title: Synthesis and anti-inflammatory effects of new piperazine and ethanolamine derivatives of H(1)-antihistaminic drugs.
abstract: In addition to their antihistamine effects, H1-receptor antagonists possess pharmacological properties that are not uniformly distributed among this class of drugs, such as anti-inflammatory, anti-allergic and antiplatelet activities. In this paper, Cyclizine (1-benzhydryl-4-methyl-piperazine, I), bromodiphenhydramine (2-[(4-bromophenyl)-phenylmethoxy]-N, N-dimethylethanamine, II) and some of their new piperazine and ethanolamine derivatives (III-VIII) inducing changes in substitution of phenyl and amine moieties were synthesized and their acute and chronic antiinflammatory effects were evaluated by standard pharmacological tests. The results showed that substitution of phenyl by tolyl, anisol and cumene groups in piperazine family could remarkably decrease acute inflammation in these new drugs. Also, substitution of dimethylamine by morpholine group could not decrease this inflammation in new synthesized ethanolamine family. But the results from the cotton pellet-induced granuloma formation in rats showed that none of drugs (I-VIII) were effective to reduce the chronic inflammation.
authors.affiliation: Department of Chemistry, Faculty of Science, Islamic Azad University, Karaj branch, Karaj, Iran. a-ahmadi@kiau.ac.ir
authors.forename: Abbas
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khalili
authors.forename: Ali
authors.initials: A
authors.lastname: Nafarie
authors.forename: Arash
authors.initials: A
authors.lastname: Yazdani
authors.forename: Babak
authors.initials: B
authors.lastname: Nahri-Niknafs
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D032561:Cotton Fiber; D004155:Diphenhydramine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D019856:Ethanolamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006099:Granuloma / Q000139:chemically induced / Q000188:drug therapy; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000737:chemistry / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006634:Histamine H1 Antagonists; D010879:Piperazines; D011969:Receptors, Histamine H1; D000077489:Piperazine; D019856:Ethanolamine; D004155:Diphenhydramine; C011410:bromodiphenhydramine