- Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents
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A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC50 value 1.58–5.02 μM. These derivatives presented 29.40–70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC50 1.58 μM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca2+-activated K+ (BKca) channel and the effect was endothelium-independent.
- Singh, Sarita,Agarwal, Karishma,Iqbal, Hina,Yadav, Pankaj,Yadav, Deepika,Chanda, Debabrata,Tandon, Sudeep,Khan, Feroz,Gupta, Anil Kumar,Gupta, Atul
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supporting information
(2019/11/26)
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- A One-Pot Synthesis of Pyranocoumarins Through Microwave-Promoted Propargyl Claisen Rearrangement/Wittig Olefination
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The reaction between propargyl ethers of hydroxybenzaldehydes and the ylide ethyl (triphenylphosphoranylidene)acetate was carried out under microwave irradiation to regioselectively afford angular pyranocoumarins. The chromene and coumarin heterocyclic scaffolds were simultaneously formed in the same synthetic step without changing the reaction conditions. The natural products seselin, braylin, and dipetalolactone were among the products synthesized by this method.
- Schmidt, Bernd,Schultze, Christiane
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p. 223 - 227
(2018/01/26)
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- Anti-AIDS agents. 37. Synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents
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To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3',4'-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3- 6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3',4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'- di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone showed EC50 and therapeutic index values of -5 μM and >2.15 x 106, respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2662 - 2672
(2007/10/03)
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- Anti-AIDS agents - XXVIII. Synthesis and anti-HIV activity of methoxy substitute 3',4'-di-O-(-)-Camphanoyl-(+)-cis-Khellactone (DCK) analogues
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Four isomeric methoxy substituted DCK analogues (3-6) were asymmetrically synthesized from different starting materials. 5-Methoxy-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (5) exhibited extremely potent anti-HIV activity against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of 0.00038 μM and >402,632, respectively, which are better than those of DCK and AZT in this assay.
- Takeuchi, Yasuo,Xie, Lan,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2573 - 2578
(2007/10/03)
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