Synthesis and pharmacological evaluation of 1,1,3-substituted urea derivatives as potent TNF-alpha production inhibitors.
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.
Enomoto
Hiroshi
H
Nara Research & Development Center, Santen Pharmaceutical Co., Ltd, Ikoma, Nara, Japan. hiroshi.enomoto@santen.co.jp
Sawa
Ayako
A
Suhara
Hiroshi
H
Yamamoto
Noriyoshi
N
Inoue
Hiroyuki
H
Setoguchi
Chikako
C
Tsuji
Fumio
F
Okamoto
Masahiro
M
Sasabuchi
Yoshimasa
Y
Horiuchi
Masato
M
Ban
Masakazu
M
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
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