91795-77-6Relevant articles and documents
NOVEL ANTIPARASITIC COMPOUNDS AND METHODS
-
Page/Page column 92, (2021/04/23)
Novel compounds for treating or inhibiting leishmaniasis and other parasitic protozoan diseases are disclosed herein. The compounds bind to Leishmania tubulin, induce parasite microtubule polymerization, stall Leishmania cell division, and have broad antiparasitic activity.
Novel triazole-sulfonamide bearing pyrimidine moieties with carbonic anhydrase inhibitory action: Design, synthesis, computational and enzyme inhibition studies
Hoda, Nasimul,Manzoor, Shoaib,Petreni, Andrea,Raza, Md Kausar,Supuran, Claudiu T.
supporting information, (2021/07/16)
A series of new triazole-sulfonamide bearing pyrimidine derivatives were designed and synthesized via click chemistry. All new compounds (SH-1 to SH-28) were validated by 1HNMR, 13CNMR, HRMS, and SH-3 was further structurally validated by X-Ray single diffraction study. These compounds (SH-1 to SH-28) were tested as inhibitors of human carbonic anhydrase (hCA) isoforms, such as hCA I, II, IX and XII, using a stopped flow CO2 hydrase assay. Most of the compounds exhibited significant inhibitory activity against hCA II and weak inhibitory activity against hCA I. The target compounds also displayed moderate to excellent inhibitory activity against tumor-related hCAs IX and XII. Some compounds, e.g., SH-20 (Ki = 9.4 nM), SH-26 (Ki = 1.8 nM) and SH-28 (Ki = 0.82 nM) exhibited excellent inhibitory activity and selectivity profile against hCAs XII over IX. SH-23 displayed promising inhibitory activity and selectivity profile against both tumor-related hCAs IX (Ki = 2.9 nM) as well as XII (Ki = 0.82 nM) over hCA I and II. To understand the molecular interactions, molecular docking study of compounds SH-20, SH-23, SH-26 and SH-28 with hCA XII and SH-23 also with hCA IX were performed. The computational study evidenced favorable interaction between the inhibitors and active residues of both proteins. Some of these derivatives are promising leads for the development of selective, anticancer agents based on CA inhibitors.
Design, synthesis, and acaricidal activity of phenyl methoxyacrylates containing 2-alkenylthiopyrimidine
Hao, Shulin,Cai, Zengfei,Cao, Yangyang,Du, Xiaohua
, (2020/09/16)
A series of novel phenyl methoxyacrylate derivatives containing a 2-alkenylthiopyrimidine substructure were designed, synthesized, and evaluated in terms of acaricidal activity. The structures of the title compounds were identified by 1H NMR, 13C NMR and high-resolution mass spectra (HRMS). Compound (E)-methyl 2-(2-((2-(3,3-dichloroallylthio)-6-(trifluoromethyl)pyrimidin-4-yloxy) methyl)phenyl)-3-methoxyacr-ylate (4j) exhibited significant acaricidal activity against Tetranychus cinnabarinus (T. cinnabarinus) in greenhouse tests possessing nearly twice the larvicidal and ovicidal activity compared to fluacrypyrim. Furthermore, the results of the field trials demonstrated that compound 4j could effectively control Panonychuscitri with long-lasting persistence and rapid action. The toxicology data in terms of LD50 value confirmed that compound 4j has a relatively low acute toxicity to mammals, birds, and honeybees.
SMALL MOLECULE INHIBITORS OF NF-kB INDUCING KINASE
-
Page/Page column 211, (2020/12/11)
The present invention relates to compounds that inhibit NIK and pharmaceutical compositions comprising such compounds and methods of using the same. These compounds and pharmaceutical compositions are envisaged to be useful for preventing or treating diseases such as cancer (such as B-cell malignancies including leukemias, lymphomas and myeloma), inflammatory disorders, autoimmune disorders, immunodermatologic disorders such as palmoplantar pustulosis and hidradenitis suppurativa, and metabolic disorders such as obesity and diabetes.
Synthesis, biological and molecular dynamics investigations with a series of triazolopyrimidine/triazole-based benzenesulfonamides as novel carbonic anhydrase inhibitors
Said, Mohamed A.,Eldehna, Wagdy M.,Nocentini, Alessio,Bonardi, Alessandro,Fahim, Samar H.,Bua, Silvia,Soliman, Dalia H.,Abdel-Aziz, Hatem A.,Gratteri, Paola,Abou-Seri, Sahar M.,Supuran, Claudiu T.
, (2019/11/26)
In the presented work, we report the design and synthesis of different new sets of triazolopyrimidine-based (9a-d) and triazole-based (11a-h, 13a-c, 15a,b, 17a,b and 21a-g) benzenesulfonamides. The newly synthesized sulfonamides were assessed for their inhibitory activities toward four human (h) metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms; hCA I, II, IX and XII. The four examined isoforms were inhibited by the prepared sulfonamides (9a-d, 11a-h, 13a-c, 15a,b, 17a,b and 21a-g) in variable degrees with KIs ranges: 94.4–4953.5 nM for hCA I, 6.9–837.6 nM for hCA II, 3.3–85.0 nM for hCA XI, and 4.4–105.0 nM for hCA XII. In particular, sulfonamides 11e, 21a and 21e emerged as single-digit nanomolar hCA IX and hCA XII inhibitors. Interestingly, triazolopyrimidine-based sulfonamide 9d and triazole-based sulfonamide 21e were found to be the most selective hCA IX inhibitors over hCA I (SI = 100.85 and 210.58, respectively) and hCA II (SI = 18.54 and 38.36, respectively). Thereafter, sulfonamides 9d and 21e were docked into the active site of CAs II, IX and XII, then poses showing the best scoring values and favorable binding interactions were subjected to a MM-GBSA based refinement and, limited to CA IX and XII, to a cycle of 100 ns molecular dynamics.
NOVEL SCAFFOLD OF ADENYLYL CYCLASE INHIBITORS FOR CHRONIC PAIN AND OPIOID DEPENDENCE
-
Paragraph 0152, (2019/02/05)
The present invention relates to a method of treatment for chronic pain, opioid dependence, alcohol use disorder or autism using a class of pyrimidinone compounds, an adenylyl cyclase 1 (AC1) inhibitor. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases in mammals using those compounds disclosed herein.
Synthesis and Growth Stimulant Properties of 2-Acetyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one Derivatives
Pivazyan, Vergush A.,Ghazaryan, Emma A.,Shainova, Roza S.,Tamazyan, Rafael A.,Ayvazyan, Armen G.,Yengoyan, Aleksandr P.
, (2017/02/10)
A convenient, accessible, and high yield method for preparing of 6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (1) by treatment of acetoacetic acid ethyl ester with thiourea in sodium methylate was developed. The alkylation of the latter with 3-chloro-pentane-2,4-dione and further regioselective cyclization of intermediate compound (2) in high yield afforded 2-acetyl-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5-one (3). The halogenation and some transformations of synthesized thiazolo[3,2-a]pyrimidine (3) due to its ketone group were carried out to obtain the corresponding carboxamide, carbothioamide, sulfonohydrazide, and oxime and its alkylated derivatives (5). At preliminary biological studies the synthesized compounds have shown growth stimulant properties. The activity of four of them was higher than 70%, compared with heteroauxin.
Laccase-catalyzed green synthesis and cytotoxic activity of novel pyrimidobenzothiazoles and catechol thioethers
Abdel-Mohsen,Conrad,Harms,Nohr,Beifuss
, p. 17427 - 17441 (2017/03/31)
The laccase-catalyzed reaction between unsubstituted catechol and 2-thioxopyrimidin-4(1H)-ones using aerial O2 as the oxidant delivers novel pyrimidobenzothiazoles with high yields in an aqueous solvent system under mild reaction conditions. With 4-substituted catechols, catechol thioethers are formed exclusively. The synthetic protocols developed provide a sustainable approach for these compound classes. In addition, the cytotoxicity of the products against HepG2 cell line is reported. Most compounds exhibit antiproliferative activities with IC50 values at the micromolar level. A structure-activity relationship study will facilitate the further development of these compounds as cytotoxic agents.
Synthesis and biological evaluation of DAPY-DPEs hybrids as non-nucleoside inhibitors of HIV-1 reverse transcriptase
Wu, Hai-Qiu,Yao, Jin,He, Qiu-Qin,Chen, Wen-Xue,Chen, Fen-Er,Pannecouque, Christophe,De Clercq, Erik,Daelemans, Dirk
, p. 624 - 631 (2015/01/30)
A series of new DAPY-DPEs hybrids, combined the important pharmacophores of DAPYs and DPEs, has been synthesized and biologically evaluated for their anti-HIV activities against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 and HIV-2 strain ROD in MT-4 cell cultures. Many promising candidates with potent inhibitory activity (wild-type) within the EC50 range from 0.16 to 0.013 μM were obtained. In particular, 3c, 3p, 3r and 3s displayed low nM level EC50 values (35, 13, 50 and 17 nM, respectively) and high selectivity (9342, 25131, 2890 and 11338, respectively), which were much more potent than NVP (EC50 = 0.31 μM, SI = 48), 3TC (EC50 = 2.24 μM, SI > 39), DDI (EC50 = 23.20 μM, SI > 9) and DLV (EC50 = 0.65 μM, SI > 67), and comparable to AZT (EC50 = 0.0071 μM, SI > 13144) and EFV (EC50 = 0.0062 μM, SI > 1014). The HIV-1 reverse transcriptase inhibitory assay confirmed that these DAPY-DPEs hybrids targeted HIV-1 RT. Molecular simulation was performed to investigate the potential binding mode of the newly synthesized compounds. And reasonable explanation for the activity results was discussed with docking method.
Synthesis of pyridinylketones, and their cyclic derivatives produced from 6-methyl-2-thiouracil
Yavolovskii,Grishchuk,Rakipov,Ivanov,Stepanov,Kamalov
experimental part, p. 725 - 728 (2012/10/07)
A possibility to obtain pyrimidines, containing oxoalkyl moiety in 2 position of the ring from the available 6-methyl-2-thiouracil was shown.
