US 11,884,661 B2
3-substituted propionic acids as αV integrin inhibitors
Guohua Zhao, Princeton, NJ (US); Pratik Devasthale, Plainsboro, NJ (US); Xiang-Yang Ye, Princeton, NJ (US); Kumaravel Selvakumar, Bangalore (IN); Suresh Dhanusu, Hosur (IN); Palanikumar Balasubramanian, Hosur (IN); Leatte R. Guernon, Pipersville, PA (US); Rita Civiello, Killingworth, CT (US); Xiaojun Han, Cheshire, CT (US); Michael Frederick Parker, Higganum, CT (US); and Swanee E. Jacutin-Porte, Madison, CT (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Feb. 24, 2021, as Appl. No. 17/184,179.
Application 17/184,179 is a continuation of application No. 16/347,844, granted, now 10,968,219, previously published as PCT/US2017/060376, filed on Nov. 7, 2017.
Claims priority of provisional application 62/418,848, filed on Nov. 8, 2016.
Prior Publication US 2021/0188847 A1, Jun. 24, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); C07D 491/04 (2006.01); C07D 519/00 (2006.01); A61P 11/00 (2006.01); A61P 19/10 (2006.01); A61P 35/00 (2006.01); A61P 37/06 (2006.01)
CPC C07D 471/04 (2013.01) [A61P 11/00 (2018.01); A61P 19/10 (2018.01); A61P 35/00 (2018.01); A61P 37/06 (2018.01); C07D 491/04 (2013.01); C07D 519/00 (2013.01)] 11 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
A is CR6b;
E is CR6b;
G is N;
L is C;
M is N;
X is a C1-6 alkylene substituted with 0, 1, or 2 R7b;
Z is a covalent bond;
R1 is:

OG Complex Work Unit Chemistry
R2 is hydrogen or C1-6 alkyl;
R3 is hydrogen;
R4 is NRaRb, ORa, S(O)nR10, C(O)NRaRb, NHC(O)ORa, NHC(O)NRaRb, NHC(O)R10, OC(O)NRaRb, OC(O)R10, NHS(O)nNRaRb, or NHS(O)nR10
R5 is hydrogen or R5a;
R5a is C1-6 alkyl, phenyl, or 5- to 7-membered heterocyclyl, wherein the alkyl, phenyl, and heterocyclyl are each independently substituted with 0 to 3 R5d;
R5d, at each occurrence, is independently halo, OH, alkoxy, oxo, or alkyl;
R6b is each independently hydrogen, halo, cyano, nitro, amino, OH, C1-6 alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, aminoalkyl, or C3-5 cycloalkyl, wherein the cycloalkyl is substituted with 0, 1, 2, or 3 halo, cyano, nitro, amino, or OH;
R7b is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, or sulfonamide;
R10 is C1-6 alkyl, 3- to 10-membered carbocyclyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; wherein the alkyl, carbocyclyl, heterocyclyl are each independently substituted with 0, 1, 2, or 3 R11;
R11 is halo, cyano, nitro, OH, amino, C1-6 alkyl, alkoxy, 3- to 10-membered carbocyclyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; wherein the aryl, alkyl, and heteroaryl are each independently substituted with 0, 1, 2, or 3 R13;
R13 and R14, at each occurrence, are independently halo, cyano, nitro, OH, amino, C1-6 alkyl, alkoxy, aminoalkyl, haloalkyl, haloalkoxy, haloaminoalkyl, 3 to 6 membered carbocyclyl, 3 to 6 membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl; wherein the aryl and heteroaryl, by themselves or as part of another group, are each independently substituted with one or more groups independently selected from halo, cyano, hydroxyl, amino, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, and sulfonamide; and the carbocyclyl and heterocyclyl, by themselves or as part of another group, are each independently substituted with one or more groups independently selected from halo, cyano, hydroxyl, amino, oxo, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, and sulfonamide;
Ra and Rb, at each occurrence, are independently hydrogen, C1-10 alkyl, 3- to 10-membered carbocyclyl, or 3- to 10-membered heterocyclyl; wherein the alkyl, carbocyclyl, heterocyclyl are each independently substituted with 0, 1, 2, or 3 R14;
Re is OH, C1-4 alkyl, halo, haloalkyl, C1-4 cycloalkyl, amino, amido, carbamate, or sulfonamide;
Rf is hydrogen, CH3, CH2CH3, or COOCH2CH3;
Rg is selected from CH3, CH2CH3, CH2CCl3, phenyl, 4-fluorophenyl, 4-methoxyphenyl, benzyl,

OG Complex Work Unit Chemistry
n is 2; and
r is an integer of 0, 1, 2, or 3.