Müller, Manfred and Knieps, Sebastian and Geßele, Karin and Dove, Stefan and Bernhardt, Günther and Buschauer, Armin (1997) Synthesis and neuropeptide Y Y-1 receptor antagonistic activity of N,N-disubstituted omega-guanidino- and omega-aminoalkianoic acid amides. ARCHIV DER PHARMAZIE, 330 (11). pp. 333-342. ISSN 0365-6233, 1521-4184
Full text not available from this repository.Abstract
Potent arpromidine-type histamine H-2 receptor agonists such as BU-E-76 (He 90481) were among the first non-peptides reported to display weak neuropeptide Y (NPY) Y-1 receptor antagonist activity. In search of new chemical leads for the development of more potent NPY antagonists, a series of N,N-disubstituted omega-guanidino and omega-aminoalkanoic acid amides were synthesized on the basis of structure-activity relationships and molecular modeling studies of arpromidine and related imidazolylpropylguanidines. In one group of compounds the imidazole ring was retained whereas in the second group it was replaced with a phenol group representing a putative mimic of Tyr(36) in NPY. Although the substitution patterns have not yet been optimized, the title compounds are NPY Y-1 antagonists in human erythroleukemia (HEL) cells (Ca2+ assay) achieving pK(B) values in the range of 6.3 - 6.6. For representative new substances tested in the isolated guinea pig right atrium histamine H-2 receptor agonism could not be found. In "the N-(diphenylalkyl)amide series, compounds with a trimethylene chain were more active Y-1 antagonists than the ethylene homologs. Concerning the spacer in the omega-amino or omega-guanidinoalkanoyl portion, the best activity was found in compounds with a four- or five-membered alklyl chain or a 1,4-cyclohexylene group, Surpris ingly, in contrast to the phenol series, in the imidazole series the compounds with a side chain amino group turned out to be considerably more potent than the corresponding strongly basic guanidines. Thus, the structure-activity relationships appear to be different for the diphenylalkylamide NPY antagonists with one or two basic groups.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BINDING; ARPROMIDINE; ANALOGS; CA-2+; neuropeptide Y; Y-1 receptor; NPY antagonists; HEL cells; calcium assay |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Mar 2023 09:08 |
| Last Modified: | 02 Mar 2023 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/50418 |
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