US 12,168,655 B2
Apelin receptor agonists and methods of use
Wei Meng, Pennington, NJ (US); Hannguang J. Chao, Nashua, NH (US); Heather Finlay, Skillman, NJ (US); R. Michael Lawrence, Yardley, PA (US); and Michael C. Myers, Newtown, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Jun. 9, 2022, as Appl. No. 17/836,596.
Application 17/836,596 is a division of application No. 15/779,194, granted, now 11,390,616, previously published as PCT/US2016/064562, filed on Dec. 2, 2016.
Claims priority of provisional application 62/263,106, filed on Dec. 4, 2015.
Prior Publication US 2022/0315569 A1, Oct. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 413/10 (2006.01); C07D 239/54 (2006.01); C07D 401/10 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/10 (2006.01); C07D 413/06 (2006.01); C07D 417/06 (2006.01); C07D 417/14 (2006.01)
CPC C07D 413/10 (2013.01) [C07D 239/54 (2013.01); C07D 401/10 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/10 (2013.01); C07D 413/06 (2013.01); C07D 417/06 (2013.01); C07D 417/14 (2013.01)] 14 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
alk is C1-6 alkyl substituted with 1-5 R4;
ring A is independently selected from 5- or 6-membered aryl and heteroaryl consisting of carbon atoms and 1-4 heteroatoms selected from N, NR3a, O, and S, each substituted with 1-3 R3;
ring B is independently selected from aryl, heteroaryl, and cycloalkyl, each substituted with 1-4 R1;
R1 is independently selected from H, halogen, NO2, —(CH2)nORb, (CH2)nS(O)pRc, —(CH2)nC(═O)Rb, —(CH2)nNRaRa, —(CH2)nCN, —(CH2)nC(═O)NRaRa, —(CH2)nNRaC(═O)Rb, —(CH2)nNRaC(═O)NRaRa, —(CH2)nNRaC(═O)ORb, —(CH2)nOC(═O)NRaRa, —(CH2)nC(═O)ORb, —(CH2)nS(O)pNRaRa, —(CH2)nNRaS(O)pNRaRa, —(CH2)nNRaS(O)pRc, C1-4 alkyl substituted with 0-3 Re, —(CH2)n—C3-6 carbocyclyl substituted with 0-3 Re, and —(CH2)n-heterocyclyl substituted with 0-3 Re;
R2 is independently selected from C2-5 alkyl substituted with 0-3 Re; C2-5 alkenyl substituted with 0-3 Re, aryl substituted with 1-3 Re, heterocyclyl substituted with 0-3 Re, and C3-6 cycloalkyl substituted with 0-3 Re; provided when R2 is C2-5 alkyl, the carbon atom and the groups attached thereto except the one attached to the pyrimidine ring may be replaced by O, N, and S;
R3 is independently selected from H, halogen, —(CH2)nORb, —(CH2)nS(O)pRc, —(CH2)nC(═O)Rb, —(CH2)nNRaRa, —(CH2)nCN, —(CH2)nC(═O)NRaRa, —(CH2)nNRaC(═O)Rb, —(CH2)nNRaC(═O)NRaRa, —(CH2)nNRaC(═O)ORb, —(CH2)nOC(═O)NRaRa, —(CH2)nC(═O)ORb, —(CH2)nS(O)pNRaRa, —(CH2)nNRaS(O)pNRaRa, —(CH2)nNRaS(O)pRc, C1-5 alkyl substituted with 0-3 Re, (CH2)n—C3-6 carbocyclyl substituted with 0-3 Re, and —(CH2)n-heterocyclyl consisting of carbon atoms and 1-4 heteroatoms selected from N, NR3a, O, S, and substituted with 0-3 Re;
R3a is independently selected from H, —S(O)pRc, —C(═O)Rb, —C(═O)NRaRa, —C(═O)ORb, —S(O)pNRaRa, C1-5 alkyl substituted with 0-3 Re, —(CH2)n—C3-6 carbocyclyl substituted with 0-3 Re, and —(CH2)n-heterocyclyl substituted with 0-3 Re;
R4 is independently selected from C1-5 alkyl substituted with 0-3 Re, (CH2)n—C3-6 carbocyclyl substituted with 0-3 Re, and —(CH2)n-heterocyclyl substituted with 0-3 Re;
Ra, at each occurrence, is independently selected from H, C1-6 alkyl substituted with 0-5 Re, C2-6 alkenyl substituted with 0-5 Re, C2-6 alkynyl substituted with 0-5 Re, —(CH2)n—C3-10carbocyclyl substituted with 0-5 Re, and —(CH2)n-heterocyclyl substituted with 0-5 Re; or Ra and Ra together with the nitrogen atom to which they are both attached form a heterocyclic ring substituted with 0-5 Re;
Rb, at each occurrence, is independently selected from H, C1-6 alkyl substituted with 0-5 Re, C2-6 alkenyl substituted with 0-5 Re, C2-6 alkynyl substituted with 0-5 Re, —(CH2)n—C3-10carbocyclyl substituted with 0-5 Re, and —(CH2)n-heterocyclyl substituted with 0-5 Re;
Rc, at each occurrence, is independently selected from C1-6 alkyl substituted with 0-5 Re, C2-6alkenyl substituted with 0-5 Re, C2-6alkynyl substituted with 0-5 Re, C3-6carbocyclyl, and heterocyclyl;
Rd, at each occurrence, is independently selected from H and C1-6 alkyl substituted with 0-5 Re;
Re, at each occurrence, is independently selected from C1-6 alkyl (optionally substituted with halogen, OH, and CN), C2-6 alkenyl, C2-6 alkynyl, —(CH2)n—C3-6 cycloalkyl, —(CH2)n—C4-6 heterocyclyl, —(CH2)n-aryl, —(CH2)n-heteroaryl, F, Cl, Br, CN, NO2, ═O, CO2H, —(CH2)nORf, S(O)pRf, C(═O)NRfRf, NRfC(═O)Rf, S(O)pNRfRf, NRfS(O)pRf, NRfC(═O)ORf, OC(═O)NRfRf and —(CH2)nNRfRf;
Rf, at each occurrence, is independently selected from H, C1-5alkyl (optionally substituted with halogen and OH), C3-6 cycloalkyl, and phenyl, or Rf and Rf together with the nitrogen atom to which they are both attached form a heterocyclic ring optionally substituted with C1-4alkyl;
n is independently selected from zero, 1, 2, and 3; and
p, at each occurrence, is independently selected from zero, 1, and 2.