发明名称 Aryl dihydropyridinone and piperidinone MGAT2 inhibitors
摘要 The present invention provides compounds of Formula (I):; or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein all of the variables are as defined herein. These compounds are monoacylglycerol acyltransferase type 2 (MGAT2) inhibitors which may be used as medicaments.
申请公布号 US8791091(B2) 申请公布日期 2014.07.29
申请号 US201213688584 申请日期 2012.11.29
申请人 Bristol-Myers Squibb Company 发明人 Turdi Huji;Hangeland Jon J.;Lawrence R. Michael;Ahmad Saleem;Meng Wei;Brigance Robert Paul;Devasthale Pratik;Zhao Guohua
分类号 A61K31/675;A61K31/4418;A61K45/06;A61K31/438;A61K31/4439;A61K31/5377;C07D401/04;C07D413/04;C07D413/14;C07F9/59;C07D401/14;C07D211/90;C07D221/20 主分类号 A61K31/675
代理机构 代理人 Sun Jing G.
主权项 1. A compound of Formula (I):or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein: designates a single or double bond; x and y can be both a single bond; when x is a double bond, then y is a single bond and R4 and R16 are absent; when y is a double bond, then x is a single bond and R5 and R16 are absent; R1 is independently selected from the group consisting of: —CONH(C4-18 alkyl), —CONHC2-8 haloalkyl, —CONH(CH2)1-8Ph, —CONHCH2COC2-8 alkyl, —(CH2)m—(C3-10 carbocycle substituted with 0-2 Rb and 0-2 Rg), —(CH2)m-(5- to 6-membered heteroaryl comprising: carbon atoms and 1-4 heteroatoms selected from N, NRe, O and S; wherein said heteroaryl is substituted with 0-1 Rb and 0-2 Rg), and a C1-12 hydrocarbon chain substituted with 0-3 Ra; wherein said hydrocarbon chain may be straight or branched, saturated or unsaturated; R2 is independently selected from the group consisting of: C1-4 alkyl, C3-4 cycloalkyl, and C1-4 haloalkyl; R3 is independently selected from the group consisting of: H, F, Cl, C1-4 alkyl and CN; R4 and R5 are independently selected from the group consisting of: H, F, Cl, and C1-4 alkyl; when x is a single bond, R3 and R4 may be combined with the carbon atom to which they are attached to form a 3- to 6-membered carbocycle; R6 is independently selected from the group consisting of: H, halo, C1-4 alkyl, NO2, Rc, —(CH2)n—(X)t—(CH2)mRc, NH2, —CONH(C1-6 alkyl), —NHCOX1SO2Rj, —NHCOCH2PO(OEt)2, —NHCOCORj, —NHCOCH(OH)Rj, —NHCOCH2CORj, —NHCONHRj, and —OCONRfRj; X is independently selected from the group consisting of: O, S, NH, CONH, and NHCO; X1 is independently C1-4 hydrocarbon chain optionally substituted with C1-4 alkyl or C3-4 cycloalkyl; when y is a single bond, R5 and R6 may be combined with the carbon atom to which they are attached to form a 3- to 6-membered carbocycle; R11, R12, R13, R14 and R15 are independently selected from the group consisting of: H, halo, C1-4 alkyl substituted with 0-2 Ri, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, —(CH2)m—C3-6 cycloalkyl, CN, NRfRj, ORj, SRj, NHCO2(C1-4 alkyl), NHSO2(C1-4 alkyl), and a 4- to 6-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S; alternatively, R11 and R12, together with the carbon atoms to which they are attached, combine to form a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring comprising: carbon atoms and 1-3 heteroatoms selected from N, NRe, O, and S; alternatively, R12 and R13, together with the carbon atoms to which they are attached, combine to form a 5- to 6-membered carbocyclic ring or a 5- to 6-membered heterocyclic ring comprising: carbon atoms and 1-3 heteroatoms selected from N, NRe, O, and S; R16 is independently selected from the group consisting of: H and C1-4 alkyl; Ra is, at each occurrence, independently selected from the group consisting of: halo, OH, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, N(C1-4 alkyl)2, —(CH2)n(X)t—(CH2)mRc, and —(CH2)n—(CH2O)m—(CH2)nRf; Rb is, at each occurrence, independently selected from the group consisting of: halo, OH, C1-10 alkyl, C1-10 alkoxy, C1-10 haloalkyl, C1-10 haloalkoxy, C1-10 alkylthio, C1-10 haloalkylthio, N(C1-4 alkyl)2, —CONH(CH2)4-20H, —O(CH2)sO(C1-6 alkyl), Rc, —(CH2)n—(X)t—(CH2)mRc, and —(CH2)n—(CH2O)m—(CH2)nRf; Rc is, at each occurrence, independently selected from the group consisting of: C3-6 cycloalkyl substituted with 0-2 Rd, C3-6 cycloalkenyl substituted with 0-2 Rd, —(CH2)m-(phenyl substituted with 0-3 Rd), and a 5- to 6-membered heterocycle comprising: carbon atoms and 1-4 heteroatoms selected from N, NRe, O, and S; wherein said heterocycle is substituted with 0-2 Rd; Rd is, at each occurrence, independently selected from the group consisting of: halo, OH, CN, NO2, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy, tetrazolyl, OBn and phenyl substituted with 0-2 Rh; Re is, at each occurrence, independently selected from the group consisting of: H, C1-8 alkyl, C1-8 haloalkyl, benzyl optionally substituted with C1-4 alkoxy, CO(C1-4 alkyl) and COBn; Rf is, at each occurrence, independently selected from the group consisting of: H and C1-4 alkyl; Rg, Rh and Ri are, at each occurrence, independently selected from the group consisting of: halo, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy; Rj is, at each occurrence, independently selected from the group consisting of: C1-4 alkyl, C3-4 cycloalkyl and phenyl; n, at each occurrence, is independently 0 or 1; m, at each occurrence, is independently 0, 1, 2, 3, or 4 s, at each occurrence, is independently 1, 2, or 3; and t, at each occurrence, is independently 0 or 1; provided that the following compound is excluded:
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