TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

Title:

TRICYCLIC SULFONES AS ROR GAMMA MODULATORS

Document Type and Number:

WIPO Patent Application WO/2018/089402

Kind Code:

Abstract:

There are described RORγ Gamma modulators of the formula (I), (I) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein all substituents are defined herein. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

Inventors:

MARCOUX DAVID (US)
BEAUDOIN BERTRAND MYRA (US)
DHAR T G MURALI (US)
YANG MICHAEL G (US)
XIAO ZILI (US)
XIAO HAI-YUN (US)
ZHU YEHENG (US)
WEIGELT CAROLYN (US)
BATT DOUGLAS G (US)

Application Number:

PCT/US2017/060501

Publication Date:

May 17, 2018

Filing Date:

November 08, 2017

Export Citation:

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Assignee:

BRISTOL MYERS SQUIBB CO (US)

International Classes:

C07D213/75; A61K31/337; A61K31/341; A61K31/381; A61K31/382; A61K31/397; A61K31/40; A61K31/41; A61K31/4152; A61K31/4164; A61K31/4166; A61K31/4196; A61K31/42; A61K31/421; A61K31/433; A61K31/437; A61K31/438; A61K31/4409; A61K31/4412; A61K31/4439; A61K31/45; A61K31/4545; A61K31/473; A61K31/495; A61K31/505; A61K31/5375; A61K31/54; A61P3/00; A61P11/06; A61P35/00; A61P37/08; C07C317/20; C07D205/04; C07D207/09; C07D207/10; C07D207/16; C07D207/28; C07D211/48; C07D211/62; C07D211/78; C07D211/96; C07D213/40; C07D213/56; C07D213/81; C07D215/36; C07D231/06; C07D231/08; C07D231/18; C07D233/64; C07D233/76; C07D233/78; C07D233/90; C07D241/08; C07D249/12; C07D257/04; C07D261/18; C07D263/20; C07D285/06; C07D295/16; C07D305/08; C07D307/22; C07D309/10; C07D333/48; C07D335/02; C07D401/04; C07D401/12; C07D405/04; C07D405/12; C07D471/04; C07D471/10; C07F9/09

Domestic Patent References:

WO2007084595A2	2007-07-26
WO2009011851A1	2009-01-22
WO2009008980A2	2009-01-15
WO2015103507A1	2015-07-09
WO2015103508A1	2015-07-09
WO2015103509A1	2015-07-09
WO2015103510A1	2015-07-09

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Attorney, Agent or Firm:

KORSEN, Elliott et al. (US)

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Claims:

WHAT IS CLAIMED IS:

1. The compound of the Formula (I)

(I)

or a stereoisomer or pharmaceutically acceptable salt thereof, wherein

X is–CR⁴R⁵-, -(CR⁴R⁵)₂, -OCR⁶R⁷-, -S(O)_pCR⁶R⁷-, -S(O)(NR^g)CR⁶R⁷- or

-NR⁶CR⁶R⁷-;

A is a monocyclic 5- or 6-membered aromatic or heteroaromatic ring;

B is a monocyclic 3-, 4-, 5-, 6- or 7-membered carbocyclic ring;

Y is a 5 or 6-membered aromatic or heteroaromatic ring;

R¹ is, independently at each occurrence, selected from hydrogen, CD3, halo, OCF3, CN, S(O)_p(C₁-C₆)alkyl, S(O)(NR^g)(C₁-C₆)alkyl, -S(O)_p(C₁-C₆)alkyl-OH, S(O)(NR^g)(C₁- C6)alkyl-OH, -thioalkoxyalkoxy, NR¹¹R¹¹, C_1-6 alkyl substituted with 0-3 R^1a, O-C_1-6 alkyl substituted with 0-3 R^1a, -(CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^1a and –(CR^1bR^1c)_r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^1a;

R^1a is, independently at each occurrence, hydrogen, =O, halo, CF₃, OCF₃, CN, NO₂, - (CR^1bR^1c)r-OR^b, -(CR^1bR^1c)r-S(O)pR^b, -(CR^1bR^1c)r-S(O)(NR^g)R^b, -(CR^1bR^1c)r-C(O)R^b, - (CR^1bR^1c)_r-C(O)OR^b, -(CR^1bR^1c)_r-OC(O)R^b, -(CR^1bR^1c)_r-NR¹¹R¹¹, -(CR^1bR^1c)_r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)r-NR^bC(O)R^c, -(CR^1bR^1c)r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹,

-S(O)_pNR¹¹R¹¹, -NR^bS(O)_pR^c, C_1-6 alkyl substituted with 0-3 R^a, C_1-6 haloalkyl, C_2-6 alkenyl substituted with 0-3 R^a, C2-6 alkynyl substituted with 0-3 R^a, -(CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^a, or–(CR^1bR^1c)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^a;

R^1b and R^1c are, independently at each occurrence, hydrogen, halogen or C1-6 alkyl; R² is, independently at each occurrence, hydrogen, C_1-6 alkyl substituted with 0-3 R^2a, =CR^2aR^2a, C2-6 alkenyl substituted with 0-3 R^2a, -( CR^2eR^2f)rOR^2b, -( CR^2eR^2f)rC(O)R^2b, -( CR^2eR^2f)rC(O)OR^2b, -( CR^2eR^2f)rOC(O)OR^2b, -( CR^2eR^2f)rOC(O)NR¹¹R¹¹, -( CR^2eR^2f)_rNR^2bC(O)NR¹¹R¹¹, -( CR^2eR^2f)_rC(O)NR¹¹R¹¹, -( CR^2eR^2f)_rS(O)_pR^c,

-( CR^2eR^2f)rS(O)(NR^g)R^c, -( CR^2eR^2f)rS(O)p NR¹¹R¹¹, -( CR^2eR^2f)rNR^2bC(O)R^2c,

-( CR^2eR^2f)_rNR^2bC(O)OR^2c , -( CR^2eR^2f)_r NR¹¹R¹¹, -( CR^2eR^2f)_rNR^2bS(O)_pR^c,

-( CR^2eR^2f)rNR^2bS(O)pNR¹¹R¹¹, -(CR^2eR^2f)r-3-10 membered carbocycle substituted with 0-3 R^2a or -( CR^2eR^2f)_r-4-10 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g) substituted with 0-3 R^2a; or one R² together with an R² on an adjacent carbon combine to form a fused ring substituted with 0-3 R^2a, wherein the fused ring is selected from 3-10 membered carbocycle substituted with 0-3 R^2a, or 3-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, P(O), S(O)_p and S(O)(NR^g), substituted with 0-3 R^2a;

R^2a is, independently at each occurrence, hydrogen, =O, halo, OCF3, CN, NO2, -(CR^2eR^2f)_r-OR^b, -(CR^2eR^2f)_r-S(O)_pR^b, -(CR^2eR^2f)_r-S(O)(NR^g)R^b, -(CR^2eR^2f)_r-C(O)R^b, -(CR^2eR^2f)r-C(O)OR^b, -(CR^2eR^2f)r-OC(O)R^b, -(CR^2eR^2f)r-OC(O)NR¹¹R¹¹, -(CR^2eR^2f)r- OC(O)OR^c, -(CR^2eR^2f)_r-NR¹¹R¹¹, -(CR^2eR^2f)_r-C(O)NR¹¹R¹¹, -(CR^2eR^2f)_r-NR^bC(O)R^c, -(CR^2eR^2f)r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹, -S(O)pNR¹¹R¹¹, -NR^bS(O)pR^c, C1-6 alkyl substituted with 0-3 R^a, C_1-6 haloalkyl, C_2-6 alkenyl substituted with 0-3 R^a, C_2-6 alkynyl substituted with 0-3 R^a, -(CR^2eR^2f)r-3-14 membered carbocycle substituted with 0-3 R^a, or– (CR^2eR^2f)_r-4-7 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^a;

R^2b is, independently at each occurrence, hydrogen, CF₃, -(CR^2eR^2f )_qOR^b,

-(CR^2eR^2f)_qS(O)_pR^b, -(CR^2eR^2f)_qS(O)(NR^g)R^b, -(CR^2eR^2f)_r-C(O)R^c, -(CR^2eR^2f)_r-C(O)OR^b, -(CR^2eR^2f)_qOC(O)R^b, -(CR^2eR^2f )_qNR¹¹R¹¹, -(CR^2eR^2f)r-C(O)NR¹¹R¹¹,

-(CR^2eR^2f)_qNR^bC(O)R^c, -(CR^2eR^2f)_qNR^bC(O)OR^c, -(CR^2eR^2f)_qNR^bC(O)NR¹¹R¹¹,

-(CR^2eR^2f)qS(O)₂NR¹¹R¹¹, -(CR^2eR^2f)qNR^bS(O)₂R^c, C_1-6 alkyl substituted with 0-2 R^a, C1-6 haloalkyl, -(CR^2eR^2f)r-3-14 membered carbocycle substituted with 0-3 R^a, or–(CR^2eR^2f)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^a;

R^2c is, independently at each occurrence, hydrogen, C_1-6 alkyl substituted with 0-3 R^a, C2-6 alkenyl substituted with 0-3 R^a, C3-10 cycloalkyl substituted with 0-3 R^a, C6-10 aryl substituted with 0-3 R^a, or–(CR^2eR^2f)_r-5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^a;

R^2e and R^2f are, independently at each occurrence, hydrogen, halogen or C_1-6 alkyl; R³ is, independently at each occurrence, selected from hydrogen, halo, N3, CN, -(CR^1bR^1c)_r-OR^3b, -(CR^1bR^1c)_r-NR¹¹R¹¹, C_1-6 alkyl substituted with 0-3 R^3a, C_3-10 cycloalkyl substituted with 0-3 R^3a; and phenyl substituted with 0-3 R^3a, or 4-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^3a , or two R³ located on adjacent carbon atoms link to form a 5-7 membered carbocycle or a 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatom selected from N, O, S(O)p and S(O)(NR^g), both optionally substituted with 0-3 R^3a;

R^3a is, independently at each occurrence, hydrogen, =O, halo, OCF3, OCHF2, CF3, CHF₂, CN, NO₂, -(CR^1bR^1c)_r-OR^b, -(CR^1bR^1c)_r-S(O)_pR^b, -(CR^1bR^1c)_r-S(O)(NR^g)R^b, - (CR^1bR^1c)r-C(O)R^b, -(CR^1bR^1c)r-C(O)OR^b, -(CR^1bR^1c)r-OC(O)R^b, -(CR^1bR^1c)r-NR¹¹R¹¹, - (CR^1bR^1c)_r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)_r-NR^bC(O)R^c, -(CR^1bR^1c)_r-NR^bC(O)OR^c, - NR^bC(O)NR¹¹R¹¹, -S(O)pNR¹¹R¹¹, -NR^bS(O)pR^c, C1-6 alkyl substituted with 0-3 R^a, C2-6 alkenyl substituted with 0-3 R^a, C_2-6 alkynyl substituted with 0-3 R^a, C_1-6 haloalkyl, - (CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^a, or–(CR^1bR^1c)r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^a;

R^3b is, independently at each occurrence, hydrogen, CF₃, -(CR^1bR^1c)_qOR^b,

-(CR^1bR^1c)qS(O)pR^b, -(CR^1bR^1c)qS(O)(NR^g)R^b, -(CR^1bR^1c)r-C(O)R^3d, -(CR^1bR^1c)r-C(O)OR^b, - (CR^1bR^1c)qOC(O)R^b, -(CR^1bR^1c)qNR¹¹R¹¹, -(CR^1bR^1c)r-C(O)NR¹¹R¹¹,

-(CR^1bR^1c)qNR^bC(O)R^3c, -(CR^1bR^1c)qNR^bC(O)OR^c, -(CR^1bR^1c)qNR^bC(O)N R¹¹R¹¹,

-(CR^1bR^1c)qS(O)₂N R¹¹R¹¹, -(CR^1bR^1c)qNR^bS(O)₂R^c, C_1-6 alkyl substituted with 0-3 R^a, C_1-6 haloalkyl, -(CR^1bR^1c)_r-3-14 membered carbocycle substituted with 0-3 R^a, or

-(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-3 R^a;

R^3c and R^3d are, independently at each occurrence, hydrogen or C1-6 alkyl;

R⁴ and R⁵ are independently hydrogen, halo, C(=O)C_1-4 alkyl, C(=O)OC_1-4 alkyl, C_1-6 alkyl or C1-6 haloalkyl, or

R⁴ and R⁵ taken together are =O, or together with the carbon atom to which they are attached form a 3- to 6-membered spirocarbocyclyl ring or a spiroheterocyclyl ring;

R⁶ and R⁷ are independently hydrogen, lkyl, C(=O)OC_1-4 alkyl, C_1-6 alkyl or C1-6 haloalkyl; or

R⁶ and R⁷ taken together are =O, or together with the carbon atom to which they are attached form a 3- to 6-membered spirocarbocyclyl ring or a spiroheterocyclyl ring; R¹¹ is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^f, CF₃, -(CR^1bR^1c)_r-C_3-10 cycloalkyl substituted with 0-3 R^f, -(CR^1bR^1c)_r-phenyl substituted with 0-3 R^d, or–(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^d;

or one R¹¹ and a second R¹¹, both attached to the same nitrogen atom, combine to form a heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^d;

R^a is, independently at each occurrence, hydrogen, =O, halo, OCF₃, CF₃, CHF₂, CN, NO2, -(CR^1bR^1c)r-OR^b, -(CR^1bR^1c)r-S(O)pR^b, -(CR^1bR^1c)r-S(O)(NR^g)R^b, -(CR^1bR^1c)r-C(O)R^b, - (CR^1bR^1c)_r-C(O)OR^b, -(CR^1bR^1c)_r-OC(O)R^b, -(CR^1bR^1c)_r-NR¹¹R¹¹, -(CR^1bR^1c)_r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)r-NR^bC(O)R^c, -(CR^1bR^1c)r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹,

-S(O)pNR¹¹R¹¹, -NR^bS(O)pR^c, -(CR^1bR^1c)r-O(CR^1bR^1cO)tP(O)(OR^b)2, -(CR^1bR^1c)r- O(CR^1bR^1cO)tS(O)2OR^b, C1-6 alkyl substituted with 0-3 R^f, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 R^e, C2-6 alkynyl substituted with 0-3 R^e, -(CR^1bR^1c)r-3-14 membered carbocycle, or–(CR^1bR^1c)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with

0-4 R^f;

R^b is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^d, C_1-6 haloalkyl, C_3-6 cycloalkyl substituted with 0-3 R^d, -(CR^1bR^1c)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^f ,or–(CR^1bR^1c)_r-6-10 membered carbocycle substituted with 0-3 R^d;

R^c is, independently at each occurrence, C1-6 alkyl substituted with 0-3 R^f,

-(CR^1bR^1c)_r-C_3-6 cycloalkyl substituted with 0-3 R^f, or–(CR^1bR^1c)_r-phenyl substituted with 0-3 R^f;

R^e is, independently at each occurrence, selected from hydrogen, C(O)NR^fR^f, C1-6 alkyl, C_3-6 cycloalkyl, -5-7 membered heterocycle or–(CR^1bR^1c)_r-phenyl substituted with 0-3 R^f; R^f is, independently at each occurrence, hydrogen, =O, halo, CN, NH2, NH(C1-6 alkyl), N(C₁-₆ alkyl)₂, SO₂(C₁-₆ alkyl), SO(NR^g)(C₁-₆ alkyl), CO₂H, CO₂(C₁-₆ alkyl), OH, C_3-6 cycloalkyl, CF3, O(C1-6 alkyl); or an optionally substituted–(CR^1bR^1c)r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), phenyl or C3-6 cycloalkyl, each group optionally substituted with halo, CN, CF3, C_1-6 alkyl or O(C₁-₆ alkyl);

R^g is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^f, C_1-6 haloalkyl, -(CR^1bR^1c)_r-C(O)R^b, -(CR^1bR^1c)_r-C(O)OR^b,-(CR^1bR^1c)_r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)r-3-14 membered carbocycle, or–(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, P(O) and S(O)_p substituted with 0-4 R^f;

m is 0, 1, 2 or 3;

p is, independently at each occurrence, 0, 1, or 2;

q is, independently at each occurrence, 2 or 3;

r is 0, 1, 2, 3, or 4; and

t is 0 or 1. 2. A compound according to claim 1 of the formula

wherein

X is–CR⁴R⁵-, -(CR⁴R⁵)2, -OCR⁶R⁷-, -S(O)pCR⁶R⁷-, -S(O)(NR^g)CR⁶R⁷- or

-NR⁶CR⁶R⁷-;

A is a monocyclic 5- or 6-membered aromatic or heteroaromatic ring;

B is a monocyclic 3-, 4-, 5-, 6- or 7-membered carbocyclic ring;

Y is a 5 or 6-membered aromatic or heteroaromatic ring; R¹ is, independently at each occurrence, selected from hydrogen, CD3, halo, OCF3, CN, S(O)_p(C₁-C₆)alkyl, S(O)(NR^g)(C₁-C₆)alkyl, -S(O)_p(C₁-C₆)alkyl-OH, S(O)(NR^g)(C₁- C6)alkyl-OH, -thioalkoxyalkoxy, NR¹¹R¹¹, lkyl substituted with 0-3 R^1a, -(CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^1a and –(CR^1bR^1c)r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^1a;

R^1a is, independently at each occurrence, hydrogen, =O, halo, CF3, OCF3, CN, NO2, - (CR^1bR^1c)r-OR^b, -(CR^1bR^1c)r-S(O)pR^b, -(CR^1bR^1c)r-S(O)(NR^g)R^b, -(CR^1bR^1c)r-C(O)R^b, - (CR^1bR^1c)_r-C(O)OR^b, -(CR^1bR^1c)_r-OC(O)R^b, -(CR^1bR^1c)_r-NR¹¹R¹¹, -(CR^1bR^1c)_r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)r-NR^bC(O)R^c, -(CR^1bR^1c)r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹,

R^1b and R^1c are, independently at each occurrence, hydrogen, halogen or C1-6 alkyl; R² is, independently at each occurrence, hydrogen, C_1-6 alkyl substituted with 0-3 R^2a, =CR^2aR^2a, C2-6 alkenyl substituted with 0-3 R^2a, -( CR^2eR^2f)rOR^2b, -( CR^2eR^2f)rC(O)R^2b, -( CR^2eR^2f)_rC(O)OR^2b, -( CR^2eR^2f)_rOC(O)OR^2b, -( CR^2eR^2f)_rOC(O)NR¹¹R¹¹,

-( CR^2eR^2f)rNR^2bC(O)NR¹¹R¹¹, -( CR^2eR^2f)rC(O)NR¹¹R¹¹, -( CR^2eR^2f)rS(O)pR^c,

-( CR^2eR^2f)_rS(O)(NR^g)R^c, -( CR^2eR^2f)_rS(O)_p NR¹¹R¹¹, -( CR^2eR^2f)_rNR^2bC(O)R^2c,

-( CR^2eR^2f)rNR^2bC(O)OR^2c , -( CR^2eR^2f)r NR¹¹R¹¹, -( CR^2eR^2f)rNR^2bS(O)pR^c,

-( CR^2eR^2f)_rNR^2bS(O)_pNR¹¹R¹¹, -(CR^2eR^2f)_r-3-10 membered carbocycle substituted with 0-3 R^2a or -( CR^2eR^2f)r-4-10 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g) substituted with 0-3 R^2a; or one R² together with an R² on an adjacent carbon combine to form a fused ring substituted with 0-3 R^2a, wherein the fused ring is selected from 3-10 membered carbocycle substituted with 0-3 R^2a, or 3-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, P(O), S(O)_p and S(O)(NR^g), substituted with 0-3 R^2a;

R^2a is, independently at each occurrence, hydrogen, =O, halo, OCF₃, CN, NO₂, -(CR^2eR^2f)r-OR^b, -(CR^2eR^2f)r-S(O)pR^b, -(CR^2eR^2f)r-S(O)(NR^g)R^b, -(CR^2eR^2f)r-C(O)R^b, -(CR^2eR^2f)_r-C(O)OR^b, -(CR^2eR^2f)_r-OC(O)R^b, -(CR^2eR^2f)_r-OC(O)NR¹¹R¹¹, -(CR^2eR^2f)_r- OC(O)OR^c, -(CR^2eR^2f)r-NR¹¹R¹¹, -(CR^2eR^2f)r-C(O)NR¹¹R¹¹, -(CR^2eR^2f)r-NR^bC(O)R^c, -(CR^2eR^2f)r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹, -S(O)pNR¹¹R¹¹, -NR^bS(O)pR^c, C1-6 alkyl substituted with 0-3 R^a, C_1-6 haloalkyl, C_2-6 alkenyl substituted with 0-3 R^a, C_2-6 alkynyl substituted with 0-3 R^a, -(CR^2eR^2f)r-3-14 membered carbocycle substituted with 0-3 R^a, or– (CR^2eR^2f)_r-4-7 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^a;

R^2b is, independently at each occurrence, hydrogen, CF₃, -(CR^2eR^2f )_qOR^b,

-(CR^2eR^2f)_qS(O)pR^b, -(CR^2eR^2f)_qS(O)(NR^g)R^b, -(CR^2eR^2f)r-C(O)R^c, -(CR^2eR^2f)r-C(O)OR^b, -(CR^2eR^2f)_qOC(O)R^b, -(CR^2eR^2f )_qNR¹¹R¹¹, -(CR^2eR^2f)r-C(O)NR¹¹R¹¹,

-(CR^2eR^2f)_qNR^bC(O)R^c, -(CR^2eR^2f)_qNR^bC(O)OR^c, -(CR^2eR^2f)_qNR^bC(O)NR¹¹R¹¹,

-(CR^2eR^2f)qS(O)₂NR¹¹R¹¹, -(CR^2eR^2f)qNR^bS(O)₂R^c, C_1-6 alkyl substituted with 0-2 R^a, C1-6 haloalkyl, -(CR^2eR^2f)_r-3-14 membered carbocycle substituted with 0-3 R^a, or–(CR^2eR^2f)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^a;

R^2e and R^2f are, independently at each occurrence, hydrogen, halogen or C_1-6 alkyl; R³ is, independently at each occurrence, selected from hydrogen, halo, N3, CN, -(CR^1bR^1c)_r-OR^3b, -(CR^1bR^1c)_r-NR¹¹R¹¹, C_1-6 alkyl substituted with 0-3 R^3a, C_3-10 cycloalkyl substituted with 0-3 R^3a; and phenyl substituted with 0-3 R^3a, or 4-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^3a , or two R³ located on adjacent carbon atoms link to form a 5-7 membered carbocycle or a 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatom selected from N, O, S(O)_p and S(O)(NR^g), both optionally substituted with 0-3 R^3a;

R^3b is, independently at each occurrence, hydrogen, CF₃, -(CR^1bR^1c)qOR^b,

-(CR^1bR^1c)_qS(O)_pR^b, -(CR^1bR^1c)_qS(O)(NR^g)R^b, -(CR^1bR^1c)_r-C(O)R^3d, -(CR^1bR^1c)_r-C(O)OR^b, - (CR^1bR^1c)qOC(O)R^b, -(CR^1bR^1c)qNR¹¹R¹¹, -(CR^1bR^1c)r-C(O)NR¹¹R¹¹,

-(CR^1bR^1c)_qNR^bC(O)R^3c, -(CR^1bR^1c)_qNR^bC(O)OR^c, -(CR^1bR^1c)_qNR^bC(O)N R¹¹R¹¹,

-(CR^1bR^1c)qS(O)₂N R¹¹R¹¹, -(CR^1bR^1c)qNR^bS(O)₂R^c, C_1-6 alkyl substituted with 0-3 R^a, C1-6 haloalkyl, -(CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^a, or

-(CR^1bR^1c)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^a;

R^3c and R^3d are, independently at each occurrence, hydrogen or C_1-6 alkyl;

R⁴ and R⁵ are independently hydrogen, halo, C(=O)C1-4 alkyl, C(=O)OC1-4 alkyl, C1-6 alkyl or C_1-6 haloalkyl, or

R⁴ and R⁵ taken together are =O, or together with the carbon atom to which they are attached form a 3- to 6-membered spirocarbocyclyl ring or a spiroheterocyclyl ring;

R⁶ and R⁷ are independently hydrogen, lkyl, C(=O)OC1-4 alkyl, C1-6 alkyl or C_1-6 haloalkyl; or

R⁶ and R⁷ taken together are =O, or together with the carbon atom to which they are attached form a 3- to 6-membered spirocarbocyclyl ring or a spiroheterocyclyl ring;

R¹¹ is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^f, CF3, -(CR^1bR^1c)r-C3-10 cycloalkyl substituted with 0-3 R^f, -(CR^1bR^1c)r-phenyl substituted with 0-3 R^d, or–(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^d;

or one R¹¹ and a second R¹¹, both attached to the same nitrogen atom, combine to form a heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-4 R^d;

R^a is, independently at each occurrence, hydrogen, =O, halo, OCF3, CF3, CHF2, CN, NO₂, -(CR^1bR^1c)_r-OR^b, -(CR^1bR^1c)_r-S(O)_pR^b, -(CR^1bR^1c)_r-S(O)(NR^g)R^b, -(CR^1bR^1c)_r-C(O)R^b, - (CR^1bR^1c)r-C(O)OR^b, -(CR^1bR^1c)r-OC(O)R^b, -(CR^1bR^1c)r-NR¹¹R¹¹, -(CR^1bR^1c)r-C(O)NR¹¹R¹¹, -(CR^1bR^1c)_r-NR^bC(O)R^c, -(CR^1bR^1c)_r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹,

-S(O)pNR¹¹R¹¹, -NR^bS(O)pR^c, -(CR^1bR^1c)r-O(CR^1bR^1cO)tP(O)(OR^b)2, -(CR^1bR^1c)r- O(CR^1bR^1cO)_tS(O)₂OR^b, C_1-6 alkyl substituted with 0-3 R^f, C_1-6 haloalkyl, C_2-6 alkenyl substituted with 0-3 R^e, C2-6 alkynyl substituted with 0-3 R^e, -(CR^1bR^1c)r-3-14 membered carbocycle, or–(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with

0-4 R^f;

R^b is, independently at each occurrence, hydrogen, C_1-6 alkyl substituted with 0-3 R^d, C1-6 haloalkyl, C3-6 cycloalkyl substituted with 0-3 R^d, -(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^f ,or–(CR^1bR^1c)r-6-10 membered carbocycle substituted with 0-3 R^d;

R^c is, independently at each occurrence, C_1-6 alkyl substituted with 0-3 R^f,

-(CR^1bR^1c)r-C3-6 cycloalkyl substituted with 0-3 R^f, or–(CR^1bR^1c)r-phenyl substituted with 0-3 R^f;

R^d is, independently at each occurrence, hydrogen, =O, halo, OCF3, CF3, CN, NO2, - OR^e, -(CR^1bR^1c)r-C(O)R^c, -NR^eR^e, -NR^eC(O)OR^c,C(O)NR^eR^e, -NR^eC(O)R^c, CO2H, CO2R^c, - NR^eSO2R^c, SO2R^c, SO(NR^g)R^c, C1-6 alkyl substituted with 0-3 R^f, C3-6 cycloalkyl substituted with 0-3 R^f, -(CR^1bR^1c)r-phenyl substituted with 0-3 R^f or–(CR^1bR^1c)r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^f;

R^e is, independently at each occurrence, selected from hydrogen, C(O)NR^fR^f, C_1-6 alkyl, C3-6 cycloalkyl, -5-7 membered heterocycle or–(CR^1bR^1c)r-phenyl substituted with 0-3 R^f;

R^f is, independently at each occurrence, hydrogen, =O, halo, CN, NH2, NH(C1-6 alkyl), N(C₁-₆ alkyl)₂, SO₂(C₁-₆ alkyl), SO(NR^g)(C₁-₆ alkyl), CO₂H, CO₂(C₁-₆ alkyl), OH, C_3-6 cycloalkyl, CF3, O(C1-6 alkyl); or an optionally substituted–(CR^1bR^1c)r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), phenyl or C3-6 cycloalkyl, each group optionally substituted with halo, CN, CF3, C_1-6 alkyl or O(C₁-₆ alkyl);

m is 0, 1, 2 or 3;

p is, independently at each occurrence, 0, 1, or 2;

q is, independently at each occurrence, 2 or 3; and

r is 0, 1, 2, 3, or 4; or a stereoisomer or pharmaceutically-acceptable salt thereof. 3. A compound according to claim 2 of the formula

wherein

X is–CR⁴R⁵-, -(CR⁴R⁵)2, -OCR⁶R⁷-, -S(O)pCR⁶R⁷-, -S(O)(NR^g)CR⁶R⁷- or

-NR⁶CR⁶R⁷-;

A is a monocyclic 5- or 6-membered aromatic or heteroaromatic ring;

Y is a 5 or 6-membered aromatic or heteroaromatic ring;

R¹ is, independently at each occurrence, selected from hydrogen, CD3, halo, OCF3, CN, S(O)p(C1-C6)alkyl, S(O)(NR^g)(C1-C6)alkyl, -S(O)p(C1-C6)alkyl-OH, S(O)(NR^g)(C1- C6)alkyl-OH, -thioalkoxyalkoxy, NR¹¹R¹¹, C_1-6 alkyl substituted with 0-3 R^1a, O-C_1-6 alkyl substituted with 0-3 R^1a, -(CR^1bR^1c)r-3-14 membered carbocycle substituted with 0-3 R^1a and –(CR^1bR^1c)_r-5-10 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^1a;

R^1b and R^1c are, independently at each occurrence, hydrogen, halogen or C_1-6 alkyl; R² is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^2a, =CR^2aR^2a, C_2-6 alkenyl substituted with 0-3 R^2a, -( CR^2eR^2f)_rOR^2b, -( CR^2eR^2f)_rC(O)R^2b, -( CR^2eR^2f)rC(O)OR^2b, -( CR^2eR^2f)rOC(O)OR^2b, -( CR^2eR^2f)rOC(O)NR¹¹R¹¹, -( CR^2eR^2f)rNR^2bC(O)NR¹¹R¹¹, -( CR^2eR^2f)rC(O)NR¹¹R¹¹, -( CR^2eR^2f)rS(O)pR^c,

-( CR^2eR^2f)_rS(O)(NR^g)R^c, -( CR^2eR^2f)_rS(O)_p NR¹¹R¹¹, -( CR^2eR^2f)_rNR^2bC(O)R^2c,

-( CR^2eR^2f)rNR^2bC(O)OR^2c , -( CR^2eR^2f)r NR¹¹R¹¹, -( CR^2eR^2f)rNR^2bS(O)pR^c,

R^2a is, independently at each occurrence, hydrogen, =O, halo, OCF₃, CN, NO₂, -(CR^2eR^2f)r-OR^b, -(CR^2eR^2f)r-S(O)pR^b, -(CR^2eR^2f)r-S(O)(NR^g)R^b, -(CR^2eR^2f)r-C(O)R^b, -(CR^2eR^2f)_r-C(O)OR^b, -(CR^2eR^2f)_r-OC(O)R^b, -(CR^2eR^2f)_r-OC(O)NR¹¹R¹¹, -(CR^2eR^2f)_r- OC(O)OR^c, -(CR^2eR^2f)r-NR¹¹R¹¹, -(CR^2eR^2f)r-C(O)NR¹¹R¹¹, -(CR^2eR^2f)r-NR^bC(O)R^c, -(CR^2eR^2f)_r-NR^bC(O)OR^c, -NR^bC(O)NR¹¹R¹¹, -S(O)_pNR¹¹R¹¹, -NR^bS(O)_pR^c, C_1-6 alkyl substituted with 0-3 R^a, C1-6 haloalkyl, C2-6 alkenyl substituted with 0-3 R^a, C2-6 alkynyl substituted with 0-3 R^a, -(CR^2eR^2f)_r-3-14 membered carbocycle substituted with 0-3 R^a, or– (CR^2eR^2f)r-4-7 membered heterocycle comprising carbon atoms, and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^a;

R^2b is, independently at each occurrence, hydrogen, CF₃, -(CR^2eR^2f )_qOR^b,

-(CR^2eR^2f)_qS(O)pR^b, -(CR^2eR^2f)_qS(O)(NR^g)R^b, -(CR^2eR^2f)r-C(O)R^c, -(CR^2eR^2f)r-C(O)OR^b, -(CR^2eR^2f)_qOC(O)R^b, -(CR^2eR^2f )_qNR¹¹R¹¹, -(CR^2eR^2f)_r-C(O)NR¹¹R¹¹,

-(CR^2eR^2f)qNR^bC(O)R^c, -(CR^2eR^2f)qNR^bC(O)OR^c, -(CR^2eR^2f)qNR^bC(O)NR¹¹R¹¹,

-(CR^2eR^2f)_qS(O)₂NR¹¹R¹¹, -(CR^2eR^2f)_qNR^bS(O)₂R^c, C_1-6 alkyl substituted with 0-2 R^a, C_1-6 haloalkyl, -(CR^2eR^2f)_r-3-14 membered carbocycle substituted with 0-3 R^a, or–(CR^2eR^2f)_r-5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^a;

R^2c is, independently at each occurrence, hydrogen, C1-6 alkyl substituted with 0-3 R^a, C_2-6 alkenyl substituted with 0-3 R^a, C_3-10 cycloalkyl substituted with 0-3 R^a, C_6-10 aryl substituted with 0-3 R^a, or–(CR^2eR^2f)r-5-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, S(O)_p and S(O)(NR^g), substituted with 0-4 R^a;

R^2e and R^2f are, independently at each occurrence, hydrogen, halogen or C1-6 alkyl; R³ is, independently at each occurrence, selected from hydrogen, halo, N3, CN, -(CR^1bR^1c)_r-OR^3b, -(CR^1bR^1c)_r-NR¹¹R¹¹, C_1-6 alkyl substituted with 0-3 R^3a, C_3-10 cycloalkyl substituted with 0-3 R^3a; and phenyl substituted with 0-3 R^3a, or 4-10 membered heterocycle containing 1-4 heteroatoms selected from N, O, S(O)p and S(O)(NR^g), substituted with 0-3 R^3a , or two R³ located on adjacent carbon atoms link to form a 5-7 membered carbocycle or a 5-7 membered heterocycle comprising carbon atoms and 1-4 heteroatom selected from N, O, S(O)p and S(O)(NR^g), both optionally substituted with 0-3 R^3a;