Synthesis of both enantiomers of 1, 2, 3, 4-tetrahydroisoquinoline derivative IPPAM-1 and enantio-dependency of its positive allosteric modulation of prostacyclin receptor. Issue 11 (1st June 2017)

• Record Type: Journal Article
• Authors: Yamamoto, Kohki; Suzuki, Toshifumi; Imamura, Riyo; Nagano, Tetsuo; Okabe, Takayoshi; Miyachi, Hiroyuki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 11(2017)
• Page Start: 2567
• Page End: 2570
• Publication Date: 2017-06-01
• Subjects: Pulmonary arterial hypertension -- Prostacyclin -- Prostacyclin receptor -- Positive allosteric modulator -- Tetrazole derivative; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.03.083
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We present a practical synthesis of both enantiomers of 1, 2, 3, 4-tetrahydroisoquinoline derivative IPPAM-1 (1 ), which is a positive allosteric modulator (PAM) of prostacyclin receptor (IP) and a candidate for treatment of pulmonary arterial hypertension without the side effects caused by IP agonists. Assay of cAMP production by CHO-K1 cells stably expressing human IP clearly demonstrated that the IPPAM activity resides exclusively on the R-form of1 .