# US 7,407,963 B2 · Cyclopropane CGRP antagonists, medicaments containing these compounds, and method for the production thereof

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- Number: US 7,407,963 B2
- Document ID: US7407963B2
- Status: Granted
- Kind: B2
- Application number: 11/169,078
- Filed: 2005-06-27
- Published: 2005-12-01
- Granted: 2008-08-05
- Earliest claimed: 1999-10-29
- Assignees: Boehringer Ingelheim Pharma GmbH & Co. KG
- Inventors: Wolfgang Eberlein; Wolfhard Engel; Klaus Rudolf; Henri Doods; Gerhard Hallermayer; Eckhart Bauer
- Web page: https://patentgrep.com/patent/US7407963B2

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/24: of the sex hormones
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of general formula (I) wherein R and R1 are as defined herein, or a tautomer, diastereomer, enantiomer, or salt thereof, particularly the physiologically acceptable salts thereof, which have valuable pharmacological properties, particularly CGRP-antagonistic properties, pharmaceutical compositions containing the compound, their use, and processes for preparing them.

## Claims

### Claim 1

A compound of general formula (I)
wherein:
R is a saturated or mono- or diunsaturated 5- to 7-membered aza, diaza, triaza, oxaza, thiaza, thiadiaza, or S,S-dioxido-thiadiaza heterocyclic group linked via a carbon or nitrogen atom, and
wherein the heterocyclic group of R:
(i) optionally contains one or two carbonyl groups adjacent to a nitrogen atom thereof,
(ii) is optionally substituted by an alkyl group at one of the nitrogen atoms, and
(iii) is optionally substituted at one or two carbon atoms thereof by identical or different substituent groups selected from:
(a) a straight-chain or branched alkyl group, or a phenyl, phenylmethyl, naphthyl, biphenylyl group, or
(b) a pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl, or 1-methylimidazolyl group,
wherein an olefinic double bond thereof is optionally fused with a benzene, pyridine, diazine, 1,3-oxazole, thiophene, furan, thiazole, pyrrole, N-methylpyrrole, quinoline, imidazole, or N-methylimidazole ring, and
wherein the phenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl, or 1-methylimidazolyl groups contained in R and the benzo, thieno, pyrido- and diazino-fused heterocyclic groups in R are optionally independently additionally mono-, di-, or trisubstituted by:
(a) a fluorine, chlorine, or bromine atom,
(b) an alkyl, dialkylaminoalkoxy, nitro, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylsulfonylamino, phenyl, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkoxy, hydroxycarbonylalkoxy, carboxy, carboxyalkyl, dialkyl-aminoalkyl, hydroxy, amino, acetylamino, propionylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, [N-alkyl-N-(dialkylaminoalkyl)amino]carbonyl, [(hydroxycarbonylalkyl)amino]carbonyl, [(alkoxycarbonylalkyl)amino]carbonyl, (4-morpholinyl)carbonyl, (1-pyrrolidinyl)carbonyl, (1-piperidinyl)carbonyl, (hexahydro-1-azepinyl)carbonyl, (4-methyl-1-piperazinyl)carbonyl, methylenedioxy, aminocarbonylamino, aminocarbonylaminoalkyl, alkylaminocarbonylamino, alkanoyl, cyano, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl, or C3-C8 cycloalkyl group,
(c) a 4- to 8-membered alkyleneimino group wherein a methylene group in the 3-, 4-, or 5-position is optionally replaced by an oxygen atom or a methylimino group, or
(d) an alkoxy group optionally substituted in the ω-position by a 5- to 7-membered heteroalicyclic group that is linked via a carbon or nitrogen atom and contains one or two heteroatoms not directly connected to each other selected from oxygen and nitrogen,
wherein multiple substitution of the aforementioned phenyl, pyridinyl, diazinyl, furyl, thienyl, pyrrolyl, 1,3-oxazolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, 1-methylpyrazolyl, imidazolyl, or 1-methylimidazolyl groups contained in R and the benzo, thieno, pyrido- and diazino-fused heterocyclic groups in R by phenyl, C3-C8 cycloalkyl or 4- to 8-membered alkyleneimino groups is excluded; and
R1 is a phenyl, 1-naphthyl, 2-naphthyl, 1,2,3,4-tetrahydro-1-naphthyl, 1H-indol-3-yl, 1-methyl-1H-indol-3-yl, 1-formyl-1H-indol-3-yl, 4-imidazolyl, 1-methyl-4-imidazolyl, 2-thienyl, 3-thienyl, thiazolyl, 1H-indazol-3-yl, 1-methyl-1H-indazol-3-yl, benzo[b]fur-3-yl, benzo[b]thien-3-yl, pyridinyl, quinolinyl, or isoquinolinyl group,
wherein each group of R1 is optionally independently mono-, di-, or trisubstituted by a substituent group selected from:
(a) a fluorine, chlorine, or bromine atom,
(b) a branched or unbranched alkyl, C3-C8 cycloalkyl, phenylalkyl, alkenyl, alkoxy, phenyl, phenylalkoxy, trifluoromethyl, alkoxycarbonylalkyl, carboxyalkyl, alkoxycarbonyl, carboxy, dialkylaminoalkyl, dialkylaminoalkoxy, nitro, hydroxy, amino, acetylamino, propionylamino, methylsulfonyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkanoyl, cyano, tetrazolyl, phenyl, pyridinyl, thiazolyl, furyl, trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl, or trifluoromethylsulfonyl group,
wherein the hydroxy, amino, indolyl and imidazolyl groups contained in the abovementioned groups are each optionally independently substituted by a protecting group selected from:
(a) a phenylalkoxycarbonyl group with 1 to 3 carbon atoms in the alkoxy moiety optionally substituted in the phenyl nucleus by a halogen atom, a nitro or phenyl group, or one or two methoxy groups,
(b) an alkoxycarbonyl group having a total of 1 to 5 carbon atoms in the alkyl moiety, or
(c) a formyl, acetyl, trifluoroacetyl, allyloxycarbonyl, 2,2,2-trichloro-(1,1-dimethylethoxy)carbonyl, or 9-fluorenylmethoxycarbonyl group,
wherein all the abovementioned alkyl and alkoxy groups and the alkyl or alkylene moieties present within the other groups specified contain 1 to 5 carbon atoms, unless otherwise stated,
or a diastereomer, enantiomer, or salt thereof.

### Claim 2 (depends on 1)

The compound of general formula (I) according to claim 1, wherein the protecting group is selected from: a formyl, acetyl, trifluoroacetyl, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, 1-methylpropoxycarbonyl, 2-methylpropoxycarbonyl, tert-butyloxycarbonyl, benzyloxycarbonyl, 2-nitrobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-methoxybenzyloxy-carbonyl, 2-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 4-biphenylyl-α,α-dimethylbenzyloxycarbonyl, allyloxycarbonyl, 3,5-dimethoxy -α,α-dimethylbenzyloxycarbonyl, 2,2,2-trichloro-(1,1-dimethylethoxy)carbonyl, or 9-fluorenylmethoxycarbonyl group.

### Claim 3 (depends on 1)

The compound of general formula (I) according to claim 1, wherein:
R is a mono- or diunsaturated 5- to 7-membered aza, diaza, triaza, or thiaza heterocyclic group linked via a carbon or nitrogen atom, and
wherein the heterocyclic group of R:
(i) optionally contains one or two carbonyl groups adjacent to a nitrogen atom thereof, and
(ii) is optionally substituted at one or two carbon atoms thereof by identical or different substituent groups selected from:
(a) a phenyl group, or
(b) a pyridinyl, diazinyl, thienyl, pyrrolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, or 1-methylpyrazolyl group,
wherein an olefinic double bond thereof is optionally fused with a benzene, pyridine, diazine, or quinoline ring, and
wherein the phenyl, pyridinyl, diazinyl, thienyl, pyrrolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl, or 1-methylpyrazolyl, groups contained in R and the benzo, thieno, pyrido- and diazino-fused heterocyclic groups in R are optionally independently additionally mono-, di-, or trisubstituted by:
(a) a fluorine, chlorine, or bromine atom,
(b) an alkyl, dialkylaminoalkoxy, nitro, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkoxy, hydroxycarbonylalkoxy, carboxy, carboxyalkyl, dialkylaminoalkyl, hydroxy, amino, acetylamino, propionylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, [N-alkyl-N-(dialkylaminoalkyl)amino]carbonyl, [(hydroxycarbonylalkyl)amino]carbonyl, [(alkoxy-carbonylalkyl)amino]carbonyl, aminocarbonylamino, aminocarbonylaminoalkyl, alkylaminocarbonylamino, alkanoyl, or trifluoromethoxy group,
(c) a 4- to 7-membered alkyleneimino group wherein a methylene group in the 3-, 4-, or 5-position is optionally replaced by an oxygen atom or a methylimino group, or
(d) an alkoxy group optionally substituted in the ω-position by a 5- to 7-membered heteroalicyclic group that is linked via a carbon or nitrogen atom and contains one or two heteroatoms not directly connected to each other selected from oxygen and nitrogen,
wherein multiple substitution of the aforementioned phenyl, pyridinyl, diazinyl, thienyl, pyrrolyl, 1,3-thiazolyl, isoxazolyl, pyrazolyl or 1-methylpyrazolyl groups contained in R and the benzo, thieno, pyrido- and diazino-fused heterocyclic groups in R by 4- to 7-membered alkyleneimino groups is excluded; and
R1 is a phenyl, 1-naphthyl, or 2-naphthyl group,
wherein each group of R1 is optionally independently mono-, di-, or trisubstituted by a substituent group selected from:
(a) a fluorine, chlorine, or bromine atom, or
(b) a branched or unbranched alkyl, alkoxy, trifluoromethyl, nitro, hydroxy, amino, or acetylamino group,
wherein all the abovementioned alkyl and alkoxy groups and the alkyl or alkylene moieties present within the other groups specified contain 1 to 4 carbon atoms, unless otherwise stated,
or a diastereomer, enantiomer, or salt thereof.

### Claim 4 (depends on 1)

The compound of general formula (I) according to claim 1, wherein:
R is a mono- unsaturated 5- to 7-membered diaza or triaza heterocyclic group linked via a carbon or nitrogen atom, and
wherein the heterocyclic group of R:
(i) optionally contains one carbonyl group adjacent to a nitrogen atom thereof, and
(ii) is optionally substituted at one carbon atom thereof by a phenyl group, or an olefinic double bond of one of the above-mentioned unsaturated heterocyclic groups in R are optionally fused with a benzene, pyridine or quinoline ring, and
wherein the phenyl groups contained in R and the benzo- and pyrido-fused heterocyclic groups in R are optionally independently additionally mono-, di-, or trisubstituted by:
(a) a fluorine, chlorine, or bromine atom,
(b) an alkyl, dialkylaminoalkoxy, nitro, trifluoromethyl, alkoxycarbonyl, alkoxycarbonylalkoxy, hydroxycarbonylalkoxy, carboxy, hydroxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, [N-alkyl-N-(dialkylaminoalkyl)amino]carbonyl, [(hydroxycarbonylalkyl)amino]carbonyl, [(alkoxycarbonylalkyl)amino]carbonyl, alkanoyl, or trifluoromethoxy group,
(c) a 5- to 7-membered alkyleneimino group wherein a methylene group in the 3- or 4-position is optionally replaced by an oxygen atom or a methylimino group, or
(d) an alkoxy group optionally substituted in the o-position by a 5- or 6-membered heteroalicyclic group, wherein the heteroalicyclic group is linked via a carbon atom and contains an oxygen atom in each of the 2- and 2′-positions or is linked via a carbon or nitrogen atom and contains one or two nitrogen atoms not directly linked to one another or an oxygen and a nitrogen atom which are separated from each other by at least one methylene group,
wherein multiple substitution of phenyl groups contained in R and the benzo- and pyrido-fused heterocyclic groups in R by 5- to 7-membered alkyleneimino groups is excluded; and
R1 is a phenyl group optionally independently mono-, di-, or trisubstituted by a substituent group selected from:
(a) a fluorine, chlorine, or bromine atom, or
(b) an alkoxy, trifluoromethyl, nitro, hydroxy, or amino group,
wherein all the abovementioned alkyl and alkoxy groups and the alkyl or alkylene moieties present within the other groups specified contain 1 to 3 carbon atoms, unless otherwise stated,
or a diastereomer, enantiomer, or salt thereof.

### Claim 5

A compound of general formula (I)
wherein:
R is a 3,4-dihydro-2(1H)-oxoquinazolin-3-yl, 1,3-dihydro-4-phenyl-2H-2-oxoimidazol-1-yl, 2,4-dihydro-5-phenyl-3(3H)-oxo-1,2,4-triazol-2-yl, 3,4-dihydro-2(1H)-oxopyrido[4,3-d]pyrimidin-3-yl, 3,4-dihydro-2(1H)-oxopyrido[3,4-d]pyrimidin-3-yl, or 1,3-dihydro-2(2H)-oxoimidazo[4,5-c]quinolin-3-yl group, and
wherein the mono- and bicyclic heterocyclic groups in R are optionally independently additionally:
(a) mono-, or di-substituted by a fluorine, chlorine, or bromine atom, or
(b) monosubstituted by a 4-methyl-1-piperazinyl, 2,5-dioxacyclopentylmethoxy, nitro, hydroxy, methoxy, 2-(4-morpholinyl)ethoxy, 2-dimethylaminoethoxy, 3-dimethylaminopropoxy, methoxycarbonylmethoxy, hydroxycarbonylmethoxy, trifluoromethyl, methoxycarbonyl, carboxy, aminocarbonyl, diethylaminocarbonyl, [N-(2-dimethylaminoethyl)-N-methylamino]carbonyl, [(methoxycarbonylmethyl)amino]carbonyl, or [(hydroxycarbonylmethyl)amino]carbonyl group; and
R1 is a phenyl group optionally independently mono-, di-, or trisubstituted by a substituent group selected from:
(a) a fluorine, chlorine, or bromine atom, or
(b) a hydroxy or amino group,
or a diastereomer, enantiomer, or salt thereof.

### Claim 6

A compound selected from the group consisting of:
(a) cis-3-{1-[2-(4-chlorobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H) -quinazolinone;
(b) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(3-methoxyphenyl)-2(2H)-imidazolone;
(c) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone;
(d) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-6-bromo-3,4-dihydro-2(1H)-quinazolinone;
(e) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-phenyl-2(2H)-imidazolone;
(f) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-[3-(trifluoromethyl)phenyl]-2(2H)-imidazolone;
(g) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(3-hydroxyphenyl)-2(2H)-imidazolone;
(h) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-hydroxy-2(1H)-quinazolinone;
(i) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[(1,3-dioxolan-2-yl)methoxy]-2(1H)-quinazolinone;
(j) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-4-(3,4-dichlorophenyl)-1,3-dihydro-2(2H)-imidazolone;
(k) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-pyrido[4,3-d]pyrimidinone;
(l) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(2-methoxyphenyl)-2(2H)-imidazolone;
(m) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-4-(3-chlorophenyl)-1,3-dihydro-2(2H)-imidazolone;
(n) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(3-nitrophenyl)-2(2H)-imidazolone;
(o) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-pyrido[3,4-d]pyrimidinone;
(p) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[2-(dimethylamino)ethoxy]-2(1H)-quinazolinone;
(q) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-(4-methyl-1-piperazinyl)-2(1H)-quinazolinone;
(r) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-[2-(trifluoromethyl)phenyl]-2(2H)-imidazolone;
(s) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[3-(dimethylamino)propoxy]-2(1H)-quinazolinone;
(t) trans-3-{1-[2-(3,5-dibromo-4-hydroxybenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone;
(u) trans-1-{1-[2-(3,5-dibromo-4-hydroxybenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-phenyl-2(2H)-imidazolone;
(v) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-(methoxycarbonylmethoxy)-2(1H)-quinazolinone;
(w) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-(hydroxycarbonylmethoxy)-2(1H)-quinazolinone;
(x) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[2-(4-morpholinyl)ethoxy]-2(1H)-quinazolinone;
(y) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-7-methoxy-2(1H)-quinazolinone;
(z) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-7-(methoxycarbonylmethoxy)-2(1H)-quinazolinone;
(aa) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-7-carboxy-3,4-dihydro-2(1H)-quinazolinone;
(ab) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-7-methoxycarbonyl-3,4-dihydro-2(1H)-quinazolinone;
(ac) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-2(2H)-imidazo[4,5-c]quinolinone;
(ad) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-7-{[(methoxycarbonylmethyl)amino]carbonyl}-2(1H)-quinazolinone;
(ae) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-7-{[N-(2-dimethylaminoethyl)-N-methylamino]carbonyl}-2(1H)-quinazolinone;
(af) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-7-diethylaminocarbonyl-3,4-dihydro-2(1H)-quinazolinone;
(ag) trans-7-aminocarbonyl-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone;
(ah) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-7-{[(hydroxycarbonylmethyl)amino]carbonyl}-2(1H)-quinazolinone; and
(ai) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-2,4-dihydro-5-phenyl-3(3H)1,2,4-triazolone,
or a salt thereof.

### Claim 7

A compound selected from the group consisting of:
(a) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(3-methoxyphenyl)-2(2H)-imidazolone;
(b) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-2(1H)-quinazolinone;
(c) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-phenyl-2(2H)-imidazolone;
(d) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-1,3-dihydro-4-(3-hydroxyphenyl)-2(2H)-imidazolone;
(e) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-hydroxy-2(1H)-quinazolinone;
(f) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[(1,3-dioxolan-2-yl)methoxy]-2(1H)-quinazolinone;
(g) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-4-(3-chlorophenyl)-1,3-dihydro-2(2H)-imidazolone;
(h) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-[3-(dimethylamino)propoxy]-2(1H)-quinazolinone;
(i) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-(methoxycarbonylmethoxy)-2(1H)-quinazolinone;
(j) trans-3-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-3,4-dihydro-6-(hydroxycarbonylmethoxy)-2(1H)-quinazolinone; and
(k) trans-1-{1-[2-(4-amino-3,5-dibromobenzoyl)cyclopropanecarbonyl]-4-piperidinyl}-2,4-dihydro-5-phenyl-3(3H)-1,2,4-triazolone,
or a salt thereof.

### Claim 8 (depends on 1)

The physiologically acceptable salt of the compound according to claim 1.

### Claim 9 (depends on 2)

The physiologically acceptable salt of the compound according to claim 2.

### Claim 10 (depends on 3)

The physiologically acceptable salt of the compound according to claim 3.

### Claim 11 (depends on 4)

The physiologically acceptable salt of the compound according to claim 4.

### Claim 12 (depends on 5)

The physiologically acceptable salt of the compound according to claim 5.

### Claim 13 (depends on 6)

The physiologically acceptable salt of the compound according to claim 6.

### Claim 14 (depends on 7)

The physiologically acceptable salt of the compound according to claim 7.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 16 (depends on 2)

A pharmaceutical composition comprising a compound according to claim 2 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 17 (depends on 3)

A pharmaceutical composition comprising a compound according to claim 3 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 18 (depends on 4)

A pharmaceutical composition comprising a compound according to claim 4 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 19 (depends on 5)

A pharmaceutical composition comprising a compound according to claim 5 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 20 (depends on 6)

A pharmaceutical composition comprising a compound according to claim 6 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 21 (depends on 7)

A pharmaceutical composition comprising a compound according to claim 7 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents.

### Claim 22 (depends on 1)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 1.

### Claim 23 (depends on 2)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 2.

### Claim 24 (depends on 3)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 3.

### Claim 25 (depends on 4)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 4.

### Claim 26 (depends on 5)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 5.

### Claim 27 (depends on 6)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 6.

### Claim 28 (depends on 7)

A method of treating headache in a patient in need thereof, the method comprising administering to the patent a therapeutically effective amount the compound according to claim 7.