47145-37-9Relevant academic research and scientific papers
Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment
Zhang, Rui,Li, Heng,Zhang, Xianglei,Li, Jian,Su, Haixia,Lu, Qiukai,Dong, Guangyu,Dou, Huixia,Fan, Chen,Gu, Zhanni,Mu, Qianwen,Tang, Wei,Xu, Yechun,Liu, Hong
supporting information, (2020/11/24)
Psoriasis is a kind of chronic inflammatory skin disorder, while the long-term use of conventional therapies for this disease are limited by severe adverse effects. Novel small molecules associated with new therapeutic mechanisms are greatly needed. It is known that phosphodiesterase 4 (PDE4) plays a central role in regulating inflammatory responses through hydrolyzing intracellular cyclic adenosine monophosphate (cAMP), making PDE4 to be an important target for the treatment of inflammatory diseases (e.g. psoriasis). In our previous work, we identified a series of novel PDE4 inhibitors with a tetrahydroisoquinoline scaffold through structure-based drug design, among which compound 1 showed moderate inhibition activity against PDE4. In this study, a series of novel tetrahydroisoquinoline derivatives were developed based on the crystal structure of PDE4D in complex with compound 1. Anti-inflammatory effects of these compounds were evaluated, and compound 36, with high safety, permeability and selectivity, exhibited significant inhibitory potency against the enzymatic activity of PDE4D and the TNF-α release from the LPS-stimulated RAW 264.7 and hPBMCs. Moreover, an in vivo study demonstrated that a topical administration of 36 achieved more significant efficacy than calcipotriol to improve the features of psoriasis-like skin inflammation. Overall, our study provides a basis for further development of tetrahydroisoquinoline-based PDE4 inhibitors against psoriasis.
Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route
Yang, Lu,Zhu, Jinmei,Sun, Chenghai,Deng, Zixin,Qu, Xudong
, p. 364 - 371 (2020/01/21)
Herein, we report a biocatalytic approach to synthesize plant tetrahydroisoquinoline alkaloids (THIQAs) from dihydroisoquinoline (DHIQ) precursors using imine reductases and N-methyltransferase (NMT). The imine reductase IR45 was engineered to significant
A highly enantioselective access to tetrahydroisoquinoline and β-carboline alkaloids with simple noyori-type catalysts in aqueous media
Evanno, Laurent,Ormala, Joel,Pihko, Petri M.
supporting information; experimental part, p. 12963 - 12967 (2010/06/16)
Silver enhancement: A very convenient modified protocol for the enantioselective transfer hydrogenation of dihydroisoquinoline skeletons under aqueous conditions is reported. Unmodified Noyori ligands can be used and the activity of the catalyst is greatly enhanced with silver additives (see scheme). The protocol was used in a very short synthesis of the alkaloids (S)-harmicine and (S)-crispine.
