Novel tetrahydropyridopyrimidine compound or salt thereof

Patent metadata

Field	Value
Publication number	US-2016244444-A1
Application number	US-201515023894-A
Country	US
Kind code	A1
Filing date	May 28, 2015
Priority date	May 29, 2014
Publication date	Aug 25, 2016
Grant date	—

Abstract

To provide a compound having an inhibitory activity for an androgen receptor. A tetrahydropyridopyrimidine compound represented by the following general formula (I) or a pharmaceutically acceptable thereof (in the formula, X and R are as defined in the specification).

First claim

1 . A tetrahydropyridopyrimidine compound represented by formula (I):

wherein, in the formula (I),
X is a halogen atom or a halogeno-C 1-3 alkyl group;
R is a C 6-14 aryl group which is substituted with R 1 and is optionally substituted simultaneously with R 2 , or a 5- or 6-membered heteroaryl group which is substituted with R 1 and is optionally substituted simultaneously with R 2 ;
R 1 is a hydrogen atom, a phenyl group, a hydroxy-C 1-6 alkyl group, a hydroxy-C 3-7 cycloalkyl group, a C 1-6 alkoxy group which may be substituted with Ra, a C 3-7 cycloalkylaminosulfonyl group, a 3- to 7-membered monocyclic heterocycloalkylsulfonyl group, a halogeno-C 1-3 alkoxycarbonylamino group, a halogeno-C 1-3 alkylcarbonylamino group, a 3- to 7-membered monocyclic heterocycloalkanecarbonyl group substituted with a hydroxy-C 1-6 alkyl group, or —(CH 2 ) n —C(═O)—NHRf;
R 2 is a hydrogen atom, a halogen atom, or a halogeno-C 1-3 alkyl group;
Ra is a C 1-6 alkylpyrazolyl group, a triazolyl group, a tetrazolyl group, or a C 1-6 alkylsulfonylpiperazinyl group;
Rf is a halogeno-C 1-3 alkyl group, a hydroxy-C 1-6 alkyl group, a hydroxy-C 3-7 cycloalkyl group, a hydroxy-C 3-7 cycloalkyl-C 1-6 alkyl group, or a C 1-6 alkyl group substituted with Rfa;
Rfa is a C 1-6 alkylpyrazolyl group, a halogeno-C 1-3 alkylthiazolyl group, an oxadiazolyl group, or a halogeno-C 1-3 alkyloxadiazolyl group; and
n is an integer of from 0 to 3,
or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , wherein X is a chlorine atom, a bromine atom, or a trifluoromethyl group,
or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 ,
wherein n is 0 or 1, or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 1 ,
wherein R is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

5 . The compound of claim 1 ,
wherein R 1 is a hydrogen atom, a phenyl group, a hydroxy-ethyl group, a hydroxy-isopropyl group, a hydroxy-cyclopropyl group, a hydroxy-cyclobutyl group, a methoxy group, an isopropoxy group, an ethoxy group substituted with a methylpyrazolyl group, an ethoxy group substituted with a triazolyl group, a 2-methylpropoxy group substituted with a triazolyl group, a 2-methylpropoxy group substituted with a tetrazolyl group, an n-propoxy group substituted with a methylsulfonylpiperazinyl group, a cyclopropylaminosulfonyl group, a 1,4-oxazepanyl sulfonyl group, a 2,2,2-trifluoroethoxycarbonylamino group, a 2,2,2-trifluoroethylcarbonylamino group, a piperidinecarbonyl group substituted with a hydroxy-isopropyl group, or —(CH 2 ) n —C(═O)—NHRf, Rf is a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a hydroxy-2-methylpropyl group, a hydroxycyclohexyl group, a hydroxycyclopropylmethyl group, a methyl group substituted with a trifluoromethylthiazolyl group, an ethyl group substituted with a methylthiazolyl group, an ethyl group substituted with an oxadiazolyl group, or an ethyl group substituted with a trifluoromethyloxazolyl group; and n is 0 or 1, or a pharmaceutically acceptable salt thereof.

6 . The compound of claim 1 ,
wherein R is selected from the group consisting of:

where R 1 is a hydrogen atom;

where R 1 is —(CH 2 ) n —C(═O)—NHRf,
Rf is a methyl group substituted with Rfa or an ethyl group substituted with Rfa, Rfa is a methylpyrazolyl group or an oxadiazolyl group, and
n is 0,

where R 1 is a phenyl group, a hydroxy-ethyl group, a hydroxy-isopropyl group, a methoxy group, an isopropoxy group, an ethoxy group substituted with a methylpyrazolyl group, or an n-propoxy group substituted with a methylsulfonylpiperazinyl group;

where R 1 is a hydroxy-isopropyl group, a hydroxy-cyclopropyl group, a hydroxy-cyclobutyl group, an isopropoxy group, an ethoxy group substituted with a triazolyl group, a 2-methylpropoxy group substituted with a triazolyl group, a 2-methylpropoxy group substituted with a tetrazolyl group, a cyclopropylaminosulfonyl group, a 2,2,2-trifluoroethoxycarbonylamino group, a 2,2,2-trifluoroethylcarbonylamino group, or —(CH 2 ) n —C(═O)—NHRf,
R 2 is a hydrogen atom, a fluorine atom, or a chlorine atom,
Rf is a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a methyl group substituted with Rfa, or an ethyl group substituted with Rfa,
Rfa is a trifluoromethylthiazolyl group, an oxadiazolyl group, or a trifluoromethyloxadiazolyl group, and
n is 0 or 1;

where R 1 is a hydroxy-isopropyl group, a 1,4-oxazepanylsulfonyl group, or —(CH 2 ) n —C(═O)—NHRf,
R 2 is a hydrogen atom or a trifluoromethyl group,
Rf is a 2,2,2-trifluoroethyl group or an ethyl group substituted with Rfa,
Rfa is an oxadiazolyl group, and
n is 0;

where R 1 is a hydroxy-isopropyl group or —(CH 2 ) n —C(═O)—NHRf,
Rf is a 2,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a hydroxy-2-methylpropyl group, a hydroxycyclohexyl group, a hydroxycyclopropylmethyl group, and
n is 0;

where R 1 is —(CH 2 ) n —C(═O)—NHRf,
Rf is a hydroxy-2-methylpropyl group, and
n is 0;

where R 1 is —(CH 2 ) n —C(═O)—NHRf,
Rf is a hydroxy-2-methylpropyl group, and
n is 0;

where R 1 is —(CH 2 ) n —C(═O)—NHRf,
Rf is a 2,2,2-trifluoroethyl group, and
n is 0;

where R 1 is a piperidinecarbonyl group substituted with a hydroxy-isopropyl group; and

where R 1 is a piperidinecarbonyl group substituted with a hydroxy-isopropyl group,
or a pharmaceutically acceptable salt thereof.

7 . The compound of claim 1 ,
wherein X is a chlorine atom, a bromine atom, or a trifluoromethyl group; and R is selected from the group consisting of:

where R 1 is a hydrogen atom, a phenyl group, a hydroxy-C 1-4 alkyl group, a hydroxy-C 3-5 cycloalkyl group, a C 1-4 alkoxy group which may be substituted with Ra, a C 3-5 cycloalkylaminosulfonyl group, a 7-membered monocyclic heterocycloalkylsulfonyl group, a fluoro-C 1-3 alkoxycarbonylamino group, a fluoro-C 1-3 alkylcarbonylamino group, a 6-membered monocyclic heterocycloalkanecarbonyl group substituted with a hydroxy-C 1-4 alkyl group, or —(CH

Assignees

• Taiho Pharmaceutical Co Ltd

Inventors

• Minamiguchi Kazuhisa
• Okajima Shigeo
• Aoki Shinichi
• Asai Masanori
• Asai Takahiro
• Yamanaka Hiroyoshi
• Dohi Suguru

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P17/10

  Anti-acne agents · CPC title

• A61P17/14

  for baldness or alopecia · CPC title