发明名称 C-17 and C-3 modified triterpenoids with HIV maturation inhibitory activity
摘要 Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, C-17 and C-3 modified triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II and III:; These compounds are useful for the treatment of HIV and AIDS.
申请公布号 US8846647(B2) 申请公布日期 2014.09.30
申请号 US201213359727 申请日期 2012.01.27
申请人 Bristol-Myers Squibb Company 发明人 Regueiro-Ren Alicia;Liu Zheng;Swidorski Jacob;Sin Ny;Venables Brian Lee;Sit Sing-Yuen;Chen Yan;Chen Jie;Meanwell Nicholas A.
分类号 A61K31/56;A61K31/58;C07J53/00;C07J63/00 主分类号 A61K31/56
代理机构 代理人 Levis John F.
主权项 1. A compound which is selected from the group consisting of: a compound of formula I a compound of formula II and a compound of formula III wherein R1 is isopropenyl or isopropyl; J and E are independently —H or —CH3, and E is absent when the double bond is present; X is a phenyl or heteroaryl ring substituted with A, wherein A is at least one member selected from the group of —H, -halo, -hydroxyl, —C1-6 alkyl, —C1-6 alkoxy, and —COOR2; R2 is —H, —C1-6 alkyl, -alkylsubstituted C1-6 alkyl or -arylsubstituted C1-6 alkyl; Y is selected from the group of —COOR2, —C(O)NR2SO2R3, —C(O)NHSO2NR2R2, —NR2SO2R2, —SO2NR2R2, —C3-6 cycloalkyl-COOR2, —C2-6 alkenyl-COOR2, —C2-6 alkynyl-COOR2, —C1-6 alkyl-COOR2, —NHC(O)(CH2)n—COOR2, —SO2NR2C(O)R2, -tetrazole, and —CONHOH, wherein n=1-6; R3 is —C1-6 alkyl or -alkylsubstituted C1-6 alkyl; R4 is selected from the group of —H, —C1-6 alkyl, —C1-6 alkyl-C(OR3)2—C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-C3-6 cycloalkyl, —C1-6 alkyl-Q1, —C1-6 alkyl-C3-6 cycloalkyl-Q1, aryl, heteroaryl, substituted heteroaryl, —COR6, —COCOR6, —SO2R7, —SO2NR2R2, wherein Q1 is selected from the group of heteroaryl, substituted heteroaryl, halogen, —CF3, —OR2, —COOR2, —NR8R9, —CONR10R11 and —SO2R7; R5 is selected from the group of —H, —C1-6 alkyl, —C3-6 cycloalkyl, —C1-6 alkylsubstituted alkyl, —C1-6 alkyl-NR8R9, —COR10, —COR6, —COCOR6, —SO2R7 and —SO2NR2R2; with the proviso that only one of R4 or R5 can be selected from the group of —COR6, —COCOR6, —SO2R7 and —SO2NR2R2; or R4 and R5 are taken together with the adjacent N to form R6 is selected from the group of —H, —C1-6 alkyl, —C1-6 alkyl-substitutedalkyl, —C3-6 cycloalkyl, —C3-6 substitutedcycloalkyl-Q2, —C1-6 alkyl-Q2, —C1-6 alkyl-substitutedalkyl-Q2, —C3-6 cycloalkyl-Q2, aryl-Q2, —NR13R14, and —OR15; wherein Q2 is selected from the group of aryl, heteroaryl, substituted heteroaryl, —OR2, —COOR2, —NR8R9, SO2R7, —CONHSO2R3, and —CONHSO2NR2R2; R7 is selected from the group of —C1-6 alkyl, —C1-6 substituted alkyl, —C3-6 cycloalkyl, aryl, and heteroaryl; R8 and R9 are independently selected from the group of —H, —C1-6 alkyl, —C1-6 substituted alkyl, aryl, heteroaryl, substituted aryl, substituted heteroaryl, —C1-6 alkyl-Q2, and —COOR3, or R8 and R9 are independently selected from the group of or R8 and R9 are taken together with the adjacent N to form a cycle selected from the group of: with the proviso that only one of R8 or R9 is COOR3; R10 and R11 are independently selected from the group of —H, —C1-6 alkyl, —C1-6 substituted alkyl and —C3-6 cycloalkyl, or R10 and R11 are taken together with the adjacent N to form the cycle R12 is selected from the group of —C1-6 alkyl, —NR2R2, —C1-6 alkyl-OH, —C1-6 alkyl, —C1-6 substituted alkyl, —C3-6 cycloalkyl, —COR7, —COONR22R23, —SOR7, and —SONR24R25; R13 and R14 are independently selected from the group of —H, —C1-6 alkyl, —C3-6 cycloalkyl, substituted alkyl, —C1-6 alkyl-Q3, —C1-6 alkyl-C3-6 cycloalkyl-Q3, C1-6 substituted alkyl-Q3 and or R13 and R14 are taken together with the adjacent N to form a cycle selected from the group of: Q3 is selected from the group of heteroaryl, substituted heteroaryl, —NR20R21, —CONR2R2, —COOR2, —OR2, and —SO2R3; R15 is selected from the group of —C1-6 alkyl, —C3-6 cycloalkyl, —C1-6 substituted alkyl, —C1-6 alkyl-Q3, —C1-6 alkyl-C3-6 cycloalkyl-Q3 and —C1-6 substituted alkyl-Q3; R16 is selected from the group of —H, —C1-6 alkyl, —NR2R2, and —COOR3; R17 is selected from the group of —H, —C1-6 alkyl, —COOR3, and aryl; R18 is selected from the group of —COOR2 and —C1-6 alkyl-COOR2; R19 is selected from the group of —H, —C1-6 alkyl, —C1-6 alkyl-Q4, —COR3, —COOR3, wherein Q4 is selected from the group of —NR2R2 and —OR2; R20 and R21 are independently selected from the group of —H, —C1-6 alkyl, —C1-6 substituted alkyl, —C1-6 substituted alkyl-OR2, and —COR3, or R20 and R21 are taken together with the adjacent N to form a cycle selected from the group of with the proviso that only one of R20 or R21 is —COR3; R22 and R23 are independently selected from the group of H, —C1-6 alkyl, —C1-6 substituted alkyl, and —C1-6 cycloalkyl, or R22 and R23 are taken together with the adjacent N to form a cycle selected from the group of R24 and R25 are independently from the group of H, —C1-6 alkyl, —C1-6 substituted alkyl, —C1-6 alkyl-Q5, —C1-6 cycloalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, and Q5 is selected from the group of halogen and SO2R3; and pharmaceutically acceptable salts thereof.
地址 Princeton NJ US