Cyclin modulator

A compound of formula (I), or a pharmaceutically acceptable salt thereof,

• wherein,
• R1 is each independently H or C1-4alkyl;
• subscript n1 is 1, 2 or 3;
• Ring Ar1 is selected from the group consisting of:
• C6-10 aromatic ring, 5 to 10 membered heteroaromatic ring, and 5 to 10 membered bridged ring;
• Ring Cr1 is selected from the group consisting of:
• H, C3-10 carbocyclyl, 3 to 10 membered heterocyclyl, C6-10 aryl, and 5 to 10 membered heteroaryl;
• Ra and Rb are each independently selected from the group consisting of:
• H, Re and R;
• or Ra and Rb together with Ring Ar1 and Ring Cr1 form
• wherein,
• X7 is each independently selected from the group consisting of:
• —O—, —S—, —N(Rc)—, —C(Rc)2—, and —C(Rc)2—C(Rc)2—;
• subscripts n5 and n6 are each independently 0, 1, 2 or 3;
• Re is each independently selected from the group consisting of:
• hydroxyl, C1-6alkyl, —O—C1-6alkyl, and —O—C1-6alkylene-Rf;
• wherein, Rf is selected from the group consisting of:
• —CN, —OH, —NH2, —NH(C1-6alkyl), and —N(C1-6alkyl)2;
• subscripts n3 and n4 are each independently 0, 1, 2, 3 or 4;
• R2 is selected from the group consisting of:
• H, CN, optionally substituted C1-6alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-8 cycloalkyl, and optionally substituted 3 to 8 membered heterocyclyl;
• X1, X2 and X6 are each independently N or C(Rc);
• X3, X4 and X5 are each independently N or C;
• M1 is selected from the group consisting of:
• null, X8, and (M4)s;
• wherein,
• X8 is N(Rc) or C(Rc)2;
• M4 is each independently selected from the group consisting of:
• O, S, C(O)O, C(O), N(Rc) and C1-4 alkylene;
• s is 1, 2 or 3;
• M2 is null or a ring of formula A;
• in formula A, X9 is the position attached to M1, X10 is the position attached to M3;
• X9 is N or C(Rm), X10 is selected from the group consisting of:
• O, S, N or C(Rm);
• X11 and X12 are each independently selected from the group consisting of:
• —C(Rm)2—, and —N(Rm)—;
• subscripts m1 and m2 are each independently 0, 1, 2 or 3, and m1+m2≥2;
• wherein, Rm is each independently Re or Rm1;
• wherein,
• Rm1 is each independently selected from the group consisting of:
• hydroxyl, optionally substituted C1-6 alkyl, optionally substituted C1-6hydroxyalkyl, optionally substituted C1-6 haloalkyl;
• or, two Rm1 together form a single bond, optionally substituted C1-4alkylene or optionally substituted 1 to 4 membered heteroalkylene;
• M3 is selected from the group consisting of:
• null, R3, and —NH—R3;
• wherein,
• R3 is selected from the group consisting of:
• H, optionally substituted C1-6alkyl, optionally substituted C1-6-hydroxyalkyl, and optionally substituted C1-6-haloalkyl;
• Rc is each independently H or C1-4alkyl;
• unless specifically defined, said optionally substituted means unsubstituted or one or more (such 1, 2, or 4) hydrogen atoms in the group are substituted with a substituent R, and R is selected from the group consisting of:
• D, halogen, C1-6alkyl, C1-6haloalkyl, C1-6hydroxyalkyl, C2-6alkenyl, C2-6 alkynyl, —CN, —OR′, —NO2, —NR′R″, —SR′, —OC(O)R′, —C(O)R′, —CO2R′, —CONR′, —OC(O)NR′R″, —NR″C(O)R′, —NR″—C(O)NR′R″, —NR″C(O)2R′, —S(O)R′, —S(O)2R′, —S(O)2NR′R″, —NR″S(O)2R′, C3-10cycloalkyl optionally substituted with one or more R′″, 4 to 10 membered heterocycloalkyl optionally substituted with one or more R′″, C6-10aryl optionally substituted with one or more R′″, 5 to 10 membered heteroaryl optionally substituted with one or more R′″, —C1-4alkylene-C3-10cycloalkyl optionally substituted with one or more R′″, —C1-4alkylene-4 to 10 membered heterocycloalkyl optionally substituted with one or more R′″, —C1-4alkylene-C6-10aryl optionally substituted with one or more R′″, and —C1-4alkylene-5 to 10 membered heteroaryl optionally substituted with one or more R′″;
• each R′ is each independently H, D, a group selected from the following group that is optionally substituted with one or more R′″:
• C1-6alkyl, C3-10 cycloalkyl, 4 to 10 membered heterocycloalkyl, C6-10aryl, 5 to 10 membered heteroaryl, —C1-4alkylene-C3-10cycloalkyl, —C1-4alkylene-4 to 10 membered heterocycloalkyl, —C1-4alkylene-C6-10aryl, and —C1-4alkylene-5 to 10 membered heteroaryl;
• each R″ is selected from the group consisting of:
• H, D, C1-4 alkyl, C1-4 haloalkyl, and C3-4 cycloalkyl;
• each R′″ is independently selected from the group consisting of:
• D, halogen, hydroxyl, nitro, CN, C1-6alkyl, and C1-6 haloalkyl.