PIPERIDINYL DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

• US 20100204274A1
• Filed: 07/23/2008
• Published: 08/12/2010
• Est. Priority Date: 07/24/2007
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Carter, Percy H., Hynes, John, Dhar, T.G. Murali, Santella, Joseph B., Gardner, Daniel S., Duncia, John V.
• Granted Patent: US 8,501,782 B2
• Time in Patent Office: Days
• US Class Current: 514/318
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 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 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 211/52 : having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present application describes modulators of MIP-1α of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R₁, R₃, R₄, R₅, R_5a and R_5b, are as defined herein. 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 atherosclerosis using the modulators of formula (I) are disclosed.

Claims

1. A compound of Formula (I):

or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein;

Q is CH or N;

Z is O or S;

W is —

CR_3aR_3aCR_3bR_3b—

;

T is a bond,

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, —

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)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

or two R₃'"'"'s together with the carbon atom to which they are attached may form a 3- to 6-membered ring;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆, —

(CR₈R₈)_rNH₂, —

(CR₈R₈)_rNHR₆, —

(CR₈R₈)_rNR₆R₆, —

(CR₈R₈)_rNHC(═

O)R₆, —

(CR₈R₈)_rNHC(═

O)NH₂, —

(CR₈R₈)_rNHC(═

O)NHR₆, —

(CR₈R₈)_rNHC(═

O)NR₆R₆, —

(CR₈R₈)_rNHC(═

O)OR₆, —

(CR₈R₈)_rC(═

O)NH₂, —

(CR₈R₈)_rC(═

O)NHR₆, —

(CR₈R₈)_rC(═

O)NR₆R₆ or —

NHS(═

O)₂R₆, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂,

—

NHC(═

O)NHR₆, —

NHC(═

O)NR₆R₆, or —

NHS(═

O)₂R₆;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is hydrogen, F, OH, CN or —

NH₂;

R₅ is hydrogen, halo, alkyl, —

CN or —

Oalkyl;

R_5a is halo, —

CN or alkynyl;

R_5b is hydrogen, halo, —

CN, —

Oalkyl or —

C(═

O)O(CR₈R₈)_rR₁₀;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

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)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

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)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-5;

provided that;

1) the compound is not a compound of the formula;

2) m is not 0 or 1 when R₁ is not a nitrogenated aromatic monocyclic group or nitrogenated aromatic fused-ring group which has at least one hydroxyl and/or amino; and

3) R₄ is not hydrogen or CN when both R_3a'"'"'s and R_3b'"'"'s are hydrogen and R₁ is benzyl or phenylcyclopropyl.

2. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein Q is CH.

3. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein R_3b, at each occurrence, is independently alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

C(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂, —

NHC(═

O)NHR₆, —

NHC(═

O)NR₆R₆, or —

NHS(═

O)₂R₆.

4. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein the compound is a compound of formula (Ia):

5. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O or S;

W is —

CR_3aR_3aCR_3bR_3b—

;

T is a bond,

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, —

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, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

or two R₃'"'"'s together with the carbon atom to which they are attached may form a 3- to 6-membered ring;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆, —

(CR₈R₈)_rNH₂, —

(CR₈R₈)_rNHR₆, —

(CR₈R₈)_rNR₆R₆, —

(CR₈R₈)_rNHC(═

O)R₆, —

(CR₈R₈)_rNHC(═

O)NH₂, —

(CR₈R₈)_rNHC(═

O)NHR₆, —

(CR₈R₈)_rNHC(═

O)NR₆R₆, —

(CR₈R₈)_rNHC(═

O)OR₆, —

(CR₈R₈)_rC(═

O)NH₂, —

(CR₈R₈)_rC(═

O)NHR₆, or —

(CR₈R₈)_rC(═

O)NR₆R₆, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl or arylalkyl, wherein the alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl or arylalkyl, may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂, —

NHC(═

O)NHR₆, —

NHC(═

O)NR₆R₆, or —

NHS(═

O)₂R₆;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is F, OH, CN or —

NH₂;

R₅ is hydrogen, alkyl, halo or —

CN;

R_5a is halo, —

CN or alkynyl;

R_5b is hydrogen, halo or —

CN;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

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, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

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, —

NHC(═

NR₁₄)NR₁₄R₁₄, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-4.

6. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O or S;

W is —

CR_3aR_3aCR_3bR_3b—

;

T is a bond,

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, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

or two R₃'"'"'s together with the carbon atom to which they are attached may form a 3- to 6-membered ring;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rOC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆, —

(CR₈R₈)_rNH₂, —

(CR₈R₈)_rNHR₆, —

(CR₈R₈)_rNR₆R₆, —

(CR₈R₈)_rNHC(═

O)R₆, —

(CR₈R₈)_rNHC(═

O)NH₂, —

(CR₈R₈)_rNHC(═

O)NHR₆, —

(CR₈R₈)_rC(═

O)NH₂ or —

(CR₈R₈)_rC(═

O)NHR₆, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkylalkyl, silylalkyl or arylalkyl, wherein the alkyl, cycloalkyl, alkenyl, cycloalkylalkyl, silylalkyl or arylalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂, —

NHC(═

O)NHR₆, —

NHC(═

O)NR₆R₆, or —

NHS(═

O)₂R₆;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is F, OH or —

NH₂;

R₅ is hydrogen, halo or —

CN;

R_5a is halo, —

CN or alkynyl;

R_5b is hydrogen, halo or —

CN;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-3.

7. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O;

W is —

CR_3aR_3aCR_3bR_3b—

,

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, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

or two R₃'"'"'s together with the carbon atom to which they are attached may form a 3- to 6-membered ring;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rOC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆, —

(CR₈R₈)_rNH₂, —

(CR₈R₈)_rNHR₆, —

(CR₈R₈)_rNR₆R₆, —

(CR₈R₈)_rNHC(═

O)R₆, —

(CR₈R₈)_rNHC(═

O)NH₂ or —

(CR₈R₈)_rC(═

O)NH₂, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkylalkyl or arylalkyl, wherein the alkyl, cycloalkyl, alkenyl, cycloalkylalkyl or arylalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂, —

NHC(═

O)NHR₆, —

NHC(═

O)NR₆R₆, or —

NHS(═

O)₂R₆;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is F, OH, or —

NH₂;

R₅ is hydrogen, halo or —

CN;

R_5a is halo, —

CN or alkynyl;

R_5b is hydrogen, halo or —

CN;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

S(O)₃H, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

S(O)₃H, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-2.

8. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O;

W is —

CR_3aR_3aCR_3bR_3b—

;

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, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆, —

(CR₈R₈)_rNH₂, —

(CR₈R₈)_rNHR₆, —

(CR₈R₈)_rNR₆R₆ or —

(CR₈R₈)_rC(═

O)NH₂, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl or arylalkyl, wherein the alkyl, cycloalkyl, alkenyl or arylalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, OH, CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, —

NHC(═

O)NH₂, —

NHC(═

O)NHR₆ or —

NHC(═

O)NR₆R₆;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is F, OH or —

NH₂;

R₅ is hydrogen, halo or —

CN;

R_5a is halo or —

CN;

R_5b is hydrogen, halo or —

CN;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

CN, —

NO₂, —

C(═

O)OH, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-2.

9. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O;

W is —

CR_3aR_3aCR_3bR_3b—

;

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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_1b;

or any two R_1a'"'"'s attached to the same carbon atom may form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, —

(CR₈R₈)_rOC(═

O)NHR₆, —

(CR₈R₈)_rOC(═

O)NR₆R₆ or —

(CR₈R₈)_rNH₂, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl, cycloalkyl or alkenyl, wherein the alkyl, cycloalkyl or alkenyl, may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, or —

NHC(═

O)NH₂;

or the two R_3a'"'"'s or R_3b'"'"'s may be taken together with the carbon atom to which they are attached to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N(R₇), O, and S;

R₄ is F or OH;

R₅ is hydrogen, halo or —

CN;

R_5a is halo or —

CN;

R_5b is hydrogen, halo or —

CN;

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

R₇ is hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₉R₉, —

S(O)₂NR₉R₉, —

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 or arylalkyl, wherein the alkyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, aryloxy and arylalkyl may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

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;

or any two R₉'"'"'s may be taken to form a 3- to 6-membered ring, wherein the carbon atoms of said ring may be optionally replaced with a heteroatom selected from N, O, and S and the N heteroatom of said ring may be optionally substituted with one or more of the following;

hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, —

C(═

O)O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

C(═

O)NR₁₄R₁₄, —

S(O)₂NR₁₄R₁₄, —

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)_rR₁₀ or arylalkyl;

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

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-2.

10. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O;

W is —

CR_3aR_3aCR_3bR_3b—

;

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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, 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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, —

(CR₈R₈)_rOH, —

(CR₈R₈)_rCN, —

(CR₈R₈)_rOR₆, —

(CR₈R₈)_rOC(═

O)R₆, —

(CR₈R₈)_rOC(═

O)NH₂, or —

(CR₈R₈)_rC(═

O)NHR₆, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

provided that both R_3a'"'"'s can not be simultaneously attached via a heteroatom;

R_3b, at each occurrence, is independently hydrogen, alkyl or cycloalkyl, wherein the alkyl or cycloalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, —

NH₂, —

NHR₆, —

NR₆R₆, —

NHC(═

O)R₆, or —

NHC(═

O)NH₂;

R₄ is F or OH;

R₅ is hydrogen, halo or —

CN;

R_5a is halo or —

CN;

R_5b is hydrogen, 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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

R₁₀, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, wherein the 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, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-2.

11. The compound of claim 1, or a stereoisomer or pharmaceutically acceptable salt from thereof, wherein:

Z is O;

W is —

CR_3aR_3aCR_3bR_3b—

;

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, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, ═

O, —

OC(═

O)NR₉R₉, aryloxy or arylalkyl, wherein the alkyl, 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, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl heterocyclylalkyl, halo, —

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₀, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₀, —

OH, —

SH, —

S(CR₈R₈)_rR₁₀, —

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, —

S(═

O)(CR₈R₈)_rR₁₀, —

S(O)₂(CR₈R₈)_rR₁₀, —

NR₉C(═

O)OR₆, —

NR₉S(O₂)R₆, aryloxy, arylalkyl or arylalkyloxyalkyl;

R₃, at each occurrence, is independently OH or alkyl;

R_3a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkylalkyl, silylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, OH, —

OR₆ or —

OC(═

O)R₆, wherein the alkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom;

R_3b, at each occurrence, is independently hydrogen, alkyl or cycloalkyl, wherein the alkyl or cycloalkyl may be optionally substituted with 0-3 fluorine atoms per carbon atom, —

OH, —

CN, —

OR₆, —

OC(═

O)R₆, —

OC(═

O)NH₂, —

OC(═

O)NHR₆, —

OC(═

O)NR₆R₆, or —

NH₂;

R₄ is OH;

R₅ is hydrogen or halo;

R_5a is halo or —

CN;

R_5b is hydrogen or halo;

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

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

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

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

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

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

CN, —

NO₂, —

C(═

O)O(CR₈R₈)_rR₁₄, —

O(CF₂)_rCF₃, —

O(CR₈R₈)_rR₁₄, —

OH, —

SH, —

S(CR₈R₈)_rR₁₄, —

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, —

S(═

O)(CR₈R₈)_rR₁₄, —

S(O)₂(CR₈R₈)_rR₁₄, —

NR₁₄C(═

O)OR₆, —

NR₁₄S(O₂)R₆, —

OC(═

O)NR₁₄R₁₄, aryloxy or arylalkyl;

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

m is 0-2; and

r is 0-2.

12. A pharmaceutical composition comprised of a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1.

13. A method for modulation of chemokine or chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 1.

14. A method for treating a disorder comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound of 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, glomerularnephritis, asthma, multiple sclerosis, artherosclerosis, rheumatoid arthritis, restinosis, organ transplantation, and cancer.

15. A method for treating inflammatory diseases comprising administering to a patient in need thereof a therapeutically effective amount of at least one compound of claim 1.