Diphenylmethane skeleton as a multi-template for nuclear receptor ligands: Preparation of FXR and PPAR ligands

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 12; pp. 3213 - 3218
• Main Authors: Kainuma, Masahiko, Kasuga, Jun-ichi, Hosoda, Shinnosuke, Wakabayashi, Ken-ichi, Tanatani, Aya, Nagasawa, Kazuo, Miyachi, Hiroyuki, Makishima, Makoto, Hashimoto, Yuichi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.06.2006; Elsevier
• Subjects: Benzhydryl Compounds - chemical synthesis; Benzhydryl Compounds - chemistry; Benzhydryl Compounds - metabolism; Biological and medical sciences; Diphenylmethane; DNA-Binding Proteins - agonists; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug design; FXR; Humans; Ligands; Medical sciences; Miscellaneous; Molecular Structure; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nuclear receptor ligands; Pharmacology. Drug treatments; PPAR; PPAR alpha - agonists; PPAR alpha - metabolism; Receptors, Cytoplasmic and Nuclear; Transcription Factors - agonists; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - genetics; FXR; Diphenylmethane; Drug design; PPAR; Nuclear receptor ligands; Farnesoid X receptor; Agonist; Nuclear receptor; Ether; Ligand; In vitro; Biological activity; PPAR-α receptor; Carboxylic acid; Chemical synthesis; Peroxisome proliferator activated receptor; Biological receptor
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.03.075

Design and preparation of novel ligands for FXR, DPPF-01, and for PPARα, DPHK-01, were described. Novel, potent farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor α (PPARα) agonists were obtained by using a diphenylmethane skeleton as a substitute for a steroid skeleton.