US 12,187,722 B2
Small molecule inhibitors of TEAD transcription factors
Xu Wu, Lexington, MA (US); Pranab Maiti, Hyderabad (IN); Chandrasekhar Abbineni, Hyderabad (IN); Krishna Chaitanya Talluri, Hyderabad (IN); Sunil Kumar Panigrahi, Boudh (IN); Gopala Krishna Jarugumilli, Malden, MA (US); and Yang Sun, Quincy, MA (US)
Assigned to The General Hospital Corporation, Boston, MA (US)
Appl. No. 17/439,735
Filed by The General Hospital Corporation, Boston, MA (US)
PCT Filed Mar. 13, 2020, PCT No. PCT/US2020/022757
§ 371(c)(1), (2) Date Sep. 15, 2021,
PCT Pub. No. WO2020/190774, PCT Pub. Date Sep. 24, 2020.
Claims priority of provisional application 62/819,347, filed on Mar. 15, 2019.
Prior Publication US 2023/0113085 A1, Apr. 13, 2023
Int. Cl. A61P 35/00 (2006.01); A61K 31/165 (2006.01); A61K 31/18 (2006.01); A61K 31/195 (2006.01); A61K 31/196 (2006.01); A61K 31/24 (2006.01); A61K 31/397 (2006.01); A61K 31/401 (2006.01); A61K 31/405 (2006.01); A61K 31/41 (2006.01); A61K 31/416 (2006.01); A61K 31/4184 (2006.01); A61K 31/4196 (2006.01); A61K 31/428 (2006.01); A61K 31/44 (2006.01); A61K 31/4439 (2006.01); A61K 31/4704 (2006.01); A61K 31/496 (2006.01); A61K 31/4965 (2006.01); C07C 211/26 (2006.01); C07C 211/55 (2006.01); C07C 211/56 (2006.01); C07C 211/60 (2006.01); C07C 225/22 (2006.01); C07C 229/44 (2006.01); C07C 229/48 (2006.01); C07C 229/58 (2006.01); C07C 237/40 (2006.01); C07C 255/58 (2006.01); C07C 311/44 (2006.01); C07C 317/28 (2006.01); C07C 323/63 (2006.01); C07D 205/04 (2006.01); C07D 207/16 (2006.01); C07D 207/34 (2006.01); C07D 209/08 (2006.01); C07D 211/62 (2006.01); C07D 213/74 (2006.01); C07D 213/79 (2006.01); C07D 213/80 (2006.01); C07D 215/227 (2006.01); C07D 231/14 (2006.01); C07D 231/56 (2006.01); C07D 233/61 (2006.01); C07D 233/64 (2006.01); C07D 235/06 (2006.01); C07D 235/08 (2006.01); C07D 235/18 (2006.01); C07D 239/42 (2006.01); C07D 239/48 (2006.01); C07D 239/88 (2006.01); C07D 241/20 (2006.01); C07D 241/28 (2006.01); C07D 249/08 (2006.01); C07D 249/10 (2006.01); C07D 257/04 (2006.01); C07D 275/06 (2006.01); C07D 277/28 (2006.01); C07D 295/135 (2006.01); C07D 295/155 (2006.01); C07D 317/32 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 471/04 (2006.01)
CPC C07D 471/04 (2013.01) [C07C 211/55 (2013.01); C07C 211/56 (2013.01); C07C 229/44 (2013.01); C07C 229/48 (2013.01); C07C 229/58 (2013.01); C07C 237/40 (2013.01); C07C 255/58 (2013.01); C07C 311/44 (2013.01); C07D 205/04 (2013.01); C07D 207/16 (2013.01); C07D 209/08 (2013.01); C07D 211/62 (2013.01); C07D 213/74 (2013.01); C07D 213/80 (2013.01); C07D 215/227 (2013.01); C07D 231/56 (2013.01); C07D 233/61 (2013.01); C07D 235/18 (2013.01); C07D 239/42 (2013.01); C07D 241/28 (2013.01); C07D 249/08 (2013.01); C07D 275/06 (2013.01); C07D 295/135 (2013.01); C07D 317/32 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01)] 23 Claims
 
1. A compound of Formula:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
RN is H or C1-6 alkyl;
R1 is OH or OC1-6 alkyl;
A3 is CR3 or N;
A5 is CH or N;
A7 is CH or N;
A10 is CH or N;
R3 is H, unsubstituted C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halogen, C1-6 haloalkyl, CN, ORa1, SRa1, NRc1Rd1, C(O)ORal, C(O)NRc1Rd1 or C1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C1-6 haloalkyl, CN, ORa1, SRa1, and NRc1Rd1,
R8 is Cy8A, OCy8A, O(C1-3 alkylenyl)Cy8A, NHCy8A, NH(C1-3 alkylenyl)Cy8A, N(C1-6 alkyl)Cy8A, or N(C1-6 alkyl)(C1-3 alkylenyl)Cy8A;
Cy8A is a group of one of the following formulae:

OG Complex Work Unit Chemistry
and
Ra1, Rb1, Rcl and Rd1 are each independently selected from H, C1-6 alkyl, HO—C1-6 alkylene, C1-6 alkoxy-C1-6 alkylene, C6-10 aryl, C2-6 alkenyl and C2-6 alkynyl.