Novel pyrrolidine compound and application as melanocortin receptor agonist

Patent metadata

Field	Value
Publication number	US-2017190697-A1
Application number	US-201515313407-A
Country	US
Kind code	A1
Filing date	May 28, 2015
Priority date	May 29, 2014
Publication date	Jul 6, 2017
Grant date	—

Abstract

The present invention relates to a novel pyrrolidine compound having melanocortin receptor agonist activity or a pharmaceutically acceptable salt thereof, and to pharmaceutical applications thereof. The present invention relates to a pyrrolidine derivative represented by formula [I], wherein ring A represents an optionally substituted aryl group or the like; R 1 represents an optionally substituted alkyl group or the like; R 2 represents a halogen atom or the like; and R 3 is an alkyl group substituted with an optionally substituted aryl group or the like, and R 4 is a hydrogen atom or the like; or R 3 and R 4 are terminally attached to each other, and together with the nitrogen atom to which they are attached, form an optionally substituted nitrogen-containing aliphatic heterocyclic ring that may partially contain a double bond; or to a pharmaceutically acceptable salt thereof.

First claim

1 . A pyrrolidine derivative represented by formula [I]:

wherein ring A represents an optionally substituted aryl group or an optionally substituted heteroaryl group;
R 1 represents an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted aryl group that may be partially hydrogenated, an optionally substituted heteroaryl group, or an optionally substituted carbamoyl group;
R 2 represents a halogen atom, an alkyl group, or an optionally substituted alkoxy group;
R 3 is an alkyl group substituted with an optionally substituted aryl group, or an alkyl group substituted with an optionally substituted heteroaryl group; and
R 4 is a hydrogen atom or an alkyl group; or
R 3 and R 4 are terminally attached to each other, and together with the nitrogen atom to which they are attached, form an optionally substituted nitrogen-containing aliphatic heterocyclic ring that may partially contain a double bond;
or a pharmaceutically acceptable salt thereof, provided that compounds represented by formulas (a) (b), (c), (d), and (e) are excluded:

2 . The compound or pharmaceutically acceptable salt thereof according to claim 1 , wherein
ring A is an optionally substituted aryl group or an optionally substituted heteroaryl group, wherein substituent(s) on each of the optionally substituted aryl group and the optionally substituted heteroaryl group is/are one to three group(s) independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, a cycloalkyl group, an alkoxy group, a haloalkoxy group, and an alkyleneoxy group; R 1 is an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted aryl group that may be partially hydrogenated, an optionally substituted heteroaryl group, or a carbamoyl group optionally substituted with one or two alkyl group(s), wherein substituent(s) on the optionally substituted alkyl group is/are one to three group(s) independently selected from the group consisting of a halogen atom; a hydroxy group; an oxo group; a cyano group; a cycloalkyl group; an alkoxy group; an alkanoyl group; a carbamoyl group optionally substituted with one or two alkyl group(s); an aliphatic heterocyclic group; an aliphatic heterocyclic carbonyl group optionally substituted with one or two group(s) independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, and an alkoxyalkyl group; an alkylsulfonyl group; an aliphatic heterocyclic sulfonyl group; and an alkyleneoxy group, and substituent(s) on each of the optionally substituted cycloalkyl group, the optionally substituted aliphatic heterocyclic group, the optionally substituted aryl group that may be partially hydrogenated, and the optionally substituted heteroaryl group is/are one to three group(s) independently selected from the group consisting of a halogen atom; a hydroxy group; an oxo group; a cyano group; an alkyl group; a haloalkyl group; a cycloalkyl group; an alkoxy group; a hydroxyalkyl group; an alkoxyalkyl group; an alkanoyl group; a carbamoyl group optionally substituted with one or two alkyl group(s); an aliphatic heterocyclic group; an aliphatic heterocyclic carbonyl group optionally substituted with one or two group(s) independently selected from the group consisting of a halogen atom, an alkyl group, a haloalkyl group, and an alkoxyalkyl group; an alkylsulfonyl group; an aliphatic heterocyclic sulfonyl group; and an alkyleneoxy group; R 2 is a halogen atom, an alkyl group, or an alkoxy group; R 3 is an alkyl group substituted with a substituted aryl group, or an alkyl group substituted with a substituted heteroaryl group, wherein a substituent on each of the substituted aryl group and the substituted heteroaryl group is an aliphatic heterocyclic group optionally substituted with a carboxyl group, and the aryl group and the heteroaryl group are each optionally further substituted with a haloalkyl group; and R 4 is a hydrogen atom or an alkyl group; or R 3 and R 4 are terminally attached to each other, and together with the nitrogen atom to which they are attached, form a group represented by formula [II]:

wherein ring B represents a nitrogen-containing aliphatic heterocyclic group that may partially contain a double bond;
ring C represents an aryl group or a heteroaryl group;
R 5 and R 6 each independently represent a group selected from the group consisting of a hydrogen atom, a halogen atom, a cyano group, an alkyl group, a haloalkyl group, a cyanoalkyl group, a hydroxyalkyl group, an alkoxyalkyl group, a carboxyl group, a carbamoyl group optionally substituted with one or two alkyl group(s), and an alkoxy group;
R 7 represents an optionally substituted alkyl group, an optionally substituted alkenyl group, an optionally substituted cycloalkyl group, an optionally substituted cycloalkenyl group, an optionally substituted aryl group, an optionally substituted heteroaryl group, an optionally substituted aliphatic heterocyclic group, an optionally substituted alkoxy group, an amino group optionally substituted with one or two alkyl group(s) optionally substituted with a carboxyl group, or a carbamoyl group optionally substituted with one or two alkyl group(s) optionally substituted with a carboxyl group,
wherein substituent(s) on the optionally substituted alkyl group is/are one or two group(s) independently selected from the group consisting of a hydroxy group; an oxo group; a cyano group; an alkoxy group; an alkanoyl group; a carboxyl group; an alkoxycarbonyl group; an aliphatic heterocyclic carbonyl group optionally substituted with a carboxyl group; a heteroaryl group optionally substituted with a hydroxy or an oxo group; an aliphatic heterocyclic group optionally substituted with one or two oxo group(s); a carbamoyl group optionally substituted with one or two group(s) independently selected from the group consisting of an alkyl group (the alkyl moiety is optionally substituted with a hydroxyl group, an alkoxy group, or a carboxyl group) and a hydroxy group; an alkylsulfonyl group; an aminosulfonyl group optionally substituted with one or two alkyl group(s); an aminosulfonylaminocarbonyl group optionally substituted with one or two alkyl group(s); an alkylsulfonylaminocarbonyl group; and an amino group optionally substituted with one or two group(s) independently selected from the group consisting of an alkyl group, an alkanoyl group, and an alkylsulfonyl group, and
substituent(s) on each of the optionally substituted alkenyl group, the optionally substituted cycloalkyl group, the optionally substituted cycloalkenyl group, the optionally substituted aryl group, the optionally substituted heteroaryl group, the optionally substituted aliphatic heterocyclic group, and the optionally substituted alkoxy group is/are one or two group(s) independently selected from the group consisting of a hydroxy group; an oxo group; a cyano group; an alkyl group optionally substituted with a carboxyl group; an alkoxy group; an alkanoyl group; a carboxyl group; an alkoxycarbonyl group; an aliphatic heterocyclic carbonyl group optionally substituted with a carboxyl group; a heteroaryl group optionally substituted with a hydroxy or an oxo group; an aliphatic hete

Assignees

• Mitsubishi Tanabe Pharma Corp

Inventors

• Yamamoto Yasuo
• Sato Atsushi
• Morokuma Kenji
• Shitama Hiroaki
• Adachi Takashi
• Miyashiro Masahiko

Classifications

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07D403/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D403/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D207/16 Primary

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title