# US 2010/0168243 A1 · Renin Inhibitors

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- Number: US 2010/0168243 A1
- Document ID: US20100168243A1
- Status: Published application
- Kind: A1
- Application number: 12/665,222
- Filed: 2008-06-20
- Published: 2010-07-01
- Earliest claimed: 2007-06-20
- Inventors: John J. Baldwin; Salvacion Cacatian; David A. Claremon; Lawrence W. Dillard; Patrick T. Flaherty; Alexey V. Ishehenko; Lanqi Jia; Gerard McGeehan; Robert D. Simpson; Suresh B. Singh; Colin M. Tice; Zhenrong Xu; Jing Yuan; Wei Zhao; Linghang Zhuang; Jing Zhang
- Web page: https://patentgrep.com/patent/US20100168243A1

## CPC

- C07C 237/24: having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
- A61P 5/40: Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/12: Antihypertensives
- C07C 237/32: having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
- C07C 2601/08: the ring being saturated
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to aspartic protease inhibitors. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using the disclosed aspartic protease inhibitors.

## Claims

### Claim 1

A compound represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
R is:
a) hydrogen;
b) (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C3-C7)cycloalkyl(C1-C3)alkyl, (C3-C7)cycloalkyl(C2-C3)alkenyl, (C3-C7)cycloalkyl(C2-C3)alkynyl, (C1-C8)alkoxy, (C3-C8)alkenyloxy, (C3-C8)alkynyloxy, (C3-C7)cycloalkoxy, (C5-C7)cycloalkenyloxy, (C3-C7)cycloalkoxy(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkoxy, (C5-C7)cycloalkenyl(C1-C3)alkoxy, (C1-C8)alkylthio, (C3-C8)alkenylthio, (C3-C8)alkynylthio, (C3-C7)cycloalkylthio(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkylthio, (C5-C7)cycloalkenyl(C1-C3)alkylthio, (C1-C8)alkylamino, di(C1-C8)alkylamino, azepano, azetidino, piperidine, pyrrolidino, (C3-C7)cycloalkylamino, ((C3-C7)cycloalkyl(C1-C3)alkyl)amino, or tri(C1-C4)alkylsilyl, each optionally and independently substituted with zero to four substituents selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)cycloalkoxy and oxo;
c) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, aryl(C1-C3)alkoxy, heteroaryl(C1-C3)alkoxy, aryl(C2-C3))alkenyl, aryl(C2-C3)alkynyl, heteroaryl(C2-C3)alkenyl, or heteroaryl(C2-C3)alkynyl, each optionally and independently substituted with zero to three substituents selected from the group consisting of: halogen, cyano, nitro, amino, hydroxy, carboxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C4-C7)cycloalkylalkyl, (C2-C6)alkynyl, (C3-C6)-cycloalkyl(C2-C4)alkynyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, halo(C4-C7)cycloalkylalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, halo(C3-C6)cycloalkoxy, halo(C4-C7)cycloalkylalkoxy, (C1-C6)alkylthio, (C3-C6)cycloalkythio, (C4-C7)cycloalkylalkylthio, halo(C1-C6)alkylthio, halo(C3-C6)cycloalkythio, halo(C4-C7)cycloalkylalkylthio, (C1-C6)alkanesulfinyl, (C3-C6)cycloalkanesulfinyl, (C4-C7)cycloalkylalkanesulfinyl, halo(C1-C6)alkanesulfinyl, halo(C3-C6)cycloalkanesulfinyl, halo(C4-C7)cycloalkylalkanesulfinyl, (C1-C6)alkanesulfonyl, (C3-C6)cycloalkanesulfonyl, (C4-C7)cycloalkylalkanesulfonyl, halo(C1-C6)alkanesulfonyl, halo(C3-C6)cycloalkanesulfonyl, halo(C4-C7)cyclo-alkylalkanesulfonyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy(C1-C6)alkoxy, halo(C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, H2NCO, H2NSO2, (C1-C6)alkylaminocarbonyl, and di(C1-C6)alkylaminocarbonyl, (C1-C6)alkylaminosulfonyl, and di(C1-C6)alkylaminosulfonyl; or
d) a divalent radical selected from —(CH2)3—, —(CH2)4—, —(CH2)5— or —(CH2)6—, which is attached to R1 to form a fused or spirofused ring system, and is optionally and independently substituted with zero to four substituents selected from: halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and oxo;
R1 is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-1,3-dioxole, benzo-1,3-dioxine, 2,3-dihydrobenzo-1,4-dioxine or (C3-C7)cycloalkyl, each optionally and independently substituted with zero to four substituents selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C4-C7)cycloalkylalkyl, (C2-C6)alkynyl, (C3-C6)-cycloalkyl(C2-C4)alkynyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, halo(C4-C7)cycloalkylalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, halo(C3-C6)cycloalkoxy, halo(C4-C7)cycloalkylalkoxy, (C1-C6)alkylthio, (C3-C6)cycloalkythio, (C4-C7)cycloalkylalkylthio, halo(C1-C6)alkylthio, halo(C3-C6)cycloalkythio, halo(C4-C7)cycloalkylalkylthio, (C1-C6)alkanesulfinyl, (C3-C6)cycloalkanesulfinyl, (C4-C7)cycloalkylalkanesulfinyl, halo(C1-C6)alkanesulfinyl, halo(C3-C6)cycloalkanesulfinyl, halo(C4-C7)cycloalkylalkanesulfinyl, (C1-C6)alkanesulfonyl, (C3-C6)cycloalkanesulfonyl, (C4-C7)cycloalkylalkanesulfonyl, halo(C1-C6)alkanesulfonyl, halo(C3-C6)cycloalkanesulfonyl, halo(C4-C7)cycloalkylalkanesulfonyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy(C1-C6)alkoxy, halo(C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, H2NSO2, H2NCO, (C1-C6)alkylaminosulfonyl, di(C1-C6)alkylaminosulfonyl, (C1-C6)alkylaminocarbonyl and di(C1-C6)alkylaminocarbonyl;
R2 is:
a) —H; or
b) (C1-C12)alkyl, (C2-C12)alkenyl, (C2-C12)alkynyl, (C1-C12)alkoxy, (C1-C12)alkylthio, (C1-C12)alkylamino, oxo(C1-C12)alkyl, oxo(C2-C12)alkenyl, oxo(C2-C12)alkynyl, oxo(C1-C12)alkoxy, oxo(C1-C12)alkylthio, oxo(C1-C12)alkylamino, (C1-C6)alkoxy(C1-C6)alkyl, (C1-C6)alkylthio(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkylthio, (C1-C6)alkoxy(C1-C6)alkylamino, (C1-C6)alkylthio(C1-C6)alkoxy, (C1-C6)alkylthio(C1-C6)alkylamino, (C1-C6)alkylthio(C1-C6)alkylthio, (C1-C6)alkylamino(C1-C6)alkoxy, (C1-C6)alkylamino(C1-C6)alkylthio, (C1-C6)alkylamino(C1-C6)alkylamino, (C1-C4)alkoxy(C1-C4)alkoxy(C1-C4)alkyl, aminocarbonylamino(C1-C12)alkyl, aminocarbonylamino(C1-C12)alkoxy, aminocarbonylamino(C1-C12)alkylthio, aminocarbonylamino(C1-C12)alkylamino, (C1-C6)alkanoylamino(C1-C6)alkyl, (C1-C6)alkanoylamino(C1-C6)alkoxy, (C1-C6)alkanoylamino(C1-C6)alkylthio, (C1-C6)alkanoylamino(C1-C6)alkylamino, (C1-C6)alkoxycarbonyl(C1-C6)alkyl, (C1-C6)alkoxycarbonyl(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl(C1-C6)alkylthio, (C1-C6)alkoxycarbonyl(C1-C6)alkylamino, (C1-C6)acyloxy(C1-C6)alkyl, (C1-C6)acyloxy(C1-C6)alkoxy, (C1-C6)acyloxy(C1-C6)alkylthio, (C1-C6)acyloxy(C1-C6)alkylamino, aminosulfonylamino(C1-C12)alkyl, aminosulfonylamino(C1-C12)alkoxy, aminosulfonylamino(C1-C12)alkylthio, aminosulfonylamino(C1-C12)alkylamino, (C1-C6)alkanesulfonylamino(C1-C6)alkyl, (C1-C6)alkanesulfonylamino(C1-C6)alkoxy, (C1-C6)alkanesulfonylamino(C1-C6)alkylthio, (C1-C6)alkanesulfonylamino(C1-C6)alkylamino, formylamino(C1-C6)alkyl, formylamino(C1-C6)alkoxy, formylamino(C1-C6)alkylthio, formylamino(C1-C6)alkylamino, (C1-C6)alkoxycarbonylamino(C1-C6)alkyl, (C1-C6)alkoxycarbonylamino(C1-C6)alkoxy, (C1-C6)alkoxycarbonylamino(C1-C6)alkylthio, (C1-C6)alkoxycarbonylamino(C1-C6)alkylamino, (C1-C6)alkylaminocarbonylamino(C1-C6)alkyl, (C1-C6)alkylaminocarbonylamino(C1-C6)alkoxy, (C1-C6)alkylaminocarbonylamino(C1-C6)alkylthio, (C1-C6)alkylaminocarbonylamino(C1-C6)alkylamino, aminocarbonyl(C1-C6)alkyl, aminocarbonyl(C1-C6)alkoxy, aminocarbonyl(C1-C6)alkylthio, aminocarbonyl(C1-C6)alkylamino, (C1-C6)alkylaminocarbonyl(C1-C6)alkyl, (C1-C6)alkylaminocarbonyl(C1-C6)alkoxy, (C1-C6)alkylaminocarbonyl(C1-C6)alkylthio, (C1-C6)alkylaminocarbonyl(C1-C6)alkyamino, aminocarboxy(C1-C6)alkyl, aminocarboxy(C1-C6)alkoxy, aminocarboxy(C1-C6)alkylthio, aminocarboxy(C1-C6)alkylamino, (C1-C6)alkylaminocarboxy(C1-C6)alkyl, (C1-C6)alkylaminocarboxy(C1-C6)alkoxy, (C1-C6)alkylaminocarboxy(C1-C6)alkylthio, (C1-C6)alkylaminocarboxy(C1-C6)alkylamino, (C1-C12)alkoxycarbonylamino, (C1-C12)alkyl aminocarbonylamino, or (C1-C12)alkanoylamino, each optionally substituted by:
1) 1 to 5 halogen atoms; and/or
2) 1 group selected from cyano, hydroxyl, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C6)cycloalkyl, and halo(C3-C6)cycloalkoxy;
wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to a thiocarbonyl groups;
T is N or CR3;
R3 is hydrogen, halogen, (C1-C6)alkyl, (C1-C6)alkoxy, hydroxyl, hydroxy(C1-C6)alkyl, hydroxy(C1-C6)alkoxy, (C1-C6)alkanoylamino, (C1-C6)alkoxycarbonylamino, (C1-C6)alkylaminocarbonylamino, di(C1-C6)alkylaminocarbonylamino, (C1-C6)alkanesulfonylamino, (C1-C6)alkylaminosulfonylamino, di(C1-C6)alkylaminosulfonylamino, phenylamino or heteroarylamino in which each phenylamino or heteroarylamino group is optionally substituted with 1 to 5 groups independently selected from the group consisting of halogen, cyano, nitro, amino, hydroxy, carboxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C4-C7)cycloalkylalkyl, (C2-C6)alkynyl, (C3-C6)-cycloalkyl(C2-C4)alkynyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, halo(C4-C7)cycloalkylalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, halo(C3-C6)cycloalkoxy, halo(C4-C7)cycloalkylalkoxy, (C1-C6)alkylthio, (C3-C6)cycloalkylthio, (C4-C7)cycloalkylalkylthio, halo(C1-C6)alkylthio, halo(C3-C6)cycloalkylthio, halo(C4-C7)cycloalkylalkylthio, (C1-C6)alkanesulfinyl, (C3-C6)cycloalkanesulfinyl, (C4-C7)cycloalkylalkanesulfinyl, halo(C1-C6)alkanesulfinyl, halo(C3-C6)cycloalkanesulfinyl, halo(C4-C7)cycloalkylalkanesulfinyl, (C1-C6)alkanesulfonyl, (C3-C6)cycloalkanesulfonyl, (C4-C7)cycloalkylalkanesulfonyl, halo(C1-C6)alkanesulfonyl, halo(C3-C6)cycloalkanesulfonyl, halo(C4-C7)cycloalkylalkanesulfonyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy(C1-C6)alkoxy, halo(C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, aminocarbonyl, (C1-C6)alkylaminocarbonyl, and di(C1-C6)alkylaminocarbonyl;
provided that:
R2 and R3 are not both hydrogen; and
ii) when T is N or T is CR3 and R3 is hydroxy, halogen, or optionally substituted phenylamino or heteroarylamino, R2 is not an optionally substituted alkoxy, alkylthio or amino group as follows: (C1-C12)alkoxy, (C1-C12)alkylthio, (C1-C12)alkylamino, oxo(C1-C12)alkoxy, oxo(C1-C12)alkylthio, oxo(C1-C12)alkylamino, (C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkylthio, (C1-C6)alkoxy(C1-C6)alkylamino, (C1-C6)alkylthio(C1-C6)alkoxy, (C1-C6)alkylthio(C1-C6)alkylamino, (C1-C6)alkylthio(C1-C6)alkylthio, (C1-C6)alkylamino(C1-C6)alkoxy, (C1-C6)alkylamino(C1-C6)alkylthio, (C1-C6)alkylamino(C1-C6)alkylamino, aminocarbonylamino(C1-C12)alkoxy, aminocarbonylamino(C1-C12)alkylthio, aminocarbonylamino(C1-C12)alkylamino, (C1-C6)alkanoylamino(C1-C6)alkoxy, (C1-C6)alkanoylamino(C1-C6)alkylthio, (C1-C6)alkanoylamino(C1-C6)alkylamino, (C1-C6)alkoxycarbonyl(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl(C1-C6)alkylthio, (C1-C6)alkoxycarbonyl(C1-C6)alkylamino, (C1-C6) acyloxy(C1-C6)alkoxy, (C1-C6)acyloxy(C1-C6)alkylthio, (C1-C6)acyloxy(C1-C6)alkylamino, aminosulfonylamino(C1-C12)alkoxy, aminosulfonylamino(C1-C2)alkylthio, aminosulfonylamino(C1-C12)alkylamino, (C1-C6)alkanesulfonylamino(C1-C6)alkoxy, (C1-C6)alkanesulfonylamino(C1-C6)alkylthio, (C1-C6)alkanesulfonylamino(C1-C6)alkylamino, formylamino(C1-C6)alkoxy, formylamino(C1-C6)alkylthio, formylamino(C1-C6)alkylamino, (C1-C6)alkoxycarbonylamino(C1-C6)alkoxy, (C1-C6)alkoxycarbonylamino(C1-C6)alkylthio, (C1-C6)alkoxycarbonylamino(C1-C6)alkylamino, (C1-C6)alkylaminocarbonylamino(C1-C6)alkoxy, (C1-C6)alkylaminocarbonylamino(C1-C6)alkylthio, (C1-C6)alkylaminocarbonylamino(C1-C6)alkylamino, aminocarbonyl(C1-C6)alkoxy, aminocarbonyl(C1-C6)alkylthio, aminocarbonyl(C1-C6)alkylamino, (C1-C6)alkylaminocarbonyl(C1-C6)alkoxy, (C1-C6)alkylaminocarbonyl(C1-C6)alkylthio, (C1-C6)alkylaminocarbonyl(C1-C6)alkylamino, aminocarboxy(C1-C6)alkoxy, aminocarboxy(C1-C6)alkylthio, aminocarboxy(C1-C6)alkylamino, (C1-C6)alkylaminocarboxy(C1-C6)alkoxy, (C1-C6)alkylaminocarboxy(C1-C6)alkylthio, (C1-C6)alkylaminocarboxy(C1-C6)alkylamino, (C1-C12)alkoxycarbonylamino, (C1-C12)alkylaminocarbonylamino, or (C1-C12)alkanoylamino, each optionally substituted by:
1) 1 to 5 halogen atoms; and/or
2) 1 group selected from cyano, hydroxy, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C6)cycloalkyl, or halo(C3-C6)cycloalkoxy;
wherein the divalent sulfur atoms are optionally and independently oxidized to sulfoxide or sulfone, and wherein the carbonyl groups are optionally and independently changed to thiocarbonyl groups;
A is represented by the following Structural Formula:
Ra and Rb, for each occurrence, are independently hydrogen, (C1-C6)alkyl, or halo(C1-C6)alkyl or Ra and Rb attached to one carbon atom taken together are an oxo;
Z is —O—, —S—, —(NR7)— or —(CRaRb)—, wherein R7 is (C1-C6)alkyl, halo(C1-C6)alkyl or (C1-C3)alkoxy(C1-C3)alkyl;
m and n are 0, 1 or 2 and m+n=2; provided when T is N and Z is —O—, —S— or —NR7—, then n is 2;
Q is a divalent radical selected from
wherein A and W or E are attached to the truncated bonds
W is a bond or a (C1-C6)alkylene; and
W is optionally and independently substituted by zero to four groups selected from:
1) (C1-C12)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C3)alkyl, (C2-C12)alkenyl, (C5-C8)cycloalkyl(C1-C3)alkenyl, (C2-C12)alkynyl, (C3-C8)cycloalkyl(C1-C3)alkynyl, (C4-C12)bicycloalkyl(C1-C3)alkyl, (C8-C14)tricycloalkyl(C1-C3)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C3-C8)cycloalkoxy(C1-C3)alkyl, (C1-C6)alkylthio(C1-C6)alkyl, (C3-C8)cycloalkylthio(C1-C3)alkyl, saturated heterocyclyl, saturated heterocyclyl(C1-C3)alkyl, hydroxy and oxo, wherein each of these groups is optionally and independently substituted by zero to six groups selected from: halogen, cyano, hydroxy, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C6)cycloalkyl, (C3-C6)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C6)cycloalkyl, halo(C3-C6)cycloalkoxy and wherein divalent sulfur atoms are optionally oxidized to sulfoxide or sulfone; or
2) phenyl, naphthyl, heteroaryl, phenyl(C1-C3)alkyl, naphthyl(C1-C3)alkyl, and heteroaryl(C1-C3)alkyl, each optionally and independently substituted with zero to three groups selected from: halogen, cyano, nitro, amino, hydroxy, carboxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C4-C7)cycloalkylalkyl, (C2-C6)alkynyl, (C3-C6)cycloalkyl-(C2-C4)alkynyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, halo(C4-C7)cycloalkylalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, halo(C3-C6)cycloalkoxy, halo(C4-C7)cycloalkylalkoxy, (C1-C6)alkylthio, (C3-C6)cycloalkylthio, (C4-C7)cycloalkylalkylthio, halo(C1-C6)alkylthio, halo(C3-C6)cycloalkylthio, halo(C4-C7)cycloalkylalkylthio, (C1-C6)alkanesulfinyl, (C3-C6)cycloalkanesulfinyl, (C4-C7)cycloalkylalkanesulfinyl, halo(C1-C6)alkanesulfinyl, halo(C3-C6)cycloalkanesulfinyl, halo(C4-C7)cycloalkylalkanesulfinyl, (C1-C6)alkanesulfonyl, (C3-C6)cycloalkanesulfonyl, (C4-C7)cycloalkylalkanesulfonyl, halo(C1-C6)alkanesulfonyl, halo(C3-C6)cycloalkanesulfonyl, halo(C4-C7)cycloalkylalkanesulfonyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy(C1-C6)alkoxy, halo(C1-C6)alkoxy(C1-C6)alkoxy, (C1-C6)alkoxycarbonyl, aminocarbonyl, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl, cyano(C1-C6)alkyl, hydroxy(C1-C6)alkyl, carboxy(C1-C6)alkyl, (C1-C6)alkoxy(C1-C6)alkyl, (C3-C8)cycloalkoxy(C1-C6)alkyl, (C4-C8)cycloalkylalkoxy(C1-C6)alkyl, halo(C1-C6)alkoxy(C1-C6)alkyl, halo(C3-C6)cycloalkoxy(C1-C6)alkyl, halo(C4-C8)cycloalkylalkoxy(C1-C6)alkyl, (C1-C8)alkylthio(C1-C6)alkyl, (C3-C8)cycloalkylthio(C1-C6)alkyl, (C4-C8)cycloalkylalkylthio(C1-C6)alkyl, halo(C1-C8)alkylthio(C1-C6)alkyl, halo(C3-C8)cycloalkylthio(C1-C6)alkyl, halo(C4-C8)cycloalkylalkylthio(C1-C6)alkyl, (C1-C8)alkanesulfinyl(C1-C6)alkyl, (C3-C8)cycloalkanesulfinyl(C1-C6)alkyl, (C4-C8)cycloalkylalkanesulfinyl(C1-C6)alkyl, halo(C1-C8)alkanesulfinyl(C1-C6)alkyl, halo(C3-C8)cycloalkanesulfinyl(C1-C6)alkyl, halo(C4-C8)cycloalkylalkanesulfinyl(C1-C6)alkyl, (C1-C8)alkanesulfonyl(C1-C6)alkyl, (C3-C8)cycloalkanesulfonyl(C1-C6)alkyl, (C4-C8)cycloalkylalkanesulfonyl(C1-C6)alkyl, halo(C1-C8)alkanesulfonyl(C1-C6)alkyl, halo(C3-C8)cycloalkanesulfonyl(C1-C6)alkyl, halo(C4-C8)cycloalkylalkanesulfonyl(C1-C6)alkyl, (C1-C8)alkylamino(C1-C6)alkyl, di(C1-C8)alkylamino(C1-C6)alkyl, (C1-C8)alkoxycarbonyl(C1-C6)alkyl, (C1-C8)acyloxy(C1-C6)alkyl, aminocarbonyl(C1-C6)alkyl, (C1-C8)alkylaminocarbonyl(C1-C6)alkyl, di(C1-C8)alkylaminocarbonyl(C1-C6)alkyl(C1-C8)acylamino(C1-C6)alkyl, (C1-C8)alkoxycarbonylamino, (C1-C8)alkoxycarbonylamino(C1-C6)alkyl, aminocarboxy(C1-C6)alkyl, (C1-C8)alkylaminocarboxy(C1-C6)alkyl and di(C1-C8)alkylaminocarboxy(C1-C6)alkyl, phenyl, naphthyl, heteroaryl, bicyclic heteroaryl, phenoxy, naphthyloxy, heteroaryloxy, bicyclic heteroaryloxy, phenylthio, naphthylthio, heteroarylthio, bicyclic heteroarylthio, phenylsulfinyl, naphthylsulfinyl, heteroarylsulfinyl, bicyclic heteroarylsulfinyl, phenylsulfonyl, naphthylsulfonyl, heteroarylsulfonyl, bicyclic heteroarylsulfonyl, phenyl(C1-C3)alkyl, naphthyl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, and bicyclic heteroaryl(C1-C3)alkyl, wherein the aromatic and heteroaromatic groups are optionally and independently substituted with zero to three groups selected from: halogen, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C3)alkanesulfonyl, and (C1-C3)alkoxycarbonyl;
E is a saturated or unsaturated 3-, 4-, 5-, 6-, or 7-membered ring which is optionally bridged by (CH2)n via bonds to two members of said ring, wherein said ring is composed of carbon atoms and zero to four hetero atoms selected from: zero to four nitrogen atoms, zero or one oxygen atoms, and zero or one sulfur atoms, said ring being optionally and independently substituted with zero to four groups selected from: halogen, hydroxy, (C1-C6)alkyl, (C3-C8)cycloalkyl(C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, and oxo groups, such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group, and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively;
n is 1 to 3;
G is hydrogen, (C1-C6)alkyl, (C4-C7)heterocyclyl, hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, —O(C1-C6)alkyl-NR4aR4, amino(C1-C6)alkylcarboxy, (C3-C8)cycloalkyl, (C1-C6)alkylamino(C1-C6)alkyl, amino(C1-C6)alkyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, di(C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, NHC(═NH)NHR4; —(C0-C6)alkyl-NR4R4a, —NHC(═NH)NR4R4a, —C(═O)(C1-C6)alkyl-NR4R4a, —C(═NH)NR4R4a, —C(═O)(C1-C4)alkylaryl,
—C(═O)(C1-C4)alkyl(C4-C7)heterocyclyl, —(C1-C4)alkyl(C3-C8)cycloalkyl, or —(C1-C4)alkyl(C4-C7)heterocyclyl, wherein the (C1-C4)alkyl moiety is optionally substituted by amino, hydroxy, or (C1-C3)alkylamino;
and where R4a is H or (C1-C3)alkyl and R4 is selected from H, (C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, and (C4-C7)heterocyclyl(C1-C6)alkyl, or R4 and R4a, taken together with the nitrogen atom to which they are attached, form a 5-6 membered saturated heterocyclic ring composed of carbon atoms and 1-3 heteroatoms selected from 1, 2, or 3 nitrogen atoms, 0 or 1 oxygen atoms, and 0 or 1 sulfur atoms, said ring being optionally substituted with up to four groups independently selected from halogen, hydroxy, amino, (C1-C6)alkyl, (C1-C6)alkylamino, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, amino(C1-C6)alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively;
provided that when T is N, E is not 1,2-cyclopentylene.

### Claim 2 (depends on 1)

The compound of claim 1, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
ring E′ is a saturated 4-, 5-, 6-, or 7-membered heterocyclic ring which is optionally bridged by (CH2)q via bonds to two members of said ring; wherein ring E′ is optionally substituted with up to four groups independently selected from halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group and when there is substitution of one or two oxo groups on sulfur it forms sulfoxide or sulfone groups, respectively;
X is a ring carbon atom or nitrogen atom bonded directly to W;
W is a bond or a (C1-C3)alkyl; and
q is 1 to 3.

### Claim 3 (depends on 2)

The compound of claim 2, wherein ring E′ is selected from the group consisting of piperidinyl, piperazinyl, and pyrrolidinyl, said group being optionally substituted with a hydroxy, (C1-C3)alkyl or halo(C1-C3)alkyl group.

### Claim 4 (depends on 3)

The compound of claim 3, wherein G is hydrogen, (C1-C6)alkyl, heterocyclyl, —(C2-C6)alkyl-OH, —(C2-C6)alkyl-NR4a, —C(═O)(C1-C6)alkyl-NR4R4a, —C(═NH)NR4R4a, —C(═O)(C1-C4)alkylaryl, —C(═O)(C1-C4)alkyl(C4-C7)heterocyclyl, —(C1-C4)alkyl(C3-C8)cycloalkyl, or —(C1-C4)alkyl(C4-C7)heterocyclyl, wherein the (C1-C4)alkyl moiety is optionally substituted by amino, hydroxy, or (C1-C3)alkylamino.

### Claim 5 (depends on 4)

The compound of claim 4, wherein G is hydrogen, heterocyclyl, —(C2-C4)alkyl-OH, —(C2-C4)alkyl-NR4R4a, —C(═O)(C1-C4)alkyl-NR4R4a, —C(═O)(C1-C4)alkylaryl, —C(═O)(C1-C4)alkyl(C4-C7)heterocyclyl, —(C1-C4)alkyl(C3-C7)cycloalkyl, or —(C1-C4)alkyl(C4-C7)heterocyclyl.

### Claim 6 (depends on 1)

The compound of claim 1, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

The compound of claim 6, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The compound of claim 7, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
p is 1 or 2; R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group; and r is 0, 1 or 2 when p is 1 or r is 0, 1, 2 or 3 when p is 2.

### Claim 10 (depends on 9)

The compound of claim 9, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl

### Claim 11 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
s is 0, 1, 2, 3 or 4 and R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 12 (depends on 11)

The compound of claim 11, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl.

### Claim 13 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
t is 0, 1, 2, 3 or 4 and R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 14 (depends on 13)

The compound of claim 13, wherein G is hydroxy, —NR4R4a, —O(C2-C6)alkyl-NR4R4a, heterocyclyl, —(C1-C6)alkyl-OH, —(C1-C6)alkyl-NR4R4a, —C(═O)(C1-C6)alkyl-NR4R4a, NR4R4a, —C(═O)(C1-C4)alkylaryl, —C(═O)(C1-C4)alkyl(C4-C7)heterocyclyl, —(C1-C4)alkyl(C3-C8)cycloalkyl, or —(C1-C4)alkyl(C4-C7)heterocyclyl, wherein the (C1-C4)alkyl moiety is optionally substituted by amino, hydroxy, or (C1-C3)alkylamino.

### Claim 15 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, wherein:
u is 0, 1, 2 or 3; and R8 halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 16 (depends on 15)

The compound of claim 15, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl.

### Claim 17 (depends on 2)

The compound of claim 2, wherein:
R is a) (C1-C5)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C3-C7)cycloalkyl(C1-C3)alkyl, (C3-C7)cycloalkyl(C2-C3)alkenyl, (C3-C7)cycloalkyl(C2-C3)alkynyl, (C1-C8)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkoxy(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkoxy, (C1-C8)alkylthio, (C3-C7)cycloalkylthio, (C3-C7)cycloalkylthio(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkylthio, azepano, azetidino, piperidino, pyrrolidino or tri(C1-C4)alkylsilyl, each optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)cycloalkoxy, and oxo; or
b) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, aryl(C1-C3)alkoxy, heteroaryl(C1-C3)alkoxy, arylethenyl, heteroarylethenyl, or arylethynyl, heteroarylethynyl, each optionally substituted with up to three substituents independently selected from the group consisting of: halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, halo(C1-C6)alkylthio, (C1-C6)alkanesulfinyl, halo(C1-C6)alkanesulfinyl, (C1-C6)alkanesulfonyl, halo(C1-C6)alkanesulfonyl, H2NCO, H2NSO2, (C1-C6)alkylaminocarbonyl, and (C1-C6)alkylaminosulfonyl; or
c) a divalent radical selected from —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system, and is optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and oxo;
R1 is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-1,3-dioxole, or (C3-C7)cycloalkyl ring optionally substituted with up to four substituents independently selected from the group consisting of fluorine, chlorine, bromine, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C1-C6)allyl, halo(C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, halo(C1-C6)alkylthio, (C1-C6)alkanesulfinyl, halo(C1-C6)alkanesulfinyl, (C1-C6)alkanesulfonyl, halo(C1-C6)alkanesulfonyl, H2NSO2, H2NCO, (C1-C3)alkylaminosulfonyl, and (C1-C3)alkylaminocarbonyl;
R2 is a) —H; or b) (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C1-C10)alkoxy, (C1-C10)alkylthio, (C1-C10)alkylamino, (C1-C5)alkoxy(C1-C5)alkyl, (C1-C5)alkylthio(C1-C5)alkyl, (C1-C5)alkylamino(C1-C5)alkyl, (C1-C5)alkoxy(C1-C5)alkoxy, (C1-C5)alkoxy(C1-C5)alkylthio, (C1-C5)alkoxy(C1-C5)alkylamino, (C1-C5)alkylthio(C1-C5)alkoxy, (C1-C5)alkylthio(C1-C5)alkylamino, (C1-C5)alkylthio(C1-C5)alkylthio, (C1-C5)alkylamino(C1-C5)alkoxy, (C1-C5)alkylamino(C1-C5)alkylthio, (C1-C5)alkylamino(C1-C5)alkylamino, (C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, aminocarbonylamino(C1-C10)alkyl, aminocarbonylamino(C1-C10)alkoxy, aminocarbonylamino(C1-C10)alkylthio, aminocarbonylamino(C1-C10)alkylamino, (C1-C5)alkanoylamino(C1-C5)alkyl, (C1-C5)alkanoylamino(C1-C5)alkoxy, (C1-C5)alkanoylamino(C1-C5)alkylthio, (C1-C5)alkanoylamino(C1-C5)alkylamino, aminosulfonylamino(C1-C10)alkyl, aminosulfonylamino(C1-C10)alkoxy, aminosulfonylamino(C1-C10)alkylthio, aminosulfonylamino(C1-C10)alkylamino, (C1-C5)alkanesulfonylamino(C1-C5)alkyl, (C1-C5)alkanesulfonylamino(C1-C5)alkoxy, (C1-C5)alkanesulfonylamino(C1-C5)alkylthio, (C1-C5)alkanesulfonylamino(C1-C5)alkylamino, formylamino(C1-C5)alkyl, formylamino(C1-C5)alkoxy, formylamino(C1-C5)alkylthio, formylamino(C1-C5)alkylamino, (C1-C5)alkoxycarbonylamino(C1-C5)alkyl, (C1-C5)alkoxycarbonylamino(C1-C5)alkoxy, (C1-C5)alkoxycarbonylamino(C1-C5)alkylthio, (C1-C5)alkoxycarbonylamino(C1-C5)alkylamino, (C1-C5)alkylaminocarbonylamino(C1-C5)alkyl, (C1-C5)alkylaminocarbonylamino(C1-C5)alkoxy, (C1-C5)alkylaminocarbonylamino(C1-C5)alkylthio, (C1-C5)alkylaminocarbonylamino(C1-C5)alkylamino, aminocarbonyl(C1-C5)alkyl, aminocarbonyl(C1-C5)alkoxy, aminocarbonyl(C1-C5)alkylthio, aminocarbonyl(C1-C5)alkylamino, (C1-C5)alkylaminocarbonyl(C1-C5)alkyl, (C1-C5)alkylaminocarbonyl(C1-C5)alkoxy, (C1-C5)alkylaminocarbonyl(C1-C5)alkylthio, (C1-C5)alkylaminocarbonyl(C1*C5)alkyamino, aminocarboxy(C1-C5)alkyl, aminocarboxy(C1-C5)alkoxy, aminocarboxy(C1-C5)alkylthio, aminocarboxy(C1-C5)alkylamino, (C1-C5)alkylaminocarboxy(C1-C5)alkyl, (C1-C5)alkylaminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkylthio, (C1-C5)alkylaminocarboxy(C1-C5)alkylamino, (C1-C10)alkoxycarbonylamino, (C1-C10)alkylaminocarbonylamino, or (C1-C10)alkanoylamino, each optionally substituted by
1) 1 to 5 fluorine atoms; and/or
2) 1 group selected from cyano, hydroxyl, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C4)cycloalkyl, (C3-C4)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C4)cycloalkyl, and halo(C3-C4)cycloalkoxy; wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone; and
R3 is —H, halogen, (C1-C3)alkyl, (C1-C3)alkoxy, hydroxyl, hydroxy(C1-C3)alkyl, hydroxy(C1-C3)alkoxy, (C1-C4)alkanoylamino, (C1-C3)alkoxycarbonylamino, (C1-C3)alkylaminocarbonylamino, di(C1-C3)alkylaminocarbonylamino, (C1-C3)alkanesulfonylamino, (C1-C3)alkylaminosulfonylamino, di(C1-C3)alkylaminosulfonylamino, or phenylamino or heteroarylamino in which each phenylamino and heteroarylamino group is optionally substituted with 1 to 3 groups independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C3)alkanesulfonyl, and (C1-C3)alkoxycarbonyl;
provided that
i) R2 and R3 are not both hydrogen and
ii) when T is N or T is CR3 and R3 is hydroxyl, halogen, or optionally substituted phenylamino or heteroarylamino, R2 is not an optionally substituted alkoxy, alkylthio or amino group as follows: (C1-C10)alkoxy, (C1-C10)alkylthio, (C1-C10)alkylamino, (C1-C5)alkoxy(C1-C5)alkoxy, (C1-C5)alkoxy(C1-C5)alkylthio, (C1-C5)alkoxy(C1-C5)alkylamino, (C1-C5)alkylthio(C1-C5)alkoxy, (C1-C5)alkylthio(C1-C5)alkylamino, (C1-C5)alkylthio(C1-C5)alkylthio, (C1-C5)alkylamino(C1-C5)alkoxy, (C1-C5)alkylamino(C1-C5)alkylthio, (C1-C5)alkylamino(C1-C5)alkylamino, aminocarbonylamino(C1-C10)alkoxy, aminocarbonylamino(C1-C10)alkylthio, aminocarbonyl-amino(C1-C10)alkylamino, (C1-C5)alkanoylamino(C1-C5)alkoxy, (C1-C5)alkanoylamino(C1-C5)alkylthio, (C1-C5)alkanoylamino(C1-C5)alkylamino, aminosulfonylamino(C1-C10)alkoxy, aminosulfonylamino(C1-C10)alkylthio, aminosulfonylamino(C1-C10)alkylamino, (C1-C5)-alkanesulfonylamino(C1-C5)alkoxy, (C1-C5)alkanesulfonylamino(C1-C5)alkylthio, (C1-C5)alkanesulfonylamino(C1-C5)alkylamino, formylamino(C1-C5)alkoxy, formylamino(C1-C5)alkylthio, formylamino(C1-C5)alkylamino, (C1-C5)alkoxycarbonylamino(C1-C5)alkoxy, (C1-C5)alkoxycarbonylamino(C1-C5)alkylthio, (C1-C5)alkoxycarbonylamino(C1-C5)alkylamino, (C1-C5)alkylaminocarbonylamino(C1-C5)alkoxy, (C1-C5)alkylaminocarbonylamino(C1-C5)alkylthio, (C1-C5)alkylaminocarbonylamino(C1-C5)alkylamino, aminocarbonyl(C1-C5)alkoxy, aminocarbonyl(C1-C5)alkylthio, aminocarbonyl(C1-C5)alkylamino, (C1-C5)alkylaminocarbonyl-(C1-C5)alkoxy, (C1-C5)alkylaminocarbonyl(C1-C5)alkylthio, (C1-C5)alkylaminocarbonyl(C1-C5)alkyamino, aminocarboxy(C1-C5)alkoxy, aminocarboxy(C1-C5)alkylthio, aminocarboxy(C1-C5)alkylamino, (C1-C5)alkylaminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkylthio, (C1-C5)alkylaminocarboxy(C1-C5)alkylamino, (C1-C10)alkoxycarbonylamino, (C1-C10)alkylaminocarbonylamino, or (C1-C10)alkanoylamino, each optionally substituted with
1) 1 to 5 fluorine atoms; and/or
2) 1 group selected from cyano, hydroxyl, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C4)cycloalkyl, (C3-C4)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C4)cycloalkyl, and halo(C3-C4)cycloalkoxy;
wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone.

### Claim 18 (depends on 17)

The compound of claim 17, wherein:
R is a) (C1-C8)alkyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C3-C7)cycloalkyl(C1-C3)alkyl, (C3-C7)cycloalkylethenyl, (C3-C7)cycloalkylethynyl, (C1-C8)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkoxy(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkoxy, piperidino, pyrrolidino or tri(C1-C3)alkylsilyl, each optionally substituted with up to 4 substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C3)alkyl, and halo(C1-C3)alkyl,
b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C1-C3)alkoxy, or monocyclic heteroaryl(C1-C3)alkoxy, each optionally substituted with up to three substituents independently selected from the group consisting of halogen, cyano, (C1-C3)alkyl, (C3-C5)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C3)alkylthio, and H2NCO; or
c) a divalent radical selected from —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system;
R1 is phenyl, monocyclic heteroaryl ring, bicyclic heteroaryl ring or benzo-1,3-dioxole, optionally substituted with up to four substituents independently selected from the group consisting of halogen, cyano, (C1-C3)alkyl, (C3-C4)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, and H2NCO;
R2 is —H, (C1-C8)alkyl, (C4-C9)cycloalkylalkyl, fluoro(C1-C8)alkyl, fluoro(C4-C9)-cycloalkyl alkyl, (C1-C8)alkoxy, (C4-C9)cycloalkylalkoxy, fluoro(C1-C8)alkoxy, hydroxy(C1-C8)alkyl, (C1-C5)alkoxy(C1-C5)alkyl, halo(C1-C5)alkylamino(C1-C5)alkyl, (C1-C5)alkoxy(C1-C5)hydroxyalkyl, (C3-C4)cycloalkoxy(C1-C5)alkyl, fluoro(C1-C5)alkoxy(C1-C5)alkyl, fluoro(C3-C4)cycloalkoxy(C1-C5)alkyl, (C1-C5)alkylthio(C1-C5)alkyl, (C1-C5)alkoxy(C1-C5)alkoxy, hydroxy(C1-C8)alkoxy, (C3-C4)cycloalkoxy(C1-C5)alkoxy, fluoro(C1-C5)alkoxy(C1-C5)alkoxy, fluoro(C3-C4)cycloalkoxy(C1-C5)alkoxy, (C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, fluoro(C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, aminocarbonylamino(C1-C8)alkyl, aminocarbonylamino(C1-C8)alkoxy, (C1-C5)alkanoylamino(C1-C5)alkyl, (C1-C5)alkanoylamino(C1-C5)alkoxy, fluoro(C1-C5)alkanoylamino(C1-C5)alkyl, fluoro(C1-C5)alkanoylamino(C1-C5)alkoxy, (C1-C3)alkoxy(C1-C5)alkanoylamino(C1-C5)alkyl, (C1-C3)alkoxy(C1-C5)alkanoylamino(C1-C5)alkoxy, (C3-C4)-cycloalkanecarbonyllamino(C1-C5)alkyl, (C3-C4)cycloalkanecarbonyllamino(C1-C5)alkoxy, aminosulfonylamino(C1-C8)alkyl, aminosulfonylamino(C1-C8)alkoxy, (C1-C5)alkane-sulfonylamino(C1-C5)alkyl, (C1-C5)alkanesulfonylamino(C1-C5)alkoxy, formylamino(C1-C5)alkyl, formylamino(C1-C5)alkoxy, (C1-C5)alkoxycarbonylamino(C1-C5)alkyl, (C1-C5)alkoxycarbonyl-amino(C1-C5)alkoxy, (C1-C5)alkylaminocarbonylamino(C1-C5)alkyl, (C1-C5)alkylamino-carbonylamino(C1C5)alkyl, di(C1-C5)alkylaminocarbonylamino(C1-C5)alkoxy, aminocarbonyl(C1-C5)alkyl, aminocarbonyl(C1-C5)alkoxy, (C1-C5)alkylaminocarbonyl(C1-C5)alkyl, (C1-C5)alkylaminocarbonyl(C1-C5)alkoxy, aminocarboxy(C1-C5)alkyl, aminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkyl, (C1-C5)alkylamino-carboxy(C1-C5)alkoxy, (C1-C8)alkoxycarbonylamino, (C1-C8)alkylaminocarbonylamino, (C1-C8)alkanoylamino, fluoro(C1-C8)alkoxycarbonylamino, fluoro(C1-C8)alkylaminocarbonylamino, or fluoro(C1-C8)alkanoylamino;
R3 is —H, halogen, OH, (C1-C4)alkanoylamino, or (C1-C3)alkoxy;
provided that
R2 and R3 are not both hydrogen; and
ii) when T is N or T is CR3 and R3 is OH or halogen, R2 is not an optionally substituted alkoxy, alkylthio or amino group as follows: (C1-C8)alkoxy, (C4-C8)cycloalkylalkoxy, fluoro(C1-C8)alkoxy, (C1-C5)alkoxy(C1-C5)alkoxy, hydroxy(C1-C8)alkoxy, (C3-C4)cycloalkoxy(C1-C5)alkoxy, fluoro(C1-C5)alkoxy(C1-C5)alkoxy, fluoro(C3-C4)cycloalkoxy(C1-C5)alkoxy, aminocarbonylamino(C1-C8)alkoxy, (C1-C5)-alkanoylamino(C1-C5)alkoxy, fluoro(C1-C5)alkanoylamino(C1-C5)alkoxy, (C1-C3)alkoxy(C1-C5)alkanoylamino(C1-C5)alkoxy, (C3-C4)cycloalkanecarbonyllamino(C1-C5)alkoxy, aminosulfonylamino(C1-C8)alkoxy, (C1-C5)alkanesulfonylamino(C1-C5)alkoxy, formylamino(C1-C5)alkoxy, (C1-C5)alkoxycarbonylamino(C1-C5)alkoxy, di(C1-C5)alkylaminocarbonylamino(C1-C5)alkoxy, aminocarbonyl(C1-C5)alkoxy, (C1-C5)alkylaminocarbonyl(C1-C5)alkoxy, aminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkoxy, (C1-C8)alkoxy-carbonylamino, (C1-C8)alkylaminocarbonylamino, (C1-C8)alkanoylamino, fluoro(C1-C8)alkoxy-carbonylamino, fluoro(C1-C8)alkylaminocarbonylamino, or fluoro(C1-C8)alkanoylamino.

### Claim 19 (depends on 18)

The compound of claim 18, wherein:
R is a) (C1-C7)alkyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkyl(C1-C3)alkoxy, piperidino, pyrrolidino or tri(C1-C3)alkylsilyl, each optionally substituted with up to 4 substituents independently selected from fluorine, hydroxy, (C1-C3)alkyl, or halo(C1-C3)alkyl; or
b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C1-C3)alkoxy, or monocyclic heteroaryl(C1-C3)alkoxy, each optionally substituted with up to 3 substituents independently selected from fluorine, chlorine, cyano, (C1-C3)alkyl, (C3-C4)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, (C1-C3)alkylthio or H2NCO; or
c) —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system;
R1 is phenyl, furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, thiazole, pyridine, pyrimidine, pyrazine, benzofuran, benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, quinazoline or benzo-1,3-dioxole, each optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—;
R2 is (C1-C3)alkoxy(C1-C5)alkyl, (C1-C3)alkoxy(C1-C5)alkoxy, (C3-C4)cycloalkyl(C1-C5)alkyl, (C3-C4)cycloalkyl(C1-C5)alkoxy, (C1-C3)alkoxycarbonylamino(C1-C5)alkyl, (C1-C3)-alkoxycarbonylamino(C1-C5)alkoxy, (C1-C3)alkanoylamino(C1-C5)alkyl, (C1-C3)-alkanoylamino(C1-C5)alkoxy, (C1-C3)alkylaminocarbonyl(C1-C5)alkyl, (C1-C3)alkylaminocarbonyl(C1-C5)alkoxy, aminocarboxy(C1-C5)alkyl, aminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkyl, (C1-C5)alkylamino-carboxy(C1-C5)alkoxy; and
R3 is hydrogen, fluoro, hydroxyl, or (C1-C4)alkanoylamino, provided that when T is N or T is CR3 and R3 is hydroxyl or fluoro, R2 is not (C1-C3)alkoxy(C1-C5)alkoxy, (C3-C4)cycloalkyl(C1-C5)alkoxy, (C1-C3)alkoxy-carbonylamino(C1-C5)alkoxy, (C1-C3)alkanoylamino(C1-C5)alkoxy or (C1-C3)alkylaminocarbonyl(C1-C5)alkoxy.

### Claim 20 (depends on 19)

The compound of claim 19, wherein G is —NHR9 or (C1-C3)alkyl-NHR9, wherein R9 is H or (C1-C6)alkyl.

### Claim 21 (depends on 20)

The compound of claim 20, wherein R2 is (C1-C3)alkoxy(C1-C5)alkyl, (C1-C3)alkoxy(C1-C5)alkoxy, (C1-C3)alkoxycarbonylamino(C1-C5)alkyl, (C1-C3)-alkoxycarbonylamino(C1-C5)alkoxy, aminocarboxy(C1-C5)alkyl, aminocarboxy(C1-C5)alkoxy, (C1-C5)alkylaminocarboxy(C1-C5)alkyl, or (C1-C5)alkylamino-carboxy(C1-C5)alkoxy.

### Claim 22 (depends on 21)

The compound of claim 21, wherein:
R1 is phenyl optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—; and
R is ethyl, isobutyl, t-butyl, 2,2-dimethyl-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2-(cyclopropyl)ethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 5-methyl-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophenoxy, 2-chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3-fluorophenoxy, 3-methylphenoxy, 4-fluorophenoxy, 4-methylphenoxy, 2-methyl-4-fluorophenoxy, 2-methyl-5-fluorophenoxy, piperidino, trimethylsilyl, —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system.

### Claim 23 (depends on 22)

The compound of claim 22, wherein:
R is phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, or 3,5-dimethylphenyl; and
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, benzofuran, benzothiophene, benzooxazole or benzo-1,3-dioxole; and
R2 is 4-methoxybutyl, 4-ethoxybutyl, 4-methoxypentyl, 3-methoxypropoxy, 3-(methoxycarbonylamino)propyl, or 2-(methoxycarbonylamino)ethoxy.

### Claim 24 (depends on 23)

The compound of claim 23, wherein R3 is hydrogen, hydroxyl or methoxycarbonylamino, provided that when R3 is hydroxyl, R2 is not 3-methoxypropoxy, 2-(acetylamino)ethoxy, or 2-(methoxycarbonylamino)ethoxy.

### Claim 25 (depends on 24)

The compound of claim 24, wherein:
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl
R7 is methyl, ethyl, propyl, or isopropyl;
Ra and Rb, for each occurrence, are independently H, methyl or Ra and Rb attached to one carbon atom taken together are an oxo; and
G is —NHR9 or CH2NHR9, wherein R9 is H, methyl or ethyl.

### Claim 26 (depends on 25)

The compound of claim 25, wherein:
R is phenyl, 3-methylphenyl or 3-ethylphenyl;
R1 is phenyl or 3-chlorophenyl;
R2 is 4-methoxybutyl;
R3 is hydroxyl;
R7 is methyl; and
G is —NH2 or —CH2NH2.

### Claim 27 (depends on 19)

The compound of claim 19, wherein R2 is 3-(acetylamino)propyl or 2-(acetylamino)ethoxy.

### Claim 28 (depends on 27)

The compound of claim 27, wherein G is —NHR9 or (C1-C3)alkyl-NHR9, wherein R9 is H or (C1-C6)alkyl.

### Claim 29 (depends on 28)

The compound of claim 28, wherein:
R1 is phenyl optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—; and
R is ethyl, isobutyl, t-butyl, 2,2-dimethyl-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2-(cyclopropyl)ethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 5-methyl-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophenoxy, 2-chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3-fluorophenoxy, 3-methylphenoxy, 4-fluorophenoxy, 4-methylphenoxy, 2-methyl-4-fluorophenoxy, 2-methyl-5-fluorophenoxy, piperidino, trimethylsilyl, —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system.

### Claim 30 (depends on 29)

The compound of claim 29, wherein:
R is phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, or 3,5-dimethylphenyl; and
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, benzofuran, benzothiophene, benzooxazole or benzo-1,3-dioxole.

### Claim 31 (depends on 30)

The compound of claim 30, wherein R3 is hydrogen, hydroxyl or methoxycarbonylamino, provided that when R3 is hydroxyl, R2 is not 2-(acetylamino)ethoxy.

### Claim 32 (depends on 31)

The compound of claim 31, wherein:
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl
R7 is methyl, ethyl, propyl, or isopropyl;
Ra and Rb, for each occurrence, are independently H, methyl or Ra and Rb attached to one carbon atom taken together are an oxo; and
G is —NHR9 or CH2NHR9, wherein R9 is H, methyl or ethyl.

### Claim 33 (depends on 32)

The compound of claim 32, wherein:
R is phenyl, 3-methylphenyl or 3-ethylphenyl;
R1 is phenyl or 3-chlorophenyl;
R3 is hydroxyl;
R7 is methyl; and
G is —NH2 or —CH2NH2.

### Claim 34 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein:
p is 1 or 2; R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl, and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group; and r is 0, 1 or 2 when p is 1 or r is 0, 1, 2 or 3 when p is 2.

### Claim 35 (depends on 34)

The compound of claim 34, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl

### Claim 36 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein:
s is 0, 1, 2, 3 or 4 and R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 37 (depends on 36)

The compound of claim 36, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl.

### Claim 38 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein:
t is 0, 1, 2, 3 or 4 and R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 39 (depends on 38)

The compound of claim 38, wherein G is hydroxy, —NR4R4a, —O(C2-C6)alkyl-NR4R4a, heterocyclyl, —(C1-C6)alkyl-OH, —(C1-C6)alkyl-NR4R4a, —C(═O)(C1-C6)alkyl-NR4R4a, —C(═NH)NR4R4a, —NHC(═NH)NR4R4a, —C(═O)(C1-C4)alkylaryl, —C(═O)(C1-C4)alkyl(C4-C7)heterocyclyl, —(C1-C4)alkyl(C3-C8)cycloalkyl, or —(C1-C4)alkyl(C4-C7)heterocyclyl, wherein the (C1-C4)alkyl moiety is optionally substituted by amino, hydroxy, or (C1-C3)alkylamino.

### Claim 40 (depends on 8)

The compound of claim 8, wherein the compound is represented by the following Structural Formula:
or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein:
u is 0, 1, 2 or 3; and R8 is selected from the group consisting of halogen, hydroxy, (C1-C6)alkyl, halo(C3-C6)alkyl, hydroxy(C1-C6)alkyl and oxo groups such that when there is substitution with one oxo group on a carbon atom it forms a carbonyl group.

### Claim 41 (depends on 40)

The compound of claim 40, wherein G is hydroxy, hydroxy(C1-C6)alkyl, —NR4aR4, (C1-C6)alkylamino, amino(C1-C6)alkyl, (C1-C6)alkylamino(C1-C6)alkyl, C(═NH)NH2, C(═NH)NHR4, NHC(═NH)NH2, or NHC(═NH)NHR4; wherein R4 is (C1-C3)alkyl.

### Claim 42 (depends on 36)

The compound of claim 36, wherein:
R is a) (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C3-C7)cycloalkyl(C1-C3)alkyl, (C3-C7)cycloalkyl(C2-C3)alkenyl, (C3-C7)cycloalkyl(C2-C3)alkynyl, (C1-C8)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkoxy(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C8)alkoxy, (C1-C8)alkylthio, (C3-C7)cycloalkylthio, (C3-C7)cycloalkylthio(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkylthio, azepano, azetidino, piperidino, pyrrolidino or tri(C1-C4)alkylsilyl, each optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C1-C6)cycloalkoxy, and oxo; or
b) aryl, heteroaryl, aryloxy, heteroaryloxy, aryl(C1-C3)alkyl, heteroaryl(C1-C3)alkyl, aryl(C1-C3)alkoxy, heteroaryl(C1-C3)alkoxy, arylethenyl, heteroarylethenyl, or arylethynyl, heteroarylethynyl, each optionally substituted with up to three substituents independently selected from the group consisting of: halogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, halo(C1-C6)alkylthio, (C1-C6)alkanesulfinyl, halo(C1-C6)alkanesulfinyl, (C1-C6)alkanesulfonyl, halo(C1-C6)alkanesulfonyl, H2NCO, H2NSO2, (C1-C6)alkylaminocarbonyl, and (C1-C6)alkylaminosulfonyl; or
c) a divalent radical selected from —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system, and is optionally substituted with up to four substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C6)alkyl, halo(C1-C6)alkyl, (C1-C6)alkoxy and oxo;
R1 is phenyl, monocyclic heteroaryl, bicyclic heteroaryl, benzo-1,3-dioxole, or (C3-C7)cycloalkyl ring optionally substituted with up to four substituents independently selected from the group consisting of fluorine, chlorine, bromine, cyano, (C1-C6)alkyl, (C3-C6)cycloalkyl, halo(C1-C6)alkyl, halo(C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkoxy, (C4-C7)cycloalkylalkoxy, halo(C1-C6)alkoxy, (C1-C6)alkylthio, halo(C1-C6)alkylthio, (C1-C6)alkanesulfinyl, halo(C1-C6)alkanesulfinyl, (C1-C6)alkanesulfonyl, halo(C1-C6)alkanesulfonyl, H2NSO2, H2NCO, (C1-C3)alkylaminosulfonyl, and (C1-C3)alkylaminocarbonyl; and
R2 is a) —H; or b) (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C1-C5)alkoxy(C1-C5)alkyl, (C1-C5)alkylthio(C1-C5)alkyl, (C1-C5)alkylamino(C1-C5)alkyl, (C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, aminocarbonylamino(C1-C10)alkyl, (C1-C5)alkanoylamino(C1-C5)alkyl, aminosulfonylamino(C1-C10)alkyl, (C1-C5)alkanesulfonylamino(C1-C5)alkyl, formylamino(C1-C5)alkyl, (C1-C5)alkoxycarbonylamino(C1-C5)alkyl, (C1-C5)alkylaminocarbonylamino(C1-C5)alkyl, aminocarbonyl(C1-C5)alkyl, (C1-C5)alkylaminocarbonyl(C1-C5)alkyl, aminocarboxy(C1-C5)alkyl, (C1-C5)alkylaminocarboxy(C1-C5)alkyl, each optionally substituted by
1) 1 to 5 fluorine atoms; and/or
2) 1 group selected from cyano, hydroxyl, (C1-C3)alkyl, (C1-C3)alkoxy, (C3-C4)cycloalkyl, (C3-C4)cycloalkoxy, halo(C1-C3)alkyl, halo(C1-C3)alkoxy, halo(C3-C4)cycloalkyl, and halo(C3-C4)cycloalkoxy; wherein the divalent sulfur atoms are independently optionally oxidized to sulfoxide or sulfone.

### Claim 43 (depends on 42)

The compound of claim 42, wherein:
R is a) (C1-C8)alkyl, (C2-C8)alkynyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C3-C7)cycloalkyl(C1-C3)alkyl, (C3-C7)cycloalkylethenyl, (C3-C7)cycloalkylethynyl, (C1-C8)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkoxy(C1-C3)alkyl, (C3-C7)cycloalkyl(C1-C3)alkoxy, piperidino, pyrrolidino or tri(C1-C3)alkylsilyl, each optionally substituted with up to 4 substituents independently selected from the group consisting of fluorine, hydroxy, (C1-C3)alkyl, and halo(C1-C3)alkyl,
b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C1-C3)alkoxy, or monocyclic heteroaryl(C1-C3)alkoxy, each optionally substituted with up to three substituents independently selected from the group consisting of halogen, cyano, (C1-C3)alkyl, (C3-C5)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, (C1-C3)alkylthio, and H2NCO; or
c) a divalent radical selected from —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system;
R1 is phenyl, monocyclic heteroaryl ring, bicyclic heteroaryl ring or benzo-1,3-dioxole, optionally substituted with up to four substituents independently selected from the group consisting of halogen, cyano, (C1-C3)alkyl, (C3-C4)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, halo(C1-C3)alkoxy, and H2NCO;
R2 is —H, (C1-C8)alkyl, (C4-C9)cycloalkylalkyl, fluoro(C1-C8)alkyl, fluoro(C4-C9)-cycloalkyl alkyl, hydroxy(C1-C8)alkyl, (C1-C5)alkoxy(C1-C5)alkyl, halo(C1-C5)alkylamino(C1-C5)alkyl, (C1-C5)alkoxy(C1-C5)hydroxyalkyl, (C3-C4)cycloalkoxy(C1-C5)alkyl, fluoro(C1-C5)alkoxy(C1-C5)alkyl, fluoro(C3-C4)cycloalkoxy(C1-C5)alkyl, (C1-C5)alkylthio(C1-C5)alkyl, (C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, fluoro(C1-C3)alkoxy(C1-C3)alkoxy(C1-C3)alkyl, aminocarbonylamino(C1-C8)alkyl, (C1-C5)alkanoylamino(C1-C5)alkyl, fluoro(C1-C5)alkanoylamino(C1-C5)alkyl, (C1-C3)alkoxy(C1-C5)alkanoylamino(C1-C5)alkyl, (C3-C4)-cycloalkanecarbonyllamino(C1-C5)alkyl, aminosulfonylamino(C1-C8)alkyl, (C1-C5)alkane-sulfonylamino(C1-C5)alkyl, formylamino(C1-C5)alkyl, (C1-C5)alkoxycarbonylamino(C1-C5)alkyl, (C1-C5)alkylaminocarbonylamino(C1-C5)alkyl, (C1-C5)alkylamino-carbonylamino(C1-C5)alkyl, aminocarbonyl(C1-C5)alkyl, aminocarbonyl(C1-C5)alkoxy, (C1-C5)alkylaminocarbonyl(C1-C5)alkyl, aminocarboxy(C1-C5)alkyl, or (C1-C5)alkylaminocarboxy(C1-C5)alkyl.

### Claim 44 (depends on 43)

The compound of claim 43, wherein:
R is a) (C1-C7)alkyl, (C3-C7)cycloalkyl, (C5-C7)cycloalkenyl, (C1-C7)alkoxy, (C3-C7)cycloalkoxy, (C3-C7)cycloalkyl(C1-C3)alkoxy, piperidino, pyrrolidino or tri(C1-C3)alkylsilyl, each optionally substituted with up to 4 substituents independently selected from fluorine, hydroxy, (C1-C3)alkyl, or halo(C1-C3)alkyl; or
b) phenyl, monocyclic heteroaryl, phenoxy, monocyclic heteroaryloxy, phenyl(C1-C3)alkoxy, or monocyclic heteroaryl(C1-C3)alkoxy, each optionally substituted with up to 3 substituents independently selected from fluorine, chlorine, cyano, (C1-C3)alkyl, (C3-C4)cycloalkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, (C1-C3)alkylthio or H2NCO; or
c) —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system;
R1 is phenyl, furan, thiophene, pyrrole, pyrazole, imidazole, oxazole, thiazole, pyridine, pyrimidine, pyrazine, benzofuran, benzothiophene, benzoxazole, benzothiazole, benzimidazole, quinoline, isoquinoline, quinazoline or benzo-1,3-dioxole, each optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—; and
R2 is (C1-C3)alkoxy(C1-C5)alkyl, (C3-C4)cycloalkyl(C1-C5)alkyl, (C1-C3)alkoxycarbonylamino(C1-C5)alkyl, (C1-C3)alkanoylamino(C1-C5)alkyl, (C1-C3)alkylaminocarbonyl(C1-C5)alkyl, aminocarboxy(C1-C5)alkyl, or (C1-C5)alkylaminocarboxy(C1-C5)alkyl.

### Claim 45 (depends on 44)

The compound of claim 44, wherein G is —NHR9 or (C1-C3)alkyl-NHR9, wherein R9 is H or (C1-C6)alkyl.

### Claim 46 (depends on 45)

The compound of claim 45, wherein R2 is (C1-C3)alkoxy(C1-C5)alkyl, (C1-C3)alkoxycarbonylamino(C1-C5)alkyl, aminocarboxy(C1-C5)alkyl, or (C1-C5)alkylaminocarboxy(C1-C5)alkyl.

### Claim 47 (depends on 46)

The compound of claim 46, wherein:
R1 is phenyl optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—; and
R is ethyl, isobutyl, t-butyl, 2,2-dimethyl-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2-(cyclopropyl)ethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropyl phenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 5-methyl-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophenoxy, 2-chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3-fluorophenoxy, 3-methylphenoxy, 4-fluorophenoxy, 4-methylphenoxy, 2-methyl-4-fluorophenoxy, 2-methyl-5-fluorophenoxy, piperidino, trimethylsilyl, —(CH2)4— or —(CH2)5—, which is attached to R1 to form a fused or spirofused ring system.

### Claim 48 (depends on 47)

The compound of claim 47, wherein:
R is phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, or 3,5-dimethylphenyl; and
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, benzofuran, benzothiophene, benzooxazole or benzo-1,3-dioxole; and
R2 is 4-methoxybutyl, 4-ethoxybutyl, 4-methoxypentyl, or 3-(methoxycarbonylamino)propyl.

### Claim 49 (depends on 48)

The compound of claim 48, wherein:
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl
R7 is methyl, ethyl, propyl, or isopropyl;
Ra and Rb, for each occurrence, are independently H, methyl or Ra and Rb attached to one carbon atom taken together are an oxo; and
G is —NHR9 or —CH2NHR9, wherein R9 is H, methyl or ethyl.

### Claim 50 (depends on 49)

The compound of claim 49, wherein:
R is phenyl, 3-methylphenyl or 3-ethylphenyl;
R1 is phenyl or 3-chlorophenyl;
R7 is methyl; and
G is —NH2 or —CH2NH2.

### Claim 51 (depends on 44)

The compound of claim 44, wherein R2 is 3-(acetylamino)propyl.

### Claim 52 (depends on 51)

The compound of claim 51, wherein G is —NHR9 or (C1-C3)alkyl-NHR9, wherein R9 is H or (C1-C6)alkyl.

### Claim 53 (depends on 52)

The compound of claim 52, wherein:
R1 is phenyl optionally substituted with up to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, (C1-C3)alkyl, halo(C1-C3)alkyl, (C1-C3)alkoxy, and H2NCO—;
R is ethyl, isobutyl, t-butyl, 2,2-dimethyl-1-propoxy, cyclopentyloxy, cyclopropylmethoxy, 2-(cyclopropyl)ethoxy, cyclobutylmethoxy, cyclopentylmethoxy, cyclohexylmethoxy, benzyloxy, 4-fluorobenzyloxy, phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropyl phenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 5-methyl-2-furyl, 2-pyridyl, 1-cyclohexenyl, phenoxy, 2-fluorophenoxy, 2-chlorophenoxy, 2-methylphenoxy, 2-ethylphenoxy, 3-fluorophenoxy, 3-methylphenoxy, 4-fluorophenoxy, 4-methylphenoxy, 2-methyl-4-fluorophenoxy, 2-methyl-5-fluorophenoxy, piperidino, trimethylsilyl, —(CH2)4— or —(CH2)5.

### Claim 54 (depends on 53)

The compound of claim 53, wherein:
R is phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-ethylphenyl, 3-isopropylphenyl, 3-cyclopropylphenyl, 3-methoxyphenyl, 3-ethoxyphenyl, 3-(methylthio)phenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, 2,3-difluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-methylphenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, or 3,5-dimethylphenyl; and
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl, benzofuran, benzothiophene, benzooxazole or benzo-1,3-dioxole.

### Claim 55 (depends on 54)

The compound of claim 54, wherein:
R1 is phenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 4-fluorophenyl, 4-cyanophenyl, 5-fluorophenyl, 6-fluorophenyl, 6-methoxyphenyl, 3,5-difluorophenyl
R7 is methyl, ethyl, propyl, or isopropyl;
Ra and Rb, for each occurrence, are independently H, methyl or Ra and Rb attached to one carbon atom taken together are an oxo; and
G is —NHR9 or —CH2NHR9, wherein R9 is H, methyl or ethyl.

### Claim 56 (depends on 55)

The compound of claim 55, wherein:
R is phenyl, 3-methylphenyl or 3-ethylphenyl;
R1 is phenyl or 3-chlorophenyl;
R7 is methyl; and
G is —NH2 or CH2NH2.

### Claim 57 (depends on 1)

The compound of claim 1, wherein the compound is selected from the group consisting of:
(1S,3R,4S)-3-amino-N-[3-(6-chloro-3′-methyl-2-biphenylyl)-3-hydroxy-7-(methyloxy)heptyl]-4-hydroxy-N-methylcyclopentanecarboxamide;
(1R,3S)-3-amino-N-[3-(6-chloro-3′-ethyl-2-biphenylyl)-3-hydroxy-7-(methyloxy)heptyl]-N-methylcyclopentanecarboxamide;
(1S,3R,4S)-3-amino-N-[3-(6-chloro-31-ethyl-2-biphenylyl)-3-hydroxy-7-(methyloxy)heptyl]-4-hydroxy-N-methylcyclopentanecarboxamide;
4-(aminomethyl)-N-[3-(6-chloro-3′-ethyl-2-biphenylyl)-3-hydroxy-7-(methyloxy)heptyl]-N-methylbenzamide;
(1R,3S)-3-amino-N-(2-{(6-chloro-3′-ethyl-2-biphenylyl)[4-(methyloxy)butyl]amino}ethyl)-N-methylcyclopentanecarboxamide;
(1S,3R,4S)-3-amino-N-(2-{(6-chloro-3′-ethyl-2-biphenylyl)[4-(methyloxy)butyl]amino}ethyl)-4-hydroxy-N-methylcyclopentanecarboxamide;
(1R,3S)-3-amino-N-(2-{(6-chloro-3′-ethyl-2-biphenyl)[4-(methyloxy)butyl]amino}-2-oxoethyl)-N-methylcyclopentanecarboxamide;
(1S,3R,4S)-3-amino-N-(2-{(6-chloro-3′-ethyl-2-biphenylyl)[4-(methyloxy)butyl]amino}-2-oxoethyl)-4-hydroxy-N-methylcyclopentanecarboxamide;
(1R,3S)-3-amino-N-(3-(6-chloro-3′-methylbiphenyl-2-yl)-3-hydroxy-7-methoxyheptyl)-N-methylcyclopentanecarboxamide;
(1S,3R,4S)—N-(3-acetamido-3-(biphenyl-2-yl)-7-methoxyheptyl)-3-amino-4-hydroxy-N-methylcyclopentanecarboxamide; and
(1S,3R,4S)-3-amino-N—((S)-3-(6-chloro-5′-methylbiphenyl-2-yl)-3-hydroxy-7-methoxyheptyl)-4-hydroxy-N-methylcyclopentanecarboxamide.

### Claim 58 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1, or an enantiomer, diastereomer, or salt thereof and a pharmaceutically acceptable carrier or excipient.

### Claim 59 (depends on 58)

The pharmaceutical composition of claim 58, further comprising an additional agent selected from the group consisting of α-blockers, β-blockers, calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, dual ACE and neutral endopeptidase (NEP) inhibitors, angiotensin-receptor blockers (ARBs), aldosterone synthase inhibitors, aldosterone-receptor antagonists, and endothelin receptor antagonists.

### Claim at position 60

-70. (canceled)