title: 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-pyrrolidine-2-carboxamide: investigation of structural variations.
abstract: We recently reported a series of 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine-2-carboxamides as AT(1) receptor ligands. The most potent compound of the series, 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-pyrrolidine-2-carboxamide, showed an interesting affinity for the receptor. To investigate the influence of structure variations on affinity, the synthesis of additional compounds belonging to this series has been performed. Biological tests run on the newly synthesized compounds on CHO-hAT(1) cells stably expressing the human AT(1) receptor confirm our previous hypothesis, i.e. that, within this series, the length of the acyl chain, the substitution of the amidic group and the nature of the acidic one are crucial for the receptor interaction, being a valeric chain, a secondary amidic function and the tetrazole moiety, respectively, the optimal ones.
authors.affiliation: Department of Medicinal Chemistry, Università degli Studi di Bari "Aldo Moro", Bari, Italy. a.catalano@farmchim.uniba.it
authors.forename: Alessia
authors.initials: A
authors.lastname: Catalano
authors.forename: Alessia
authors.initials: A
authors.lastname: Carocci
authors.forename: Antonia
authors.initials: A
authors.lastname: Di Mola
authors.forename: Claudio
authors.initials: C
authors.lastname: Bruno
authors.forename: Patrick M L
authors.initials: PM
authors.lastname: Vanderheyden
authors.forename: Carlo
authors.initials: C
authors.lastname: Franchini
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008024:Ligands; D019808:Losartan / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011485:Protein Binding; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000737:chemistry
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D008024:Ligands; D019808:Losartan; D011759:Pyrrolidines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C571002:1-pentanoyl-N-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)pyrrolidine-2-carboxamide; C045574:1H-tetrazole; C010574:biphenyl