4-PhCOOtBu-4-PhNHCOOCH3-4-PhCOOtBu4-PhCOOH4-PhCOOH4-PhCOOH-4-PhCOOEt4-PhCOOH,RCyclopropanamine2-(1H-imidazol-4-yl)ethanamineAnilineN-(4-aminophenyl)acetamideEthylN-(2-aminoethyl)acetamide3-aminopropanamidemethyl 2-aminoacetate3-methoxyanilineDimethylamineMethylamine,RR′-4-PhCOOH-4-Ph—F-4-PhCOOEt-4-PhCOOtBu4-PhCN-4-Ph—F-4-PhCOOH-4-PhCOOH-4-PhNHCOOCH3-4-Ph—F-4-PhCOOtBu-4-PhCOOH-4-Ph—COOEt-4-Ph—COOEt-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhNHCOOCH3-4-PhNHCOOCH3-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-Ph—Cl-4-PhCOOnBu-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOEt-4-Ph—Cl-4-Ph—Cl-4-PhCOOnBu-4-PhCOOnBu-4-PhCOOH-4-PhCOOH4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOiPr-4-PhCOOiBu-4-Ph—COOEt-4-Ph—COOEt-4-PhCOOEt-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOMe-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH -4-PhCOOH,RR′-4-PhCOOtBu-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOEt-4-PhCOOBzl-4-PhCOOCH2CON(CH3)2-4-PhCOOCH3-4-PhCOOH-4-PhCOOEt-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH,RR′—COOEt—COOEt—COOH—COOH—COOEt—COOEt,RR′—COOH—COOH—COOEt—COOEt—COOH—COOH—COOH—COOH—COOEt—COOH—COOH,RR′-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH,RR′R″-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOH-4-PhCOOEt-4-PhCOOH-4-PhCOOH, wherein R is selected from: wherein R is selected from:RR′4-PhCOOEt4-PhCOOH
,RR′4-PhCOOH4-PhCOOtBu4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH4-PhCOOH, andRR′