US 12,274,898 B2
Substituted benzodiazepines as antibody-drug conjugates
Taekyo Park, Daejeon (KR); Sung Ho Woo, Daejeon (KR); Sunyoung Kim, Daejeon (KR); Suho Park, Daejeon (KR); Jongun Cho, Daejeon (KR); Doohwan Jung, Daejeon (KR); Donghoon Seo, Daejeon (KR); Jaeho Lee, Daejeon (KR); Sangkwang Lee, Daejeon (KR); Sanghyeon Yun, Daejeon (KR); Hyang Sook Lee, Daejeon (KR); Okku Park, Daejeon (KR); Beomseok Seo, Daejeon (KR); Sena Kim, Daejeon (KR); and Minah Seol, Daejeon (KR)
Assigned to IntoCell, Inc., Daejeon (KR)
Appl. No. 17/289,545
Filed by IntoCell, Inc., Daejeon (KR)
PCT Filed Oct. 30, 2019, PCT No. PCT/IB2019/001175
§ 371(c)(1), (2) Date Apr. 28, 2021,
PCT Pub. No. WO2020/089687, PCT Pub. Date May 7, 2020.
Claims priority of provisional application 62/753,605, filed on Oct. 31, 2018.
Prior Publication US 2022/0009946 A1, Jan. 13, 2022
Int. Cl. A61K 31/55 (2006.01); A61K 47/54 (2017.01); A61K 47/68 (2017.01); A61P 31/00 (2006.01); C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC A61K 47/6889 (2017.08) [A61K 47/545 (2017.08); A61K 47/6803 (2017.08); A61K 47/6851 (2017.08); A61K 47/6883 (2017.08); A61P 31/00 (2018.01); C07D 519/00 (2013.01)] 19 Claims
 
1. A compound having the structure of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof,
wherein:
Ring A is selected from:

OG Complex Work Unit Chemistry
each Ra1 is independently selected from H and alkyl;
each Ra2 is independently selected from H, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
Ring B is selected from:

OG Complex Work Unit Chemistry
each Rb1 is independently selected from H and alkyl;
each Rb2 is independently selected from H, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
each Rb3 is independently selected from H, halogen, cyano, nitro, alkyl, CH2N(CH3)2, NRARA, N+RARARA, OH, O(alkyl), SH, S(alkyl), cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
each Rc is independently selected from H, halogen, cyano, alkyl, CH2N(CH3)2, NRARA, N+RARARA, OH, aryl, and heteroaryl, wherein each aryl and heteroaryl is optionally and independently substituted with one or more substituents independently selected from the group consisting of H, halogen, cyano, alkyl, CH2N(CH3)2, NRARA, N+RARARA, OH, O(alkyl), SH, S(alkyl), and aryl;
Rc′ is selected from H, halogen, cyano, alkyl, alkylidenyl, NRARA, N+RARARA, OH, aryl, and heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of H, halogen, cyano, alkyl, CH2N(CH3)2, NRARA, N+RARARA, OH, O(alkyl), SH, S(alkyl), and aryl;
Z1 is

OG Complex Work Unit Chemistry
each Y1 is independently CRY1;
each RY1 is independently selected from H, (CH2)yRY1a, C(O)NRARA, NRARA, N+RARARA, and OH;
each RY1a is independently selected from NRARA, N+RARARA, aryl, and heteroaryl;
each y is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;
R1 is alkyl;
R2 is alkyl;
each RA is independently selected from H and alkyl;
na is 1;
n1 is 1; and
n2 is 1.