# US 8,785,445 B2 · 7-phenoxychroman carboxylic acid derivatives

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- Number: US 8,785,445 B2
- Document ID: US8785445B2
- Status: Granted
- Kind: B2
- Application number: 13/141,675
- Filed: 2009-12-18
- Published: 2012-04-26
- Granted: 2014-07-22
- Earliest claimed: 2008-12-22
- Assignees: Array BioPharma Inc.
- Applicants: Adam Cook; Kevin W. Hunt; Robert Kirk Delisle; Todd Romoff; Christopher T. Clark; Ganghyeok Kim; Christopher P. Corrette; George A. Doherty; Laurence E. Burgess
- Inventors: Adam Cook; Kevin W. Hunt; Robert Kirk Delisle; Todd Romoff; Christopher T. Clark; Ganghyeok Kim; Christopher P. Corrette; George A. Doherty; Laurence E. Burgess
- Web page: https://patentgrep.com/patent/US8785445B2

## CPC

- C07D 405/12: linked by a chain containing hetero atoms as chain links
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/04: Antipruritics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 27/14: Decongestants or antiallergics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- C07D 405/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of Formula I: (I) in which A, A1, R1, R7a, R7b, R8 and R10 have the meanings given in the specification, are DP2 receptor inhibitors useful in the treatment of useful in the treatment and prevention of immunologic diseases, allergic diseases such as asthma, allergic rhinitis and atopic dermatitis, and other inflammatory diseases mediated by prostaglandin D2 (PGD2). The compounds of Formula I may also be useful in treating diseases or medical conditions involving the Th2 T cell via production of IL-4, IL-5 and/or IL-13.

## Claims

### Claim 1

A compound of general formula (I)
or a pharmaceutically acceptable salt thereof, wherein:
A is H, CN, Cl, F, cyclopropyl, (1-4 C)alkyl or OMe;
A1 is H, Cl, Br, F, cyclopropyl, (1-4 C)alkyl or OMe;
R1 is —W-L1-hetAr1;
W is —CONR3a— or —NR3bCO—;
R3a and R3b are each H or methyl;
L1 is a —(CRaRb)n— or
n is 0 or 2;
Ra and Rb are independently H, F, methyl, or cyclopropyl, or
Ra and Rb together with the carbon to which they are attached form a cyclopropyl ring;
hetAr1 is heteroaryl ring having the structure:
wherein m is 0 or 1 and said heteroaryl ring is optionally substituted with one or more Rc substituents,
zero or one of D4, D5 and D6 is N, the remainder being CH;
each Rc is independently selected from halogen, CF3, (1-6C)alkyl, —O(1-6C alkyl), cyclopropyl, —O—(CH2CH2)OMe, —S(1-6C alkyl), di(1-6C alkyl)amino, and a 5-6 membered azacycle;
Ar is phenyl optionally substituted with one or more Rd substituents;
each Rd is independently selected from (1-6C)alkyl, —O(1-6C)alkyl, halogen, —S(1-6C alkyl), and CF3,
or two adjacent Rd substituents together with the atoms to which they are attached form a 5-6 membered oxacyclic ring;
R7a, R7b and R8 are independently H or methyl; and
R10 is H, Me or NH2.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein:
A is H, CN, Cl, F, cyclopropyl, (1-4 C)alkyl or OMe;
A1 is H, Cl, Br, F, cyclopropyl, (1-4 C)alkyl, or OMe;
R1 is —W-L1-hetAr1;
W is —CONR3a— or —NR3bCO—;
R3a and R3b are each H or methyl;
L1 is —(CRaRb)n—;
n is 0 or 2;
Ra and Rb are independently H, F, methyl, or cyclopropyl, or
Ra and Rb together with the carbon to which they are attached form a cyclopropyl ring;
hetAr1 is heteroaryl ring having the structure:
wherein m is 0 or 1 and said heteroaryl ring is optionally substituted with one or more Rc substituents,
zero or one of D4, D5 and D6 is N, the remainder being CH;
each Rc is independently selected from halogen, CF3, (1-6C)alkyl, —O(1-6C alkyl), cyclopropyl, —O—(CH2CH2)OMe, —S(1-6C alkyl) and di(1-6C alkyl)amino;
Ar is phenyl optionally substituted with one or more Rd substituents;
each Rd is independently selected from (1-6C)alkyl, —O(1-6C)alkyl, halogen, —S(1-6C alkyl), and CF3,
or two adjacent Rd substituents together with the atoms to which they are attached form a 5-6 membered oxacyclic ring;
R7a, R7b and R8 are independently H or methyl; and
R10 is H, Me or NH2.

### Claim 3 (depends on 1)

A compound of claim 1, wherein —W-L1- is —NHCO, —NHCOCH2CH2—, —CONH—, —CONHCH2CH2—, CONHCH2cyclopropylidene-, or CONHcyclopropylidene-.

### Claim 4 (depends on 1)

A compound according to claim 1, wherein —W-L1- is —CONH— or CONHCH2CH2—.

### Claim 5 (depends on 1)

A compound of claim 1, wherein m is 1.

### Claim 6 (depends on 1)

A compound according to claim 1, wherein A is Cl.

### Claim 7 (depends on 1)

A compound according to claim 1, wherein A is CN, Cl, or cyclopropyl and A1 is H, cyclopropyl, Br or Cl.

### Claim 8 (depends on 1)

A compound according to claim 1, wherein R7a; and R7b are each hydrogen.

### Claim 9 (depends on 1)

A compound according to claim 1, wherein R8 is hydrogen.

### Claim 10 (depends on 1)

A compound according to claim 1, wherein R10 is hydrogen.

### Claim 11 (depends on 1)

A pharmaceutical composition, which comprises a compound of Formula I as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.

### Claim 12 (depends on 1)

A process for preparing a compound of claim 1 or a pharmaceutically acceptable salt thereof, which comprises:
(a) for a compound of Formula I in which A is CN and A1 is hydrogen, reacting a corresponding compound having the formula (II):
in which P1 represents a hydrogen atom or a (1-6C)alkyl group and Z1 represents a halogen or triflate, with a corresponding compound having the formula (III)
in the presence of a base; or
(b) for a compound of Formula I in which A is H, Cl, (1-4C alkyl), OMe or cyclopropyl and A1 is H, Cl, (1-4C alkyl), OMe or cyclopropyl, reacting a corresponding compound having the formula (IV)
in which P2 is as defined for P1, with a corresponding compound having the formula (V)
wherein E is an NO2 group and Z2 is a halogen, in the presence of an alkali metal carbonate, and if desired removing said NO2 group; or
(c) for a compound of Formula I in which A is H, Cl, (1-4C alkyl) or cyclopropyl and A1 is (1-4C alkyl), Cl, Br or cyclopropyl, reacting a corresponding compound having the formula (VI)
in which P2 is as defined for P1, with a corresponding compound having the formula (VII)
in the presence of a copper salt or a palladium catalyst in the presence of a ligand selected from 2,2,6,6-tetramethyl-3,5-heptanedione, pyridine-type ligands, and phosphine-type ligands, and an alkali metal carbonate; or
(d) for a compound of Formula I in which hetAr1 is a heteroaryl ring having the structure
where m is 1, reacting a corresponding compound having the formula (VIIIa)
where P3 is as defined for P1, and X1 is halogen or triflate, with a compound having the formula ArB(OH)2 or ArZnBr in the presence of a palladium catalyst and an alkali metal carbonate; or
(e) reacting a corresponding compound of formula (IX)
in which P4 is as defined for P1, and R1a represents H—XaH in which Xa is HN or OC(═O), or an acid chloride thereof; with a compound of formula (X)
R1-L1-Xb—H (X)
in which Xb represents C(═O)O or NH, or a reactive derivative thereof;
(f) for a compound of Formula I where L1 is a bond, reacting a corresponding compound having the formula (XI)
in which P5 is as defined for P1, with a compound having the formula X2—R1, where X2 is a triflate or halogen, in the presence of a palladium catalyst and a phosphine-type ligand;
(g) for a compound of Formula I where A is cyclopropyl, A1 is cyclopropyl, and W is C(═O)NH, reacting a corresponding compound having the formula (XII)
wherein P6 is as defined for P1, E is an NO2 group, and B is —O-tert-butyl, —NH2 or —NH-L1-R1, with about 4 equivalents of cyclopropylboronic acid in the presence of an alkali metal phosphate, a metal catalyst and a ligand at temperatures between about 100° C. and 150° C., followed by removal of the NO2 group, if desired, and reacting with a compound having the formula H2N-L1-R1 when B is O-tBu or reacting with a compound having the formula X3-L1-R1 when B is NH2, where X3 is a triflate or halogen; or
(h) for a compound of Formula I where A is cyclopropyl, A1 is hydrogen, and W is C(═O)NH, reacting a corresponding compound having the formula (XIII)
wherein P7 is as defined for P1, E is an NO2 group, and B is O-tertbutyl, NH2 or NH-L1-R1, with about 3 equivalents of cyclopropylboronic acid in the presence of a an alkali metal phosphate, a metal catalyst and a ligand at temperatures between about 90° C. and 150° C., followed by removal of the NO2 group, if desired, and reacting with a compound having the formula H2N-L1-R1 when B is O-tBu or reacting with a compound having the formula X3-L1-R1 when B is NH2, where X3 is a triflate or halogen; and
removing any protecting group or groups and, if desired, forming a salt.

### Claim 13 (depends on 1)

A compound according to claim 1, selected from:
7-(4-((5-(Trifluoromethyl)pyridin-2-yl)carbamoyl)phenoxy)-6-cyanochroman-4-carboxylic acid;
7-(4-(5-Chloropyridin-2-ylcarbamoyl)phenoxy)-6-cyanochroman-4-carboxylic acid;
7-(4-((6-(Trifluoromethyl)pyridin-3-yl)carbamoyl)phenoxy)-6-cyanochroman-4-carboxylic acid;
6-Cyano-7-(4-(2-(6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(3,4-dimethylphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(2-methyl-4-(6-(trifluoromethyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-phenylpyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(trifluoromethyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(trifluoromethyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-phenylpyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(2-(5-(trifluoromethyl)pyridin-2-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(3,4-dimethylphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(2,3-dimethylphenyl)pyridin-2-ylcarbamoyl)-phenoxy)-chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(3-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)-phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)-phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chlorophenyl)-5-fluoropyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Cyano-7-(4-(6-(2,4-dichlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-(3-Chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)-6-cyanochroman-4-carboxylic acid;
7-(4-(6-(4-Chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)-6-cyanochroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3,4-dichlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chloro-3-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(2-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-p-tolylpyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-methoxyphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(2-chloro-4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(3-chloro-4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(5-(4-(trifluoromethyl)phenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-p-tolylpyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-methoxyphenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-(methylthio)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(3,4-dichlorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-fluorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chloro-3-fluorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(2-fluoro-4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(2,4-difluorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chloro-2-fluorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-(trifluoromethyl)phenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-ethoxypyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chlorophenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-methoxy-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3,4-difluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(2,4-difluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-(methylthio)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-fluoro-3-methylphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-(4-tert-Butylphenyl)pyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chloro-3-fluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chloro-2-fluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-fluoro-4-methylphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(3,5-difluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(2,3-difluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-(tert-Butylthio)pyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-chlorophenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(3-(trifluoromethyl)phenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(4-chlorophenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(3-chlorophenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-chlorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(3-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(4-chlorophenyl)pyrimidin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chlorophenyl)-2-methylpyrimidin-4-ylcarbamoyl)phenoxy) chroman-4-carboxylic acid;
6-chloro-7-(4-(6-methyl-2-(4-(trifluoromethyl)phenyl)pyrimidin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(2,4-dichlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chloro-2-methoxyphenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-isobutylpyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
8-bromo-6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)-6,8-dicyclopropylchroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)-8-cyclopropylchroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-fluorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-cyclopropylpyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-tert-Butylpyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(3-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(2-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(4-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(3-(trifluoromethyl)phenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(3-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(2-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(3-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(2-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(4-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(3-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(2-(4-chlorophenyl)pyridin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(2-(3-chlorophenyl)pyridin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(4-(trifluoromethyl)phenyl)pyrimidin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(3-(trifluoromethyl)phenyl)pyrimidin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(4-chlorophenyl)pyrimidin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(4-(3-chlorophenyl)pyrimidin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(5-(3-chlorophenyl)pyrimidin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(2-(3-chlorophenyl)pyrimidin-5-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6,8-Dichloro-7-(4-(6-(4-chlorophenyl)pyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6,8-Dichloro-7-(4-(2-(4-chlorophenyl)pyrimidin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(3,5-dichloropyridin-2-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-(dimethylamino)-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2,6-dimethoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid, Enantiomer 1;
6-Chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid, Enantiomer 2;
6,8-dichloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)-chroman-4-carboxylic acid;
6,8-dichloro-7-(4-(6-(3-chlorophenyl)pyridin-3-ylcarbamoyl)phenoxy)-chroman-4-carboxylic acid;
Enantiomer 2 of 6-Chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(2-(6-cyclopropyl-2-methoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
Enantiomer 2 of 6-Chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-Chloro-7-(4-(2-(2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(6-cyclopropyl-2-(dimethylamino)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
(R)-6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
7-(4-(6-(tert-butylthio)pyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylic acid;
6-chloro-7-(4-(6-(4-chlorophenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(1-(6-(trifluoromethyl)pyridin-2-yl)piperidin-4-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-ethoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(6-(4-methoxyphenyl)pyridin-2-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(6-methoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(6-methoxypyridin-2-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2,4-dimethoxypyrimidin-5-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(6-(2-chlorophenyl)pyridin-2-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-cyclopropylpyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-(2-chlorophenyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-(dimethylamino)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-(piperidin-1-yl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-methoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
6-chloro-7-(4-(2-(2-isopropoxypyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylic acid;
and salts thereof.

### Claim 14 (depends on 13)

The compound of claim 13, wherein the salt is a sodium salt.