# US 11,026,946 B2 · Pharmacologically active alicyclic-substituted pyrazolo[1,5-a]pyrimidine derivatives

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- Number: US 11,026,946 B2
- Document ID: US11026946B2
- Status: Granted
- Kind: B2
- Application number: 16/493,453
- Filed: 2018-03-12
- Published: 2020-04-30
- Granted: 2021-06-08
- Earliest claimed: 2017-03-13
- Assignees: Richter Gedeon Nyrt.
- Applicants: Richter Gedeon Nyrt.
- Inventors: István Borza; Viktor Román; János Éles; Zsuzsa Hadady
- Web page: https://patentgrep.com/patent/US11026946B2

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 19/00: Drugs for skeletal disorders
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C07D 487/04: Ortho-condensed systems
- C07D 491/147: the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to new pyrazolo[1,5-a]pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts, biologically active metabolites, pro-drugs, racemates, enantiomers, diastereomers, solvates and hydrates thereof that serve as GABAB receptor positive allosteric modulators. The invention al so relates to the process for producing such compounds. The invention further relates to pharmaceutical compositions comprising such compounds optionally in combination with two or more different therapeutic agents and the use of such compounds in methods for treating diseases and conditions mediated and modulated by the GABAB receptor positive allosteric mechanism. The invention al so provides a method for manufacture of medicaments useful in the treatment of such disorders.

## Claims

### Claim 1

A compound of formula (I) wherein:
R1 and R2 are independently selected from hydrogen, halogen atom, C1-6alkyl, or haloC1-6alkyl;
R3 is hydrogen, halogen atom, C1-6alkyl, or cyano group;
R4 is C1-6alkyl;
R5 is C1-6alkyl optionally substituted by a halogen atom, halogen atoms, C3-5 cycloalkyl; C3-5 cycloalkylC1-6alkyl, dialkylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkylthio group, tetrahydrofuranyl, tetrahydrofuranylC1-6alkyl, tetrahydropyranyl, or tetrahydropyranylC1-6alkyl;
or R4 and R5 together form a 3 to 7-membered saturated ring, wherein the 3 to 7-membered saturated ring is unsubstituted or substituted by one or more C1-3alkyl, C1-3alkoxy, haloC1-3alkyl, or C1-3alkylcarbonyl, and wherein the members of the ring are selected from the group consisting of carbon, nitrogen, oxygen, and sulphur;
R6 is hydrogen, halogen atom, C1-6alkyl, hydroxyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, haloC1-6alkyl, or an amino group; or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof.

### Claim 2 (depends on 1)

A compound according to claim 1 wherein R1 and R2 are independently selected from hydrogen, halogen atom, C1-6alkyl, or haloC1-6alkyl;
R3 is hydrogen, halogen atom, C1-6alkyl, or cyano group;
R4 is C1-6alkyl;
R5 is C1-6alkyl optionally substituted by a halogen atom, halogen atoms, C3-5 cycloalkyl, C3-5 cycloalkylC1-6alkyl, dialkylamino, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkylthio group, tetrahydrofuranyl, tetrahydrofuranylC1-6alkyl, tetrahydropyranyl, or tetrahydropyranylC1-6alkyl;
R6 is hydrogen, halogen atom, C1-6alkyl, hydroxyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, haloC1-6alkyl, or an amino group; or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof.

### Claim 3 (depends on 1)

A compound according to claim 1 wherein
R1 and R2 are independently selected from hydrogen, halogen atom, C1-6alkyl, or haloC1-6alkyl;
R3 is hydrogen, halogen atom, C1-6alkyl, or cyano group;
R4 and R5 together form a 3 to 7-membered saturated ring, wherein the 3 to 7-membered saturated ring is unsubstituted or substituted by one or more C1-3alkyl, C1-3alkoxy, haloC1-3alkyl, or C1-3alkylcarbonyl, and wherein the members of the ring are selected from the group consisting of carbon, nitrogen, oxygen, and sulphur;
R6 is hydrogen, halogen atom, C1-6alkyl, hydroxyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, haloC1-6alkyl, or an amino group; or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof.

### Claim 4 (depends on 1)

A compound according to claim 1 wherein R4 is methyl; and R5 is isopropyl or C1-6alkoxyC1-6alkyl.

### Claim 5 (depends on 1)

A compound according to claim 1 selected from the group consisting of
(3S)-1[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-1[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-(propan-2-yl)piperidine-3-carboxylic acid;
(3R)-3-Methyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]-3-propylpiperidine-3-carboxylic acid;
(3S)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-propylpiperidine-3-carboxylic acid;
(3R)-3-(Fluoromethyl)-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-3-(Fluoromethyl)-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-3-Methyl-1-[(8S)-8-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]-5H,6H,7H,8H-pyrazolo[3, 2-b]quinazolin-9-yl]piperidine-3-carboxylic acid;
(3R)-3-Methyl-1-[(8R)-8-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]-5H,6H,7H,8H-pyrazolo[3, 2-b]quinazolin-9-yl]piperidine-3-carboxylic acid;
(3R)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-3-Methyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-3-Ethyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]-3-(propan-2-yl)piperidine-3-carboxylic acid;
(3S)-1-[3-Fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3R)-1-[3-Fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3S)-3-Ethyl-1-[3-fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-[3-fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)- 1-{3-Fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid;
(3R)- 1-{3-Fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid;
(3S)-3-Ethyl-1-{6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}piperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-{6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}piperidine-3-carboxylic acid;
(3S)-1-{3-Fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid;
(3R)- 1-{3-Fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cydohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid;
(3S)-3-Ethyl-1-{3-fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl) cydohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}piperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-{3-fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}piperidine-3-carboxylic acid;
(3R)-1-{6-Ethyl-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-{6-ethyl-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl}piperidine-3-carboxylic acid;
(3S)-1-[2-(4,4-Difluorocydohexyl)-5-methyl-6-(propan-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3R)-1-[2-(4,4-Difluorocyclohexyl)-5-methyl-6-(propan-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3S)-1-[2-(4,4-Difluorocydohexyl)-5-methyl-6-(propan-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylpiperidine-3-carboxylic acid;
(3R)-1-[2-(4,4-Difluorocyclohexyl)-5-methyl-6-(propan-2-yl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylpiperidine-3-carboxylic acid;
(3R)-1-[2-(4,4-Difluorocydohexyl)-5,6-diethylpyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3R)-3-Methyl-1-{2-[trans-4-(trifluoromethyl)cyclohexyl]-5H,6H,7H,8H-pyrazolo [3,2-b]quinazolin-9-yl}piperidine-3-carboxylic acid;
(3R)-3-Methyl-1-{5-[trans-4-(trifluoromethyl)cyclohexyl]-2,6,7-triazatricyclo[7.5.0.03,7]tetradeca-1,3, 5,8-tetraen-8-yl}piperidine-3-carboxylic acid;
(3R)-3-Methyl-1-{5-[trans)-4-(trifluoromethyl)cyclohexyl]-11-oxa-2,6,7-triazatricyclo[7.4.0.03,7]trideca-1,3,5,8-tetraen-8-yl}piperidine-3-carboxylic acid;
(3S)-3-Methyl-1-{5-[trans-4-(trifluoromethyl)cyclohexyl]-12-oxa-2,6,7-triazatricyclo [7.4.0.03,7]trideca-1,3,5,8-tetraen-8-yl}piperidine-3-carboxylic acid;
(3S)-1-[3-Cyano-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3R)-1-[3-Cyano-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3R)-1-[2-(4,4-Difluorocydohexyl)-3-fluoro-5-methyl-6-(propan-2-yl)pyrazolo[1, 5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid; and
(3R)-1-[6-(2-methoxyethyl)-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid.

### Claim 6 (depends on 1)

A process for preparing the compounds of formula (I) according to claim 1 characterized by
step 1) reacting a carboxylic acid ester of formula (II) or carboxylic acid chloride of formula (III)
with an acetonitrile of formula (IV)
then
step 2) reacting the obtained acylacetonitrile of formula (V)
2a) with hydrazine hydrate to provide a compound of formula (VI)
wherein R3 is hydrogen, halogen atom, or C1-6alkyl group; or
2b) with trimethyl orthoformate to provide the malononitrile of formula (XIV)
wherein R3 is a cyano group; which is then reacted with hydrazine hydrate to provide a compound of formula (VI)
then
step 3) the compound of formula (VI) is reacted with an acylacetic ester of formula (VII)
then
step 4) chlorinating the obtained compound of formula (VIII)
to obtain a chloro compound of formula (IX)
and
step 5) reacting the chloro compound of formula (IX) with either
5c) a nipecotic acid of formula (X)
, or
5d) an alkali salt of formula (XI)
, wherein K is an alkali metal, or
5e) a nipecotic acid ester of formula (XII)
wherein Alk is an alkyl group, to provide the ester of formula (XIII)
and saponifying the ester of formula (XIII) with a strong base or hydrolyzing the ester of formula (XIII) with a strong acid.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof according to claim 1 as active ingredient and a pharmaceutically acceptable carrier.

### Claim 8 (depends on 1)

A combination comprising a compound of formula (I) or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof according to claim 1 and one or more therapeutically active co-agents.

### Claim 9 (depends on 1)

A process for manufacturing a pharmaceutical composition having GABAB receptor positive allosteric modulator effect characterized by mixing a compound of formula (I) or pharmaceutically acceptable salts, hydrolysable esters, racemates, enantiomers, diastereomers, solvates and hydrates thereof according to claim 1, or optical antipodes or racemates and/or salts thereof, as active ingredients with pharmaceutically acceptable excipients.

### Claim 10 (depends on 1)

A method for positive allosteric modulation of the GABAB receptor in a subject suffering from a disorder which requires positive allosteric modulation of the GABAB receptor characterized by administering to the subject an effective amount of a compound of formula (I) as claimed in claim 1, or optical antipodes or racemates and/or salts thereof.

### Claim 11 (depends on 10)

The method according to claim 10 wherein the disorder is selected from the group of psychiatric disorders, neurodevelopmental disorders, cognitive disorders, epilepsy, spasticity, skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, essential tremor, pain, substance abuse, obesity, binge eating, asthma, cough, urinary incontinence, gastroesophageal reflux disease, transient lower esophageal sphincter relaxation, and irritable bowel syndrome.

### Claim 12 (depends on 10)

The method of claim 10, wherein the compound of formula (I) is combined with pharmaceutically acceptable excipients.

### Claim 13 (depends on 11)

The method of claim 11, wherein the psychiatric disorder is selected from anxiety, panic disorder, posttraumatic disorder, depression, and schizophrenia.

### Claim 14 (depends on 11)

The method of claim 11, wherein the neurodevelopmental disorder is selected from autism spectrum disorder, obsessive-compulsive disorder, and Fragile X syndrome.

### Claim 15 (depends on 11)

The method of claim 11, wherein the pain is selected from neuropathic, visceral, and osteoarthritic pain.

### Claim 16 (depends on 14)

The method of claim 14, wherein the neurodevelopmental disorder is autism spectrum disorder.

### Claim 17 (depends on 6)

The process of claim 6, wherein reacting the carboxylic acid ester derivative of formula (II) or carboxylic acid chloride derivative of formula (III) with an acetonitrile derivative of formula (IV) is carried out in the presence of a strong base.

### Claim 18 (depends on 6)

The process of claim 6, wherein the compound of formula (VI) is reacted with the acylacetic ester derivative of formula (VII) under heat.

### Claim 19 (depends on 6)

The process of claim 6, wherein the compound of formula (VIII) is chlorinated under heat.

### Claim 20 (depends on 5)

A compound according to claim 5 selected from the group consisting of
(3R)-3-Methyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-3-(Fluoromethyl)-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-3-Ethyl-1-[5-methyl-6-(propan-2-yl)-2- [trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-1-[3-Fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid; and
(3R)-3-Ethyl-1-[3-fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid.

### Claim 21 (depends on 5)

A compound according to claim 5 selected from the group consisting of
(3S)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-(propan-2-yl) piperidine-3-carboxylic acid;
(3R)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]-3-propylpiperidine-3-carboxylic acid; and
(3S)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-propylpiperidine-3-carboxylic acid.

### Claim 22 (depends on 5)

A compound according to claim 5 selected from the group consisting of
(3R)-3-(Fluoromethyl)-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3R)-1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid;
(3S)-3-Methyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid; and
(3S)-3-Ethyl-1-[5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid.

### Claim 23 (depends on 5)

A compound according to claim 5 selected from the group consisting of
(3R) -1-[5-Methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo [1,5-a]pyrimidin-7-yl]-3-(propan-2-yl)piperidine-3-carboxylic acid;
(3S)-1-[3 -Fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid;
(3S)-3-Ethyl-1-[3-fluoro-5-methyl-6-(propan-2-yl)-2-[trans-4-(trifluoromethyl) cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl]piperidine-3-carboxylic acid; and
(3S)-1-{3-Fluoro-6-methoxy-5-methyl-2-[trans-4-(trifluoromethyl)cyclohexyl]pyrazolo[1,5-a]pyrimidin-7-yl}-3-methylpiperidine-3-carboxylic acid.

### Claim 24 (depends on 11)

The method of claim 11, wherein the disorder is urinary incontinence.