US 11,834,430 B2
Compounds useful as inhibitors of isoprenylcysteine carboxyl methyltransferase
Soo Yei Ho, Singapore (SG); Anders Poulsen, Singapore (SG); Sum Wai Eldwin Tan, Singapore (SG); Shi Hua Ang, Singapore (SG); and Thomas Hugo Keller, Singapore (SG)
Assigned to AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH, Singapore (SG)
Appl. No. 16/646,693
Filed by AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH, Singapore (SG)
PCT Filed Sep. 12, 2018, PCT No. PCT/SG2018/050466
§ 371(c)(1), (2) Date Mar. 12, 2020,
PCT Pub. No. WO2019/054944, PCT Pub. Date Mar. 21, 2019.
Claims priority of application No. 10201707444W (SG), filed on Sep. 12, 2017.
Prior Publication US 2021/0130317 A1, May 6, 2021
Int. Cl. C07D 401/04 (2006.01); C07D 231/12 (2006.01); C07D 233/12 (2006.01); C07D 249/08 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); A61P 35/00 (2006.01); C07D 233/06 (2006.01); C07D 233/60 (2006.01); C07D 261/08 (2006.01); C07D 277/24 (2006.01); C07D 403/12 (2006.01)
CPC C07D 401/04 (2013.01) [A61P 35/00 (2018.01); C07D 231/12 (2013.01); C07D 233/06 (2013.01); C07D 233/60 (2013.01); C07D 249/08 (2013.01); C07D 261/08 (2013.01); C07D 277/24 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01)] 20 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a tautomer, enantiomer, solvate, hydrate, prodrug, or pharmaceutically acceptable salt thereof;
wherein:

OG Complex Work Unit Chemistry
represents an aromatic ring system;
Ring A is selected from the group consisting of formulas (ab), (a1) to (a8), and (a1′) to (a10″):
formula (ab):

OG Complex Work Unit Chemistry
wherein:
* represents the point of attachment to Ring B;
A1 is N or C;
A2 is N, S, or CH;
A3 is CH or N;
A4 is N; and
A5 is C, CH, O, or N;
formulas (a1) to (a8):

OG Complex Work Unit Chemistry
wherein * represents the point of attachment to Ring B;
formulas (a1′) to (a8′):

OG Complex Work Unit Chemistry
wherein * represents the point of attachment to Ring B; and
formulas (a1″) to (a10″):

OG Complex Work Unit Chemistry
wherein * represents the point of attachment to Ring B;
B1, B2, and B3 are independently selected from C, CH, or N, wherein one of B1, B2, or B3 is N, and the remaining B1, B2, or B3 is C or CH;
Ring B is of formula (bb1) or formula (bb2):

OG Complex Work Unit Chemistry
wherein:
* represents the point of attachment to Ring A, and
** represents the point of attachment to the —O(CHR4)— moiety of formula (I);
Ring C is a 5- or 6-membered substituted or unsubstituted carbocyclic ring system, wherein 1 to 3 carbon atoms may be optionally replaced with a heteroatom;
R1 is absent or selected from the group consisting of H, OH, halogen, optionally substituted alkyl, CF3, CHF2, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted amino, optionally substituted acyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, and optionally substituted heteroaryl;
R2 is absent or selected from the group consisting of H, OH, cyano, halogen, optionally substituted alkyl, CF3, CHF2, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted amino, optionally substituted acyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;
R3 is absent or selected from the group consisting of H, OH, cyano, halogen, optionally substituted alkyl, CF3, CHF2, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted amino, optionally substituted acyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted heterocycloalkyl, and optionally substituted aryl;
R4 and R5 are independently selected from the group consisting of H and aliphatic;
n is an integer selected from 0 to 5, wherein when n is more than 1, and each R1 substituted on Ring A may be the same or different;
m is an integer selected from 0 to 4, wherein when m is more than 1, each R2 substituted on Ring B may be the same or different, and m is 1 when R2 is halogen; and
p is an integer selected from 0 to 5, wherein when p is more than 1, and each R3 substituted on Ring C may be the same or different.