发明名称 Partially saturated tricyclic compounds and methods of making and using same
摘要 The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
申请公布号 US9290472(B2) 申请公布日期 2016.03.22
申请号 US201214116023 申请日期 2012.05.07
申请人 Zafgen, Inc. 发明人 Cramp Susan Mary;Dyke Hazel Joan;Pallin Thomas David;Zahler Robert
分类号 C07D311/94;C07D453/02;C07D405/12;C07D491/048;C07D493/04 主分类号 C07D311/94
代理机构 Goodwin Procter LLP 代理人 Goodwin Procter LLP
主权项 1. A tricyclic compound represented by: wherein: the ring B2 is optionally substituted by one or more fluorine atoms on any of the available carbon atoms; B2 is fused to ring D2 such that the two atoms shared by B2 and D2 are both carbon; X2 is +—W2—C(RD5RD6)—*; wherein the + and * indicate the attachment points of X2 as indicated in Formula II; Y is a bond; wherein the * and # indicate the attachment points of Y as indicated in Formula II; W2 is O; A is phenyl; RB1 and RB2 are independently selected from the group consisting of H, F, OH, CN, C1-2alkoxy or C1-3alkyl; wherein C1-3alkyl and C1-2alkoxy are optionally substituted by a group selected from OH, C1-2alkoxy, CN or one or more fluorine atoms; RA1 is selected, independently for each occurrence, from the group consisting of hydrogen, hydroxyl, cyano, halogen, C1-4alkyl or C1-3alkoxy; wherein or C1-3alkoxy may be optionally substituted by one or more fluorines; n is 0, 1, or 2; RA2 is selected from the group consisting of hydrogen, RiRjN—, heterocyclyl, C1-6alkyl, C3-6alkenyl, C3-6cycloalkyl, C1-6alkoxy; wherein said heterocyclyl may optionally be substituted by one or more groups Rg; and wherein if said heterocyclyl contains a —NH moiety, that nitrogen may optionally be substituted by one or more groups Rh; and wherein said C1-6alkyl, C3-6alkenyl, C3-6cycloalkyl and C1-6alkoxy may optionally be substituted by one or more groups RP; RD5 and RD6 are each independently selected from the group consisting of hydrogen, fluorine, hydroxyl, cyano, C1-2alkyl or C1-2alkoxy; wherein the C1-2alkyl and C1-2alkoxy may optionally be substituted by a substituent or substituents selected from the group consisting of: one or more fluorine atoms, cyano, hydroxyl or N(RaRb); Ra and Rb are independently selected, for each occurrence, from the group consisting of hydrogen and C1-3alkyl; wherein C1-3alkyl may optionally be substituted by one or more substituents selected from fluorine, cyano, oxo and hydroxyl; or Ra and Rb, together with the nitrogen to which they are attached, may form a 4-6 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-6 membered heterocyclic ring may optionally be substituted by one or more substituents selected from the group consisting of fluorine, cyano, oxo or hydroxyl; Rg is independently selected for each occurrence from the group consisting of RP, hydrogen, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, C1-6alkyl-S(O)w—, (wherein w is 0, 1 or 2), C1-6alkylcarbonyl-N(Ra)— and C1-6alkoxycarbonyl-N(Ra)—; wherein C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkoxy may be optionally substituted by one or more substituents selected from RP; Rh is independently selected for each occurrence from the group consisting of hydrogen, C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2—, C1-6alkoxycarbonyl-, RiRjN-carbonyl- and RiRjN—SO2—; wherein C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C3-6cycloalkyl may optionally be substituted by one or more substituents selected from RP; Ri and Rj are selected independently for each occurrence from the group consisting of hydrogen, C1-4alkyl C3-6cycloalkyl, heterocyclyl and heterocyclylcarbonyl; wherein C1-4alkyl and C3-6cycloalkyl may be optionally substituted by one or more substituents selected from fluorine, hydroxyl, cyano, RaRbN—, RaRbN-carbonyl- and C1-3alkoxy and wherein heterocyclyl and heterocyclylcarbonyl may be optionally substituted by one or more substituents selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkoxy, halo-C1-6-alkyl, hydroxyl-C1-6-alkyl, RaRbN—C1-6alkyl- and C1-6-alkoxy-C1-6-alkyl group; and wherein if said heterocyclyl or heterocyclylcarbonyl contains a —NH moiety that nitrogen may optionally be substituted by one or more groups C1-6alkyl, C3-6alkenyl, C3-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2— and C1-6-alkylcarbonyl; or Ri and Rj taken together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted on carbon by one or more substituents selected from the group consisting of fluorine, hydroxyl, oxo, cyano, C1-6alkyl, C1-6alkoxy, RaRbN—, RaRbN—SO2— and RaRbN-carbonyl-; wherein said C1-6alkyl or C1-6alkoxy may optionally be substituted by fluorine, hydroxyl or cyano; and wherein the 4-7 membered heterocyclic ring may be optionally substituted on nitrogen by one or more substituents selected from the group consisting of C1-6alkyl and RaRbN-carbonyl-; and wherein said C1-6alkyl may be optionally substituted by one or more substituents selected from the group consisting of fluorine, hydroxyl, cyano; RP is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, C1-6alkoxy, RiRjN—, RiRjN-carbonyl-, RiRjN—SO2— and RiRjN-carbonyl-N(Ra)—; and pharmaceutically acceptable salts, and stereoisomers thereof.
地址 Boston MA US