US 11,685,734 B2
ATM kinase inhibitors and compositions and methods of use thereof
Leticia M. Toledo-Sherman, Santa Monica, CA (US); Celia Dominguez, Los Angeles, CA (US); Perla Breccia, Cambridge (GB); Amanda J. Van De Poël, Saffron Walden (GB); Grant Wishart, Airdrie (GB); Huw D. Vater, Saffron Walden (GB); William R. K. Esmieu, Cambridge (GB); Cole Clissold, Cambridge (GB); and Wesley P. Blackaby, Longstowe (GB)
Assigned to CHDI Foundation, Inc., New York, NY (US)
Filed by CHDI Foundation, Inc., New York, NY (US)
Filed on Dec. 3, 2020, as Appl. No. 17/111,307.
Claims priority of provisional application 62/943,694, filed on Dec. 4, 2019.
Prior Publication US 2021/0188827 A1, Jun. 24, 2021
Int. Cl. C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 407/14 (2006.01); C07D 409/14 (2006.01); C07D 413/04 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); A61K 31/55 (2006.01); A61K 31/5377 (2006.01); A61K 31/505 (2006.01); A61P 21/00 (2006.01); A61P 25/08 (2006.01); A61P 25/14 (2006.01); A61P 25/16 (2006.01); A61P 27/02 (2006.01)
CPC C07D 413/14 (2013.01) [C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/04 (2013.01)] 35 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, stereoisomer, or mixture of stereoisomers thereof;
wherein:
ring B is a heterocycloalkyl ring optionally having 1 to 3 additional heteroatoms selected from O, N, and S;
X is CH or N;
(i) Z is N and Y is —CH(R1)— or —CH2—; or
(ii) Z—Y is —C═C(R1)— or —C═C(H)—;
L is C1-3 alkylene optionally substituted with C1-4alkoxy;
each R1 is independently C1-4alkyl, halo-C1-4alkyl, C1-4alkoxy, halo-C1-4alkoxy, or C3-6 cycloalkyl;
or two R1, together with the carbon atoms to which they are attached, join to form a cycloalkyl ring;
each R2 is independently selected from hydroxy, halo, C1-4alkyl optionally substituted with C1-4alkoxy, halo-C1-4alkyl optionally substituted with C1-4alkoxy, C1-4alkoxy optionally substituted with cycloalkyl, halo-C1-4alkoxy, C3-6 cycloalkyl, and C3-6 cycloalkoxy;
or two R2, when present on the same carbon atom, join to form oxo;
or two R2, together with the carbon atoms to which they are attached, join to form a C3-7 cycloalkyl ring optionally substituted with 1 to 3 halo or a 3- to 7-membered heterocycloalkyl ring optionally substituted with 1 to 3 halo, wherein the heterocycloalkyl ring contains 1 to 3 heteroatoms selected from N, O, and S;
R3 is H or C1-6alkyl optionally substituted with —N(R8)(R9), C1-4alkoxy, or C3-6 cycloalkyl;
R4 is H or halo;
R5 is an aryl or 5- to 10-membered heteroaryl having 1, 2, 3, or 4 heteroatoms selected from N, O, and S, each of which is optionally substituted with 1 to 3 R6;
each R6 is independently halo, C1-6alkyl, halo-C1-6alkyl, or —OR7;
each R7 is independently selected from heterocycloalkyl and C1-6alkyl optionally substituted with C1-4alkoxy or halo;
R8 and R9 are each independently selected from H and C1-6alkyl;
p is 0, 1, 2, or 3; and
m is 0, 1, 2, or 3.