IP Library Granted Patent US 7,566,734
Granted Patent B2
US 7,566,734 · App. 10/333,556 · Granted Jul 28, 2009

Imidazolyl derivatives

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Quick Facts
Patent No.
US 7,566,734
App. No.
10/333,556
Granted
Jul 28, 2009
Kind
B2
Abstract

The present invention is directed to imidazolyl derivatives of formula (I) where the substituents are defined in the specification, which are useful as agonists or antagonists of somatostatin receptors.

Claims (133)

1. A compound selected from the group consisting of:

N-{1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-5-methylhexyl}-N-cyclohexylamine;

N-{1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)heptyl}cyclohexanamine;

(4-phenyl-1H-imidazol-2-yl)methanamine;

(1S)-3-methyl-1-(4-phenyl-1H-imidazol-2-yl)-1-butanamine;

(1R)-N-benzyl-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine;

N-benzyl(4-phenyl-1H-imidazol-2-yl)methanamine;

tert-butyl (R,S)-1-(4-phenyl-1H-imidazol-2-yl)heptylcarbamate;

(4-(1,1′-biphenyl)-4-yl-1-methyl-1H-imidazol-2-yl)methanamine;

(R,S)-N-benzyl-1-(1-benzyl-4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

N-benzyl-N-((4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)methyl)-1-hexanamine;

N-benzyl(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-N-methylmethanamine;

(R,S)-4-(2-{1-((tert-butoxycarbonyl)amino)pentyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(R,S)-N-benzyl-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-pentanamine;

(R,S)-N,N-dihexyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

tert-butyl (R,S)-1-(4-phenyl-1H-imidazol-2-yl)hexylcarbamate;

(R,S)-N-hexyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-1-(4-phenyl-1H-imidazol-2-yl)hexylamine;

(R,S)-N-benzyl-1-(4-(4-methoxyphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-(2,6-dichlorobenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-(4-chlorobenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-1-(4-(3-methoxyphenyl)-1H-imidazol-2-yl)heptylamine;

(R,S)-N-(2-chlorobenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-(2-fluorobenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-butyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-isopentyl-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)amine;

(R,S)-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-N-hexyl-1-heptanamine;

(R,S)-N-pentyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)cyclohexanamine;

(R,S)-N-benzyl-1-(4-(3,4-dichlorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

butyl (4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)methylcarbamate;

(R,S)-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)cyclopentanamine;

(R,S)-N-{1-(4-(2-chlorophenyl)-1H-imidazol-2-yl)heptyl}-cyclohexanamine;

(R,S)-N-{1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)heptyl}-cyclobutanamine;

(R,S)-2-phenyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine;

tert-butyl (4-phenyl-1H-imidazol-2-yl)methylcarbamate;

tert-butyl (1-benzyl-4-phenyl-1H-imidazol-2-yl)methylcarbamate;

(1-benzyl-4-phenyl-1H-imidazol-2-yl)methanamine;

N-benzyl(1-benzyl-4-phenyl-1H-imidazol-2-yl)methanamine;

(1R)-2-(1-benzothien-3-yl)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine;

tert-butyl (1R)-3-methyl-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate;

(1R)-N-benzyl-3-methyl-1-(4-phenyl-1H-imidazol-2-yl)-1-butanamine;

tert-butyl (R,S)-phenyl(4-phenyl-1H-imidazol-2-yl)methylcarbamate;

(R,S)-phenyl(4-phenyl-1H-imidazol-2-yl)methylamine;

tert-butyl (1R)-3-phenyl-1-(4-phenyl-1H-imidazol-2-yl)-propylcarbamate;

(1R)-3-phenyl-1-(4-phenyl-1H-imidazol-2-yl)-1-propanamine;

(R,S)-N-benzyl(phenyl)(4-phenyl-1H-imidazol-2-yl)methanamine;

(1R)-N-benzyl-3-phenyl-1-(4-phenyl-1H-imidazol-2-yl)-1-propanamine;

4-(2-{((tert-butoxycarbonyl)amino)methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(1-benzyl-4-phenyl-1H-imidazol-2-yl)-N,N-dimethylmethanamine;

4-(1-benzyl-2-{((tert-butoxycarbonyl)amino)methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)methanamine;

(R,S) 1-(4-phenyl-1H-imidazol-2-yl)heptylamine;

(1-benzyl-4(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)methanamine;

(R,S)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

4-(2-{((tert-butoxycarbonyl)amino)methyl}-1-methyl-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{((tert-butoxycarbonyl)(methyl)amino)methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

tert-butyl methyl((5-methyl-4-phenyl-1H-imidazol-2-yl)-methyl)carbamate;

(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-N-methylmethanamine;

N-methyl-(5-methyl-4-phenyl-1H-imidazol-2-yl)methanamine;

4-(2-{(benzyl(tert-butoxycarbonyl)amino)methyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(1R)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-3-phenyl-1-propanamine;

N-benzyl(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)methanamine;

(1R)-N-benzyl-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-3-phenyl-1-propanamine;

tert-butyl (R,S)-1-(4-phenyl-1H-imidazol-2-yl)pentylcarbamate;

(R,S)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-pentanamine;

(R,S)-1-(4-phenyl-1H-imidazol-2-yl)pentylamine;

tert-butyl (R,S)-1-(4-(4-methylphenyl)-1H-imidazol-2-yl)-heptylcarbamate;

tert-butyl (R,S)-1-(4-(2-methoxyphenyl)-1H-imidazol-2-yl)-heptylcarbamate;

(R,S)-1-(4-(4-methylphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-1-(4-(2-methoxyphenyl)-1H-imidazol-2-yl)heptylamine;

(R,S)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)-1-pentanamine;

tert-butyl (R,S)-1-(4-(4-methoxyphenyl)-1H-imidazol-2-yl)heptylcarbamate;

(R,S)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-heptanamine;

tert-butyl (R,S)-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-heptylcarbamate;

(R,S)-1-(4-(4-methoxyphenyl)-1H-imidazol-2-yl)heptylamine;

(R,S)-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-4-(2-{1-((tert-butoxycarbonyl)amino)heptyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(R,S)-N-benzyl-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-1-heptanamine;

4-(2-{(1S)-1-((tert-butoxycarbonyl)amino)propyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(R,S)-N-benzyl-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-heptanamine;

(1S)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-propanamine;

(1S)-N-benzyl-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-propanamine;

(R,S)-N-benzyl-1-(4-(4-methylphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-(2-methoxyphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)-1-hexanamine;

(R,S)-4-(2-(1-aminoheptyl)-1H-imidazol-4-yl)benzonitrile;

(R,S)-1-(4-(4-bromophenyl)-1H-imidazol-2-yl)-1-heptanamine;

tert-butyl (1R)-1-(4-phenyl-1H-imidazol-2-yl)butylcarbamate;

4-(2-{(1R)-1-((tert-butoxycarbonyl)amino)butyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(1R)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-butanamine;

(R,S)-4-(2-(1-aminoheptyl)-1H-imidazol-4-yl)-2,6-di(tert-butyl)-phenol;

(1R)-1-(4-phenyl-1H-imidazol-2-yl)-1-butanamine;

(R,S)-N-benzyl-1-(4-(4-bromophenyl)-1H-imidazol-2-yl)-1-heptanamine;

(1R)-N-benzyl-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)-1-butanamine;

(1R)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)-1-butanamine;

(R,S)-N-(3-chlorobenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-(3-methoxyphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-4-{2-(1-(benzylamino)heptyl)-1H-imidazol-4-yl}benzonitrile;

(R,S)-4-(2-(1-aminoheptyl)-1H-imidazol-4-yl)-N,N-diethylaniline;

(1R)-1-(4-phenyl-1H-imidazol-2-yl)ethanamine;

(R,S)-1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-1-(4-(2-chlorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

N-((1S)-1-(4-(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)propyl)-1-butanamine;

(1R)-N-benzyl-1-(4-phenyl-1H-imidazol-2-yl)ethanamine;

(R,S)-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)-N-propylamine;

(R,S)-N-benzyl-1-(4-(3-methoxyphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-4-{2-(1-(benzylamino)heptyl)-1H-imidazol-4-yl}benzonitrile;

(R,S)-N-(4-methoxybenzyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-(2-chlorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-N-(1-{4-(4-(diethylamino)phenyl)-1H-imidazol-2-yl}heptyl)amine;

(R,S)-1-(4-(3,4-dichlorophenyl)-1H-imidazol-2-yl)-1-heptanamine;

tert-butyl (R,S)-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-5-methylhexylcarbamate;

(R,S)-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-5-methyl-1-hexanamine;

(R,S)-N-isobutyl-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-benzyl-1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-5-methyl-1-hexanamine;

(R,S)-N-benzyl-1-(4-(4-methoxyphenyl)-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)cyclobutanamine;

4-(2-{(1S)-1-((butoxycarbonyl)amino)ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

4-(2-{(1R)-1-((butoxycarbonyl)amino)ethyl}-1H-imidazol-4-yl)-1,1′-biphenyl;

(R,S)-N-isopropyl-N-(1-(4-phenyl-1H-imidazol-2-yl)heptyl)amine;

(R,S)-N-{1-(4-(3,4-dichlorophenyl)-1H-imidazol-2-yl)heptyl}-cyclohexanamine;

(R,S)-N-(1-(4(1,1′-biphenyl)-4-yl-1H-imidazol-2-yl)heptyl)-cyclohexanamine;

N-{(4-(3-bromophenyl)-1H-imidazol-2-yl)methyl}cyclohexanamine;

(R,S)-N-{1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-4-methylpentyl}-cyclohexanamine;

(R,S)-N-(cyclohexylmethyl)-1-(4-phenyl-1H-imidazol-2-yl)-1-heptanamine;

(R,S)-N-{1-(4-(3-bromophenyl)-1H-imidazol-2-yl)-5-methylhexyl}-cyclohexanamine; and

N-{(1R)-1-(4-(4-fluorophenyl)-1H-imidazol-2-yl)-2-methylpropyl}-cyclohexanamine;

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

3. A method of treating acromegaly, restenosis, Crohn's disease, systemic sclerosis, external and internal pancreatic pseudocysts and ascites, VIPoma, nesidoblastosis, hyperinsulinism, gastrinoma, Zollinger-Ellison Syndrome, diarrhea, AIDS related diarrhea, chemotherapy related diarrhea, scleroderma, Irritable Bowel Syndrome, pancreatitis, small bowel obstruction, gastroesophageal reflux, duodenogastric reflux, Cushing's Syndrome, hyperparathyroidism, Graves' Disease, Paget's disease, polycystic ovary disease, TSH secreting adenomas, in a subject in need thereof, which comprises administering an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof to said subject.

4. A method of treating peptic ulcers, enterocutaneous and pancreaticocutaneous fistula, Dumping syndrome, watery diarrhea syndrome, acute or chronic pancreatitis, gastrointestinal hormone secreting tumors, chronic allograft rejection, graft vessel bleeding or gastrointestinal bleeding in a subject in need thereof, which comprises administering an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof to said subject.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY NAME PREVIOUSLY RECORDED ON REEL 023640 FRAME 0166. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded May 23, 2016
From: SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES, S.A.S.
To: SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES, S.A.S.
Reel/Frame 038772/0729 →
CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY NAME PREVIOUSLY RECORDED AT REEL: 023638 FRAME: 0555. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF NAME. Recorded May 23, 2016
From: SOCIETE DE CONSEILS DE RECHERCHES ET D'APPLICATIONS SCIENTIFIQUES, S.A.S.
To: IPSEN PHARMA S.A.S.
Reel/Frame 038779/0043 →
CORRECTIVE ASSIGNMENT TO CORRECT THE NAME. NEED TO ADD S.A.S. TO END OF NAME IPSEN PHARMA. CORRECT NAME SHOULD SHOW AS IPSEN PHARMA S.A.S. PREVIOUSLY RECORDED ON REEL 023638 FRAME 0555. ASSIGNOR(S) HEREBY CONFIRMS THE CORRECT NAME SHOULD SHOW AS IPSEN PHARMA S.A.S.. Recorded Jan 12, 2010
From: S.C.R.A.S.
To: IPSEN PHARMA S.A.S.
Reel/Frame 023763/0615 →
CHANGE OF NAME Recorded Dec 11, 2009
From: S.C.R.A.S.
To: IPSEN PHARMA
Reel/Frame 023638/0555 →
CHANGE OF ADDRESS Recorded Dec 11, 2009
From: S.C.R.A.S.
To: S.C.R.A.S.
Reel/Frame 023640/0166 →