PIPERIDINYL DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

• US 20090298833A1
• Filed: 07/20/2009
• Published: 12/03/2009
• Est. Priority Date: 01/27/2006
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Carter, Percy H., Hynes, John, Cavallaro, Cullen L., Santella, Joseph B., Gardner, Daniel S., Liu, Rui-Qin, Duncia, John V., Dodd, Dharmpal S.
• Granted Patent: US 7,985,861 B2
• Time in Patent Office: Days
• US Class Current: 514/236.8
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/18 : with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 211/38 : Halogen atoms or nitro radicals
• CPC Class Codes: C07D 211/52 : having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 211/58 : attached in position 4
• CPC Class Codes: C07D 211/70 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/10 : Spiro-condensed systems
• CPC Class Codes: C07D 491/107 : with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

The present application describes substituted piperidinyl modulators of MIP-1α or CCR-1 or stereoisomers or pharmaceutically acceptable salts thereof. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and transplant rejection using said modulators are disclosed.

Claims

1. A compound of Formula (I):

or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein;

the dashed line represents an optional double bond;

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, or alkenyl, wherein the alkyl may be optionally substituted with —

OH;

R₃, at each occurrence, is alkyl;

or any two R₃'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring;

W is hydrogen, F, —

OH, —

CN, —

NH₂;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-3; and

r is 0-5.

2. The compound of claim 1, wherein the compound is a compound of formula (Ia):

3. The compound of claim 2, wherein:

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, or alkenyl, wherein the alkyl may be optionally substituted with —

OH;

R₃, at each occurrence, is alkyl;

or any two R₃'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring;

W is hydrogen, F, —

OH, —

NH₂;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-2; and

r is 0-4.

4. The compound of claim 2, wherein:

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, or cycloalkylalkyl, wherein the alkyl may be optionally substituted with —

OH;

R₃, at each occurrence, is alkyl;

or any two R₃'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring;

W is hydrogen, F, —

OH, —

NH₂;

R₅ is halo or —

CN;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-2; and

r is 0-3.

5. The compound of claim 2, wherein:

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl or cycloalkyl, wherein the alkyl may be optionally substituted with —

OH;

R₃, at each occurrence, is alkyl;

or any two R₃'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring;

W is hydrogen, F, —

OH, —

NH₂;

R₅ is halo;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-2; and

r is 0-2.

15. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more compounds according to claim 1.

16. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more compounds according to claim 1, wherein said disorder is selected from osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn'"'"'s disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, arthrosclerosis, rheumatoid arthritis, restinosis, organ transplantation, psoriatic arthritis, multiple myeloma, allergies, hepatocellular carcinoma, osteoporosis, renal fibrosis and cancer.

6. A compound of Formula (Ib):

or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, —

CH₂CH₂CH₂NHC(═

NR₁₄)NR₁₄R₁₄, —

CH₂CH₂S(CR₈R₈)_rR₁₀ or —

CH₂CH₂CN, wherein the alkyl and arylalkyl may be optionally substituted with —

OH;

R₄, at each occurrence, is F, —

OH or alkyl;

or any two alkyl R₄'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S;

W is hydrogen, F, —

OH, —

CN, —

NH₂;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2; and

r is 0-5.

7. The compound of claim 6, wherein the compound is a compound of formula (Ib′

);

wherein

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, —

CH₂CH₂CH₂—

NHC(═

NH)NH₂, —

CH₂CH₂SCH₃, —

CH₂CH₂CN,

 

wherein the alkyl may be optionally substituted with —

OH;

R₄, at each occurrence, is —

OH or alkyl;

or any two alkyl R₄'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S;

W is hydrogen or OH;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m is 1 or 2; and

r is 0-4.

8. The compound of claim 7, wherein:

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, —

CH₂CH₂SCH₃, —

CH₂CH₂CN,

 

wherein the alkyl may be optionally substituted with —

OH;

R₄, at each occurrence, is —

OH or alkyl;

or any two alkyl R₄'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S;

R₅ is halo or —

CN;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl; and

r is 0-3.

9. The compound of claim 7, wherein:

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl,

 

wherein the alkyl may be optionally substituted with —

OH;

R₄, at each occurrence, is alkyl;

or any two alkyl R₄'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S;

R₅ is halo;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl; and

r is 0-2.

10. The compound of claim 7, wherein R₂ is isopropyl, sec-butyl or cyclopropyl;

R₄ is methyl;

R₅ is Cl, F or Br; and

R₁ is alkyl, cycloalkyl, aryl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a.

11. The compound of claim 10, wherein:

T is

17. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more compounds according to claim 7.

18. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more compounds according to claim 7, wherein said disorder is selected from osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn'"'"'s disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, arthrosclerosis, rheumatoid arthritis, restinosis, organ transplantation, psoriatic arthritis, multiple myeloma, allergies, hepatocellular carcinoma, osteoporosis, renal fibrosis and cancer.

12. A compound of formula (Ic):

or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein;

R₁₅ is —

NHR₁, heteroaryl or aryl, wherein the heteroaryl and aryl may be optionally substituted with 0-3 R_1a;

R₁ is aryl or heteroaryl, both of which may be optionally substituted with 0-3 R_1a, provided that when R₁ is phenyl, R_1a cannot be ortho-methoxy;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl or cycloalkylalkyl, wherein the alkyl may be optionally substituted with —

OH;

R₄, at each occurrence, is F, —

OH or alkyl;

or any two alkyl R₄'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, which optionally may contain 1-4 heteroatoms selected from N, O, and S;

W is hydrogen, F, —

OH or —

NH₂;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 1[k'"'"'aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-3; and

r is 0-5.

13. The compound of claim 12, wherein the compound is a compound of formula (Id):

19. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of one or more compounds according to claim 12.

20. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of one or more compounds according to claim 12, wherein said disorder is selected from osteoarthritis, aneurysm, fever, cardiovascular effects, Crohn'"'"'s disease, congestive heart failure, autoimmune diseases, HIV-infection, HIV-associated dementia, psoriasis, idiopathic pulmonary fibrosis, transplant arteriosclerosis, physically- or chemically-induced brain trauma, inflammatory bowel disease, alveolitis, colitis, systemic lupus erythematosus, nephrotoxic serum nephritis, glomerulonephritis, asthma, multiple sclerosis, arthrosclerosis, rheumatoid arthritis, restinosis, organ transplantation, psoriatic arthritis, multiple myeloma, allergies, hepatocellular carcinoma, osteoporosis, renal fibrosis and cancer.

14. A compound of Formula (Ie):

or stereoisomers or pharmaceutically acceptable salt forms thereof, wherein;

the dashed line represents an optional double bond;

T is

R₁ is alkyl, cycloalkyl, aryl, heterocyclyl or heteroaryl, all of which may be optionally substituted with 0-5 R_1a;

R_1a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, —

S(O)₂NR₉C(O)R₆, aryloxy or arylalkyl, wherein the aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₉R₉, —

NR₉R₉, —

S(O)₂NR₉R₉, —

NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₉S(O)₂R₆, —

S(O)₂NR₉C(═

O)OR₆, —

S(O)₂NR₉C(═

O)NR₉R₉, —

C(═

O)NR₉S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₀, —

NR₉C(═

O)H, —

NR₉C(═

O)(CR₈R₈)_rR₁₀, —

OC(═

O)(CR₈R₈)_rR₁₀, —

C(═

NR₁₄)NR₉R₉, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₈, —

NR₉S(O₂)R₈, aryloxy or arylalkyl;

R₂ is alkyl, cycloalkyl, cycloalkylalkyl, or alkenyl, wherein the alkyl may be optionally substituted with —

OH;

R₅ is halo, —

CN or —

Oalkyl;

R₆, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;

R₈, at each occurrence, is independently hydrogen or alkyl;

R₉, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-5 R_9a, and the heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the alkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl may be optionally substituted with 0-3 R_10a, and the heterocyclyl and heterocyclylalkyl contain 1-4 heteroatoms selected from N, O, and S;

R_10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

NH₂, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

P(O)₃H₂, —

C(═

O)NR₁₄R₁₄, —

NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)NR₁₄S(O)₂R₆, —

S(O)₂NR₁₄C(═

O)OR₆, —

S(O)₂NR₁₄C(═

O)NR₁₄R₁₄, —

C(═

O)NR₁₄S(O)₂(CF₂)_rCF₃, —

C(═

O)(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)H, —

NR₁₄C(═

O)(CR₈R₈)_rR₁₄, —

OC(═

O)(CR₈R₈)_rR₁₄, —

C(═

NR₁₄)NR₁₄R₁₄, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₈, —

NR₁₄S(O₂)R₈, aryloxy or arylalkyl;

R₁₄, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl or phenyl;

m, at each occurrence, is 0-2;

n is 1-3; and

r is 0-5.