Diaminopyrimidine derivatives and processes for the preparation thereof

Patent metadata

Field	Value
Publication number	US-9890138-B2
Application number	US-201214001489-A
Country	US
Kind code	B2
Filing date	Feb 24, 2012
Priority date	Feb 25, 2011
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT 4 receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.

First claim

The invention claimed is:

1. A compound or its pharmaceutically acceptable salt selected from the group consisting of:
N-(4-fluorophenyl)-4-propyl-6-(pyrrolidin-1-yl)pyrimidin-2-amine;
(S)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;
1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ol;
(R)-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;
{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-yl}methanol;
N-(4-fluorophenyl)-4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-amine;
(S)-N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(R)-N-(4-fluorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-2-carboxamide;
N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
(R)-N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
2,2,2-trifluoro-N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
4-[3-(dimethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
(S)-N-(4-fluorophenyl)-4-propyl-6-[2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl]pyrimidin-2-amine;
(S)-N-(4-fluorophenyl)-4-{2-[(phenylamino)methyl]pyrrolidin-1-yl}-6-propylpyrimidin-2-amine;
(S)-N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
(S)-4-[3-(ethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
(S)-tert-butyl 1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate;
4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
4-[3-(diethylamino)pyrrolidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
(S)-N-(4-fluorophenyl)-4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide;
(S)-1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ol;
(S)-N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-6-amine;
(S)-N-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indol-5-amine;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine;
(S)-N-(3-chlorophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-N-(4-fluoro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;
(S)-N-(4-chloro-3-nitrophenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-3-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;
(S)-7-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one;
(S)-N-(5-chloro-2-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-N-(3-chloro-4-methylphenyl)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-4-[2-(methoxymethyl)pyrrolidin-1-yl]-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;
(S)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-amine;
(S)-N 1 -{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;
(S)-2-fluoro-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;
(S)-2-amino-5-{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-N 1 -{4-[2-(methoxymethyl)pyrrolidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;
(S)-4-(3-aminopyrrolidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;
(S)-tert-butyl 1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-ylcarbamate;
3-{4-[3-(diethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-N-methylacetamide;
(S)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
(R)-3-[4-(2-methylpyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
(S)-3-{4-[3-(ethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(R)-tert-butyl {1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}methylcarbamate;
(R)-3-[4-(3-hydroxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
(S)-3-[4-(3-methoxypyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
3-{4-[3-(methylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-3-[4-(3-aminopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}butyramide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}cyclopentanecarboxamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-(piperidin-1-yl)propanamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}benzamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-fluorobenzamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-phenylacetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(4-fluorophenyl)acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-phenoxypropanamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3-isobutoxypropanamide;
(S)-2-(4-benzylpiperazin-1-yl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(piperidin-1-yl)acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-oxo-4-phenylbutanamide;
(S)-2-(4-aminophenyl)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-cyclopentylacetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-methoxyacetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-2-yl)acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-3-yl)acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(pyridin-4-yl)acetamide;
(S,E)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-4-phenylbut-3-enamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-2-(thiophen-2-yl)acetamide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}isobutyramide;
(S)-N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]pyrrolidin-3-yl}-3,3,3-trifluoropropanamide;
3-[4-(2-oxopyrrolidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;
(S)-3-{4-[3-(hexylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-3-{4-propyl-6-[3-(propylamino)pyrrolidin-1-yl]pyrimidin-2-ylamino}benzonitrile;
(S)-3-{4-[3-(cyclohexylmethylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-3-{4-[3-(benzylamino)pyrrolidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;
(S)-3-{4-[3-(phenethylamino)pyrrolidin-1-yl]-6-

Assignees

• Lee Hyun Joo
• Kim Dong Hoon
• Kim Tae Kyun
• Yoon Young Ae
• Sim Jae Young
• Cha Myung Hun
• Jung Eun Jung
• Ahn Kyoung Kyu
• Lee Tai Au
• Yuhan Corp

Inventors

• Lee Hyun Joo
• Kim Dong Hoon
• Kim Tae Kyun
• Yoon Young Ae
• Sim Jae Young
• Cha Myung Hun
• Jung Eun Jung
• Ahn Kyoung Kyu
• Lee Tai Au

Classifications

• A61P43/00

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

• C07D413/04

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

• C07D403/04 Primary

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

• C07D403/14

  containing three or more hetero rings · CPC title

• A61P1/10

  Laxatives · CPC title