16502-01-5Relevant articles and documents
An insight into tetrahydro-β-carboline-tetrazole hybrids: Synthesis and bioevaluation as potent antileishmanial agents
Purohit, Pooja,Pandey, Anand Kumar,Singh, Deepti,Chouhan, Pradeep Singh,Ramalingam, Karthik,Shukla, Mahendra,Goyal, Neena,Lal, Jawahar,Chauhan, Prem M. S.
, p. 1824 - 1834 (2017)
A series of 2,3,4,9-tetrahydro-β-carboline tetrazole derivatives (14a-u) have been synthesized utilizing the Ugi multicomponent reaction and were identified as potential antileishmanial chemotypes. Most of the screened derivatives exhibited significant in vitro activity against the promastigote (IC50 from 0.59 ± 0.35 to 31 ± 1.27 μM) and intracellular amastigote forms (IC50 from 1.57 ± 0.12 to 17.6 ± 0.2 μM) of L. donovani, and their activity is comparable with standard drugs miltefosine and sodium stibogluconate. The most active compound 14t was further studied in vivo against the L. donovani/golden hamster model at a dose of 50 mg kg-1 through the intraperitoneal route for 5 consecutive days, which displayed 75.04 ± 7.28% inhibition of splenic parasite burden. Pharmacokinetics of compound 14t was studied in the golden Syrian hamster, and following a 50 mg kg-1 oral dose, the compound was detected in hamster serum for up to 24 h. It exhibited a large volume of distribution (651.8 L kg-1), high clearance (43.2 L h-1 kg-1) and long mean residence time (10 h).
Synthesis of C-14-labeled novel IKK inhibitor: 2-[14C]-N-(6- chloro-9H-pyrido [3,4-b]indol-8-yl)-3-pyridinecarboxamide
Li, Yuexian,Prakash, Shimoga R.
, p. 323 - 330 (2005)
2-[14C]-N-(6-Chloro-9H-pyrido [3,4-b]indol-8-yl)-3- pyridinecarboxamide (9A, also referred to as [14C]-PS-1145) was synthesized from [14C]-paraformaldehyde in five steps in an overall radiochemical yield of 15%. The key intermediate 1-[14C]-6-chloro-1, 2,3,4-tetrahydro-β-carboline was obtained by Pictet-Spengler cyclization of chlorotryptamine with [14C]-paraformaldehyde. Similar reactions were conducted with tryptamine to address the generality of the methodology. Copyright
Visible-Light-Mediated Synthesis of Rutaecarpine Alkaloids through C-N Cross-Coupling Reaction
Chen, Dong,Li, Shiqing,Wang, Jinhua,Gou, Tiantian,Zhang, Linfeng,Wang, Guixia,Kong, Xiangfei
, p. 987 - 992 (2021)
A visible-light-initiated cross-dehydrogenative-coupling amination is described, featuring metal- and photocatalyst-free, at room temperature, and using air as an oxidant. The reaction provides a facile approach for the synthesis of rutaecarpine and its derivatives. The substrates with electron-withdrawing groups give higher yields than those with electron-donating groups, but the substituent position has a negligible influence on the yield. Using binaphthyl-diyl hydrogen phosphate and dibenzyl phosphate as catalysts both deliver satisfying yields. This straightforward light-driven strategy might be applicable to the synthesis of quinazolinone derivatives.
Using Methanol as a Formaldehyde Surrogate for Sustainable Synthesis of N-Heterocycles via Manganese-Catalyzed Dehydrogenative Cyclization
Li, Yibiao,Liu, Qiang,Shao, Zhihui,Yuan, Shanshan
supporting information, (2022/02/23)
The development of an efficient and sustainable synthetic route for formaldehyde production from renewable feedstock, especially in combination with a subsequent transformation to straightforwardly construct valuable chemicals, is highly desirable. Herein, we report a novel manganese-catalyzed dehydrogenative cyclization of methanol as a formaldehyde surrogate with a variety of dinucleophiles for facile synthesis of N-heterocycles. The in situ generated formaldehyde via catalytic methanol dehydrogenation can be selectively trapped by diverse dinucleophiles to avoid several possible side reactions. The utility of this transformation is further highlighted by its successful application to the synthesis of 13C-labeled N-heterocycles using 13CH3OH as a readily accessible 13C-isotope reagent.
Structural simplification of evodiamine: Discovery of novel tetrahydro-β-carboline derivatives as potent antitumor agents
Ma, Zonglin,Huang, Yahui,Wan, Kun,Zhu, Fugui,Sheng, Chunquan,Chen, Shuqiang,Liu, Dan,Dong, Guoqiang
, (2021/04/02)
Natural products (NPs) have played a crucial role in the discovery and development of antitumor drugs. However, the high structural complexity of NPs generally results in unfavorable physicochemical profiles and poor drug-likeness. A powerful strategy to tackle this obstacle is the structural simplification of NPs by truncating nonessential structures. Herein, a series of tetrahydro-β-carboline derivatives were designed by elimination of the D ring of NP evodiamine. Structure-activity relationship studies led to the discovery of compound 45, which displayed highly potent antitumor activity against all the tested cancer cell lines and excellent in vivo antitumor activity in the HCT116 xenograft model with low toxicity. Further mechanistic research indicated that compound 45 acted by dual Top1/2 inhibition and induced caspase-dependent cell apoptosis coupled with G2/M cell cycle arrest. This proof-of-concept study validated the effectiveness of structural simplification in NP-based drug development, discovered compound 45 as a potent antitumor lead compound and enriched the structure–activity relationships of evodiamine.
