127971-24-8Relevant articles and documents
Interplay between Conjugative and Steric Effects in Cyclopropylarenes
Drumright, R. E.,Mas, R. H.,Merola, J. S.,Tanko, J. M.
, p. 4098 - 4102 (1990)
The X-ray crystal structures of three cyclopropylarenes are reported.The data suggest that, for the series phenyl -> α-naphthyl -> 9-anthryl, increasing steric interactions force a distortion from the normally preferred bisected conformation to the perpendicular conformation.In the bisected conformation, orbital alignment between the aromatic ?-system and the cyclopropyl HOMO is maximal and electron donation from the cyclopropyl to the arene can be detected by an asymmetry in the lengths of the vicinal and distal C-C bonds of the cyclopropane ring.In the perpendicular conformation, the ?-system of the arene is orthogonal to the HOMO, but aligned with the LUMO of the cyclopropyl group.Consequently, the cyclopropyl group can only act as an electron acceptor.Within experimental error, there was no apparent asymmetry in the lenghts of the vicinal and distal C-C bonds, suggesting no significant electronic interaction between the arene and the cyclopropyl group in the perpendicular conformation.
Preparation method of 4-cyclopropyl-1-naphthylamine
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Paragraph 0019-0021; 0025-0026, (2019/07/16)
The invention relates to a novel preparation method of 4-cyclopropyl-1-naphthylamine. The raw materials needed for the preparation method are cheap in price and easy to obtain, the reaction step operation is simple, and the total yield is better than that of the prior art level. Moreover, the nitrification, hydrogenation reduction, Suzuki coupling and other reactions are avoided to use, and thus the production difficulty and production cost is greatly reduced. A relatively economical, efficient, safe and environment-friendly synthetic route is provided for the preparation of 4-cyclopropyl-1-naphthylamine.
Discovery of flexible naphthyltriazolylmethane-based thioacetic acids as highly active uric acid transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia of gout
Zhang, Xiansheng,Wu, Jingwei,Liu, Wei,Liu, Yuqiang,Xie, Yafei,Shang, Qian,Zhou, Zhixing,Xu, Weiren,Tang, Lida,Wang, Jianwu,Zhao, Guilong
, p. 260 - 281 (2017/05/31)
Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT1) was the promising therapeutic target for urate-lowering therapy. Objective: The goal of this work is to understand the structure-activity relationship (SAR) of a potent lesinurad-based hit, sodium 2-((5-bromo-4-((4-cyclopropyl-naphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1c), and based on that discover a more potent URAT1 inhibitor. Methods: The SAR of 1c was systematically explored and the in vitro URAT1 inhibitory activity of synthesized compounds 1a-1t was determined by the inhibition of URAT1-mediated [8-14C]uric acid uptake by human embryonic kidney 293 (HEK293) cells stably expressing human URAT1. Results: Twenty compounds 1a-1t were synthesized. SAR analysis was performed. Two highly active URAT1 inhibitors, sodium 2-((5-bromo-4-((4-n-propylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1j) and sodium 2-((5-bromo-4-((4-bromonaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1m), were identified, which were 78- and 76-fold more active than parent lesinurad in in vitro URAT1 inhibitory assay, respectively (IC50 values for 1j and 1m were 0.092 μM and 0.094 μM, respectively, against human URAT1 vs 7.18 μM for lesinurad). Conclusion: Two highly active URAT1 inhibitors were discovered. The SAR exploration also identified more flexible naphthyltriazolylmethane as a novel molecular skeleton that will be valuable for the design of URAT1 inhibitors, as indicated by the observation that many of the synthesized naphthyltriazolylmethane-bearing derivatives (1b-1d, 1g, 1j and 1m) showed significantly improved UART1 inhibitory activity (sub-micromolar IC50 values) as compared with lesinurad which has the rigid naphthyltriazole skeleton.
