title: The P1N-isopropyl motif bearing hydroxyethylene dipeptide isostere analogues of aliskiren are in vitro potent inhibitors of the human aspartyl protease renin.
abstract: Novel nonpeptide small molecule renin inhibitors bearing an N-isopropyl P(1) motif were designed based on initial lead structures 1 and aliskiren (2). (P(3)-P(1))-Benzamide derivatives such as 9a and 34, as well as the corresponding P(1) basic tertiary amine derivatives 10 and 35 were found to display low nanomolar inhibition against human renin in vitro.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan.
authors.forename: Yasuchika
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Keith
authors.initials: K
authors.lastname: Menear
authors.forename: Nissim-Claude
authors.initials: NC
authors.lastname: Cohen
authors.forename: Robert
authors.initials: R
authors.lastname: Mah
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cumin
authors.forename: Christian
authors.initials: C
authors.lastname: Schnell
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Wood
authors.forename: Jürgen
authors.initials: J
authors.lastname: Maibaum
mesh_terms: D000284:Administration, Oral; D000577:Amides / Q000737:chemistry*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002144:Callithrix; D005030:Ethylenes / Q000737:chemistry*; D005650:Fumarates / Q000737:chemistry*; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012083:Renin / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D001549:Benzamides; D005030:Ethylenes; D005650:Fumarates; D011480:Protease Inhibitors; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren; C067254:hydroxyethylene