US 11,884,624 B2
Difluorolactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
Stephen Douglas Barrett, Hartland, MI (US); Fred Lawrence Ciske, Dexter, MI (US); Joseph Michael Colombo, Ann Arbor, MI (US); Gregory William Endres, Saline, MI (US); Bradlee David Germain, Ann Arbor, MI (US); Andriy Kornilov, Ypsilanti, MI (US); James Bernard Kramer, Sylvania, OH (US); Adam Uzieblo, Farmington Hills, MI (US); and Kirk M. Maxey, Ann Arbor, MI (US)
Assigned to CAYMAN CHEMICAL COMPANY, INC., Ann Arbor, MI (US)
Filed by Cayman Chemical Company, Inc., Ann Arbor, MI (US)
Filed on Jun. 9, 2021, as Appl. No. 17/343,038.
Application 17/343,038 is a division of application No. 16/732,537, filed on Jan. 2, 2020, granted, now 11,066,361.
Application 16/732,537 is a division of application No. 16/155,400, filed on Oct. 9, 2018, granted, now 10,556,862, issued on Feb. 11, 2020.
Application 16/155,400 is a division of application No. 15/267,440, filed on Sep. 16, 2016, abandoned.
Application 15/267,440 is a continuation of application No. 14/872,967, filed on Oct. 1, 2015, granted, now 9,487,478, issued on Nov. 8, 2016.
Application 14/872,967 is a continuation of application No. 14/415,506, granted, now 9,180,116, issued on Nov. 10, 2015, previously published as PCT/US2013/051263, filed on Jul. 19, 2013.
Claims priority of provisional application 61/793,929, filed on Mar. 15, 2013.
Claims priority of provisional application 61/673,514, filed on Jul. 19, 2012.
Prior Publication US 2023/0050318 A1, Feb. 16, 2023
Int. Cl. C07D 207/273 (2006.01); C07D 207/26 (2006.01); C07D 409/06 (2006.01); A61K 31/4025 (2006.01); A61K 31/4015 (2006.01); A61L 24/00 (2006.01); A61L 24/02 (2006.01); A61L 27/12 (2006.01); A61L 27/36 (2006.01); A61L 27/54 (2006.01); A61L 27/58 (2006.01)
CPC C07D 207/273 (2013.01) [A61K 31/4015 (2013.01); A61K 31/4025 (2013.01); A61L 24/0015 (2013.01); A61L 24/0042 (2013.01); A61L 24/02 (2013.01); A61L 27/12 (2013.01); A61L 27/365 (2013.01); A61L 27/3608 (2013.01); A61L 27/54 (2013.01); A61L 27/58 (2013.01); C07D 207/26 (2013.01); C07D 409/06 (2013.01); A61L 2300/412 (2013.01); A61L 2300/604 (2013.01); A61L 2430/02 (2013.01)] 3 Claims
 
1. A compound of formula (13):

OG Complex Work Unit Chemistry
wherein:
L1 is
a) C3-C7alkylene, C3-C7alkenylene, or C3-C7alkynylene; or
b) —(CH2)n1-G2- (CH2)p—, —(CH2)n2—C≡C-G2-, or —(CH2)n2—C(R12)═C(R12)-G2-, wherein n1 is 2, 3, 4, or 5, n2 is 1, 2, or 3, p is 0, 1, 2, or 3, and n1+p=2, 3, 4, 5, or 6;
G2 is

OG Complex Work Unit Chemistry
R1 is a protected carboxylic acid;
R12, at each occurrence, is independently H or C1-C4alkyl; and
R20 is H or a hydroxyl protecting group.