# US 2014/0155413 A1 · TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF

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- Number: US 2014/0155413 A1
- Document ID: US20140155413A1
- Status: Published application
- Kind: A1
- Application number: 14/131,861
- Filed: 2012-07-06
- Published: 2014-06-05
- Earliest claimed: 2011-07-12
- Assignees: Merck Sharp & Dohme Corp.
- Inventors: Barbara Hanney; Peter Manley; Michael T. Rudd; John M. Sanders; Shawn J. Stachel; Darrell Henze
- Web page: https://patentgrep.com/patent/US20140155413A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- 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 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention is directed to compounds of formula I and 1a: which are tropomyosin-related kinase (Trk) family protein kinase inhibitors, and hence are useful in the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

## Claims

### Claim at position 1

1-21. (canceled)

### Claim 22

A compound of formula (I): and (Ia)
and pharmaceutically acceptable salts thereof, wherein
----- is a bond that when present forms a double bond with bond a or bond b;
X1 is N, —N═O or —CR3;
X2, X3 and Y are independently selected from —N, or —CH;
R is a C6-10 aryl, C5-10 heteroaryl, halo, or hydrogen, said aryl and heteroaryl optionally substituted with 1 to 3 groups of Ra;
R1 is a (CH2)nC6-10 aryl, (CH2)nC5-10 heteroaryl, or hydrogen, said aryl and heteroaryl optionally substituted with 1 to 3 groups of Rb;
R2 is H, or C1-6 alkyl;
A is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —(CH2)nO—, —(CH2)nS(O)2—, —CH2C(O)NH—, —O—, or —NR2—,
R3 is hydrogen, CN, or C5-10 heterocyclyl, said heterocyclyl optionally substituted with 1 to 3 groups of Ra
Ra is —CN, —C1-4haloalkyl, halo, —C1-6alkyl, OR, NR2R2, or NH(CH2)nOH;
Rb is —CN, —C1-4haloalkyl, —OC1-4halo alkyl, —O(CH2)nhaloalkyl, −C1-6 alkyl, —C1-6alkenyl, —C1-6alkynyl, —(CH2)nC6-10 aryl, —(CH2)nC5-10 heterocyclyl, —(CH2)nO—C6-10 aryl, —(CH2)nO—C5-10 heterocyclyl, —C(O)C6-10aryl, —NHC6-10aryl, halo, —OR, —NR2R2, SO2R2, said aryl and heterocyclyl optionally substituted with 1 to 3 groups of Ra; and
n is 0-4.

### Claim 23 (depends on 22)

The compound according to claim 22 of formula I wherein X1 is N and Y and X2 are CH2.

### Claim 24 (depends on 22)

The compound according to claim 22 of formula I wherein X1 is —NCR3 and Y and X2 are CH2.

### Claim 25 (depends on 24)

The compound according to claim 24 wherein R3 is CN or optionally substituted C5-10 heterocyclyl selected from the group consisting of pyrazolyl, pyrazinyl, pyrimidinyl, isothiazolyl, pyridyl, furanyl, and thiazolyl.

### Claim 26 (depends on 22)

The compound according to claim 22 of formula I and Ia wherein R2 is hydrogen.

### Claim 27 (depends on 26)

The compound according to claim 26 of formula I and Ia wherein A is selected from the group consisting of C1-6 alkyl, —(CH2)nO—, and —NR2.

### Claim 28 (depends on 22)

The compound according to claim 22 of formula I and Ia wherein R1 is optionally substituted phenyl, oxadiazolyl, pyrrolidinyl, pyrazolyl, oxopyrrolidinyl, piperidinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, pyridyl, and pyrimidinyl.

### Claim 29 (depends on 28)

The compound according to claim 28 wherein R1 is phenyl.

### Claim 30 (depends on 22)

The compound according to claim 22 of formula I and Ia wherein R is hydrogen, fluorine, chlorine, and optionally substituted phenyl, quinolinyl, indolyl, isoquinolinyl, pyridyl, thiazolyl, and pyrimidinyl.

### Claim 31 (depends on 30)

The compound according to claim 30 wherein R is optionally substituted phenyl.

### Claim 32 (depends on 22)

The compound according to claim 22 of formula I represented by structural formula II:
and pharmaceutically acceptable salts thereof, wherein R is optionally substituted phenyl, quinolinyl, indolyl, isoquinolinyl, pyridyl, thiazolyl, or pyrimidinyl, A is —(CH2)nO— or C1-6 alkyl, and R1 is optionally substituted phenyl, oxadiazolyl, pyrrolidinyl, pyrazolyl, oxopyrrolidinyl, piperidinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, pyridyl, or pyrimidinyl.

### Claim 33 (depends on 32)

The compound according to claim 32 wherein R is optionally substituted phenyl, A is —(CH2)nO—, and R1 is optionally substituted phenyl.

### Claim 34 (depends on 22)

The compound according to claim 22 of formula I represented by structural formula IIa:
and pharmaceutically acceptable salts thereof, wherein R is optionally substituted phenyl, quinolinyl, indolyl, isoquinolinyl, pyridyl, thiazolyl, or pyrimidinyl, A is —(CH2)nO— or C1-6 alkyl, R1 is optionally substituted phenyl, oxadiazolyl, pyrrolidinyl, pyrazolyl, oxopyrrolidinyl, piperidinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, pyridyl, or pyrimidinyl, and R3 is CN or optionally substituted pyrazolyl, pyrazinyl, pyrimidinyl, isothiazolyl, pyridyl, furanyl, or thiazolyl.

### Claim 35 (depends on 34)

The compound according to claim 34 wherein R is optionally substituted phenyl, A is —(CH2)nO—, and R1 is optionally substituted phenyl.

### Claim 36 (depends on 22)

The compound according to claim 22 of formula I represented by structural formula IIb:
and pharmaceutically acceptable salts thereof, wherein R is optionally substituted phenyl, quinolinyl, indolyl, isoquinolinyl, pyridyl, thiazolyl, or pyrimidinyl, A is —(CH2)nO— or C1-6 alkyl, and R1 is optionally substituted phenyl, oxadiazolyl, pyrrolidinyl, pyrazolyl, oxopyrrolidinyl, piperidinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, pyridyl, or pyrimidinyl.

### Claim 37 (depends on 1)

The compound according to claim 1 of formula Ia represented by structural formula Ia′:
and pharmaceutically acceptable salts thereof, wherein R is optionally substituted phenyl, quinolinyl, indolyl, isoquinolinyl, pyridyl, thiazolyl, or pyrimidinyl, A is —(CH2)nO— or C1-6 alkyl, and R1 is optionally substituted phenyl, oxadiazolyl, pyrrolidinyl, pyrazolyl, oxopyrrolidinyl, piperidinyl, thiazolyl, oxazolyl, quinolinyl, isoquinolinyl, pyridyl, or pyrimidinyl.

### Claim 38

A compound which is:
4-(3-Methoxyphenyl)-1-(3-phenylpropyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Methoxyphenyl)-1-[(2E)-3-phenylprop-2-en-1-yl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
3: 4-(3-Methoxyphenyl)-1-[2-oxo-2-(phenylamino)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(Benzylamino)-2-oxoethyl]-4-(3-methoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
5: 4-(3-Methoxyphenyl)-1-(3-phenylprop-2-yn-1-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-(2-phenoxyethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-(2-phenylethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-(3-phenoxypropyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-chlorophenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-(biphenyl-4-ylmethyl)-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(benzylsulfonyl)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(phenylsulfonyl)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(benzyloxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-(4-phenoxybenzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[4-(phenoxymethyl)benzyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]-4-(quinolin-5-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-chlorophenoxy)ethyl]-4-[3-(propan-2-yloxy)phenyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-chlorophenoxy)ethyl]-4-(3-propoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-chlorophenoxy)ethyl]-4-[3-(2-methylpropoxy)phenyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-7-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid,
4-(3-Ethoxyphenyl)-1-[(1-phenylpyrrolidin-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-[(5-phenyl-1H-pyrazol-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[(5-oxo-1-phenylpyrrolidin-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-(2-{[1-(phenylcarbonyl)piperidin-4-yl]oxy}ethyl)-4-(3-prop oxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-{2-[(1-benzylpiperidin-4-yl)oxy]ethyl}-4-(3-propoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-({2-[4-(trifluoromethoxy)phenyl]-1,3-thiazol-4-yl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-({2-[4-(trifluoromethoxy)phenyl]-1,3-oxazol-4-yl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(quinolin-5-yloxy)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(isoquinolin-5-yloxy)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(isoquinolin-8-yloxy)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(2,4-dichlorophenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(3,4-dichlorophenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-cyanophenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(methylsulfonyl)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(trifluoromethyl)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-(2-{[6-(trifluoromethyl)pyridin-3-yl]oxy}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-{2-[(5-chloropyridin-2-yl)oxy]ethyl}-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(2,2,2-trifluoroethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(4-phenoxyphenoxy)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-(2-{[2-(trifluoromethyl)pyrimidin-5-yl]oxy}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-(2-{[1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]oxy}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-benzylphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(phenylamino)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(tetrahydro-2h-pyran-4-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(tetrahydrofuran-3-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine,
4-[(3-Methoxyphenyl)amino]-1-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[(5-Phenyl-1,2,4-oxadiazol-3-yl)methyl]-4-(quinolin-8-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(isoquinolin-5-yl)-1-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(1-methyl-1H-indol-4-yl)-1-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(Isoquinolin-4-yl)-1-[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-Chlorophenoxy)ethyl]-4-(2-ethoxypyridin-4-yl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(2-Ethoxy-1,3-thiazol-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-[2-(propylamino)pyridin-4-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-[2-(propylamino)-1,3-thiazol-5-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-[2-(propylamino)pyrimidin-4-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-{2-[(2-Hydroxyethyl)amino]pyridin-4-yl}-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-(2-{[4-(2,2,2-trifluoroethoxy)phenyl]amino}ethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid4-[2-(3-Methylpyrrolidin-1-yl)-1,3-thiazol-5-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-Tert-butoxyphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(isoquinolin-5-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(quinolin-5-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(quinolin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(isoquinolin-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-{2-[4-(pyridin-3-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(pyridin-2-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(pyridin-4-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(pyrimidin-2-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(pyrimidin-5-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(pyrazin-2-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-{2-[4-(1,3-thiazol-2-yloxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-{2-[4-(Trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-(1H-pyrazol-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-(pyrazin-2-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-pyrimidin-5-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-(1H-pyrazol-3-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-isothiazol-4-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-pyridin-3-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-furan-3-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-pyrimidin-4-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-pyridin-4-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-isothiazol-3-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-(1,3-thiazol-2-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-(1,3-thiazol-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-pyridin-2-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-furan-2-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
7-chloro-3-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid,
7-(3-ethoxyphenyl)-3-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid,
8-(3-ethoxyphenyl)-3-{2-[4-(trifluoromethoxy)phenoxy]ethyl}imidazo[1,2-c]pyrazine-2-carboxylic acid,
and pharmaceutically acceptable salts thereof.

### Claim 39 (depends on 38)

A compound according to claim 38 which is:
4-[2-(propylamino)pyrimidin-4-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-[2-(propylamino)pyridin-4-yl]-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid.
1-[2-(4-Tert-butoxyphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid.
5-pyrimidin-5-yl-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid.
5-(1H-pyrazol-4-yl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
5-cyano-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-indole-2-carboxylic acid,
7-(3-ethoxyphenyl)-3-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[2,3-c]pyridine-2-carboxylic acid,
8-(3-ethoxyphenyl)-3-{2-[4-(trifluoromethoxy)phenoxy]ethyl}imidazo[1,2-c]pyrazine-2-carboxylic acid,
4-(3-Ethoxyphenyl)-1-{2-[4-(trifluoromethoxy)phenoxy]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
4-(3-ethoxyphenyl)-1-[2-(4-phenoxyphenoxy)ethyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid,
1-[2-(4-benzylphenoxy)ethyl]-4-(3-ethoxyphenyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid
and pharmaceutically acceptable salts thereof.

### Claim 40 (depends on 22)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 22 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

### Claim 41 (depends on 1)

A method of treating a disease or disorder mediated by the TrK receptors, wherein said disease or disorder is selected from the group consisting of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA. in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.