title: Synthesis and pharmacological evaluation of 1,1,3-substituted urea derivatives as potent TNF-alpha production inhibitors.
abstract: A three substituted urea derivative, SA13353 (compound 1a), exhibited potent inhibitory activity against lipopolysaccharide (LPS)-induced TNF-alpha production. We focused on the 1,1-substituted moiety (R(1) and R(2)) of SA13353 and investigated substituent effects of this moiety on LPS-induced TNF-alpha production by oral administration in rats. The synthesis of the urea derivatives was performed rapidly in a one-pot manner using a manual synthesizer. Several compounds containing hydrophobic substituents at this moiety showed more potent inhibitory activities than SA13353.
authors.affiliation: Nara Research & Development Center, Santen Pharmaceutical Co., Ltd, Ikoma, Nara, Japan. hiroshi.enomoto@santen.co.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Enomoto
authors.forename: Ayako
authors.initials: A
authors.lastname: Sawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suhara
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Chikako
authors.initials: C
authors.lastname: Setoguchi
authors.forename: Fumio
authors.initials: F
authors.lastname: Tsuji
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okamoto
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sasabuchi
authors.forename: Masato
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ban
mesh_terms: D000284:Administration, Oral; D000818:Animals; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013434:Sulfenic Acids / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C530925:1-(2-(1-adamantyl)ethyl)-1-pentyl-3-(3-(4-pyridyl)propyl)urea; D011725:Pyridines; D013434:Sulfenic Acids; D014409:Tumor Necrosis Factor-alpha; C001071:2,4-dinitrobenzenesulfenamide; D014508:Urea