US 5,965,580 AGranted

Piperidine derivatives, process for obtaining them and pharmaceutical compositions containing them

AssigneeSanofi

InventorsNathalie Chabert, Jean-Philippe Ducoux, Xavier Emonds-Alt, Patrick Gueule, Vincenzo Proietto, Didier Van Broeck

Life of this patent

Estimating the term…

Abstract

Piperidine derivatives, process for obtaining them and pharmaceutical compositions containing them, of formula ##STR1## used as neurokinin receptor antagonists, which are, in particular, useful for the treatment of all substance P- and neurokinin-dependent pathologies.

Claims13

Dependent claims

A compound of formula:

##STR81## in which x is zero or one;
R'.sub.2 represents a (C.sub.1 -C.sub.7)alkyl;
Y' represents a group chosen from:
Y.sub.3) --O--CH.sub.2 CH.sub.2 --OR.sub.4 ;
Y.sub.6) --CH.sub.2).sub.q --OCONH--(C.sub.1 -C.sub.7)alky;
Y.sub.11) --(CH.sub.2).sub.q --NR.sub.13 COOR.sub.15 ;
Y.sub.12) --(CH.sub.2).sub.q --NR.sub.13 SO.sub.2 R.sub.16 ;
Y.sub.14) --CONR.sub.19 R.sub.20 ;
Y.sub.15) --CH.sub.2 --COOR.sub.21 ;
Y.sub.17) ##STR82## Y.sub.18) ##STR83## Y.sub.19) --CO--NR.sub.25 --NR.sub.26 R.sub.27 ;
in which groups:
q is zero, one or two;
R.sub.4 represents a hydrogen;
a (C.sub.1 -C.sub.7)alkyl;
a formyl, a (C.sub.1 -C.sub.7)alkylcarbonyl;
R.sub.13 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.15 represents a (C.sub.1 -C.sub.7)alkyl or a phenyl;
R.sub.16 represents a (C.sub.1 -C.sub.7)alkyl;
an amino, free or substituted with one or two (C.sub.1 -C.sub.7)alkyls;
a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a (C.sub.1 -C.sub.7)alkyl, a trifluoromethyl, a hydroxyl, a (C.sub.1 -C.sub.7)alkoxy, a carboxyl, a (C.sub.1 -C.sub.7)alkoxycarbonyl, a (C.sub.1 -C.sub.7)alkylcarbonyloxy, a cyano, a nitro, an amino, free or substituted with one or two (C.sub.1 -C.sub.7)alkyls, the said substituents being identical or different;
R.sub.19 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.20 represents a (C.sub.3 -C.sub.7)cycloalkyl;
a (C.sub.3 -C.sub.7)cycloalkylmethyl;
a hydroxyl;
a (C.sub.1 -C.sub.4)alkoxy;
a benzyl;
a phenyl;
a hydrogen;
a (C.sub.1 -C.sub.7)alkyl;
or alternatively R.sub.19 and R.sub.20, together with the nitrogen atom to which they are linked, constitute a heterocycle chosen from:
azetidine, perhydroazepine, pyrrolidine, and piperidine
R.sub.21 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.22 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.23 and R.sub.24 each independently represent a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.2 can, in addition, represent a formyl or a (C.sub.1 -C.sub.7)alkylcarbonyl;
R.sub.25 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.26 and R.sub.27 each independently represent a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
Ar'.sub.1 represents a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a (C.sub.1 -C.sub.4)alkyl, a trifluoromethyl, a methylenedioxy, the said substituents being identical or different;
Ar'.sub.2 represents a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a (C.sub.1 -C.sub.4)alkyl, a trifluoromethyl, a methylenedioxy, the said substituents being identical or different;
A' represents a direct bond or a --CH.sub.2 -- group;
Z' represents:
a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom;
a trifluoromethyl;
a cyano;
a hydroxyl;
a nitro;
a phenyl unsubstituted or substituted one or more times with a halogen, a trifluoromethyl, a (C.sub.1 -C.sub.4)alkyl, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, the said substituents being identical or different;
an amino unsubstituted or substituted once or twice with a (C.sub.1 -C.sub.4)alkyl;
a benzylamino;
a carboxyl;
a (C.sub.1 -C.sub.10)alkyl;
a (C.sub.3 -C.sub.8)cycloalkyl unsubstituted or substituted one or more times with a methyl;
a (C.sub.1 -C.sub.10)alkoxy;
a (C.sub.3 -C.sub.8)cycloalkyloxy unsubstituted or substituted one or more times with a methyl;
a mercapto;
a (C.sub.1 -C.sub.10)alkylthio;
a formyloxy;
a (C.sub.1 -C.sub.6)alkylcarbonyloxy;
a formylamino;
a (C.sub.1 -C.sub.6)alkylcarbonylamino;
a benzoylamino;
a (C.sub.1 -C.sub.4)alkoxycarbonyl;
a (C.sub.3 -C.sub.7)cycloallyloxycarbonyl;
a carbamoyl unsubstituted or substituted once or twice with a (C.sub.1 -C.sub.4)alkyl;
a ureido unsubstituted or substituted once or twice at position 3 with a (C.sub.1 -C.sub.4)alkyl or a (C.sub.3 -C.sub.7)cycloalkyl;
a (1-pyrrolidinyl)carbonylamino, the said substituents being identical or different;
a naphthyl unsubstituted or substituted one or more times with a halogen, a trifluoromethyl, a (C.sub.1 -C.sub.4)alkyl, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy;
a pyridyl;
a thienyl;
an indolyl;
a quinolyl;
a benzothienyl;
an imidazolyl;
and its salts with inorganic or organic acids.

75 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/035,823Filed 6 Mar 1998 · division
Priority: FR 95 1014225 Aug 1995
Granted: 12 Oct 1999
Term ends: Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07D 417/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Family

Serial703,952Parent of this division · filed 28 Aug 1996
US 5,830,906 AParent of this division
US 5,965,580 AThis patent

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

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Abstract

A compound of formula:

##STR81## in which x is zero or one;
R'.sub.2 represents a (C.sub.1 -C.sub.7)alkyl;
Y' represents a group chosen from:
Y.sub.3) --O--CH.sub.2 CH.sub.2 --OR.sub.4 ;
Y.sub.6) --CH.sub.2).sub.q --OCONH--(C.sub.1 -C.sub.7)alky;
Y.sub.11) --(CH.sub.2).sub.q --NR.sub.13 COOR.sub.15 ;
Y.sub.12) --(CH.sub.2).sub.q --NR.sub.13 SO.sub.2 R.sub.16 ;
Y.sub.14) --CONR.sub.19 R.sub.20 ;
Y.sub.15) --CH.sub.2 --COOR.sub.21 ;
Y.sub.17) ##STR82## Y.sub.18) ##STR83## Y.sub.19) --CO--NR.sub.25 --NR.sub.26 R.sub.27 ;
in which groups:
q is zero, one or two;
R.sub.4 represents a hydrogen;
a (C.sub.1 -C.sub.7)alkyl;
a formyl, a (C.sub.1 -C.sub.7)alkylcarbonyl;
R.sub.13 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.15 represents a (C.sub.1 -C.sub.7)alkyl or a phenyl;
R.sub.16 represents a (C.sub.1 -C.sub.7)alkyl;
an amino, free or substituted with one or two (C.sub.1 -C.sub.7)alkyls;
a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a (C.sub.1 -C.sub.7)alkyl, a trifluoromethyl, a hydroxyl, a (C.sub.1 -C.sub.7)alkoxy, a carboxyl, a (C.sub.1 -C.sub.7)alkoxycarbonyl, a (C.sub.1 -C.sub.7)alkylcarbonyloxy, a cyano, a nitro, an amino, free or substituted with one or two (C.sub.1 -C.sub.7)alkyls, the said substituents being identical or different;
R.sub.19 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.20 represents a (C.sub.3 -C.sub.7)cycloalkyl;
a (C.sub.3 -C.sub.7)cycloalkylmethyl;
a hydroxyl;
a (C.sub.1 -C.sub.4)alkoxy;
a benzyl;
a phenyl;
a hydrogen;
a (C.sub.1 -C.sub.7)alkyl;
or alternatively R.sub.19 and R.sub.20, together with the nitrogen atom to which they are linked, constitute a heterocycle chosen from:
azetidine, perhydroazepine, pyrrolidine, and piperidine
R.sub.21 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.22 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.23 and R.sub.24 each independently represent a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.2 can, in addition, represent a formyl or a (C.sub.1 -C.sub.7)alkylcarbonyl;
R.sub.25 represents a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
R.sub.26 and R.sub.27 each independently represent a hydrogen or a (C.sub.1 -C.sub.7)alkyl;
Ar'.sub.1 represents a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a (C.sub.1 -C.sub.4)alkyl, a trifluoromethyl, a methylenedioxy, the said substituents being identical or different;
Ar'.sub.2 represents a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, a (C.sub.1 -C.sub.4)alkyl, a trifluoromethyl, a methylenedioxy, the said substituents being identical or different;
A' represents a direct bond or a --CH.sub.2 -- group;
Z' represents:
a phenyl unsubstituted or substituted one or more times with a substituent chosen from:
a halogen atom;
a trifluoromethyl;
a cyano;
a hydroxyl;
a nitro;
a phenyl unsubstituted or substituted one or more times with a halogen, a trifluoromethyl, a (C.sub.1 -C.sub.4)alkyl, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy, the said substituents being identical or different;
an amino unsubstituted or substituted once or twice with a (C.sub.1 -C.sub.4)alkyl;
a benzylamino;
a carboxyl;
a (C.sub.1 -C.sub.10)alkyl;
a (C.sub.3 -C.sub.8)cycloalkyl unsubstituted or substituted one or more times with a methyl;
a (C.sub.1 -C.sub.10)alkoxy;
a (C.sub.3 -C.sub.8)cycloalkyloxy unsubstituted or substituted one or more times with a methyl;
a mercapto;
a (C.sub.1 -C.sub.10)alkylthio;
a formyloxy;
a (C.sub.1 -C.sub.6)alkylcarbonyloxy;
a formylamino;
a (C.sub.1 -C.sub.6)alkylcarbonylamino;
a benzoylamino;
a (C.sub.1 -C.sub.4)alkoxycarbonyl;
a (C.sub.3 -C.sub.7)cycloallyloxycarbonyl;
a carbamoyl unsubstituted or substituted once or twice with a (C.sub.1 -C.sub.4)alkyl;
a ureido unsubstituted or substituted once or twice at position 3 with a (C.sub.1 -C.sub.4)alkyl or a (C.sub.3 -C.sub.7)cycloalkyl;
a (1-pyrrolidinyl)carbonylamino, the said substituents being identical or different;
a naphthyl unsubstituted or substituted one or more times with a halogen, a trifluoromethyl, a (C.sub.1 -C.sub.4)alkyl, a hydroxyl, a (C.sub.1 -C.sub.4)alkoxy;
a pyridyl;
a thienyl;
an indolyl;
a quinolyl;
a benzothienyl;
an imidazolyl;
and its salts with inorganic or organic acids.

75 more elements

Facts

Application

09/035,823Filed 6 Mar 1998 · division

Priority

FR 95 1014225 Aug 1995

Granted

12 Oct 1999

Term ends

Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07D 417/04
Containing two hetero rings: directly linked by a ring-member-to-ring-member bond
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors