1621065-35-7

Upstream product

• 6380-23-0 3,4-dimethoxystyrene 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 7417-21-2 2-(3,4-dimethoxyphenyl)ethyl alcohol 
• 1694-92-4 2-Nitrobenzenesulfonyl chloride 
• 135276-88-9 N-(2-nitrophenylsulfonyl)-2-benzylsulfanyl-1,4,5,6-tetrahydropyrimidine 
• 135276-91-4 1,2,3,4-tetrahydropyrimido<1,2-c><1,2,4>benzothiadiazine 6,6-dioxide 
• 75803-23-5 methanesulphonic acid,2-(3,4-dimethoxyphenyl)ethyl ester 

Relevant academic research and scientific papers

Synthesis and Biological Evaluation of N-[2-(4-Hydroxyphenylamino)-pyridin-3-yl]-4-methoxy-benzenesulfonamide (ABT-751) Tricyclic Analogues as Antimitotic and Antivascular Agents with Potent in Vivo Antitumor Activity

Benzopyridothiadiazepine (2a) and benzopyridooxathiazepine (2b) were modified to produce tricyclic quinazolinone 15-18 or benzothiadiazine 26-27 derivatives. These compounds were evaluated in cytotoxicity and tubulin inhibition assays and led to potent inhibitors of tubulin polymerization. N-[2(4-Methoxyphenyl)ethyl]-1,2-dihydro-pyrimidino[2,1-b]quinazolin-6-one (16a) exhibited the best in vitro cytotoxic activity (GI50 10-66.9 nM) against the NCI 60 human tumor cell line and significant potency against tubulin assembly (IC50 0.812 μM). In mechanism studies, 16a was shown to block cell cycle in G2/M phase and to disrupt microtubule formation and displayed good antivascular properties as inhibition of cell migration, invasion, and endothelial tube formation. Compound 16a was evaluated in C57BL/6 mouse melanoma B16F10 xenograft model to validate its antitumor activity, in comparison with reference ABT-751 (1). Compound 16a displayed strong in vivo antitumor and antivascular activities at a dose of 5 mg/kg without obvious toxicity, whereas 1 needed a 10-fold higher concentration to reach similar effects.

Unexpected heteroannulation and chlorination of benzothiadiazine derivatives mediated by DDQ

In the course of studies directed toward the synthesis of new tubulin polymerization inhibitors, several benzothiadiazine derivatives were prepared. The oxidative dehydrogenation reaction with DDQ unexpectedly led to heteroannulation and chlorination of the benzothiadiazine tricycles. A rationale for their formation is proposed.