IP Library › Granted Patent US 12,274,898
Granted Patent B2
US 12,274,898 · App. 17/289,545 · Granted Apr 15, 2025

Substituted benzodiazepines as antibody-drug conjugates

Inventors: 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); Minah Seol (Daejeon, KR)
Assignee: IntoCell, Inc.
A61K47/6889A61K47/545A61K47/6803A61K47/6851A61K47/6883A61P31/00C07D519/00
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Quick Facts
Patent No.
US 12,274,898
App. No.
17/289,545
Granted
Apr 15, 2025
Kind
B2
Abstract

The present disclosure provides compounds and compositions comprising substituted benzodiazepines of the class of Formula I:

Claims (60)

1. A compound having the structure of Formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

Ring A is selected from:

each R a1 is independently selected from H and alkyl;

each R a2 is independently selected from H, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

Ring B is selected from:

each R b1 is independently selected from H and alkyl;

each R b2 is independently selected from H, halogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

each R b3 is independently selected from H, halogen, cyano, nitro, alkyl, CH 2 N(CH 3 ) 2 , NR A R A , N + R A R A R A , OH, O(alkyl), SH, S(alkyl), cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;

each R c is independently selected from H, halogen, cyano, alkyl, CH 2 N(CH 3 ) 2 , NR A R A , N + R A R A R A , 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, CH 2 N(CH 3 ) 2 , NR A R A , N + R A R A R A , OH, O(alkyl), SH, S(alkyl), and aryl;

R c′ is selected from H, halogen, cyano, alkyl, alkylidenyl, NR A R A , N + R A R A R A , 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, CH 2 N(CH 3 ) 2 , NR A R A , N + R A R A R A , OH, O(alkyl), SH, S(alkyl), and aryl;

Z 1 is

each Y 1 is independently CR Y1 ;

each R Y1 is independently selected from H, (CH 2 ) y R Y1a , C(O)NR A R A , NR A R A , N + R A R A R A , and OH;

each R Y1a is independently selected from NR A R A , N + R A R A R A , aryl, and heteroaryl;

each y is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;

R 1 is alkyl;

R 2 is alkyl;

each R A is independently selected from H and alkyl;

n a is 1;

n 1 is 1; and

n 2 is 1.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from:

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from:

4. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein each R a1 is independently C 1 -C 4 alkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is selected from:

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is selected from:

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, wherein Ring B is selected from:

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is selected from:

9. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein Ring B is selected from:

10. The compound of claim 8 , or a pharmaceutically acceptable salt thereof, wherein R b1 is C 1 -C 4 alkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is:

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is selected from:

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ring A is selected from:

each R a1 is independently selected from H and alkyl;

each R a2 is independently selected from H, halogen, and alkyl;

Ring B is selected from:

each R b1 is independently selected from H and alkyl;

each R b2 is independently selected from H, halogen, and alkyl;

each R b3 is independently selected from H, halogen, alkyl, and O(alkyl);

Z 1 is

each Y 1 is independently CR Y1 ;

each R Y1 is independently selected from (CH 2 ) y R Y1a and OH; and

each R Y1a is independently NR A R A .

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ring A is selected from:

Ring B is selected from:

Z 1 is

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Ring A is selected from:

Ring B is selected from:

Z 1 is

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein: R 1 and R 2 are the same.

17. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

18. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound of claim 1 , or a pharmaceutically acceptable salt thereof.

19. A method for treating a disease or disorder in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof;

wherein the disease or disorder is selected from the group consisting of an autoimmune disease, a cancer, a chronic inflammatory disorder, an infection, and an immune deficiency.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 20, 2021
From: PARK, TAEKYO; WOO, SUNG HO; KIM, SUNYOUNG; PARK, SUHO; CHO, JONGUN; JUNG, DOOHWAN; SEO, DONGHOON; LEE, JAEHO; LEE, SANGKWANG; YUN, SANGHYEON; LEE, HYANG SOOK; PARK, OKKU; SEO, BEOMSEOK; KIM, SENA; SEOL, MINAH
To: INTOCELL, INC.
Reel/Frame 057532/0171 →
Continuity (2)
Provisional Application 62753605 · Oct 31, 2018
Related Publication 20220009946A1 · Jan 13, 2022
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