US 11,701,371 B2
ENPP1 inhibitors and their use for the treatment of cancer
Lingyin Li, Stanford, CA (US); Mark Smith, San Francisco, CA (US); Kelsey Erin Shaw, Atlanta, GA (US); Jacqueline Ann Carozza, Stanford, CA (US); and Volker Boehnert, Palo Alto, CA (US)
Assigned to THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
Appl. No. 16/645,300
Filed by THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, Stanford, CA (US)
PCT Filed Sep. 7, 2018, PCT No. PCT/US2018/050018
§ 371(c)(1), (2) Date Mar. 6, 2020,
PCT Pub. No. WO2019/051269, PCT Pub. Date Mar. 14, 2019.
Claims priority of provisional application 62/556,117, filed on Sep. 8, 2017.
Prior Publication US 2021/0369747 A1, Dec. 2, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/675 (2006.01); A61P 35/00 (2006.01); C07D 401/04 (2006.01); C07F 5/02 (2006.01); C07F 9/00 (2006.01); C07F 9/09 (2006.01); C07F 9/165 (2006.01); C07F 9/38 (2006.01); C07F 9/44 (2006.01); A61K 31/519 (2006.01); C07F 9/40 (2006.01); A61K 31/517 (2006.01); C07D 401/14 (2006.01)
CPC A61K 31/675 (2013.01) [A61P 35/00 (2018.01)] 7 Claims
 
1. An ENPP1 inhibitor of the formula:

OG Complex Work Unit Chemistry
wherein,
X is a hydrophilic head group selected from phosphonic acid, phosphonate, phosphonate ester, phosphate, phosphate ester, thiophosphate, thiophosphate ester, phosphoramidate and thiophosphoramidate;
L is selected from —CH2—, —(CH2)2—, —(CH2)3—, —(CH2)4—, —(CH2)5— and —(CH2)6—;
Z1 and Z2 are each independently selected from CR1 and N;
Z3 and Z4 are each independently selected from CR and N, wherein R is H, alkyl or substituted alkyl;
each R1 is independently selected from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, heterocycle and substituted heterocycle;
R2 and R5 are each independently selected from H, OH, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, —OCF3, halogen, amine, substituted amine, amide, heterocycle and substituted heterocycle;
R3 and R4 are each independently selected from H, OH, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkoxy, substituted alkoxy, —OCF3, halogen, amine, substituted amine, amide, heterocycle and substituted heterocycle; or R3 and R4 together with the carbon atoms to which they are attached form a fused ring selected from heterocycle, substituted heterocycle, cycloalkyl, substituted cycloalkyl, aryl and substituted aryl;
or a pharmaceutically acceptable salt or a solvate thereof.