US 12,037,324 B2
Biarylmethyl heterocycles
Eldon Scott Priestley, Hopewell, NJ (US); Samuel Kaye Reznik, Brookline, MA (US); Edward H. Ruediger, Montreal (CA); James R. Gillard, Montreal (CA); Oz Scott Halpern, Hopewell, NJ (US); Wen Jiang, Hopewell, NJ (US); Jeremy Richter, Hopewell, NJ (US); Rejean Ruel, Montreal (CA); Sasmita Tripathy, Montreal (CA); Wu Yang, Hopewell, NJ (US); and Xiaojun Zhang, Hopewell, NJ (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US); and Université de Montréal, (CA)
Filed by Université de Montréal, Montréal (CA); and Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed on Jul. 11, 2022, as Appl. No. 17/861,809.
Application 17/861,809 is a division of application No. 16/311,835, granted, now 11,407,733, previously published as PCT/US2017/039646, filed on Jun. 28, 2017.
Claims priority of provisional application 62/356,215, filed on Jun. 29, 2016.
Prior Publication US 2023/0045357 A1, Feb. 9, 2023
Int. Cl. C07D 401/14 (2006.01); A61K 31/41 (2006.01); A61K 31/4245 (2006.01); A61K 31/427 (2006.01); A61K 31/437 (2006.01); A61K 31/4439 (2006.01); A61K 31/4709 (2006.01); A61K 31/497 (2006.01); A61K 31/501 (2006.01); A61P 9/04 (2006.01); C07D 233/90 (2006.01); C07D 235/26 (2006.01); C07D 239/20 (2006.01); C07D 257/04 (2006.01); C07D 271/07 (2006.01); C07D 401/10 (2006.01); C07D 403/10 (2006.01); C07D 403/14 (2006.01); C07D 405/14 (2006.01); C07D 413/10 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 498/10 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 31/41 (2013.01); A61K 31/4245 (2013.01); A61K 31/427 (2013.01); A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/4709 (2013.01); A61K 31/497 (2013.01); A61K 31/501 (2013.01); A61P 9/04 (2018.01); C07D 233/90 (2013.01); C07D 235/26 (2013.01); C07D 239/20 (2013.01); C07D 257/04 (2013.01); C07D 271/07 (2013.01); C07D 401/10 (2013.01); C07D 403/10 (2013.01); C07D 403/14 (2013.01); C07D 405/14 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 498/10 (2013.01)] 17 Claims
 
1. A compound of formula (I), or salt thereof:

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wherein
ring A is

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W is N, or CR16
W′, at each occurrence, is independently selected from N, O, S and CR16 where at least one W′ is not CR16, and at most only one W′ is selected as O or S;
R1 and R2 are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxyalkyl, and C3-C6 cycloalkyl;
alternatively, R1 and R2, together with the atom to which they are attached, join together to form a C3-C6 cycloalkyl, or a 4 to 6 membered heterocycle having 1-2 heteroatoms, the cycloalkyl or heterocycle is substituted with 0-4 F and 0-1 OH;
R16, at each occurrence, is independently selected from H, F, Cl, Br, I, CN, OH, N(Ra)2, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3-alkoxy, C1-C4-hydroxyalkyl, C1-C3-haloalkoxy, C3-C6-cycloalkyl, and C3-C6-halocycloalkyl
Ra is, at each occurrence, independently selected from H, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-hydroxyalkyl, and C3-C6-cycloalkyl;
or two Ra, along with the nitrogen atom to which they are attached, join to form a 5 to 6 membered heterocycle containing 0-2 additional heteroatoms selected from N, O and S;
Y is 5-tetrazolyl, SO3H, PO2H2, PO3H2, COOR,

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R, at each occurrence, is independently selected from H, C1-C6 alkyl, C1-C6-haloalkyl, C1-C6-hydroxyalkyl, C3-C7 cycloalkyl, C6aryl-C1-C6 alkyl heterocycle-C1-C6 alkyl, wherein said heterocycle is a 4-10 membered group having 1-3 heteroatoms selected from N, O, or S, said aryl and heterocycle are each substituted with 0-3 groups chosen from C1-C3 alkyl, halo, OH, or C1-C3 fluoroalkyl;
R8 at each occurrence, is independently selected from H, C1-C6 alkyl, C1-C6-haloalkyl, C1-C6-hydroxyalkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C3 alkyl, C6-10 aryl, C6-10-aryl-C1-C6-alkyl, heteroaryl, heteroaryl-C1-C6-alkyl, heterocyclyl, heterocycle-C1-C6-alkyl, wherein the heteroaryl and heterocycle are each a 4-10 membered group having 1-3 heteroatoms selected from N, O, or S;
Z, at each occurrence, is independently selected from a bond, O, S, N(Rz), C(Rz)2, C═O, C(═O)N(Rz), N(Rz)C(═O), C(Rz)2C(Rz)2, OC(Rz)2, SC(Rz)2, N(Rz)C(Rz)2, C(Rz)2O, C(Rz)2S, C(Rz)2N(Rz);
Rz is at each occurrence independently selected from H, C1-C4-alkyl, C1-C4-hydroxyalkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl or, alternatively, two Rz groups either on the same atom or on adjacent atoms can join to form a C3-C6-cycloalkyl or a 4 to 7 membered heterocycle containing 1-2 heteroatoms selected from N, O and S;
G is selected from a 4 to 11 membered heterocycle having 1-4 atoms selected from N, O, and S, a C3-C8-cycloalkyl, C6-C10-aryl or a 5 to 10 membered heteroaryl having 1-4 atoms selected from N, O, and S; wherein the heterocycle, cycloalkyl, aryl and heteroaryl are substituted with 0-3 substituents independently selected from the group consisting of ═O, F, Cl, Br, I, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-haloalkyl, C1-C6-hydroxyalkyl, OH, ORx, SRx, N(Rx)2, CO(Rx), CON(Rx)2, CO2Rx, N(Rx)CO2(Rx), N(Rx)CO(Rx), N(Rx)CON(Rx)2, S(O)2(Rx), S(O)2N(Rx)2, or N(Rx)S(O)2(Rx);
Rx is H, C1-6 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, phenyl, CH2-phenyl; ring B is

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Group C is

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R5 is C1-6 alkyl, C1-6 haloalkyl C1-6 alkoxyalkyl, C3-6-cycloalkylC0-4-alkyl which may be substituted with 1-3 halogens or a C1-3-alkoxy group;
R6 is H, F, Cl, Br, CF3, CN, N(Rz)2, CON(Rz)2, C1-4 alkyl, C1-4 haloalkyl C1-4 alkoxyalkyl, C1-4 hydroxyalkyl, C3-6-cycloalkyl, C3-6-halocycloalkyl, C3-6-alkoxycycloalkyl, or C3-6-hydroxycycloalkyl;
R9 is COOR, CON(Rz)2; and
r is 0 to 3;
provided that the compounds of Formula (I) are not

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