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Peripheral Selective Oxadiazolylphenyl Alanine Derivatives as Tryptophan Hydroxylase 1 Inhibitors for Obesity and Fatty Liver Disease.
Bae, Eun Jung; Choi, Won Gun; Pagire, Haushabhau S; Pagire, Suvarna H; Parameswaran, Saravanan; Choi, Jun-Ho; Yoon, Jihyeon; Choi, Won-Il; Lee, Ji Hun; Song, Jin Sook; Bae, Myung Ae; Kim, Mijin; Jeon, Jae-Han; Lee, In-Kyu; Kim, Hail; Ahn, Jin Hee.
Afiliación
  • Bae EJ; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Choi WG; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
  • Pagire HS; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Pagire SH; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Parameswaran S; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Choi JH; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Yoon J; Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea.
  • Choi WI; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
  • Lee JH; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • Song JS; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • Bae MA; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
  • Kim M; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Republic of Korea.
  • Jeon JH; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Republic of Korea.
  • Lee IK; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
  • Kim H; Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41404, Republic of Korea.
  • Ahn JH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
J Med Chem ; 64(2): 1037-1053, 2021 01 28.
Article en En | MEDLINE | ID: mdl-33417443
Tryptophan hydroxylase 1 (TPH1) has been recently suggested as a promising therapeutic target for treating obesity and fatty liver disease. A new series of 1,2,4-oxadiazolylphenyl alanine derivatives were identified as TPH1 inhibitors. Among them, compound 23a was the most active in vitro, with an IC50 (half-maximal inhibitory concentration) value of 42 nM, showed good liver microsomal stability, and showed no significant inhibition of CYP and hERG. Compound 23a inhibited TPH1 in the peripheral tissue with limited BBB penetration. In high-fat diet-fed mice, 23a reduced body weight gain, body fat, and hepatic lipid accumulation. Also, 23a improved glucose intolerance and energy expenditure. Taken together, compound 23a shows promise as a therapeutic agent for the treatment of obesity and fatty liver diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triptófano Hidroxilasa / Fármacos Antiobesidad / Alanina / Hígado Graso Límite: Animals / Humans Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triptófano Hidroxilasa / Fármacos Antiobesidad / Alanina / Hígado Graso Límite: Animals / Humans Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos