发明名称 MACROCYCLIC INHIBITORS OF THE PD-1/PD-L1 AND CD80(B7-1)/PD-L1 PROTEIN/PROTEIN INTERACTIONS
摘要 The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.
申请公布号 US2014294898(A1) 申请公布日期 2014.10.02
申请号 US201414201977 申请日期 2014.03.10
申请人 Bristol-Myers Squibb Company 发明人 Miller Michael Matthew;Mapelli Claudio;Allen Martin Patrick;Bowsher Michael S.;Boy Kenneth M.;Gillis Eric P.;Langley David R.;Mull Eric;Poirier Maude A.;Sanghvi Nishith;Sun Li-Qiang;Tenney Daniel J.;Yeung Kap-Sun;Zhu Juliang;Reid Patrick C.;Scola Paul Michael
分类号 C07K7/08;A61K45/06;A61K38/10;A61K39/39 主分类号 C07K7/08
代理机构 代理人
主权项 1. A compound of formula (I)or a pharmaceutically acceptable salt thereof, wherein: A is selected from a bond,wherein: denotes the point of attachment to the carbonyl group and denotes the point of attachment to the nitrogen atom; n is 0 or 1; R14 and R15 are independently selected from hydrogen and methyl; and R16 is selected from hydrogen, —CHR17C(O)NH2, —CHR17C(O)NHCHR18C(O)NH2, and —CHR17C(O)NHCHR18C(O)NHCH2C(O)NH2;wherein R17 is selected from hydrogen and —CH2OH and wherein R18 is selected from hydrogen and methyl; Rc, Rf, Rh, Rm, and Rn are hydrogen; Ra, Re, Rj, and Rk, are each independently selected from hydrogen and methyl; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are independently selected from a natural amino acid side chain and an unnatural amino acid side chain or form a ring with the corresponding vicinal R group as described below; Re and Rk can each form a ring with the corresponding vicinal R group and the atoms to which they are attached selected from azetidine, pyrollidine, morpholine, piperidine, piperazine, and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, and hydroxy; Rb is methyl or, Rb and R2, together with the atoms to which they are attached, form a ring selected from azetidine, pyrollidine, morpholine, piperidine, piperazine, and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, and hydroxy; Rd is hydrogen or methyl, or, Rd and R4, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrollidine, morpholine, piperidine, piperazine, and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, hydroxy, and phenyl; Rg is hydrogen or methyl or Rg and R7, together with the atoms to which they are attached, can form a ring selected from azetidine, pyrollidine, morpholine, piperidine, piperazine, and tetrahydrothiazole; wherein each ring is optionally substituted with one to four groups independently selected from amino, benzyl optionally substituted with a halo group, benzyloxy, cyano, cyclohexyl, methyl, halo, hydroxy, isoquinolinyloxy optionally substituted with a methoxy group, quinolinyloxy optionally substituted with a halo group, and tetrazolyl; and wherein the pyrrolidine and the piperidine ring are optionally fused to a cyclohexyl, phenyl, or indole group; and R1 is methyl or, R1 and R12, together with the atoms to which they are attached, form a ring selected from azetidine and pyrollidine, wherein each ring is optionally substituted with one to four groups independently selected from amino, cyano, methyl, halo, and hydroxy.
地址 Princeton NJ US