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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Synthesis, structure-activity relationship and biological evaluation of novel arylpiperzines as α1A/1D-AR
Fang Xu1, Hong Chen2, Jingyi Xu3
1Institute of Tumor Pharmacology, College of Pharmacy, Jinan University, 601 West Huangpu Blvd, Guangzhou 510632, People's Republic of China.
Abstract:
A series of novel arylpiperazine derivatives as α1A/1D-adrenergic receptors (AR) subtype selective antagonists were designed, synthesized and evaluated for their antagonistic activities towards α1-ARs (α1A, α1B, and α1D). Compounds 9, 12, 13, 15, 17, 18, 21, 22, 25 and 26 exerted strong antagonistic effects on α1A and/or α1D subtypes over α1B in vitro. SAR analysis indicated that chloride at the ortho-phenyl position for compound 17 was beneficial for the highest α1A/D-AR sub-selectivity. Moreover, molecular docking study of compound 17 with the homology-modeled α1-ARs (α1A, α1B, and α1D) structures exhibited differences of key amino resides in the docking pocket which may influence the subtype selectivity. ILE 193 of α1A was validated as the key residues for binding ligand. This work provides useful information for finding more new potential drugs in clinic in treating benign prostatic hyperplasia (BPH).
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