Imidazolyl derivatives
View Patent ↗The present invention is directed to imidazolyl derivatives of the formula: where the substituents are defined in the specification, or a pharmaceutically acceptable salt thereof. The derivatives bind selectively to the somatostatin subtype receptors and elicit either an agonist or antagonist effect from the somatostatin subtype receptors. The derivatives are useful for treating a variety of diseases including 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, gonadotropinoma, hyperparathyroidism, Graves' Disease, diabetic neuropathy, Paget's disease, polycystic ovary disease, cancer, cancer cachexia, hypotension, postprandial hypotension, panic attacks, GH secreting adenomas or TSH secreting adenomas.
1. A compound of the formula
the racemic-diastereomeric mixtures and optical isomers of said compound or a pharmaceutically acceptable salt thereof,
wherein
R 3 is —(CH 2 ) m —E—(CH 2 ) m —Z 2 ;
E is O, S, —C(O)—, —C(O)—O—, —NH—C(O)—O—, —N—(C 1 -C 6 )alkyl-C(O)—O— or a bond;
Z 2 is H, (C 1 -C 12 )alkyl, amino, (C 1 -C 12 )alkylamino, N,N-di-(C 1 -C 12 )alkylamino, (C 1 -C 12 )alkylguanidino, or an unsubstituted or substituted moiety selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl and naphthyl;
Z 3 is
X 1 is —(CH 2 ) 2 —N(CH 3 ) 2 and X 2 is benzyl; or
X 1 and X 2 are taken together with the nitrogen atom to which they are attached, to form
2. A compound of the formula
3. A compound of the formula