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• 6964-21-2 thiophen-3-yl-acetic acid 
• 120-20-7 2-(3,4-dimethoxyphenyl)-ethylamine 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of tetrahydroisoquinolines derivatives as novel, selective PDE4 inhibitors for antipsoriasis treatment

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.

STUDIES ON HETEROCYCLIC COMPOUNDS VI. Synthesis of Thiophene Isoesters of Protoberberine Alkaloids

Synthesis of thiophene isosters of protoberberine alkaloids (6, 12, 19) is described.The Mannich type reaction of the tetrahydroisoquinolines (5, 11) and the thienopyridine (18) with formaldehyde in glacial acetic acid afforded the title compounds.Cyclization of the tetrahydroisoquinoline derivative (23) failed to furnish the D-ring protoberberine isoster (25), but gave an unexpected product, the oxazepinoisoquinoline derivative (24).The conversion of the compound (24) to the 2-substituted isoquinoline (27) is also described.

Studies on Heterocyclic Compounds: Part II - Synthesis of Thiophene Isosters of Aporphine Alkaloids

Photosynthesis of N-carbethoxy-1,2-dimethoxy-4,5,6-trihydrobenzothienoquinoline (6a) and the 1-benzyloxy compound (6b), which are D-ring thiophene isosters of N-carbethoxy aporphine derivatives, is described.The synthetic sequence involves Bisc