US 5,605,896 AGranted

Bicyclic heterocyclic derivatives having .alpha..sub.1 adrenergic and 5HT.sub.1A activities

AssigneeRecordati S.A., Chemical and Pharmaceutical Company

InventorsAmedeo Leonardi, Gianni Motta, Carlo Riva, Rodolfo Testa

Life of this patent

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Abstract

This invention provides bicyclic heterocyclic derivatives and their pharmaceutically acceptable salts useful for the treatment of hypertension, urethral and lower urinary tract contractions, and other disorders. The compounds are also useful for binding .alpha..sub.1 -adrenergic and 5HT.sub.1A serotonergic receptors, in vitro or in vivo.

Claims24

Dependent claims

A compound having the general formula I ##STR22## wherein ---- represents a single or double bond;

X represents a nitrogen, oxygen or sulfur atom, an amino or alkylamino, a sulfinyl or sulfonyl group;
W represents a carbonyl, thiocarbonyl, hydroxymethylene, a methylene group or a bond;
or
X is nitrogen and W is methine, and the fused rings represent quinolyl ring;
R.sub.2 represents a hydrogen atom or an alkyl, alkenyl, alkynyl, carbocyclic or heterocyclic group, each of which groups may optionally be substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy, alkoxy, halogen, phenyl, phenoxy, trifluoromethyl, nitro, acylamino, alkylsulfonylamino and benzoyl;
or R.sub.2 itself represents a trifluoromethyl or an aroyl group;
wherein the carbocyclic group may be substituted with amino, alkylamino or dialkylamino;
with the proviso that the heterocyclic group cannot be linked through a nitrogen atom;
R.sub.3 represents a hydrogen atom or an alkyl, hydroxyalkyl, phenyl, hydroxy, O--R.sub.4, or alkyl-OR.sub.4 group, where R.sub.4 represents an alkyl group optionally substituted with an aryl group;
R.sub.6 represents a hydrogen or halogen atom or a nitro, amino, acetylamino, alkylamino, dialkylamino, cyano, hydroxy, alkoxy or alkyl group;
R.sub.7 represents a hydrogen atom;
Y represents one of the following groups, each of which is depicted with its left hand end being the end which attaches to the heterobicyclic ring and its right hand end being the end which attaches to the group Z:
##STR23## Z a linear or branched chain alkylene group having from 1 to 6 carbon atoms and optionally having one hydroxy substituent;
and
represents one of the following groups:
##STR24## wherein n is 1 or 2 and A represents a phenyl group;
wherein said phenyl group is unsubstituted or substituted by one or more substituents selected from the group consisting of alkoxy, alkyl, halogen, hydroxy, or A represents a 2-pyrimidinyl group or a bicyclic ring of formula ##STR25## where ---- represents a single or double bond and E represents an oxygen atom or a bond;
##STR26## wherein L represents one or two groups selected among phenyl, 4-fluorobenzoyl or a 2-oxo-1-benzimidozolinyl group or a group of the formula (CH.sub.2).sub.n -O-A wherein n=0, 1, or 2 and A has the same meaning defined under B1, ##STR27## wherein each of R.sub.10 and R.sub.11 independently represents a hydrogen atom or an alkoxy or alkylthio group, R.sub.12 represents a hydrogen atom or an alkyl group and n is 2 or 3, ##STR28## wherein R.sub.12 has the meaning defined under B3 and R.sub.13 represents a hydrogen atom or a alkoxy group, ##STR29## wherein R.sub.12 has the meaning defined under B3, or an enantiomer, a diastereomer, an N-oxide, a prodrug, a metabolite, a prodrug of a metabolite, or a pharmaceutically acceptable salt of said compound.

15 more elements

Compound selected from the group consisting of:

8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-1-oxoethyl}-3-methyl-4-oxo-2-pheny l-4H-1-benzopyran;
8-{2-[4-(2-methylphenyl)-1-piperazinyl]-1-oxoethyl}-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran;
8-{2-[4-(2-ethoxyphenyl)-1-piperazinyl]-1-oxoethyl}-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran;
8-{3-[4-(2-methoxy-phenyl)-1-piperazinyl]-1-oxopropyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propoxycarbonyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethoxycarbonyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{3-[4-(2-chlorophenyl)-1-piperazinyl]-propoxycarbonyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-[3-(4-phenyl-1-piperazinyl)-propoxycarbonyl]-3-methyl-4-oxo-2-phenyl-4H-1 -benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-2-methyl-2-propoxycarbonyl}-3-meth yl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl-carbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{3-[2-(2-methoxyphenoxy)-ethylamino]-propylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-[3-(4-phenyl-1-piperazinyl)-propylcarbamoyl]-3-methyl-4-oxo-2-phenyl-4H-1 -benzopyran;
8-{N-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylcarbamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
8-{1-hydroxy-2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{1-hydroxy-2-[4-(2-methylphenyl)-1-piperazinyl]-ethyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{1-hydroxy-2-[4-(2-ethoxyphenyl)-1-piperazinyl]-ethyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{1-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propyl}-3-methyl-4-oxo-2 -phenyl-4H-1-benzopyran;
8-{1-hydroxy-4-[4-(2-methoxyphenyl)-1-piperazinyl]-butyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{1-ethoxy-2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{N-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylaminomethyl}-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran;
8-{N-acetyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylaminomethyl}-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran;
8-[4-(2-methoxyphenyl)-1-piperazinylacetamidomethyl]-3-methyl-4-oxo-2-pheny l-4H-1-benzopyran;
8-{N-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]-acetamidomethyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethoxymethyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{2-[2-(2-ethoxyphenoxy)-ethylamino]-ethoxymethyl}-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylthiomethyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylsulfinylmethyl}-3-methyl-4-ox o-2-phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylsulfonylmethyl}-3-methyl-4-ox o-2-phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylamino}-3-methyl-4-oxo-2-pheny l-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylamino}-3-methyl-4-oxo-2-phen yl-4H-1-benzopyran;
8- {4-[4-(2-methoxyphenyl)-1-piperazinyl]-butylamino}-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran;
8-{N-methyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylamino}-3-methyl-4-o xo-2-phenyl-4H-1-benzopyran;
8-{N-acetyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylamino}-3-methyl-4-o xo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propionamido}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylureido}-3-methyl-4-oxo-2-phen yl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethoxy}-3-methyl-4-oxo-2-phenyl-4H -1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propoxy}-3-methyl-4-oxo-2-phenyl-4 H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]-butoxy}-3-methyl-4-oxo-2-phenyl-4H -1-benzopyran;
8-{5-[4-(2-methoxyphenyl)-1-piperazinyl]-pentoxy}-3-methyl-4-oxo-2-phenyl-4 H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-oxo-1-piperazinyl]-propoxy}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{2-[2-(2,6-dimethoxyphenoxy)-ethylamino]-ethoxy}-3-methyl-4-oxo-2-phenyl- 4H-1-benzopyran;
8-{2-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propoxy}-3-methyl-4-oxo- 2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylthio}-3-methyl-4-oxo-2-pheny l-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylsulfonyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylsulfamyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{N-methyl-2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylsulfamyl}-3-methyl-4- oxo-2-phenyl-4H-1-benzopyran;
8-{N-aminocarbonyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]propylamino}-3-meth yl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]-1-oxobutyl}-3-methyl-4-oxo-2-pheny l-4H-1-benzopyran;
8-{3-[2-(1,4-benzodioxanyl)methylamino]propylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl}-3-methyl-4-oxo-2-phenyl-4H-1 -benzopyran;
8-[3-(4-phenyl-1-piperidinyl)propylcarbamoyl]-3-methyl-4-oxo-2-phenyl-4H-1- benzopyran;
8-[3-(4,4-Diphenyl-1-piperidinyl)propylcarbamoyl]-3-methyl-4-oxo-2-phenyl-4 H-1-benzopyran;
8-{3-[4-(4-fluorobenzoyl)-1-piperidinyl]propylcarbamoyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{3-[4-(2-oxo-1-benzimidazolinyl)-1-piperidinyl]propyl-carbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-pyrimidinyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{3-[4-(2-hydroxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylsulfamyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[N-methyl-2-(2-methoxyphenoxy)-ethylamino]propylcarbamoyl}-3-methyl-4- oxo-2-phenyl-4H-1-benzopyran;
8-{N-methyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]propionamido}-3-methyl-4-o xo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-phenyl-4-oxo-4H- 1-benzopyran;
8-{3-[2-(3,4-dihydro-1, (2H)-naphthalenonyl)methylamino]propylcarbamoyl}-3-methyl-4-oxo-2-phenyl-4 H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethoxycarbonylmethyl}-3-methyl-4-o xo-2-phenyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butylsulfamyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{N, 2-tetrahydropyranyloxy-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamo yl}-3-methyl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butyramido}-3-methyl-4-oxo-2-phenyl -4H-1-benzopyran;
E-8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethoxyiminomethyl}-3-methyl-4-oxo -2-phenyl-4H-1-benzopyran;
8-{N-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran;
E-8-{2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethylcarbamoyl]ethenyl}-3-met hyl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butylsulfinyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{3-[3-(2-methoxyphenoxy)propylamino]propylcarbamoyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
3-methyl-8-{3-[2-(2-methylthiophenoxy)ethylamino]propyl carbamoyl}-4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[2-(2,6-dimethoxyphenoxy)ethylamino]propylcarbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{3-[4-(5-chloro-2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
(E)-8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]-1-butenyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
(E)-8-{2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethoxycarbonyl]ethenyl}-3-me thyl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylcarbamoyl}methyl}-4-oxo-2-phe nyl-4H-1-benzopyran;
8-{N-acetyl-N,3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethylsulfonylamino}-3-methyl-4-oxo- 2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylthiocarbamoyl}-3-methyl-4-oxo -2-phenyl-4H-1-benzopyran;
8-{4-[4-(2-methoxyphenyl)-1-piperazinyl]butylsulfonyl}-3-methyl-4-oxo-2-phe nyl-4H-1-benzopyran;
3-hydroxymethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4- oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-2-phenyl-4H- 1-benzopyran;
2,3-dihydro-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo- 4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-4H-1-benzopy ran;
6-bromo-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4 -oxo-2-phenyl-4H-1-benzopyran;
6-methoxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
6-hydroxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
3,6-dimethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo -2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-6-nitro-4 -oxo-2-phenyl-4H-1-benzopyran;
6-amino-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4 -oxo-2-phenyl-4H-1-benzopyran;
6-acetylamino-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-me thyl-4-oxo-2-phenyl-4H-1-benzopyran;
6-ethylamino-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-met hyl-4-oxo-2-phenyl-4H-1-benzopyran;
6-dimethylamino-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3- methyl-4-oxo-2-phenyl-4H-1-benzopyran;
7-methoxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-( 4-trifluoromethylphenyl)-4H-1-benzopyran;
2-(4-benzoylphenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl }-3-methyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-( 4-phenoxyphenyl)-4H-1-benzopyran;
2. 3-dimethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-ox o-4H-1-benzopyran;
2-tert-butyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-met hyl-4-oxo-4H-1-benzopyran;
2-cyclohexyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-met hyl-4-oxo-4H-1-benzopyran;
2-(2-furyl)-8-{3-[4-(2-methoxylphenyl)-1-piperazinyl]propylcarbamoyl}-3-met hyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-t hienyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-2-phenyl-4H- 1-benzothiopyran;
(E)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo -2-(2-phenylethenyl)-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(4-meth ylphenyl)-4-oxo-4H-1-benzopyran;
2-(4-methoxyphenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl }-3-methyl-4-oxo-4H-1-benzopyran;
2-(4-fluorophenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl carbamoyl}-3-methyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-methyl-6-methan esulfonylamino-4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(4-nitr ophenyl)-4-oxo-4H-1-benzopyran;
6-diethoxyphosphonyloxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarba moyl}-3-methyl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-t rifluoromethyl-4H-1-benzopyran;
8-{N,3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl-N-methylcarbamoyl}-3-methy l-4-oxo-2-phenyl-4H-1-benzopyran;
2-benzoyl-3-ethyl-7-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propcarbamoyl}ben zo[b]furan;
2-(4-biphenylyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3 -methyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-( 3-pyridyl)-4H-1-benzopyran;
8-{3-[4-(2-acetoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran;
3-methyl-8-{3-[4-(2-methylaminocarbonyloxyphenyl)-1-piperazinyl]propylcarba moyl}-4-oxo-2-phenyl-4H-1-benzopyran;
6-acetoxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
(R,S)-2,3-dihydro-4-hydroxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylc arbamoyl}-4H-1-benzopyran;
2-(4-aminophenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}- 3-methyl-4-oxo-4H-1-benzopyran;
2-(4-acetylaminophenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarb amoyl}-3-methyl-4H-1-benzopyran;
2-(4-hydroxyphenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoy l}-3-methyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-2-phenyl-4, N.sub.1, N4-trioxo-4H-1-benzothiopyran;
7-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-2-phenylbenzo[b]fu ran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl-N-methylsulfamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]butyl-N-methylsulphamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
2-(4-dimethylaminophenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcar bamoyl}-3-methyl-4-oxo-4H-1-benzopyran;
3-benzyloxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo- 2-phenyl-4H-1-benzopyran;
8-{3-[4-(4-hydroxy-2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[2-(8-methoxy-1,4-benzodioxanyl)methylamino]propylcarbamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-2-phenyl-4-thioxo- 4H-1-benzopyran;
8-{[2,2-dimethyl-3-(4-(2-methoxyphenyl)-1-piperazinyl)propyl]-carbamoyl}-3- methyl-4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-( 2-phenylethyl)-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-2-phenyl-1,1,4-tri oxo-4H-1-benzothiopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran-N.sub.1 -oxide;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-p henyl-4H-1-benzopyran N.sub.1, N.sub.4 -dioxide;
8-{3-[4-(5-fluoro-2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-2-phenyl-4(1H)-qui nolone;
2-(4-cyanophenyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}- 3-methyl-4-oxo-4H-1-benzopyran;
6-cyano-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4 -oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(4-fluoro-2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl- 4-oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-(3-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{3-[4-(4-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
3-methoxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-2- phenyl-4H-1-benzopyran;
3-Hydroxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-2- phenyl-4H-1-benzopyran;
2-Cyclohexyl-3,4-dihydro-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarb amoyl}-2H-1-benzopyran;
2-benzyl-3-ethyl-7-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}be nzo[b]furan;
8-{3-[4-(2-isopropoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo- 2-phenyl-4H-1-benzopyran;
8-{[3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl]-methyl}3-methyl-4 -oxo-2-phenyl-4H-1-benzopyran;
8-{3-[4-[5-(1,4-benzodioxanyl)]-1-piperazinyl]propylcarbamoyl}-3-methyl-4-o xo-2-phenyl-4H-1-benzopyran;
3-ethoxymethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-o xo-2-phenyl-4H-1-benzopyran;
8-{[3-[4-(2-methoxyphenyl)-1-piperazinyl]propylamino]methyl}-3-methyl-4-oxo -2-phenyl-4H-1-benzopyran;
7-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-2-(4-nitrophenyl)i ndole;
8-{3-[4-(5-hydroxy-2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl -4-oxo-2-phenyl-4H-1-benzopyran;
3-ethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenoxy)-1-piperidinyl]propylcarbamoyl}-3-methyl-4-oxo-2- phenyl-4H-1-benzopyran;
8-{3-[4-(2,3-dihydrobenzo[b]furan-7-yl)-1-piperazinyl]propylcarbamoyl}-3-me thyl-4-oxo-2-phenyl-4H-1-benzopyran;
2-(2-biphenylyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3 -methyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(1-naph thyl)-4-oxo-4H-1-benzopyran;
3-benzyloxymethyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}- 2-phenyl-4H-1-benzopyran;
3-methyl-8-{3-[4-[2-[(4-morpholinylmethyl)benzoyloxy]phenyl]-1-piperazinyl] propylcarbamoyl}-4-oxo-2-phenyl-4H-1-benzopyran;
8-{2-[4-(2-methoxyphenyl)-1-piperazinyl}ethoxycarbonylamino]-3-methyl-4-oxo -2-phenyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl]-3-methyl-2-(3-nitr ophenyl)-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-(1,4-diazepinyl)]propylcarbamoyl}-3-methyl-4-ox o-2-phenyl-4H-1-benzopyran;
2-cyclohexyl-3,4-dihydro-4-hydroxy-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl] propylcarbamoyl}-2H-1-benzopyran;
3,4-dihydro-4-hydroxy-8-{3-[4-(2-methoxyphenyl)1-piperazinyl]propylcarbamoy l}-2-phenyl-2H-1-benzopyran;
2-(1-adamantyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3- methyl-4-oxo-4H-1-benzopyran;
8-{5-[4-(2-methoxyphenyl)-1-piperazinyl]pentylsulfonyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-( 3,4,5-triiodophenyl)-4H-1-benzopyran;
2-cyclopropyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-me thyl-4-oxo-4H-1-benzopyran;
8-{5-[4-(2-methoxyphenyl)-1-piperazinyl]pentyl}-3-methyl-4-oxo-2-phenyl-4H- 1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(4-meth ylcyclohexyl)-4-oxo-4H-1-benzopyran;
2-cyclopentyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-me thyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(1-phen ylcyclopentyl)-4-oxo-4H-1-benzopyran;
8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-2-(1-meth ylcyclohexyl)-4-oxo-4H-1-benzopyran;
2-(bicyclo[2.2.1]hept-5-en-2-yl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]pr opylcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran, mixture of endo-exo isomers;
2-(bicyclo[2.2.1]hept-5-en-2-yl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]pr opylcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran, endo isomer;
2-(bicyclo[2.2.1]hept-5-en-2-yl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]pr opylcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran, exo isomer;
2-(bicyclo[2.2.1]heptan-2-yl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propy lcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran, mixture of endo-exo isomers;
2-(bicyclo[2.2.1]heptan-2-yl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propy lcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran, exo isomer;
2-cycloheptyl-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]-propylcarbamoyl}-3-m ethyl-4-oxo-4H-1-benzopyran;
8-[3-[4-(2-methoxyphenyl)-1-piperazinyl]propylcarbamoyl}-1-methyl-2-phenyl- 1,2,3,4-tetrahydroquinoline;
(trans)-2-(4-methoxycyclohexyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]pro pylcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran;
(cis)-2-(4-methoxycyclohexyl)-8-{3-[4-(2-methoxyphenyl)-1-piperazinyl]propy lcarbamoyl}-3-methyl-4-oxo-4H-1-benzopyran;
8-{3-[4-(7-benzofuranyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[4-(2-chlorophenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
8-{3-[4-(4-chlorophenyl)-1-piperazinyl]propylcarbamoyl}-3-methyl-4-oxo-2-ph enyl-4H-1-benzopyran;
or a pharmaceutically acceptable salt thereof.

187 more elements

Dependencies are inferred from the claim text.

Facts

Application: 08/299,188Filed 31 Aug 1994 · continuation in part
Priority: IT MI92A040825 Feb 1992
Granted: 25 Feb 1997
Term ends: Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 307/79
Benzo [b] furans; Hydrogenated benzo [b] furans: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to…
C07D 307/80
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring: radicals…
C07D 311/22
Benzo[b]pyrans, not hydrogenated in the carbocyclic ring: with oxygen or sulfur atoms directly attached in position 4
C07D 311/30
With aromatic rings attached in position 2 only: not hydrogenated in the hetero ring, e.g. flavones

Family

Serial888,775Parent of this continuation-in-part · filed 26 May 1992
Serial67,861Parent of this continuation-in-part · filed 26 May 1993
US 5,474,994 AParent of this continuation-in-part
US 5,403,842 AParent of this continuation-in-part
US 5,605,896 AThis patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound having the general formula I ##STR22## wherein ---- represents a single or double bond;

X represents a nitrogen, oxygen or sulfur atom, an amino or alkylamino, a sulfinyl or sulfonyl group;
W represents a carbonyl, thiocarbonyl, hydroxymethylene, a methylene group or a bond;
or
X is nitrogen and W is methine, and the fused rings represent quinolyl ring;
R.sub.2 represents a hydrogen atom or an alkyl, alkenyl, alkynyl, carbocyclic or heterocyclic group, each of which groups may optionally be substituted by one or more substituents selected from the group consisting of alkyl, cyano, hydroxy, alkoxy, halogen, phenyl, phenoxy, trifluoromethyl, nitro, acylamino, alkylsulfonylamino and benzoyl;
or R.sub.2 itself represents a trifluoromethyl or an aroyl group;
wherein the carbocyclic group may be substituted with amino, alkylamino or dialkylamino;
with the proviso that the heterocyclic group cannot be linked through a nitrogen atom;
R.sub.3 represents a hydrogen atom or an alkyl, hydroxyalkyl, phenyl, hydroxy, O--R.sub.4, or alkyl-OR.sub.4 group, where R.sub.4 represents an alkyl group optionally substituted with an aryl group;
R.sub.6 represents a hydrogen or halogen atom or a nitro, amino, acetylamino, alkylamino, dialkylamino, cyano, hydroxy, alkoxy or alkyl group;
R.sub.7 represents a hydrogen atom;
Y represents one of the following groups, each of which is depicted with its left hand end being the end which attaches to the heterobicyclic ring and its right hand end being the end which attaches to the group Z:
##STR23## Z a linear or branched chain alkylene group having from 1 to 6 carbon atoms and optionally having one hydroxy substituent;
and
represents one of the following groups:
##STR24## wherein n is 1 or 2 and A represents a phenyl group;
wherein said phenyl group is unsubstituted or substituted by one or more substituents selected from the group consisting of alkoxy, alkyl, halogen, hydroxy, or A represents a 2-pyrimidinyl group or a bicyclic ring of formula ##STR25## where ---- represents a single or double bond and E represents an oxygen atom or a bond;
##STR26## wherein L represents one or two groups selected among phenyl, 4-fluorobenzoyl or a 2-oxo-1-benzimidozolinyl group or a group of the formula (CH.sub.2).sub.n -O-A wherein n=0, 1, or 2 and A has the same meaning defined under B1, ##STR27## wherein each of R.sub.10 and R.sub.11 independently represents a hydrogen atom or an alkoxy or alkylthio group, R.sub.12 represents a hydrogen atom or an alkyl group and n is 2 or 3, ##STR28## wherein R.sub.12 has the meaning defined under B3 and R.sub.13 represents a hydrogen atom or a alkoxy group, ##STR29## wherein R.sub.12 has the meaning defined under B3, or an enantiomer, a diastereomer, an N-oxide, a prodrug, a metabolite, a prodrug of a metabolite, or a pharmaceutically acceptable salt of said compound.

15 more elements

Facts

Application

08/299,188Filed 31 Aug 1994 · continuation in part

Priority

IT MI92A040825 Feb 1992

Granted

25 Feb 1997

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

C07D 307/79
Benzo [b] furans; Hydrogenated benzo [b] furans: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to…
C07D 307/80
With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring: radicals…
C07D 311/22
Benzo[b]pyrans, not hydrogenated in the carbocyclic ring: with oxygen or sulfur atoms directly attached in position 4
C07D 311/30
With aromatic rings attached in position 2 only: not hydrogenated in the hetero ring, e.g. flavones

Family

Serial888,775Parent of this continuation-in-part · filed 26 May 1992

Serial67,861Parent of this continuation-in-part · filed 26 May 1993

US 5,474,994 AParent of this continuation-in-part

US 5,403,842 AParent of this continuation-in-part

US 5,605,896 AThis patent

From the US filing history. Foreign family members aren’t listed.