# US 10,118,900 B2 · Benzimidazole derivatives useful as CB-1 inverse agonists

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- Number: US 10,118,900 B2
- Document ID: US10118900B2
- Status: Granted
- Kind: B2
- Application number: 15/244,372
- Filed: 2016-08-23
- Published: 2017-03-02
- Granted: 2018-11-06
- Earliest claimed: 2015-08-25
- Assignees: Janssen Pharmaceutica NV
- Applicants: Janssen Pharmaceutica NV
- Inventors: Mark J. Macielag; Rui Zhang; Yue-Mei Zhang; Bin Zhu; Michael H. Parker; Donald W. Ludovici; Daniel J. Parks; Bart L. DeCorte; Michael N. Greco
- Web page: https://patentgrep.com/patent/US10118900B2

## CPC

- C07D 235/18: with aryl radicals directly attached in position 2
- C07C 53/18: containing fluorine
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 401/14: containing three or more hetero rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/14: containing three or more hetero rings
- C07D 409/10: linked by a carbon chain containing aromatic rings
- C07D 409/14: containing three or more hetero rings
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 417/14: containing three or more hetero rings
- C07D 471/08: Bridged systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

The present invention is directed to benzimidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions mediated by the CB-1 receptor; more particularly, use in the treatment of disorders and conditions responsive to inverse agonism of the CB-1 receptor. More particularly, the compounds of the present invention are useful in the treatment of metabolic disorders.

## Claims

### Claim 1

A compound of formula (I)
wherein
R0 is selected from the group consisting of hydrogen, —OH, —C(O)OH, —C(O)O—(C1-4alkyl), —CH2—OH, —CH2—O—(C1-2alkyl) and —CH2—O—(C1-2alkyl)-CO2H;
is selected from the group consisting of cylopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, furyl, thienyl, thiazolyl, benzothiazolyl and benzo[d][1,3]dioxolyl;
wherein the phenyl, furyl, thienyl, thiazolyl or benzothiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, cyano, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)NRARB and NRARB; wherein RA and RB are each independently selected from the group consisting of hydrogen, alkyl and hydroxy substituted C1-2alkyl; provided that each substituent is bound to a carbon atom;
is selected from the group consisting of cylopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, furyl, thienyl, thiazolyl, benzothiazolyl and benzo[d][1,3]dioxolyl;
wherein the phenyl, furyl, thienyl, thiazolyl or benzothiazolyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, cyano, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)NRCRD and NRCRD; wherein RC and RD are each independently selected from the group consisting of hydrogen, alkyl and hydroxy substituted C1-2alkyl; provided that each substituent is bound to a carbon atom;
R1 is selected from the group consisting of hydrogen, hydroxy and C1-4alkoxy;
R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-NRERF, —(C2-4alkenyl)-OH, —C(O)OH, —C(O)O—(C1-2alkyl), —NRERF, C3-6cycloalkyl, phenyl, furyl, thienyl, pyridyl, azetidin-3-yl, oxetan-3-yl, tetrahydrofuran-2-yl and tetrahydropyran-4-yl;
wherein the phenyl is optionally substituted with one to two halogen; wherein the azetidin-3-yl is optionally substituted with —C(O)O—(C1-4alkyl); and wherein RE and RF are each independently selected from the group consisting of hydrogen and C1-4alkyl;
provided that when R2 is selected from the group consisting of pyridyl, furyl and thienyl, then the R2 is bound to the benzimidazole core through a carbon atom;
R3 is selected from the group consisting of (a) through (k); wherein
(a) is
wherein R4 is selected from the group consisting of hydrogen, —C(O)OH, —C(O)O—(C1-2alkyl), —C(O)NRGRH, —NH-(phenyl), and —NH—SO2-(phenyl); wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy and carboxy; and wherein RG and RH are each independently selected from the group consisting of hydrogen and C1-4alkyl;
(b) is
(c) is
(d) is
(e) is
(f) is
wherein a is an integer from 0 to 1;
wherein L1 is selected from the group consisting of —CH2—, —CH2—CH2, —CH2CH2CH2—, —CH(CH3)CH2— and —CH2—CH(CH3)—;
wherein R5 is selected from the group consisting of hydrogen, C1-2alkyl, fluorinated C1-2alkyl, C2-4alkenyl, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C2-3alkyl)-O-(phenyl), —C(O)—(C1-2alkyl)-OH, —C(O)—(C1-2alkyl)-C(O)OH, —C(O)—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—(C1-2alkyl)-C(O)—NH2, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)O—(C3-5cycloalkyl), —C(O)—NRJRK, —C(O)NH—(C3-5cycloalkyl), —C(O)NH-(phenyl), —C(O)NH—(C1-2alkyl)-(phenyl), —SO2—(C1-2alkyl), —SO2-(fluorinated C1-2alkyl), —SO2—(C1-2alkyl)-C(O)OH, —SO2—(C1-2alkyl)-C(O)O—(C1-2alkyl), —SO2—NRJRK, —SO2—(C1-2alkyl)-C(O)NRJRK, phenyl, —(C1-3alkyl)-phenyl, —C(O)-(phenyl), —C(O)O-(phenyl), —C(O)O—(C1-2alkyl)-(phenyl), —SO2-(phenyl), pyrimidin-2-yl, pyridyl, —(C1-2alkyl)-pyridyl, —C(O)-(pyridyl), —SO2-(pyridyl), furyl, —(C1-2alkyl)-furyl, —C(O)-furyl, —SO2-(furyl), thienyl, —(C1-2alkyl)-thienyl, —C(O)-thienyl, —SO2-(thienyl), —C(O)-(1,2,3-triazol-4-yl), —C(O)-(1,2,4,-triazol-3-yl) and —SO2—(C1-2alkyl)-(piperazin-1-yl);
wherein the phenyl, pyrimidin-2-yl, pyridyl, furyl, thienyl or pyridyl, is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C1-2alkyl)-C(O)—NRLRM, —O—(C1-4alkyl), —O-(fluorinated C1-2alkyl), —O—(C2-6alkenyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)NRLRM, —O—(C1-2alkyl)-C(O)—NRLRM, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)—NRLRM, —C(O)—NH—(C1-3alkyl)-OH, —C(O)—NH—(C1-2alkyl)-C(O)OH, —C(O)—NH—(C1-2alkyl)-C(O)O—(C1-2alkyl), —NRLRM and —SO2—NRLRM;
wherein RJ and RK are each independently selected from the group consisting of hydrogen and C1-4alkyl; and wherein RL and RM are each independently selected from the group consisting of hydrogen and C1-4alkyl;
(g) is
wherein b is an integer from 0 to 1;
wherein L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—, —CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2CH2—O—, —CH2—CH(OH)—, —CH(CH3)—CH(OH) and —CH2CH2CH2—NH—SO2—;
wherein R6 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH, —C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—NRNRP, —O—(C1-2alkyl)-C(O)—NRNRP, phenyl, furyl and thienyl; wherein the phenyl, furyl or thienyl is optionally substituted with a substituent selected from the group consisting of halogen, C1-4alkyl and carboxy; and wherein RN and RP are each independently selected from the group consisting of hydrogen and C1-4alkyl;
wherein R7 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-4alkyl, fluorinated C1-2alkyl, C1-4alkoxy, fluorinated C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
(h) is
wherein L3 is selected from the group consisting of —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH(CH3)CH2—, —CH2CH(CH3)— and —CH2CH2—O—;
wherein R8 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, C1-4alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
(i) is
wherein c is an integer from 0 to 1;
and wherein L4 is selected from the group consisting of —CH2— and —CH2—CH2—;
(j) is
and (k) is
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

A compound as in claim 1, wherein
R0 is selected from the group consisting of hydrogen, —OH, —C(O)OH, —C(O)O—(C1-2alkyl), —CH2—OH, —CH2—O—(C1-2alkyl) and —CH2—O—(C1-2alkyl)-CO2H;
is selected from the group consisting of phenyl, thiazolyl, and benzo[d][1,3]dioxolyl;
wherein the phenyl or thiazolyl is optionally substituted with one to two substituents independently selected from the group consisting of halogen C1-4alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
is selected from the group consisting of phenyl, thiazolyl and benzo[d][1,3]dioxolyl;
wherein the phenyl or thiazolyl is optionally substituted with one to two substituents independently selected from the group consisting of halogen C1-4alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
R1 is selected from the group consisting of hydrogen, hydroxy and C1-2alkoxy;
R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-NH2, —(C2-4alkenyl)-OH, —C(O)O—(C1-2alkyl), —NRERF, C3-6cycloalkyl, phenyl, furyl, thienyl, pyridyl, oxetan-3-yl, azetidin-3-yl, tetrahydrofuran-2-yl and tetrahydropyran-4-yl;
wherein the phenyl is optionally substituted with one to two halogen; wherein the azetidin-3-yl is optionally substituted with —C(O)O—(C1-4alkyl); and wherein RE and RF are each independently selected from the group consisting of hydrogen and C1-4alkyl;
provided that when R2 is selected from the group consisting of pyridyl, furyl and thienyl, then the R2 is bound to the benzimidazole core through a carbon atom;
R3 is selected from the group consisting of (a) through (k); wherein
(a) is
wherein R4 is selected from the group consisting of hydrogen, —C(O)OH, —C(O)O—(C1-2alkyl), —C(O)NRGRH, —NH-(phenyl), and —NH—SO2-(phenyl);
wherein the phenyl is optionally substituted with hydroxy or carboxy; and wherein RG and RH are each independently selected from the group consisting of hydrogen and methyl;
(b) is
(c) is
(d) is
(e) is
(f) is
wherein a is an integer from 0 to 1;
wherein L1 is selected from the group consisting of —CH2—, —CH2—CH2, —CH(CH3)CH2— and —CH2—CH(CH3)—;
wherein R5 is selected from the group consisting of hydrogen, C1-2alkyl, fluorinated C1-2alkyl, C2-4alkenyl, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C2alkyl)-O-(phenyl), —C(O)—(C1-2alkyl)-OH, —C(O)—(C1-2alkyl)-C(O)OH, —C(O)—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—(C1-2alkyl)-C(O)—NH2, —C(O)O—(C1-4alkyl), —C(O)O—(C3-5cycloalkyl), —C(O)O-(phenyl), —C(O)O—CH2-(phenyl), —C(O)—NH2, —C(O)NH—(C1-2alkyl), —C(O)NH—(C3-5cycloalkyl), —C(O)NH-(phenyl), —C(O)NH—(C1-2alkyl)-(phenyl), —SO2—(C1-2alkyl), —SO2-(fluorinated C1-2alkyl), —SO2—(C1-2alkyl)-C(O)OH, —SO2—(C1-2alkyl)-C(O)O—(C1-2alkyl), —SO2—NH2, —SO2—NH—(C1-2alkyl), —SO2—(C1-2alkyl)-C(O)NH2, phenyl, —(C1-3alkyl)-phenyl, —C(O)-(phenyl), —C(O)O-(phenyl), —C(O)O—(C1-2alkyl)-(phenyl), —SO2-(phenyl), pyrimidin-2-yl, pyrid-2-yl, pyrid-3-yl, —(C1-2alkyl)-pyrid-2-yl, —(C1-2alkyl)-pyrid-3-yl, —(C1-2alkyl)-fur-2-yl, —(C1-2alkyl)-thien-2-yl, —C(O)-fur-2-yl, —C(O)-thien-2-yl, —C(O)-(pyrid-3-yl), —C(O)-(1,2,3-triazol-4-yl), —C(O)-(1,2,4,-triazol-3-yl), —SO2—(C1-2alkyl)-(piperazin-1-yl), —SO2-(fury-2-yl), —SO2-(thien-2-yl) and —SO2-(pyrid-3-yl);
wherein the phenyl, pyrimidin-2-yl, pyridyl, furyl, thienyl or pyridyl, is optionally substituted with one to three substituents independently selected from the group consisting of halogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —C(1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —O—(C1-2alkyl), —O-(fluorinated C1-2alkyl), —O—(C2-6alkenyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)NH2, —C(O)OH, —C(O)O—(C1-4alkyl), —C(O)—NH2, —C(O)—NH—(C1-2alkyl), —C(O)—NH—(C1-3alkyl)-OH, —C(O)—NH—(C1-2alkyl)-C(O)OH, —C(O)—NH—(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C1-2alkyl)-C(O)—NH2, —O—(C1-2alkyl)-C(O)—NH2, —O—(C1-2alkyl)-C(O)OH, —NH2, —NH(C1-2alkyl), —SO2—NH2 and —SO2—NH(C1-2alkyl);
(g) is
wherein b is an integer from 0 to 1;
wherein L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—, —CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2CH2—O—, —CH2—CH(OH)—, —CH(CH3)—CH(OH) and —CH2CH2CH2—NH—SO2—;
wherein R6 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH, —C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—NH2, —O—(C1-2alkyl)-C(O)—NH2, phenyl, furyl and thienyl; wherein the phenyl, furyl or thienyl is optionally substituted with carboxy;
and wherein R7 is selected from the group consisting of hydrogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, C1-2alkoxy, fluorinated C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
(h) is
wherein L3 is selected from the group consisting of —CH2—, —CH2CH2— and —CH2CH2—O—;
and wherein R8 is selected from the group consisting of hydrogen, -halogen, C1-2alkyl, C1-2alkoxy, —C(O)OH and —C(O)O—(C1-4alkyl);
(i) is
wherein c is an integer from 0 to 1;
and wherein L4 is selected from the group consisting of —CH2— and —CH2—CH2—;
(j) is
and (k) is
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

A compound as in claim 2, wherein
R0 is selected from the group consisting of hydrogen, —OH, —C(O)OH, —C(O)O—(C1-2alkyl), —CH2—OH, —CH2—O—(C1-2alkyl) and —CH2—O—(C1-2alkyl)-CO2H;
is phenyl; wherein the phenyl is optionally substituted a substituent selected from the group consisting of halogen and C1-2alkoxy;
is selected from the group consisting of phenyl, thiazol-2-yl and benzo[d][1,3]dioxol-5-yl; wherein the phenyl or thiazol-2-yl is optionally substituted with a substituent selected from the group consisting of halogen, C1-4alkyl, fluorinated C1-2alkyl, C1-2alkoxy and —C(O)OH;
R1 is selected from the group consisting of hydrogen, hydroxy and C1-2alkoxy;
R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, fluorinated C1-2alkyl, —(C1-2alkyl)-OH, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-NH2, —(C2-4alkenyl)-OH, —C(O)O—(C1-2alkyl), —NRERF, C3-6cycloalkyl, phenyl, fur-2-yl, fur-3-yl, thien-3-yl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, oxetan-3-yl, azetidin-3-yl, tetrahydrofuran-2-yl and tetrahydro-pyran-4-yl;
wherein the phenyl is optionally substituted with one to two halogen; wherein the azetidin-3-yl is optionally substituted with —C(O)O—(C1-4alkyl); and wherein RE and RF are each independently selected from the group consisting of hydrogen, methyl and ethyl;
R3 is selected from the group consisting of (a) through (k); wherein
(a) is
wherein R4 is selected from the group consisting of hydrogen, —C(O)OH, —C(O)NRGRH, —NH-(phenyl) and —NH—SO2-(phenyl); wherein the phenyl is optionally substituted with hydroxy or carboxy; wherein RG and RH are each independently selected from the group consisting of hydrogen and methyl;
(b) is
(c) is
(d) is
(e) is
(f) is
wherein a is an integer from 0 to 1; and wherein L1 is selected from the group consisting of —CH2— and —CH2—CH(CH3)—;
wherein R5 is selected from the group consisting of hydrogen, C2-4alkenyl, —(C1-2alkyl)-C(O)OH, —(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C2alkyl)-O-(phenyl), —C(O)—(C1-2alkyl)-OH, —C(O)—(C1-2alkyl)-C(O)OH, —C(O)—(C1-2alkyl)-C(O)—NH2, —C(O)O—(C1-4alkyl), —C(O)O-(hydroxy substituted C1-4alkyl), —C(O)O—(C3-5cycloalkyl), —C(O)NH—(C1-2alkyl), —C(O)NH—(C3-5cycloalkyl), —C(O)NH-(phenyl), —C(O)NH—(C1-2alkyl)-(phenyl), —SO2—(C1-2alkyl), —SO2-(fluorinated C1-2alkyl), —SO2—(C1-2alkyl)-C(O)OH, —SO2—NH2, —SO2—NH—(C1-2alkyl), —SO2—(C1-2alkyl)-C(O)NH2, phenyl, —(C1-3alkyl)-phenyl, —C(O)-(phenyl), —C(O)O-(phenyl), —C(O)O—(C1-2alkyl)-(phenyl), —SO2-(phenyl), pyrimidin-2-yl, —(C1-2alkyl)-pyrid-2-yl, —(C1-2alkyl)-pyrid-3-yl, —(C1-2alkyl)-fur-2-yl, —(C1-2alkyl)-thien-2-yl, —C(O)-(pyrid-3-yl), —C(O)-(1,2,3-triazol-4-yl), —C(O)-(1,2,4,-triazol-3-yl), —SO2—(C1-2alkyl)-(piperazin-1-yl), —SO2-(fury-2-yl), —SO2-(thien-2-yl) and —SO2-(pyrid-3-yl);
wherein the phenyl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, hydroxy, C1-2alkyl, fluorinated C1-2alkyl, —O—(C1-2alkyl), —O-(fluorinated C1-2alkyl), —O—(C2-6alkenyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)NH2, —C(O)OH, —C(O)O—(C1-2alkyl), —C(1-2alkyl)-C(O)OH, —C(O)—NH2, —C(O)—NH—(C1-2alkyl), —C(O)—NH—(C1-3alkyl)-OH, —C(O)—NH—(C1-2alkyl)-C(O)OH, —C(O)—NH—(C1-2alkyl)-C(O)O—(C1-2alkyl), —(C1-2alkyl)-C(O)—NH2, —O—(C1-2alkyl)-C(O)—NH2, —O—(C1-2alkyl)-C(O)OH, —NH2 and —SO2—NH2;
and wherein the pyrimidin-2-yl, pyrid-2-yl, pyrid-3-yl, fur-2-yl or thien-2-yl is optionally substituted with one to two substituents independently selected from the group consisting of C1-2alkyl, —(C1-2alkyl)-OH, —C(O)OH, —C(O)O—(C1-2alkyl), —C(O)—NH2, —C(O)NH—(C1-2alkyl)-OH, —C(O)NH—(C1-2alkyl)-C(O)OH and —C(O)NH—(C1-2alkyl)-C(O)O—(C1-2alkyl);
(g) is
wherein b is an integer from 0 to 1; and wherein L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—, —CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2CH2—O—, —CH2—CH(OH)—, —CH(CH3)—CH(OH) and —CH2CH2CH2—NH—SO2—;
wherein R6 is selected from the group consisting of hydrogen, halogen, hydroxy, C1-2alkoxy, fluorinated C1-2alkyl, —C(O)OH, —C(O)O—(C1-2alkyl), —O—(C1-2alkyl)-C(O)OH, —O—(C1-2alkyl)-C(O)O—(C1-2alkyl), —C(O)—NH2, —O—(C1-2alkyl)-C(O)—NH2, phenyl and thienyl; wherein the phenyl or thienyl is optionally substituted with carboxy; and wherein R7 is selected from the group consisting of hydrogen and fluorinated C1-2alkyl;
(h) is
wherein L3 is selected from the group consisting of —CH2— and —CH2CH2—O—; and wherein R8 is selected from the group consisting of hydrogen, —C(O)OH and —C(O)O—(C1-2alkyl);
(i) is
wherein c is an integer from 0 to 1; wherein L4 is —CH2—;
(j) is
and (k) is
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

A compound as in claim 3, wherein
R0 is selected from the group consisting of hydrogen, —OH, —C(O)OH, —C(O)OCH3, —CH2—OH, —CH2—OCH3 and —CH2—OCH2—CO2H;
is selected from the group consisting of phenyl, 2-chlorophenyl, 4-chlorophenyl and 4-methoxyphenyl;
is selected from the group consisting of phenyl, 4-chlorophenyl, 4-fluorophenyl, 4-methylphenyl, 4-trifluoromethyl-phenyl, 4-carboxyphenyl, 4-methoxyphenyl, thiazol-2-yl, 4-ethyl-thiazol-2-yl, 5-ethyl-thiazol-2-yl, 4-t-butyl-thiazol-2-yl, 4-trifluoromethyl-thiazol-2-yl and benzo[d][1,3]dioxol-5-yl,
R1 is selected from the group consisting of hydrogen, hydroxy and methoxy;
R2 is selected from the group consisting of hydrogen, chloro, methyl, ethyl, n-propyl, isopropyl, isobutyl, t-butyl, —CHF2, —CF3, —CH2—CF3, —CH2OH, —CH2CH2—C(O)OH, —CH2CH2—NH2, —C(═CH2)—CH2OH, —C(O)OCH3, —C(O)OCH2CH3, —NH2, —N(CH3)2, cyclopropyl, cyclobutyl, cyclopentyl, oxetan-3-yl, azetidin-3-yl, 1-(t-butoxycarbonyl)-azetidin-3-yl, tetrahydrofuran-2-yl, tetrahydro-pyran-4-yl, 4-chlorophenyl, 2,4-dichlorophenyl, pyrid-2-yl, pyrid-3-yl, pyrid-4-yl, fur-2-yl, fur-3-yl and thien-3-yl;
R3 is selected from the group consisting of (a) through (k); wherein
(a) is
wherein R4 is selected from the group consisting of hydrogen, —C(O)OH, —C(O)NH2, —NH—SO2-(3-carboxyphenyl), —NH-(3-hydroxyphenyl), —NH-(3-carboxyphenyl), —NH-(4-carboxyphenyl) and —NH—SO2-(4-carboxyphenyl); and wherein the cyclohexyl is bound to the benzimidazole core in a cis-, trans- or racemic stereo-orientation;
(b) is
wherein a 0; and wherein R5 is selected from the group consisting of 3-carboxybenzyl-, 4-carboxyphenyl-sulfonyl- and 5-carboxyfur-2-yl-sulfonyl-;
(c) is
wherein a is 0; and wherein R5 is selected from the group consisting of 3-carboxybenzyl-, 4-carboxyphenyl-sulfonyl- and 5-carboxy-fur-2-yl-sulfonyl-;
(d) is
wherein a is an integer from 0 to 1;
wherein L1 is selected from the group consisting of —CH2— and —CH2—CH(R*—CH3)—;
wherein R5 is selected from the group consisting of hydrogen, propyn-3-yl, carboxy-methyl-, methoxy-carbonyl-methyl-, 3-carboxyphenyl-oxy-ethyl-, 2-hydroxyethyl-carbonyl-, hydroxymethyl-carbonyl-, 2-carboxy-ethyl-carbonyl-, aminocarbonyl-methyl-carbonyl-, 2-(aminocarbonyl)-ethyl-carbonyl-, ethoxycarbonyl-, t-butoxycarbonyl-, cyclopentyloxy-carbonyl-, 2,3,4-trihydroxy-n-butyloxy-carbonyl-, 3-carboxyphenyl, 4-carboxyphenyl, 3-(carboxy-methyl)-phenyl, 4-(carboxy-methyl)-phenyl, 3-(methoxycarbonyl)-phenyl, 3-(aminocarbonyl)-phenyl, 4-(aminocarbonyl)-phenyl, 3-(aminocarbonyl-methyl)-phenyl, 4-(aminocarbonyl-methyl)-phenyl, 3-(aminocarbonyl-methoxy)-phenyl, 4-(aminocarbonyl-methoxy)-phenyl, 3-(carboxy-methoxy)-phenyl, 4-(carboxy-methoxy)-phenyl, 3-hydroxy-benzyl, 3-(hex-2-en-1-yloxy)-benzyl, 2-trifluoromethyl-benzyl, 3-carboxy-benzyl, 4-carboxy-benzyl, 3-(methoxycarbonyl)-benzyl, 3-(aminocarbonyl)-benzyl, 4-(aminocarbonyl)-benzyl, 3-(2-hydroxyethyl-aminocarbonyl)-benzyl, 2-hydroxy-3-carboxy-benzyl, 2-hydroxy-5-carboxy-benzyl, 2-fluoro-3-carboxy-benzyl, 2-fluoro-5-carboxy-benzyl, 2-chloro-3-carboxy-benzyl, 2-chloro-5-carboxy-benzyl, 2-trifluoromethyl-5-carboxy-benzyl, 3-fluoro-5-carboxy-benzyl, 3-carboxy-4-fluoro-benzyl, 3-carboxy-4-hydroxy-benzyl, 3-trifluoromethyl-5-carboxy-benzyl, 1-(3-hydroxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-ethyl-, 1R*-(3-carboxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-n-propyl-, 4-carboxy-pyrimidin-2-yl, 5-carboxy-pyrimidin-2-yl, 5-methoxycarbonyl-pyrimidin-2-yl, 2-carboxy-pyrid-4-yl-methyl-, 4-carboxy-pyrid-2-yl-methyl-, 5-carboxy-pyrid-2-yl-methyl-, 6-carboxy-pyrid-2-yl-methyl-, 5-carboxy-pyrid-3-yl-methyl-, 6-carboxy-pyrid-3-yl-methyl-, 5-aminocarbonyl-pyrid-2-yl-methyl-, 6-aminocarbonyl-pyrid-2-yl-methyl-, 5-aminocarbonyl-pyrid-3-yl-methyl-, 6-aminocarbonyl-pyrid-3-yl-methyl-, 1-(4-carboxy-pyrid-2-yl)-ethyl-, 5-carboxy-fur-2-yl-methyl-, 5-aminocarbonyl-fur-2-yl-methyl-, 1-(5-carboxy-fur-2-yl)-ethyl-, 4-carboxy-thien-2-yl-methyl-, 5-carboxy-thien-2-yl-methyl-, 5-aminocarbonyl-thien-2-yl-methyl-, 4-aminocarbonyl-thien-2-yl-methyl-, phenoxy-carbonyl-, benzyloxy-carbonyl-, ethylamino-carbonyl-, cyclopentyl-amino-carbonyl-, phenyl-aminocarbonyl-, benzyl-amino-carbonyl-, 4-carboxy-phenyl-carbonyl-, 4-aminoarbonyl-phenyl-carbonyl-, 3-aminosulfonyl-phenyl-carbonyl-, 4-aminosulfonyl-phenyl-carbonyl-, 6-carboxy-pyrid-3-yl-carbonyl-, 6-aminocarbonyl-pyrid-3-yl-carbonyl-, 1,2,3-triazol-4-yl-carbonyl-, 1,2,4-triazol-3-yl-carbonyl-, methyl-sulfonyl-, trifluoromethyl-sulfonyl-, carboxymethyl-sulfonyl-, carboxyethyl-sulfonyl-, amino-sulfonyl-, amino-ethyl-sulfonyl-, aminocarbonyl-methyl-sulfonyl-, phenyl-sulfonyl-, 4-fluorophenyl-sulfonyl-, 4-chlorophenyl-sulfonyl, 2-hydroxyphenyl-sulfonyl-, 3-hydroxyphenyl-sulfonyl-, 4-hydroxyphenyl-sulfonyl-, 2-methoxy-phenyl-sulfonyl-, 3-methoxy-phenyl-sulfonyl-, 4-methoxy-phenyl-sulfonyl-, 2-trifluoromethyl-phenyl-sulfonyl-, 3-trifluoromethyl-phenyl-sulfonyl-, 4-trifluoromethyl-phenyl-sulfonyl-, 4-trifluoromethoxy-phenyl-sulfonyl-, 2-carboxyphenyl-sulfonyl-, 3-carboxyphenyl-sulfonyl-, 4-carboxyphenyl-sulfonyl-, 4-carboxy-methoxy-phenyl-sulfonyl-, 3-aminophenyl-sulfonyl-, 4-aminophenyl-sulfonyl-, 2-aminocarbonyl-phenyl-sulfonyl-, 3-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-methoxy-phenyl-sulfonyl-, 3-(methylamino-carbonyl)-phenyl-sulfonyl-, 3-(carboxy-ethyl-amino-carbonyl)-phenyl-sulfonyl-, 3-(3-hydroxy-n-propyl-amino-carbonyl)-phenyl-sulfonyl-, 3-(2-(methoxycarbonyl)-ethyl-amino-carbonyl)-phenyl-sulfonyl-, 3-(2-hydroxyethyl-amino-carbonyl)-phenyl-sulfonyl-, 3-fluoro-4-hydroxy-phenyl-sulfonyl-, 3-fluoro-4-methoxy-phenyl-sulfonyl-, 3-fluoro-4-aminocabonyl-phenyl-sulfonyl-, 3-fluoro-4-carboxy-phenyl-sulfonyl-, 3-chloro-4-aminocarbonyl-phenyl-sulfonyl-, 3-chloro-4-carboxy-phenyl-sulfonyl-, 3-methyl-4-aminocarbonyl-phenyl-sulfonyl-, 3-methyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-aminocarbonyl-phenyl-sulfonyl, 3-methoxy-4-carboxy-phenyl-sulfonyl, 3-methoxy-4-aminocarbonyl-phenyl-sulfonyl-, 3-carboxy-4-chloro-phenyl-sulfonyl-, 3-carboxy-4-fluoro-phenyl-sulfonyl-, 3-carboxy-4-methyl-phenyl-sulfonyl-, 3-carboxy-4-methoxy-phenyl-sulfonyl-, 3-aminocarbonyl-4-fluoro-phenyl-sulfonyl-, 3-aminocarbonyl-4-methyl-phenyl-sulfonyl-, 3-aminocarbonyl-4-methoxy-phenyl-sulfonyl-, 3,5-dichloro-4-hydroxy-phenyl-sulfonyl-, piperazin-1-yl-ethyl-sulfonyl-, 5-(hydroxymethyl)-fur-2-yl-sulfonyl-, 5-carboxy-fur-2-yl-sulfonyl-, 5-(aminocarbonyl)-fur-2-yl-sulfonyl-, 4-carboxy-thien-2-yl-sulfonyl-, 4-(aminocarbonyl)-thien-2-yl-sulfonyl-, 3-methyl-5-carboxy-thien-2-yl-sulfonyl-, 3-methyl-5-(aminocarbonyl)-thien-2-yl-sulfonyl-, 6-carboxy-pyrid-3-yl-sulfonyl-, 6-am inocarbonyl-pyrid-3-yl-sulfonyl-, 6-(2-hydroxyethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl-, 6-(carboxyethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl- and 6-(methoxycarbonyl-ethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl-;
(e) is
wherein a is 0; and wherein R5 is selected from the group consisting of ethoxycarbonyl- and trifluoromethyl-sulfonyl-;
(f) is
wherein R5 is trifluoromethyl-sulfonyl-;
(g) is
wherein b is an integer from 0 to 1;
wherein L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—, —CH(CH3)—CH2—, —CH2—CH(CH3)—, —CH2—CH(R*—CH3)—, —CH2—CH(S*—CH3)—, —CH2CH2—O—, —CH2—CH(OH)—, —CH2—CH(R*—OH), —CH(CH3)—CH(OH) and —CH2CH2CH2—NH—SO2—;
wherein R6 is selected from the group consisting of hydrogen, 3-bromo, 3-chloro, 4-chloro, 3-hydroxy, 4-hydroxy, 3-methoxy, 4-methoxy, 4-trifluoromethyl, 3-carboxy, 4-carboxy, 3-carboxy-methoxy-, 4-carboxy-methoxy-, 3-methoxycarbonyl-, 4-methoxycarbonyl-, 3-ethoxy-carbonyl-methoxy-, 4-ethoxy-carbonyl-methoxy-, 4-aminocarbonyl-, 3-amino-carbonyl-methoxy-, 4-amino-carbonyl-methoxy-, 3-(3-carboxyphenyl), 3-(4-carboxy-phenyl), 4-(3-carboxyphenyl), 4-(4-carboxyphenyl) and 3-(5-carboxy-thien-2-yl);
and wherein R7 is selected from the group consisting of hydrogen and 5-trifluoromethyl;
(h) is
wherein L3 is selected from the group consisting of —CH2— and —CH2CH2—O—; and wherein R8 is selected from the group consisting of hydrogen, carboxy and methoxycarbonyl-;
(i) is
wherein c is an integer from 0 to 1; and wherein L4 is —CH2—;
(j) is
and (k) is
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 4)

A compound as in claim 4, wherein
R0 is selected from the group consisting of hydrogen, —OH, —CO2H, —C(O)OCH3 and —CH2OCH3;
is selected from the group consisting of 4-chlorophenyl, 4-fluorophenyl, 4-methylphenyl and 4-methoxyphenyl;
is selected from the group consisting of phenyl, 4-chlorophenyl, 4-fluorphenyl, 4-methylphenyl, 4-trifluoromethyl-phenyl, 4-methoxyphenyl, 4-carboxyphenyl, thiazol-2-yl and benzo[d][1.3]dioxol-5-yl;
R1 is selected from the group consisting of hydrogen, —OH and —OCH3;
R2 is selected from the group consisting of hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, amino-ethyl-, —C═(CH2)—CH2OH, oxetan-3-yl, tetrahydrofur-2-yl and pyrid-3-yl;
R3 is selected from the group consisting of (a), (b), (d), (f), (g), (h) and (i); wherein
(a) is
wherein the cyclohexyl group is bound in a cis-, trans- or racemic orientation; and wherein R4 is selected from the group consisting of hydrogen, aminocarbonyl-, 3-hydroxyphenyl-amino-, 3-carboxyphenyl-amino-, 4-carboxyphenyl-amino-, 3-carboxyphenyl-sulfonyl-amino- and 4-carboxyphenyl-sulfonyl-amino-;
(b) is
wherein a 0; and wherein R5 is selected from the group consisting of 3-carboxybenzyl- and 4-carboxyphenyl-sulfonyl-;
(d) is
wherein a is an integer from 0 to 1; wherein L1 is —CH2—; and wherein R5 is selected from the group consisting of propyn-3-yl, methoxy-carbonyl-methyl-, 3-carboxyphenyl-oxy-ethyl-, 2-hydroxyethyl-carbonyl-, hydroxymethyl-carbonyl-, aminocarbonyl-methyl-carbonyl-, aminocarbonyl-ethyl-carbonyl-, ethoxycarbonyl-, t-butoxycarbonyl-, cyclopentyloxy-carbonyl-, 2,3,4-trihydroxy-n-butyloxy-carbonyl-, 3-carboxyphenyl, 4-carboxyphenyl, 3-(aminocarbonyl)-phenyl, 4-(aminocarbonyl)-phenyl, 3-(aminocarbonyl-methyl)-phenyl, 4-(aminocarbonyl-methyl)-phenyl, 3-(aminocarbonyl-methoxy)-phenyl, 4-(aminocarbonyl-methoxy)-phenyl, 3-hydroxy-benzyl, 2-trifluoromethyl-benzyl, 3-carboxy-benzyl, 4-carboxy-benzyl, 3-(aminocarbonyl)-benzyl, 4-(aminocarbonyl)-benzyl, 3-(2-hydroxyethyl-aminocarbonyl)-benzyl, 2-hydroxy-3-carboxy-benzyl, 2-fluoro-5-carboxy-benzyl, 3-fluoro-5-carboxy-benzyl, 2-chloro-3-carboxy-benzyl, 2-chloro-5-carboxy-benzyl, 2-trifluoromethyl-5-carboxy-benzyl, 3-carboxy-4-fluoro-benzyl, 3-carboxy-4-hydroxy-benzyl, 1-(3-hydroxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-ethyl-, 1R*-(3-carboxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-n-propyl-, 5-carboxy-pyrimidin-2-yl, 5-methoxycarbonyl-pyrimidin-2-yl, 2-carboxy-pyrid-4-yl-methyl-, 4-carboxy-pyrid-2-yl-methyl-, 5-carboxy-pyrid-2-yl-methyl-, 6-carboxy-pyrid-2-yl-methyl-, 5-carboxy-pyrid-3-yl-methyl-, 6-carboxy-pyrid-3-yl-methyl-, 5-aminocarbonyl-pyrid-2-yl-methyl-, 6-aminocarbonyl-pyrid-2-yl-methyl-, 5-aminocarbonyl-pyrid-3-yl-methyl-, 6-aminocarbonyl-pyrid-3-yl-methyl-, 1-(4-carboxy-pyrid-2-yl)-ethyl-, 5-carboxy-fur-2-yl-methyl-, 1-(5-carboxy-fur-2-yl)-ethyl-, 5-aminocarbonyl-fur-2-yl-methyl-, 4-carboxy-thien-2-yl-methyl-, 5-carboxy-thien-2-yl-methyl-, 5-aminocarbonyl-thien-2-yl-methyl-, 4-aminocarbonyl-thien-2-yl-methyl-, phenoxy-carbonyl-, benzyloxy-carbonyl-, ethylamino-carbonyl-, cyclopentyl-amino-carbonyl-, phenyl-aminocarbonyl-, benzyl-amino-carbonyl-, 4-aminocarbonyl-phenyl-carbonyl-, 3-aminosulfonyl-phenyl-carbonyl-, 4-aminosulfonyl-phenyl-carbonyl-, 6-aminocarbonyl-pyrid-3-yl-carbonyl-, 1,2,4-triazol-3-yl-carbonyl-, methylsulfonyl-, trifluoromethyl-sulfonyl-, phenyl-sulfonyl-, 4-fluorophenyl-sulfonyl-, 4-chlorophenyl-sulfonyl, 2-hydroxyphenyl-sulfonyl-, 3-hydroxyphenyl-sulfonyl-, 4-hydroxyphenyl-sulfonyl-, 2-methoxy-phenyl-sulfonyl-, 3-methoxy-phenyl-sulfonyl-, 4-methoxy-phenyl-sulfonyl-, 2-trifluoromethyl-phenyl-sulfonyl-, 3-trifluoromethyl-phenyl-sulfonyl-, 4-trifluoromethyl-phenyl-sulfonyl-, 4-trifluoromethoxy-phenyl-sulfonyl-, 3-carboxyphenyl-sulfonyl-, 4-carboxyphenyl-sulfonyl-, 3-aminophenyl-sulfonyl-, 4-aminophenyl-sulfonyl-, 2-aminocarbonyl-phenyl-sulfonyl-, 3-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-methoxy-phenyl-sulfonyl-, 3-(methylamino-carbonyl)-phenyl-sulfonyl-, 3-(3-hydroxy-n-propyl-amino-carbonyl)-phenyl-sulfonyl-, 3-(2-(methoxycarbonyl)-ethyl-amino-carbonyl)-phenyl-sulfonyl-, 3-(2-hydroxyethyl-amino-carbonyl)-phenyl-sulfonyl-, 3-fluoro-4-methoxy-phenyl-sulfonyl-, 3-fluoro-4-aminocabonyl-phenyl-sulfonyl-, 3-fluoro-4-carboxy-phenyl-sulfonyl-, 3-chloro-4-aminocarbonyl-phenyl-sulfonyl-, 3-chloro-4-carboxy-phenyl-sulfonyl, 3-methyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-aminocarbonyl-phenyl-sulfonyl, 3-methoxy-4-aminocarbonyl-phenyl-sulfonyl-, 3-methoxy-4-carboxy-phenyl-sulfonyl-, 3-carboxy-4-chloro-phenyl-sulfonyl-, 3-carboxy-4-fluoro-phenyl-sulfonyl-, 3-aminocarbonyl-4-fluoro-phenyl-sulfonyl-, 3-aminocarbonyl-4-methyl-phenyl-sulfonyl-, 3-aminocarbonyl-4-methoxy-phenyl-sulfonyl-, 3,5-dichloro-4-hydroxy-phenyl-sulfonyl-, 5-(hydroxymethyl)-fur-2-yl-sulfonyl-, 5-carboxy-fur-2-yl-sulfonyl-, 5-(aminocarbonyl)-fur-2-yl-sulfonyl-, 4-carboxy-thien-2-yl-sulfonyl-, 4-(am inocarbonyl)-thien-2-yl-sulfonyl-, 3-methyl-5-carboxy-thien-2-yl-sulfonyl-, 3-methyl-5-(aminocarbonyl)-thien-2-yl-sulfonyl-, 6-carboxy-pyrid-3-yl-sulfonyl-, 6-aminocarbonyl-pyrid-3-yl-sulfonyl-, 6-(2-hydroxyethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl-, 6-(carboxyethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl- and 6-(methoxycarbonyl-ethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl-;
(f) is
wherein R5 is trifluoromethyl-sulfonyl-;
(g) is
wherein b is an integer from 0 to 1; L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH(CH3)—CH2—, —CH2—CH(R*—CH3)—, —CH2—CH(S*—CH3)—, —CH2CH2—O—, —CH2—CH(OH)— and —CH2CH2CH2—NH—SO2—; and wherein R6 is selected from the group consisting of hydrogen, 3-chloro-, 4-chloro-, 3-bromo-, 4-bromo-, 3-hydroxy, 4-hydroxy-, 4-trifluoromethyl, 3-methoxy-, 4-methoxy-, 4-methoxycarbonyl-, 3-(ethoxy-carbonyl-methoxy)-, 4-(ethoxy-carbonyl-methoxy)-, 3-(aminocarbonyl-methoxy)-, 4-(aminocarbonyl-methoxy)-, 3-(3-carboxyphenyl), 3-(4-carboxyphenyl) and 3-(5-carboxy-thein-2-yl); and R7 is selected from the group consisting of hydrogen and 5-trifluoromethyl;
(h) is
wherein L3 is —CH2CH2— and wherein R8 is 5-methoxycarbonyl-;
and (i) is
wherein c is an integer from 0 to 1; and wherein L4 is —CH2—;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 4)

A compound as in claim 4, wherein
R0 is selected from the group consisting of hydrogen, —OH, —CO2H and —C(O)OCH3;
is selected from the group consisting of 4-chlorophenyl, 4-fluorophenyl and 4-methylphenyl;
is selected from the group consisting of phenyl, 4-chlorophenyl, 4-fluorphenyl, 4-methylphenyl, 4-trifluoromethyl-phenyl, thiazol-2-yl and benzo[d][1.3]dioxol-5-yl;
R1 is selected from the group consisting of hydrogen, —OH and —OCH3;
R2 is selected from the group consisting of hydrogen, methyl, ethyl, cyclopropyl, cyclobutyl, oxetan-3-yl and tetrahydrofur-2-yl;
R3 is selected from the group consisting of (a), (b), (d), (f), (g) and (i); wherein
(a) is
wherein the cyclohexyl group is bound in trans-orientation; and wherein R4 is 3-hydroxyphenyl-amino-;
(b) is
wherein a 0; and wherein R5 is 3-carboxybenzyl-;
(d) is
wherein a is an integer from 0 to 1; wherein L1 is —CH2—; and wherein R5 is selected from the group consisting of propyn-3-yl, methoxy-carbonyl-methyl-, 3-carboxyphenyl-oxy-ethyl-, 2-hydroxyethyl-carbonyl-, hydroxymethyl-carbonyl-, ethoxycarbonyl-cyclopentyloxy-carbonyl-, 4-carboxyphenyl, 3-(aminocarbonyl)-phenyl, 4-(am inocarbonyl)-phenyl, 3-(aminocarbonyl-methyl)-phenyl, 4-(am inocarbonyl-methyl)-phenyl, 3-(aminocarbonyl-methoxy)-phenyl, 4-(aminocarbonyl-methoxy)-phenyl, 3-hydroxy-benzyl, 3-carboxy-benzyl, 4-carboxy-benzyl, 3-(aminocarbonyl)-benzyl, 4-(aminocarbonyl)-benzyl, 3-(2-hydroxyethyl-aminocarbonyl)-benzyl, 2-fluoro-5-carboxy-benzyl, 3-fluoro-5-carboxy-benzyl, 2-chloro-5-carboxy-benzyl, 3-carboxy-4-fluoro-benzyl, 3-carboxy-4-hydroxy-benzyl, 1-(3-hydroxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-ethyl-, 1R*-(3-carboxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-n-propyl-, 5-carboxy-pyrimidin-2-yl, 5-carboxy-pyrid-3-yl-methyl-, 6-carboxy-pyrid-3-yl-methyl-, 5-am inocarbonyl-pyrid-2-yl-methyl-, 6-aminocarbonyl-pyrid-2-yl-methyl-, 5-aminocarbonyl-pyrid-3-yl-methyl-, 6-aminocarbonyl-pyrid-3-yl-methyl-, 1-(4-carboxy-pyrid-2-yl)-ethyl-, 5-carboxy-fur-2-yl-methyl-, 5-aminocarbonyl-fur-2-yl-methyl-, 1-(5-carboxy-fur-2-yl)-ethyl-, 4-carboxy-thien-2-yl-methyl-, 5-carboxy-thien-2-yl-methyl-, 5-aminocarbonyl-thien-2-yl-methyl-, 4-aminocarbonyl-thien-2-yl-methyl-, phenoxy-carbonyl-, benzyloxy-carbonyl-, ethylamino-carbonyl-, 3-aminosulfonyl-phenyl-carbonyl-, 6-aminocarbonyl-pyrid-3-yl-carbonyl-, methylsulfonyl-, trifluoromethyl-sulfonyl-, phenyl-sulfonyl-, 4-fluorophenyl-sulfonyl-, 4-chlorophenyl-sulfonyl, 2-hydroxyphenyl-sulfonyl-, 3-hydroxyphenyl-sulfonyl-, 4-hydroxyphenyl-sulfonyl-, 2-methoxy-phenyl-sulfonyl-, 3-methoxy-phenyl-sulfonyl-, 4-methoxy-phenyl-sulfonyl-, 2-trifluoromethyl-phenyl-sulfonyl-, 3-trifluoromethyl-phenyl-sulfonyl-, 4-trifluoromethyl-phenyl-sulfonyl-, 3-carboxyphenyl-sulfonyl-, 4-carboxyphenyl-sulfonyl-, 3-aminophenyl-sulfonyl-, 3-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-methoxy-phenyl-sulfonyl-, 3-(methylamino-carbonyl)-phenyl-sulfonyl-, 3-(3-hydroxy-n-propyl-amino-carbonyl)-phenyl-sulfonyl-, 3-fluoro-4-aminocabonyl-phenyl-sulfonyl-, 3-fluoro-4-carboxy-phenyl-sulfonyl-, 3-chloro-4-aminocarbonyl-phenyl-sulfonyl-, 3-chloro-4-carboxy-phenyl-sulfonyl, 3-methyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-carboxy-phenyl-sulfonyl-, 3-methoxy-4-am inocarbonyl-phenyl-sulfonyl-, 3-m ethoxy-4-carboxy-phenyl-sulfonyl-, 3-carboxy-4-chloro-phenyl-sulfonyl-, 3-carboxy-4-fluoro-phenyl-sulfonyl-, 3-aminocarbonyl-4-fluoro-phenyl-sulfonyl-, 3,5-dichloro-4-hydroxy-phenyl-sulfonyl-, 5-(hydroxymethyl)-fur-2-yl-sulfonyl-, 5-carboxy-fur-2-yl-sulfonyl-, 5-(aminocarbonyl)-fur-2-yl-sulfonyl-, 4-carboxy-thien-2-yl-sulfonyl-, 4-(aminocarbonyl)-thien-2-yl-sulfonyl-, 3-methyl-5-carboxy-thien-2-yl-sulfonyl-, 3-methyl-5-(aminocarbonyl)-thien-2-yl-sulfonyl-, 6-carboxy-pyrid-3-yl-sulfonyl-, 6-aminocarbonyl-pyrid-3-yl-sulfonyl- and 6-(methoxycarbonyl-ethyl-amino-carbonyl)-pyrid-3-yl-sulfonyl-;
(f) is
wherein R5 is trifluoromethyl-sulfonyl-;
(g) is
wherein b is an integer from 0 to 1; L2 is selected from the group consisting of —CH2—, —CH2CH2—, —CH2—CH(R*—CH3)—, —CH2CH2—O—, —CH2—CH(OH)— and —CH2CH2CH2—NH—SO2—; and wherein R6 is selected from the group consisting of hydrogen, 3-chloro-, 3-bromo-, 4-bromo-, 3-hydroxy, 4-trifluoromethyl, 3-methoxy-, 4-methoxy-, 3-(ethoxy-carbonyl-methoxy)-, 4-(ethoxy-carbonyl-methoxy)-, and 3-(5-carboxy-thein-2-yl); and R7 is hydrogen;
and (i) is
wherein c is 1; and wherein L4 is —CH2—;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 4)

A compound as in claim 4, wherein
R0 is selected from the group consisting of hydrogen, —OH and —CO2H;
is 4-chlorophenyl;
is selected from the group consisting of 4-chlorophenyl, thiazol-2-yl and benzo[d][1.3]dioxol-5-yl;
R1 is selected from the group consisting of hydrogen and —OCH3;
R2 is selected from the group consisting of ethyl, cyclopropyl, cyclobutyl, oxetan-3-yl and tetrahydrofur-2-yl;
R3 is selected from the group consisting of (d), (f) and (g); wherein
(d) is
wherein a is an integer from 0 to 1; wherein L1 is —CH2—; and wherein R5 is selected from the group consisting of propyn-3-yl, methoxy-carbonyl-methyl-, 3-(aminocarbonyl)-phenyl, 4-(aminocarbonyl)-phenyl, 3-(aminocarbonyl-methyl)-phenyl, 3-(aminocarbonyl-methoxy)-phenyl, 3-carboxy-benzyl, 3-(aminocarbonyl)-benzyl, 3-(2-hydroxyethyl-aminocarbonyl)-benzyl, 3-fluoro-5-carboxy-benzyl, 1-(3-carboxyphenyl)-ethyl-, 1R*-(3-carboxyphenyl)-ethyl-, 1-(3-carboxyphenyl)-n-propyl-, 5-carboxy-pyrimidin-2-yl, 5-aminocarbonyl-pyrid-2-yl-methyl-, 5-am inocarbonyl-pyrid-3-yl-methyl-, 6-aminocarbonyl-pyrid-3-yl-methyl-, 1-(4-carboxy-pyrid-2-yl)-ethyl-, 5-aminocarbonyl-fur-2-yl-methyl-, 5-carboxy-thien-2-yl-methyl-, 5-aminocarbonyl-thien-2-yl-methyl-, 4-aminocarbonyl-thien-2-yl-methyl-, benzyloxy-carbonyl-, methylsulfonyl-, trifluoromethyl-sulfonyl-, phenyl-sulfonyl-, 4-fluorophenyl-sulfonyl-, 4-chlorophenyl-sulfonyl, 3-hydroxyphenyl-sulfonyl-, 4-hydroxyphenyl-sulfonyl-, 2-methoxy-phenyl-sulfonyl-, 3-trifluoromethyl-phenyl-sulfonyl-, 4-carboxyphenyl-sulfonyl-, 3-aminophenyl-sulfonyl-, 3-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-methoxy-phenyl-sulfonyl-, 3-chloro-4-carboxy-phenyl-sulfonyl, 3-methyl-4-carboxy-phenyl-sulfonyl-, 3-trifluoromethyl-4-carboxy-phenyl-sulfonyl-, 3-methoxy-4-aminocarbonyl-phenyl-sulfonyl-, 3-methoxy-4-carboxy-phenyl-sulfonyl-, 5-(am inocarbonyl)-fur-2-yl-sulfonyl-, 4-carboxy-thien-2-yl-sulfonyl-, 4-(am inocarbonyl)-thien-2-yl-sulfonyl-, 3-methyl-5-carboxy-thien-2-yl-sulfonyl-, 3-methyl-5-(am inocarbonyl)-thien-2-yl-sulfonyl- and 6-aminocarbonyl-pyrid-3-yl-sulfonyl-;
(f) is
wherein R5 is trifluoromethyl-sulfonyl-;
and (g) is
wherein b is an integer from 0 to 1; L2 is —CH2CH2—; and wherein R6 is selected from the group consisting of 3-chloro-, 4-trifluoromethyl, 4-methoxy- and 4-(ethoxy-carbonyl-methoxy)-; and R7 is hydrogen;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 4)

A compound as in claim 4, wherein
R0 is selected from the group consisting of hydrogen and —OH;
is 4-chlorophenyl;
is 4-chlorophenyl;
R1 is selected from the group consisting of hydrogen and —OCH3;
R2 is selected from the group consisting of cyclopropyl, cyclobutyl and tetrahydrofur-2-yl;
R3 is selected from the group consisting of (d), (f) and (g); wherein
(d) is
wherein a is an integer from 0 to 1; wherein L1 is —CH2—; and wherein R5 is selected from the group consisting of methoxy-carbonyl-methyl-, 3-(aminocarbonyl)-benzyl, 1R*-(3-carboxyphenyl)-ethyl-, 5-aminocarbonyl-pyrid-2-yl-methyl-, 1-(4-carboxy-pyrid-2-yl)-ethyl 5-aminocarbonyl-thien-2-yl-methyl-, 4-aminocarbonyl-thien-2-yl-methyl-, trifluoromethyl-sulfonyl-, phenyl-sulfonyl-, 4-chlorophenyl-sulfonyl, 3-hydroxyphenyl-sulfonyl-, 2-methoxy-phenyl-sulfonyl-, 3-aminocarbonyl-phenyl-sulfonyl-, 4-aminocarbonyl-methoxy-phenyl-sulfonyl-, 3-chloro-4-carboxy-phenyl-sulfonyl, 3-trifluoromethyl-4-carboxy-phenyl-sulfonyl3-methyl-5-(am inocarbonyl)-thien-2-yl-sulfonyl- and 6-aminocarbonyl-pyrid-3-yl-sulfonyl-;
(f) is
wherein R5 is trifluoromethyl-sulfonyl-;
and (g) is
wherein b is an integer from 0 to 1; L2 is —CH2CH2—; and
wherein R6 is selected from the group consisting of 4-trifluoromethyl, 4-methoxy- and 4-(ethoxy-carbonyl-methoxy)-; and R7 is hydrogen;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 4)

A compound as in claim 4, wherein
R0 is hydrogen;
is selected from the group consisting of 4-chlorophenyl and 4-methoxyphenyl;
is selected from the group consisting of 4-chlorophenyl, 4-methoxyphenyl and thiazol-2-yl;
R1 is hydrogen;
R2 is selected from the group consisting of ethyl, cyclopropyl and cyclobutyl;
R3 is selected from the group consisting of 1-(3-fluoro-5-carboxy-benzyl)-piperidin-4-yl, 1-(2-fluoro-5-carboxy-benzyl)-piperidin-4-yl, 1-(5-carboxy-pyrid-2-yl-methyl)-piperidin-4-yl, 1-(6-carboxy-pyrid-2-yl-methyl)-piperidin-4-yl, 1-(5-carboxy-thien-2-yl-methyl)-piperidin-4-yl, 1-(4-carboxy-thien-2-yl-sulfonyl)-piperidin-4-yl, 1-(5-carboxy-fur-2-yl-sulfonyl)-piperidin-4-yl, 1-(3-carboxy-benzyl)-piperidin-4-yl, 1-(3-carboxy-phenyl-sulfonyl)-piperidin-4-yl, 1-(3-hydroxy-phenyl-sulfonyl)-piperidin-4-yl, 1-(4-carboxy-phenyl-sulfonyl)-piperidin-4-yl, 1-trifluoromethyl-sulfonyl-piperidin-4-yl-methyl- and 1-trifluoromethyl-sulfonyl-piperidin-4-yl;
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 4)

A compound as in claim 4, wherein
R0 is hydrogen,
is selected from the group consisting of 4-chlorophenyl and 4-methoxyphenyl;
is selected from the group consisting of 4-chlorophenyl and 4-methoxyphenyl;
R1 is hydrogen;
R2 is selected from the group consisting of ethyl, cyclopropyl and cyclobutyl;
R3 is selected from the group consisting of 1-(3-fluoro-5-carboxy-benzyl)-piperidin-4-yl, 1-(2-fluoro-5-carboxy-benzyl)-piperidin-4-yl, 1-(5-carboxy-pyrid-2-yl-methyl)-piperidin-4-yl, 1-(6-carboxy-pyrid-2-yl-methyl)-piperidin-4-yl, 1-(5-carboxy-thien-2-yl-methyl)-piperidin-4-yl, 1-(3-carboxy-benzyl)-piperidin-4-yl, 1-(3-carboxy-phenyl-sulfonyl)-piperidin-4-yl, 1-(3-hydroxy-phenyl-sulfonyl)-piperidin-4-yl, 1-trifluoromethyl-sulfonyl-piperidin-4-yl-methyl-, 1-trifluoromethyl-sulfonyl-piperidin-4-yl,
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 11

A compound of formula (II)
or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1, 11)

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 or claim 11.

### Claim 13 (depends on 1, 11)

A pharmaceutical composition made by mixing a compound of claim 1 or claim 11 and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 1, 11)

A process for making a pharmaceutical composition comprising mixing a compound of claim 1 or claim 11 and a pharmaceutically acceptable carrier.