PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY

• US 20100222366A1
• Filed: 07/23/2008
• Published: 09/02/2010
• Est. Priority Date: 07/24/2007
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Hynes, John, Santella, Joseph B., Gardner, Daniel S.
• Granted Patent: US 8,536,198 B2
• Time in Patent Office: Days
• US Class Current: 514/255.50
• 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 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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 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 27/02 Ophthalmic agents
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• 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 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• 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: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• 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 405/06 : linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links

Abstract

The present application describes modulators of MIP-1 of formula (I): or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R1, R3, R4, R5, R5a and R5b, are as set forth above. 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 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

X is C(R₈);

Y is CH(R_1a), CH₂, O, S, S(O), S(O)₂, N(R₈), C(═

O) or

Z₁ is CH(R₇), CH₂, O, S, N(R₈), S(O) or S(O)₂;

T is a bond,

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

provided that R₁ is not unsubstituted phenyl when T is

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;

R₄ is hydrogen, F, OH, CN or —

NH₂;

R₅ is hydrogen, halo, —

CN or —

Oalkyl;

R_5a is hydrogen, halo, —

CN or alkynyl;

R_5b is hydrogen, halo, —

CN or —

Oalkyl;

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

R₇, 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_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;

r is 0-5;

provided that;

(1) R⁵, R^5a and R^5b are not all H when T is a bond and R⁴ is H or OH; and

(2) R⁴ is not piperidin-4-yl, pyridine-4-yl, or pyrimidin-4-yl, when T is a bond and R⁴ is H.

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

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

Z is O or S;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O, S, S(O), S(O)₂, N(R₈), C(═

O) or

Z₁ is CH(R₇), CH₂, O, S, N(R₈), S(O) or S(O)₂;

T is

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

provided that R₁ is not unsubstituted phenyl when T is

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;

R₄ is hydrogen, F, OH, CN 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, 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_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.

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

Z is O or S;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O, S, S(O)₂, N(R₈), C(═

O) or

Z₁ is CH(R₇), CH₂, O, S, N(R₈) or S(O)₂;

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, —

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;

R₄ is hydrogen, F, OH, CN 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, 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_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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O, S, S(O)₂, N(R₈) or C(═

O);

Z₁ is CH(R₇), CH₂, O, S or N(R₈);

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;

R₄ is hydrogen, 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, 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_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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O, S, S(O)₂, N(R₈), or C(═

O);

Z₁ is CH(R₇), CH₂, O or N(R₈);

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;

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

R₄ is hydrogen, 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, 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_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(═

)NR₁₄H₁₄, 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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O, S or S(O)₂;

Z₁ is CH(R₇), CH₂ or O;

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;

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

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, 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_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(═

)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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a), CH₂, O or S;

Z₁ is CH(R₇) or CH₂;

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;

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

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, 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_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;

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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a), CH₂ or O;

Z₁ is CH(R₇) or CH₂;

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 alkyl;

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;

R₇, 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_7b;

R_7b, 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;

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.

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

Z is O;

W is

X is C(R₈);

Y is CH(R_1a) or CH₂;

Z₁ is CH(R₇) or CH₂;

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, heteroaryl, heterocyclyl, 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, or aryloxy, wherein the alkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl and aryloxy may be optionally substituted with 0-3 R_1b;

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, 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, or aryloxy;

R₃, at each occurrence, is alkyl;

R₄ is OH;

R₅ is hydrogen or halo;

R_5a is halo;

R_5b is hydrogen or halo;

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

R₇, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, 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 or aryloxy, wherein the alkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl and aryloxy may be optionally substituted with 0-3 R_7b;

R_7b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, 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 or aryloxy;

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, heteroaryl, heterocyclyl, 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, or aryloxy;

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, heteroaryl, heterocyclyl, 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 or aryloxy;

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

X is CH;

Y is CH₂;

Z₁ is CH₂;

T is

R₁ is alkyl, cycloalkyl, aryl 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, heteroaryl, heterocyclyl, 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, —

OC(═

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

R_1b, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, 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, or aryloxy;

R₃, at each occurrence, is alkyl;

R₄ is OH;

R₅ is hydrogen or halo;

R_5a is chloro;

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, heteroaryl, heterocyclyl, 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, or aryloxy;

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, heteroaryl, heterocyclyl, 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 or aryloxy;

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.