Structure-activity relationships of a series of 1-substituted-4-methylbenzimidazole neuropeptide Y-1 receptor antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 5; pp. 473 - 476
• Main Authors: Zimmerman, Dennis M., Cantrell, Buddy E., Smith, Edward C.R., Nixon, James A., Bruns, Robert F., Gitter, Bruce, Hipskind, Philip A., Ornstein, Paul L., Zarrinmayeh, Hamideh, Britton, Thomas C., Schober, Douglas A., Gehlert, Donald R.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 03.03.1998; Elsevier
• Subjects: Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Biological and medical sciences; Cell Line; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Receptors, Neuropeptide Y - antagonists & inhibitors; Recombinant Proteins - antagonists & inhibitors; Structure-Activity Relationship; Neuropeptide Y; Ether; Nitrogen heterocycle; In vitro; Structure activity relation; Benzimidazole derivatives; Chlorine Organic compounds; Piperidine derivatives; Bicyclic compound; Peptidergic receptor; Aromatic compound; Antagonist; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00048-1

The characterization of a novel series of NPY-1 receptor antagonists derived from the 4-methylbenzimidazole 4 is described. Appropriate substitution on the piperidyl nitrogen of 4 led to systematic increases in Y-1 receptor affinity, to approximately 50-fold, and to the discovery of the importance of a second basic substituent. The characterization of a novel series of NPY-1 antagonists 3 is described.