发明名称 C-3 cycloalkenyl 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-3 cycloalkenyl triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II, III and IV:; wherein X can be a C4-8 cycloalkyl, C4-8 cycloalkenyl, C4-9 spirocycloalkyl, C4-9 spirocycloalkenyl, C4-8 oxacycloalkyl, C4-8 dioxacycloalkyl, C6-8 oxacycloalkenyl, C6-8 dioxacycloalkenyl, C6-9 oxaspirocycloalkyl, or C6-9 oxaspirocycloalkenyl ring. These compounds are useful for the treatment of HIV and AIDS.
申请公布号 US8906889(B2) 申请公布日期 2014.12.09
申请号 US201313760726 申请日期 2013.02.06
申请人 Bristol-Myers Squibb Company 发明人 Swidorski Jacob;Meanwell Nicholas A.;Regueiro-Ren Alicia;Sit Sing-Yuen;Chen Jie;Chen Yan
分类号 A61K31/56;A61K31/58;C07J53/00;C07J63/00;A61K45/06 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 a compound of formula III and a compound of formula IV 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 selected from the group of C4-8 cycloalkyl, C4-8 cycloalkenyl, C4-9 spirocycloalkyl, C4-9 spirocycloalkenyl, C4-8 oxacycloalkyl, C4-8 dioxacycloalkyl, C6-8 oxacycloalkenyl, C6-8 dioxacycloalkenyl, C6 cyclodialkenyl, C6 oxacyclodialkenyl, C6-9 oxaspirocycloalkyl and C6-9 oxaspirocycloalkenyl ring, wherein X is substituted with A, wherein A is at least one member selected from the group of —H, -halo, -hydroxyl, —C1-6 alkyl, —C1-6 alkoxy, —C1-6 alkyl-Q, -alkylsubstituted C1-6 alkyl-Q, —CN, —CF2Q, —NR8R9, —COOR2 and —CONR2R2; X is also selected from the group of: wherein Q is selected from the group of aryl, heteroaryl, substituted heteroaryl, —OR2, —COOR3, —NR2R2, —SO2R7, —CONHSO2R3, and —CONHSO2NR2R2; 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, -alkylsubstituted C1-6 alkyl, —COOR2, CF2—COOR2, —NHC(O)(CH2)n—COOR2, —SO2NR2C(O)R2, _tetrazole, and —CONHOH, wherein n=1-6; W is absent, CH2 or CO; R3 is —C1-6 alkyl or -alkylsubstituted C1-6 alkyl; R4 is selected from the group of —H, —C1-6 alkyl, —C1-6alkyl-C(OR3)2—C3-6cycloalkyl, —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, with the proviso that R4 or R5 cannot be COR6 or COCOR6 when W is CO; 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, —C1-6alkyl-NR8R9, —COR10, —COR6, —COCOR6, —SO2R7 and —SO2NR2R2; with the proviso that only one of R4 or R5 is selected from the group of —COR6, —COCOR6, —SO2R7 and —SO2NR2R2; or when W is absent or is CH2, then R4 and R5 is 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, —CF3, 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, and R8 and R9 are also 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, —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, —C1-6 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
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