Back to results
US 2016/0102122 A1Published application
Immunomodulators
AssigneeBristol-Myers Squibb Company
InventorsLi-Qiang Sun, Qian Zhao, Eric Mull, Eric P. Gillis, Paul Michael Scola
Life of this patent
Estimating the term…
Abstract
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.
Claims20
A compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein:
- A is selected from —CH2CH2—;
- wherein:
- denotes the point of attachment to the carbonyl group and denotes the point of attachment to the nitrogen atom;
- n is 0, 1, or 2;
- m is 1 or 2;
- m′ is 0 or 1;
- z is 1 or 2;
- when z is 1, w is 2;
- when z is 2, w is 1 or 2;
- p is 0, 1, or 2;
- R14 and R15 are independently selected from hydrogen and methyl;
- Rx is selected from hydrogen, amino, hydroxy, and methyl;
- and
- Rz is selected from hydrogen and —C(O)NHR16;
- wherein 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;
- Rv is hydrogen, methyl, or a natural amino acid side chain;
- Rc, Rf, Rh, Ri, and Rm are hydrogen;
- Rn is hydrogen or methyl or Rv and Rn form a pyrrolidine ring;
- 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
- RL is methyl or, RL 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.
30 more elements
A compound selected from
- Example 5001, Example 5002, Example 5003, Example 5004, Example 5005, Example 5006, Example 5007, Example 5008, Example 5009, Example 10001, Example 10002, Example 10003, Example 10004, Example 10005, Example 10006, Example 10007, Example 10008, Example 10009, Example 10010, Example 10011, Example 10012, Example 10013, Example 10014, Example 10015, Example 10016, Example 10017, Example 10018, Example 10019, Example 10020, Example 10021, Example 10022, Example 10023, Example 10024, Example 10025, Example 10026, Example 10027, Example 10028, Example 10500, Example 10501, Example 10502, Example 10503, Example 9005, Example 9006, Example 9007, Example 9008, Example 9009, Example 9010, Example 9011, Example 9012, Example 9013, Example 9014, Example 9015, Example 9016, Example 9017, Example 9018, Example 9019, Example 9020, Example 9021, Example 9022, Example 9023, Example 9024, Example 9025, Example 9026, Example 9027, Example 9028, Example 9029, Example 9030, Example 9031, Example 9032, Example 9033, Example 9034, Example 9035, Example 9036, Example 9037, Example 9038, Example 9039, Example 9040, Example 9041, Example 9042, Example 9043, Example 9044, Example 9045, Example 9046, Example 9047, Example 9048, Example 9049, Example 9050, Example 9051, Example 9052, Example 9053, Example 9054, Example 9055, Example 9056, Example 9057, Example 9058, Example 9059, Example 10029, Example 10030, Example 10031, Example 10032, Example 10033, Example 10034, Example 10035, Example 10036, Example 10037, Example 10038, Example 10039, Example 10040, Example 10041, Example 10042, Example 10504, Example 10505, Example 10506, Example 10507, Example 10508, Example 10509, Example 10510, Example 10511, Example 10512, Example 10513, Example 10514, Example 10515, Example 10516, Example 10517, Example 10518, Example 10519, Example 10520, Example 10521, Example 10522, Example 10525, Example 10526, Example 10527, Example 10528, Example 10529, 10530, Example 10531, Example 10532, Example 10533, Example 10534, Example 10535, Example 10536, Example 10537, Example 10538, Example 10539, Example 10540, Example 10541, Example 10542, Example 10543, Example 10544, Example 10545, Example 10546, Example 10547, Example 10548, Example 10549, Example 10550, Example 10551, Example 10552, Example 10553, Example 10554, Example 10555, Example 10556, Example 10557, Example 10558, Example 10559, Example 10560, Example 10561, Example 10562, Example 10563, Example 10564,
- Example 10566, Example 10567, Example 10568, Example 10569, Example 10570, Example 10571, and Example 10572, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.