18956-87-1

Usage

Chemical Properties

Light green or yellow-brown crystalline powder

InChI:InChI=1/C21H28/c1-20(2,3)18-11-7-16(8-12-18)15-17-9-13-19(14-10-17)21(4,5)6/h7-14H,15H2,1-6H3

Upstream product

• 75-44-5 phosgene 
• 98546-66-8 2-ethanesulfonylmethyl-5-bromo-thiophene 
• 92-84-2 10H-phenothiazine 
• 32315-10-9 bis(trichloromethyl) carbonate 

Downstream Products

• 518-63-8 dimethoxanate hydrochloride 
• 20828-88-0 N,N-diethyl-10H-phenothiazine-10-carboxamide 
• 98546-66-8 2-ethanesulfonylmethyl-5-bromo-thiophene 
• 603-54-3 N,N-diphenylurea 
• 82-00-8 2-(N,N-diethylamino)ethyl phenothiazine carbamate 
• 92-84-2 10H-phenothiazine 
• 522-24-7 fenethazine 
• 58-40-2 promazine 
• 60-91-3 diethazine 
• 47205-14-1 chlorproethazine 
• 6631-94-3 2-acetylphenothiazine 
• 1041173-12-9 C₂₀H₁₅NO₃S 
• 1041173-13-0 C₁₉H₁₂ClNO₂S 
• 1041173-16-3 C₂₃H₂₁NO₂S 

Relevant academic research and scientific papers

Synthesis and Biological Evaluation of Celastrol Derivatives with Improved Cytotoxic Selectivity and Antitumor Activities

Cdc37 associates kinase clients to Hsp90 and promotes the development of cancers. Celastrol, a natural friedelane triterpenoid, can disrupt the Hsp90-Cdc37 interaction to provide antitumor effects. In this study, 31 new celastrol derivatives, 2a - 2d , 3a - 3g , and 4a - 4t , were designed and synthesized, and their Hsp90-Cdc37 disruption activities and antiproliferative activities against cancer cells were evaluated. Among these compounds, 4f , with the highest tumor cell selectivity (15.4-fold), potent Hsp90-Cdc37 disruption activity (IC50= 1.9 μM), and antiproliferative activity against MDA-MB-231 cells (IC50= 0.2 μM), was selected as the lead compound. Further studies demonstrated 4f has strong antitumor activities both in vitro and in vivo through disrupting the Hsp90-Cdc37 interaction and inhibiting angiogenesis. In addition, 4f exhibited less toxicity than celastrol and showed a good pharmacokinetics profile in vivo. These findings suggest that 4f may be a promising candidate for development of new cancer therapies.

N-heterocyclic (4-phenylpiperazin-1-yl)methanones derived from phenoxazine and phenothiazine as highly potent inhibitors of tubulin polymerization

We report here a series of 27 10-(4-phenylpiperazin-1-yl)methanones derived from tricyclic heterocycles which were screened for effects on tumor cell growth, inhibition of tubulin polymerization, and induction of cell cycle arrest. Several analogues, among them the 10-(4-(3-methoxyphenyl)piperazine-1-carbonyl)-10H-phenoxazine-3-carbonitrile (16o), showed excellent antiproliferative properties, with low nanomolar GI50 values (16o, mean GI50 of 3.3 nM) against a large number (93) of cancer cell lines. Fifteen compounds potently inhibited tubulin polymerization. Analysis of cell cycle by flow cytometry revealed that inhibition of tumor cell growth was related to an induction of G2/M phase cell cycle blockade. Western blotting and molecular docking studies suggested that these compounds bind efficiently to β-tubulin at the colchicine binding site. Our studies demonstrate the suitability of the phenoxazine and phenothiazine core and also of the phenylpiperazine moiety for the development of novel and potent tubulin polymerization inhibitors.