Small molecule regulators of alveolar type 2 cell proliferation for the treatment of pulmonary diseases

A compound of formula (I):

• wherein
• each — represents a single bond that, when optionally present, form a fused cyclopropyl ring;
• L1A is —NHCH2— or —CH(NH2)—;
• X1 is selected from —O—, —S—, —S(O)—, S(O)2—, and —NH—;
• L1B is a C2-C12-alkyl wherein one or more —CH2— are optionally and independently replaced by a moiety selected from —O—, —C(O)—, and —NH—,
• Z1 is selected from H, C6-C10-aryl, and 5- to 10-membered heteroaryl (wherein 1-4 heteroaryl members are independently selected from N, O, and S);
• m1 is an integer that is 0 when Z1 is H, and is 1 when Z1 is other than H;
• n1 is an integer selected from 0, 1, 2, and 3;
• R1 is selected from H, C1-C10-alkyl, and —C1-C10-alkyl-(C6-C10-aryl), and is optionally substituted with one to six —OH;
• R2 is C1-C10-alkyl substituted with one to six —OH;
• OR
• a compound of formula (II):
• wherein
• W is CH or N;
• is an integer selected from 1, 2, and 3;
• R3 is selected from C1-C6-alkyl, C1-C6-hydroxyalkyl, and —(CH2CH2O)xH (wherein x is an integer selected from 1, 2, 3, 4, and 5);
• R4 is C2-C8-alkynyl;
• R5a, R5b, R5c, and R5d are independently selected from H, C1-C6-alkyl, halo, —NRARB (wherein RA and RB are independently selected from H and C1-C10-alkyl), —C(O)OH, —B(OH)2, —C(O)NRARB, —C(O)ORA, and —C(O)-L2-Z2—[(CH2)n2—NR6R7]m2, wherein
• L2 is a C2-C12-alkyl wherein one or more —CH2— are optionally and independently replaced by a moiety selected from —O—, —C(O)—, and —NH—;
• Z2 is selected from H, C6-C10-aryl, and 5- to 10-membered heteroaryl (wherein 1-4 heteroaryl members are independently selected from N, O, and S);
• R6 is selected from H, C1-C10-alkyl, and —C1-C10-alkyl-(C6-C10-aryl), and is optionally substituted with one to six —OH;
• R7 is C1-C10-alkyl substituted with one to six —OH;
• m2 is an integer that is 0 when Z1 is H, and is 1 when Z1 is other than H;
• and
• n2 is an integer selected from 0, 1, 2, and 3;
• wherein at least one of R5a, R5b, R5c, and R5d is other than H;
• and
• wherein when W is CH, then R5a and R5d are not selected from —C(O)OH, —C(O)OMe, and —C(O)OEt;
• OR
• a compound of formula (III):
• wherein
• X3 is —O— or —NH—;
• L3 is a bond or C2-C12-alkyl wherein one or more —CH2— are optionally and independently replaced by a moiety selected from —O—, —C(O)—, and —NH—;
• Z3 is selected from H, —N3, C6-C10-aryl, 5- to 10-membered heteroaryl (wherein 1-4 heteroaryl members are independently selected from N, O, and S), and (3- to 14-membered heterocycloalkyl (wherein 1-4 ring members are independently selected from N, O, and S),
• wherein heteroaryl and heterocycloalkyl are optionally substituted with 1 to 6 substituents selected from the group consisting of halo, NO2, OH, CN, and C1-C6-haloalkyl;
• m3 is an integer that is 0 when Z3 is H or —N3, and is 1 when Z3 is other than H or —N3;
• n3 is an integer selected from 0, 1, 2, and 3;
• R8 is selected from H, C1-C10-alkyl, and —C1-C10-alkyl-(C6-C10-aryl), and is optionally substituted with one to six —OH;
• R9 is C1-C10-alkyl substituted with one to six —OH;
• R10 is C1-C6-haloalkyl;
• each R11 is independently selected from H, C1-C6-alkyl, and halo;
• o3 is an integer selected from 0, 1, 2, and 3;
• p3 is an integer selected from 0, 1, 2, and 3;
• q3 is an integer selected from 0, 1, 2, and 3;
• or a pharmaceutically acceptable salt thereof,
• with the proviso that the following compounds are excluded: