US 11,884,647 B2
Compounds and methods for targeting pathogenic blood vessels
Hui Sun, Culver City, CA (US); Pu Sun, San Jose, CA (US); Guo Cheng, Los Angeles, CA (US); Adrian Chichuen Au, Los Angeles, CA (US); and Ming Zhong, Nanjing (CN)
Assigned to The Regents of the University of California, Oakland, CA (US); and Atengen, Inc., Los Angeles, CA (US)
Filed by THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, Oakland, CA (US); and ATENGEN, INC., Los Angeles, CA (US)
Filed on Oct. 16, 2020, as Appl. No. 17/072,844.
Claims priority of provisional application 62/916,983, filed on Oct. 18, 2019.
Prior Publication US 2021/0147385 A1, May 20, 2021
Int. Cl. C07D 401/14 (2006.01); A61P 35/00 (2006.01); C07D 215/42 (2006.01); C07D 215/44 (2006.01); C07D 215/46 (2006.01); C07D 401/04 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 409/12 (2006.01); C07D 417/12 (2006.01); C07D 487/08 (2006.01); C07D 491/113 (2006.01); C07D 498/04 (2006.01); C07H 15/26 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 35/00 (2018.01); C07D 215/42 (2013.01); C07D 215/44 (2013.01); C07D 215/46 (2013.01); C07D 401/04 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 409/12 (2013.01); C07D 417/12 (2013.01); C07D 487/08 (2013.01); C07D 491/113 (2013.01); C07D 498/04 (2013.01); C07H 15/26 (2013.01)] 29 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, isotopically enriched analog, stereoisomer, mixture of stereoisomers, or tautomer thereof;
wherein
n is 0, 1, 2, 3 or 4;
R1 is selected from amino, optionally substituted heterocyclyl, optionally substituted cycloheptyl, and optionally substituted heteroaryl;
R2 is selected from H, halo, alkyl, alkenyl, alkynyl, —OH, alkoxy, —CN, —NO2, alkylthio, sulfoxido, sulfonyl, and amino;
R5, R7 and R8 are each independently selected from H, halo, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO2, amino, and amido;
R6 is selected from halo, alkyl, hydroxy, alkoxy, alkylthio, sulfoxido, sulfonyl, carboxy, ester, —CN, —NO2, amino, amido, sulfinamido, sulfonamido, heterocyclyl, heteroaryl, poly(ethylene glycol), and methoxypoly(ethylene glycol), or
R6 and R7 together with atoms to which they are attached form a cycloalkyl, heterocyclyl, aryl, or heteroaryl; and
each R9 is independently selected from halo, alkyl, —OH, alkoxy, —CN, and amino;
wherein the compound has at least one of the following:
1) R2 is selected from C2-30alkyl, —OH, C1-40alkoxy, C1-40alkenoxy, C1-40alkynoxy, —NO2, alkylthio, sulfoxido, sulfonyl, and amino, where
a) when R2 is ethyl, then R6 is not methyl or methoxy, and/or
b) when R2 is methoxy, then R6 is not halo, C1-2 alkyl or C1-2 alkoxy;
2) R1 is optionally substituted heteroaryl, optionally substituted bridged heterocyclyl, optionally substituted fused heterocyclyl, or optionally substituted cycloheptyl;
3) R1 is heterocyclyl substituted with one halo, amino, hydroxy, alkoxy, —CN, —NO2, alkyl, carboxy, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, poly(ethylene glycol), or methoxypoly(ethylene glycol),
where if the substituent is alkyl, the alkyl is further substituted with one substituent selected from halo, amino, alkoxy, —CN, —NO2, carboxy, ester, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, cycloalkyl, heterocyclyl, poly(ethylene glycol), methoxypoly(ethylene glycol), pyrrolidinyl and piperidinyl; or the alkyl is substituted with at least one —OR31, wherein R31 is poly(ethylene glycol) or methoxypoly(ethylene glycol);
4) R1 is amino substituted with at least one substituent selected from alkyl, cycloalkyl, heterocyclyl, heteroaryl, poly(ethylene glycol) or methoxypoly(ethylene glycol) and amino,
where the alkyl is substituted with at least one substituent selected from halo, amino, hydroxy, alkoxy, —CN, —NO2, amido, carboxy, ester, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, cycloalkyl, heterocyclyl, and heteroaryl;
5) R6 is alkyl substituted with at least one substituent selected from halo, amino, hydroxy, alkoxy, cycloalkoxy, heterocycloalkoxy, aryloxy, heteroaryloxy, poly(ethylene glycol)-oxy, methoxypoly(ethylene glycol)-oxy, —CN, —NO2, oxo, amido, carboxy, ester, alkylthio, sulfoxido, sulfonyl, sulfinamido, sulfonamido, heterocyclyl, cycloalkyl, aryl, heteroaryl, poly(ethylene glycol) and methoxypoly(ethylene glycol).