51792-65-5

Upstream product

• 5460-32-2 1-iodo-3,4-dimethoxybenzene 
• 115-19-5 2-methyl-but-3-yn-2-ol 
• 91-16-7 1,2-dimethoxybenzene 
• 2859-78-1 4-Bromoveratrole 
• 33731-42-9 (3,4-dimethoxy-phenyl)-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methanone 

Downstream Products

• 4302-52-7 4-ethynylveratrole 
• 1446318-98-4 (E)-1,2-dimethoxy-4-(3-methylbuta-1,3-dien-1-yl)benzene 
• 1224625-37-9 4-(3,4-dimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole 
• 1222771-74-5 1,4-bis(3,4-dimethoxyphenyl)-1H-1,2,3-triazole 
• 4143-62-8 3',4'-dimethoxyflavone 
• 1322774-64-0 2-[3-(3,4-dimethoxyphenyl)propynoyl]phenol 
• 1322775-60-9 3-(3,4-dimethoxyphenyl)-1-(2-hydroxyphenyl)-2-propynol 

Relevant academic research and scientific papers

Anti-inflammatory, ulcerogenic and platelet activation evaluation of novel 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids

This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs 8–13 (L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non– ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids 8–13 (L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.

Design, synthesis, antileishmanial, and antifungal biological evaluation of novel 3,5-disubstituted isoxazole compounds based on 5-nitrofuran scaffolds

Nineteen 3,5-disubstituted-isoxazole analogs were synthesized based on nitrofuran scaffolds, by a [3 + 2] cycloaddition reaction between terminal acetylenes and 5-nitrofuran chloro-oxime. The compounds were obtained in moderate to very good yields (45–91%). The antileishmanial activity was assayed against the promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Alkylchlorinated compounds 14p–r were active on both the promastigote and amastigote forms, with emphasis on compound 14p, which showed strong activity against the amastigote form (IC50 = 0.6 μM and selectivity index [SI] = 5.2). In the alkyl series, compound 14o stands out with an IC50 = 8.5 μM and SI = 8.0 on the amastigote form. In the aromatic series, the most active compounds were those containing electron-donor groups, such as trimethoxy isoxazole 14g (IC50 = 1.2 μM and SI = 20.2); compound 14h, with IC50 = 7.0 μM and SI = 6.1; and compound 14j containing the 4-SCH3 group, with IC50 = 5.7 μM and SI = 10.2. In addition, the antifungal activity of 19 nitrofuran isoxazoles was evaluated against five strains of Candida (C. albicans, C. parapsilosis, C. krusei, C. tropicalis, and C. glabrata). Eleven isoxazole derivatives were active against C. parapsilosis, and compound 14o was found to be the most active (minimal inhibitory concentration [MIC] = 3.4 μM) for this strain. Compound 14p was active against all the strains tested, with an MIC = 17.5 μM for C. glabrata, lower than that of the fluconazole used as the reference drug.

One-pot synthesis of unsymmetrical 1,3-butadiyne derivatives and their application in the synthesis of unsymmetrical 2,5-diarylthiophenes

A one-pot protocol was developed for the synthesis of unsymmetrical 1,3-butadiynes. The procedure is based on two sequential reactions: deprotection of R–C≡C–C≡C– C(Me)2OH derivatives in a retro-Favorskii reaction to furnish a terminal 1,3-butadiyne compound, which reacted with aryl iod-ides in a Sonogashira-type cross-coupling reaction catalyzed by Pd(PPh3)4 and CuI, using TBAOH as activator and toluene as solvent under reflux for 10 min. We also studied in situ thiocycli-zation of 1,3-butadiynes, leading to unsymmetrical 2,5-diaryl-thiophenes. The principal features of this method are operational simplicity, good substrate scope, very fast reaction, and high yields.

Design, synthesis and antitrypanosomatid activities of 3,5-diaryl-isoxazole analogues based on neolignans veraguensin, grandisin and machilin G

Using bioisosterism as a medicinal chemistry tool, 16 3,5-diaryl-isoxazole analogues of the tetrahydrofuran neolignans veraguensin, grandisin and machilin G were synthesized via 1,3-dipolar cycloaddition reactions, with yields from 43% to 90%. Antitrypanosomatid activities were evaluated against Trypanosoma cruzi, Leishmania (L.) amazonensis and Leishmania (V.) braziliensis. All compounds were selective for the Leishmania genus and inactive against T.?cruzi. Isoxazole analogues showed a standard activity on both promastigotes of L.?amazonensis and L.?braziliensis. The most active compounds were 15, 16 and 19 with IC50 values of 2.0, 3.3 and 9.5?μM against L.?amazonensis and IC50 values of 1.2, 2.1 and 6.4?μM on L.?braziliensis, respectively. All compounds were noncytotoxic, showing lower cytotoxicity (>250?μM) than pentamidine (78.9?μM). Regarding the structure–activity relationship (SAR), the methylenedioxy group was essential to antileishmanial activity against promastigotes. Replacement of the tetrahydrofuran nucleus by an isoxazole core improved the antileishmanial activity.

One Pot Synthesis of γ-Benzopyranones via Iron-Catalyzed Aerobic Oxidation and Subsequent 4-Dimethylaminopyridine Catalyzed 6-endo Cyclization

One-pot synthesis of γ-benzopyranones was realized in decent yields and excellent regioselectivities via iron-catalyzed aerobic oxidation and 4-dimethylaminopyridine-catalyzed cyclization of related propargylic alcohols. Derivatizations to aromatic substituted γ-benzopyranones and synthesis of naturally occurring 3′,4′-dimethoxyflavone have also been realized. (Figure presented.).

Antileishmanial activity and structure-activity relationship of triazolic compounds derived from the neolignans grandisin, veraguensin, and machilin G

Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 μM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 μM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

Synthesis and Antitrypanosomastid Activity of 1,4-Diaryl-1,2,3-triazole Analogues of Neolignans Veraguensin, Grandisin and Machilin G

Sixteen 1,4-diaryl-1,2,3-triazole compounds derived from the natural products veraguensin, grandisin and machilin G were synthesized, with yields of 78-92percent. Biological activity tests against Leishmania amazonensis promastigotes showed that three of these compounds were the most active, with maximum inhibitory concentration (IC50 ) values of 1.1, 3.71 and 7.23 μM. One compound was highly active against Leishmania infantum, with an IC50 value of 5.2 μM, and one derivative showed an IC50 value of 28.6 μM against Trypanosoma cruzi trypomastigotes. Regarding structureactivity relationship (SAR), hybrid 1,2,3-triazolic compounds containing a methylenedioxy group, showed the best antileishmanial and antitrypanosomal activities.

Specific features of the chemical behavior of acetylenic derivatives of benzocrown ethers

4′-Ethynylbenzo-12-crown-4 (8), 4′-ethynylbenzo-15-crown-5 (9), and 4′-ethynylbenzo-18-crown-6 (10) were synthesized by cross-coupling of the corresponding aryl iodides 1-3 with 2-methylbut-3-yn-2-ol (4a) followed by the retro-Favorsky cleavage of the res