Diaminopyrimidine derivatives and processes for the preparation thereof

• US 9,850,227 B2
• Filed: 02/24/2012
• Issued: 12/26/2017
• Est. Priority Date: 02/25/2011
• Status: Active Grant

• Current Assignee: Yuhan Corporation
• Original Assignee: Yuhan Corporation
• 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
• Primary Examiner(s): Soroush, Layla
• Application Number:
  US14/001,475
• Publication Number:
  US 20130331377A1
• Time in Patent Office: 2,132 Days
• Field of Search: 514217
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/10 Laxatives
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond

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-HT₄ 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.

Claims

1. A method for agonizing a 5-HT₄ receptor, comprising administering an effective amount of a compound of Formula 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof:

2. The method of claim 1,

wherein,

R₁ is a phenyl group substituted with one or more substituents selected from the group consisting of amino, halogen, cyano, nitro, C_1-3 alkyl (where the C_1-3 alkyl is optionally substituted with halogen), C_1-5 alkoxy, C_1-5 alkylthio, and aminocarbonyl;

or

a heteroaryl group selected from the group consisting of quinolinyl, chromenonyl, benzofuranyl, indolyl, indolinyl, benzimidazol-5-yl, benzimidazol-6-yl, and indazolyl, wherein the heteroaryl group may be optionally substituted with one or more C_1-5 alkyl (where the C_1-5 alkyl is optionally substituted with halogen),

R₂ is a nitrogen-containing cyclic group of the following Formula B (where * in Formula B represents the position attached to the compound of Formula

     1),

3. The method of claim 1, wherein the compound is selected from the group consisting of:

N-(4-fluorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-fluorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(4-fluorophenyl)-4-(2-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-fluorophenyl)-4-(3-methylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-fluorophenyl)-4-(decahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(4-fluorophenyl)-4-(piperazin-1-yl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;

2-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

ethyl 1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-carboxylate;

4-butyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;

4-butyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;

2-{1-[6-butyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;

4-butyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;

2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-(1-{2-[3-(methylthio)phenylamino]-6-propylpyrimidin-4-yl}piperidin-2-yl)ethanol;

N-{1-[2-(4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

4-[3-(benzyloxy)piperidin-1-yl]-N-(4-fluorophenyl)-6-propylpyrimidin-2-amine;

N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;

N-(3-chloro-4-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;

4-(piperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;

N-[3-(methylthio)phenyl]-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(5-methoxy-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(5-chloro-2-methylphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-fluoro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(3-methoxyphenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(3-chlorophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(4-chloro-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

3-[4-(piperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

N-(4-methyl-3-nitrophenyl)-4-(piperidin-1-yl)-6-propylpyrimidin-2-amine;

N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;

2-{1-[2-(1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

N-[4-(piperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;

N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-6-amine;

N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;

(R)-3-[4-(3-ethylmorpholino)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

4-morpholino-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;

N-(4-fluoro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(4-chloro-3-nitrophenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(3-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(4-methoxyphenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-[3-(methylthio)phenyl]-4-morpholino-6-propylpyrimidin-2-amine;

N-(3-chlorophenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(3-chloro-4-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;

4-morpholino-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

N-(4-morpholino-6-propylpyrimidin-2-yl)-1H-indol-5-amine;

N-(4-morpholino-6-propylpyrimidin-2-yl)-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;

N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-6-amine;

3-(4-morpholino-6-propylpyrimidin-2-ylamino)benzonitrile;

N-(5-methoxy-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(5-chloro-2-methylphenyl)-4-morpholino-6-propylpyrimidin-2-amine;

N-(4-morpholino-6-propylpyrimidin-2-yl)quinolin-3-amine;

4-(2-ethylpiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-N-(4-fluoro-3-nitrophenyl)-6-propylpyrimidin-2-amine;

N-(4-chloro-3-nitrophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-N-(3-methoxyphenyl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-N-(4-methoxyphenyl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-N-[3-(methylthio)phenyl]-6-propylpyrimidin-2-amine;

N-(3-chlorophenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

N-(3-chloro-4-methylphenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

4-(2-ethylpiperidin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;

N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-6-amine;

N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;

3-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

4-(2-ethylpiperidin-1-yl)-N-(5-methoxy-2-methylphenyl)-6-propylpyrimidin-2-amine;

N-(5-chloro-2-methylphenyl)-4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-amine;

N-[4-(2-ethylpiperidin-1-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;

(R)—

N-(4-chloro-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;

(R)—

N-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;

(R)—

N-(2-methylpiperazin-1-yl)-6-propyl-N-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

(R)—

N-(2-methylpiperazin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;

(R)—

N-(4-fluoro-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;

(R)—

N-(4-methyl-3-nitrophenyl)-4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-amine;

(R)-4-fluoro-N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]benzene-1,3-diamine;

(R)—

N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;

(R)-2-fluoro-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-2-methyl-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-2-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)—

N¹-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;

(R)-3-amino-5-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-3-[4-(2-methylpiperazin-1-yl)-6-propylpyrimidin-2-ylamino]benzamide;

3-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

2-{1-[2-(1-ethyl-1H-indol-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(1H-indol-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-(1-{6-propyl-2-[2-(trifluoromethyl)-1H-benzo[d]imidazol-6-ylamino]pyrimidin-4-yl}piperidin-2-yl)ethanol;

2-{1-[2-(4-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-methoxyphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(5-methoxy-2-methylphenyamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(4-fluoro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(2,3-dimethylbenzofuran-5-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[6-propyl-2-(quinolin-6-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

7-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-4-methyl-2H-chromen-2-one;

2-{1-[6-propyl-2-(3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[6-propyl-2-(quinolin-3-ylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;

(S)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(S)-4-(3-aminopiperidin-1-yl)-N-(3-nitrophenyl)-6-propylpyrimidin-2-amine;

(S)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(S)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(S)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;

(S)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;

(S)-5-(4-{3-[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;

(S)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(S)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(S)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(S)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-yl amino)-2-methylbenzonitrile;

(R)-5-(4-{3-[bis(cyclopropylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;

4-ethyl-N-(4-fluorophenyl)-6-(piperidin-1-yl)pyrimidin-2-amine;

4-ethyl-N-(4-fluorophenyl)-6-(octahydroquinolin-1(2H)-yl)pyrimidin-2-amine;

4-ethyl-6-(2-ethylpiperidin-1-yl)-N-(4-fluorophenyl)pyrimidin-2-amine;

2-{1-[6-ethyl-2-(4-fluorophenylamino)pyrimidin-4-yl]piperidin-2-yl}ethanol;

4-ethyl-N-(4-fluorophenyl)-6-morpholinopyrimidin-2-amine;

2-{1-[2-(4-methyl-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

2-fluoro-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

2-amino-5-{4-[2-(2-hydroxyethyl)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

2-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

2-{1-[2-(indolin-6-ylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

(S)-2-{1-[2-(4-chloro-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

(S)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

(R)-2-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-2-yl}ethanol;

3-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

N-(3-nitrophenyl)-4-(octahydroquinoin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(4-fluoro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(4-chloro-3-nitrophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(3-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(5-methoxy-2-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(4-methoxyphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

4-(octahydroquinolin-1(2H)-yl)-6-propyl-N-(3-trifluoromethylphenyl)pyrimidin-2-amine;

N-(3-chlorophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(5-chloro-2-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(3-chloro-4-methylphenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-(3-methylthiophenyl)-4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amine;

N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-1H-indol-5-amine;

N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]-2-(trifluoromethyl)-1H-benzo[d]imidazol-5-amine;

N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-6-amine;

4-methyl-7-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-amino]-2H-chromen-2-one;

N-[4-(octahydroquinolin-1(2H)-yl)-6-propylpyrimidin-2-yl]quinolin-3-amine;

(R)-5-{4-[3-(ethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-{4-[3-(butylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-2-methyl-5-{4-[3-(pentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-5-{4-[3-(isobutylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-{4-[3-(isopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-2-methyl-5-{4-[3-(neopentylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-5-{4-[3-(isopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-(4-{3-[(1H-pyrrol-2-yl)methylamino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;

(R)-2-methyl-5-(4-propyl-6-{3-[(thiophen-2-ylmethyl)amino]piperidin-1-yl}pyrimidin-2-ylamino)benzonitrile;

(R)-5-(4-{3-[(4,5-dimethylfuran-2-ylmethyl)amino]piperidin-1-yl}-6-propylpyrimidin-2-ylamino)-2-methylbenzonitrile;

(R)-2-methyl-5-{4-[3-(3-methylthiopropylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-{4-[3-(cyclopentylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)-5-{4-[3-(4-hydroxybenzylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-methylbenzonitrile;

(R)—

N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)-3-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-5-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;

(R)-3-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-3-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-2-fluoro-5-{4-[3-(propylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}-2-fluorobenzonitrile;

(R)—

N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;

(R)—

N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;

(R)-3-amino-5-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-ylamino}benzonitrile;

(R)—

N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;

(R)—

N¹-{4-[3-(cyclopropylmethylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;

(R)—

N-{1-[2-(4-amino-3-nitrophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[6-butyl-2-(4-methyl-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[6-butyl-2-(4-fluoro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[6-butyl-2-(4-chloro-3-nitrophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-amino-5-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-amino-5-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(4-amino-3-trifluoromethylphenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[6-butyl-2-(4-fluoro-3-trifluoromethylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[6-butyl-2-(3-cyano-4-fluorophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-amino-4-fluorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-amino-4-chlorophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(4-amino-3-cyanophenylamino)-6-butylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-cyano-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;

(R)—

N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;

(R)—

N-(1-{2-[4-fluoro-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-amino-4-chlorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-amino-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N-{1-[2-(3-chloro-4-methylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)-2-hydroxy-N-(1-{2-[4-methyl-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;

(R)—

N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}-2-hydroxyacetamide;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;

(R)-4-(3-aminopiperidin-1-yl)-N-(3-fluoro-4-methylphenyl)-6-propylpyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;

(R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;

(R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amino}benzonitrile;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-chlorobenzene-1,3-diamine;

(R)-4-(3-aminopiperidin-1-yl)-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-propylpyrimidin-2-amine;

(R)—

N-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-1H-indol-6-amine;

(R)-4-(3-aminopiperidin-1-yl)-N-(4-methyl-3-nitrophenyl)-6-propylpyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;

(R)—

N-{1-[2-(3-cyano-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(R)-5-[4-(3-diethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;

(R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-fluorobenzonitrile;

(R)—

N-{1-[6-butyl-2-(3-cyanophenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(3-amino-5-cyanophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

N-{1-[2-(4-amino-3-nitrophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

N-{1-[2-(3-amino-4-fluorophenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-{1-[2-(4-fluoro-3-trifluoromethylphenylamino)-6-propylpyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)—

N-(1-{2-[3-amino-5-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;

(R)—

N-(1-{2-[4-amino-3-(trifluoromethyl)phenylamino]-6-propylpyrimidin-4-yl}piperidin-3-yl)acetamide;

(R)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(R)-2-fluoro-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-2-methyl-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)—

N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;

(R)—

N¹-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;

(R)-3-amino-5-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-(4-fluoro-3-trifluoromethylphenyl)-[4-(3-methylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]amine;

(R)—

N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;

(R)—

N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;

(R)—

N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;

(R)—

N¹-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;

(R)-3-amino-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]benzonitrile;

(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-methylbenzonitrile;

(R)-5-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-ylamino]-2-fluorobenzonitrile;

(R)—

N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(S)-5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

5-[4-(3-ethylaminopiperidin-1-yl)-6-propylpyrimidin-2-ylamino]-2-methylbenzonitrile;

N-{1-[6-butyl-2-(3-cyano-4-methylphenylamino)pyrimidin-4-yl]piperidin-3-yl}acetamide;

(R)-5-({4-butyl-6-[3-(ethylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(butylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(pentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(isobutylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(isopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(neopentylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-{[4-butyl-6-(3-{[3-(methylthio)propyl]amino}piperidin-1-yl)pyrimidin-2-yl]amino}-2-methylbenzonitrile;

(R)-4-fluoro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;

(R)-4-chloro-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;

(R)-2-amino-5-({4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}amino)benzonitrile;

(R)—

N-(3-methoxy-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;

(R)-4-methyl-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;

(R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-methylbenzonitrile;

(R)-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)-2-fluorobenzonitrile;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-5-(trifluoromethyl)benzene-1,3-diamine;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-(trifluoromethyl)benzene-1,4-diamine;

(R)-3-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;

(R)-2-amino-5-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-fluorobenzene-1,3-diamine;

(R)-4-butyl-N-(3-methoxy-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methylbenzene-1,3-diamine;

(R)-4-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;

(R)—

N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;

(R)—

N-(3,4-dimethylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;

(R)—

N-(3-fluoro-4-methylphenyl)-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;

(R)—

N-[4-methyl-3-(trifluoromethyl)phenyl]-4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-amine;

(R)-4-methoxy-N¹-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,3-diamine;

(R)—

N-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}-1H-indazol-6-amine;

(R)—

N⁴-{4-[3-(methylamino)piperidin-1-yl]-6-propylpyrimidin-2-yl}benzene-1,2,4-triamine;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-3-nitrobenzene-1,4-diamine;

(R)-3-({4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}amino)benzonitrile;

(R)-4-butyl-N-(3,4-dimethylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;

(R)-4-butyl-N-(3-fluoro-4-methylphenyl)-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;

(R)-4-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-amine;

(R)—

N¹-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-4-methoxybenzene-1,3-diamine;

(R)—

N-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}-1H-indazol-6-amine;

(R)—

N⁴-{4-butyl-6-[3-(methylamino)piperidin-1-yl]pyrimidin-2-yl}benzene-1,2,4-triamine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-nitrophenyl)pyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-nitrobenzene-1,4-diamine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-fluoro-3-nitrophenyl)pyrimidin-2-amine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-methyl-3-nitrophenyl)pyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-3-(trifluoromethyl)benzene-1,4-diamine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-5-(trifluoromethyl)benzene-1,3-diamine;

(R)-3-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-methyl-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-fluoro-4-methylphenyl)pyrimidin-2-amine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3-methoxy-4-methylphenyl)pyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-methylbenzene-1,3-diamine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(3,4-dimethylphenyl)pyrimidin-2-amine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-[4-fluoro-3-(trifluoromethyl)phenyl]pyrimidin-2-amine;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]-4-fluorobenzene-1,3-diamine;

(R)-2-amino-5-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;

(R)-3-{[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]amino}benzonitrile;

(R)—

N¹-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,4-diamine;

(R)-4-(3-aminopiperidin-1-yl)-6-butyl-N-(4-chloro-3-nitrophenyl)pyrimidin-2-amine; and

(R)—

N⁴-[4-(3-aminopiperidin-1-yl)-6-butylpyrimidin-2-yl]benzene-1,2,4-triamine.