Day: November 21, 2022

Drapier, Thomas published the artcileEnhancing Action of Positive Allosteric Modulators through the Design of Dimeric Compounds, Safety of 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, the publication is Journal of Medicinal Chemistry (2018), 61(12), 5279-5291, database is CAplus and MEDLINE.

The present study describes the identification of highly potent dimeric 1,2,4-benzothiadiazine 1,1-dioxide (BTD)-type pos. allosteric modulators of the AMPA receptors (AMPApams) obtained by linking two monomeric BTD scaffolds through their resp. 6-positions. Using previous X-ray data from monomeric BTDs cocrystd. with the GluA2 ligand-binding domain (LBD), a mol. modeling approach was performed to predict the preferred dimeric combinations. Two 6,6-ethylene-linked dimeric BTD compounds (16 and 22) were prepared and evaluated as AMPApams on HEK293 cells expressing GluA2_o(Q) (calcium flux experiment). These compounds were found to be about 10,000 times more potent than their resp. monomers, the most active dimeric compound being the bis-4-cyclopropyl-substituted compound 22 [6,6′-(ethane-1,2-diyl)bis(4-cyclopropyl-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide], with an EC₅₀ value of 1.4 nM. As a proof of concept, the bis-4-methyl-substituted dimeric compound 16 (EC₅₀ = 13 nM) was successfully cocrystd. with the GluA2_o-LBD and was found to occupy the two BTD binding sites at the LBD dimer interface.

Journal of Medicinal Chemistry published new progress about 1204572-55-3. 1204572-55-3 belongs to thiazole, auxiliary class Neuronal Signaling,GluR, name is 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide, and the molecular formula is C10H11FN2O2S, Safety of 4-Cyclopropyl-7-fluoro-3,4-dihydro-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Campos, Ludmila E. published the artcileSearching new structural scaffolds for BRAF inhibitors. An integrative study using theoretical and experimental techniques, COA of Formula: C6H8N2O2S, the publication is Bioorganic Chemistry (2019), 103125, database is CAplus and MEDLINE.

The identification of the V600E activating mutation in the protein kinase BRAF in around 50% of melanoma patients has driven the development of highly potent small inhibitors (BRAFi) of the mutated protein. To date, Dabrafenib and Vemurafenib, two specific BRAFi, have been clin. approved for the treatment of metastatic melanoma. Unfortunately, after the initial response, tumors become resistant and patients develop a progressive and lethal disease, making imperative the development of new therapeutic options. The main objective of this work was to find new BRAF inhibitors with different structural scaffolds than those of the known inhibitors. Our study was carried out in different stages; in the first step we performed a virtual screening that allowed us to identify potential new inhibitors. In the second step, we synthesized and tested the inhibitory activity of the novel compounds founded. Finally, we conducted a mol. modeling study that allowed us to understand interactions at the mol. level that stabilize the formation of the different mol. complexes. Our theor. and exptl. study allowed the identification of four new structural scaffolds, which could be used as starting structures for the design and development of new inhibitors of BRAF. Our exptl. data indicate that the most active compounds reduced significantly ERK1/2 phosphorylation, a measure of BRAF inhibition, and cell viability. Thus, from our theor. and exptl. results, we propose new substituted hydroxynaphthalenecarboxamides, N-(hetero)aryl-piperazinylhydroxyalkylphenylcarbamates, substituted piperazinylethanols and substituted piperazinylpropandiols as initial structures for the development of new inhibitors for BRAF. Moreover, by performing QTAIM anal., we are able to describe in detail the mol. interactions that stabilize the different Ligand-Receptor complexes. Such anal. indicates which portion of the different mols. must be changed in order to obtain an increase in the binding affinity of these new ligands.

Bioorganic Chemistry published new progress about 64987-16-2. 64987-16-2 belongs to thiazole, auxiliary class Thiazole,Amine,Ester, name is Methyl 2-(2-aminothiazol-4-yl)acetate, and the molecular formula is C6H8N2O2S, COA of Formula: C6H8N2O2S.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Moloney, Gerard P. published the artcileSynthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT_1B receptor, Recommanded Product: 2-(4-Aminophenyl)-6-methylbenzothiazole, the publication is European Journal of Medicinal Chemistry (2004), 39(4), 305-321, database is CAplus and MEDLINE.

The synthesis and vascular 5-HT_1B receptor activity of a novel series of substituted 3-amido phenylpiperazine and 4-(4-methyl-1-piperazinyl)-1-benzo[b]thiophene derivatives is described. Modifications to the amido linked sidechains of the 3-amidophenyl piperazine derivatives and to the 2-side-chain of the 1-benzo[b]thiophene derivatives have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT_1B receptor of pK_B > 7.0. From the 3-amidophenyl-piperazine series, N-[5-(4-chlorophenyl)-2-thiazolyl]-3-(4-methyl-1-piperazinyl)benzamide (I) and from the benzo[b]thiophene-4-piperazine series N-(2-ethylphenyl)-4-(4-methyl-1-piperazinyl)benzo[b]thiophene-2-carboxamide (II) were identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT_1B receptor mediated agonist activity in the rabbit femoral artery) and competitive vascular 5-HT_1B receptor antagonist. The affinity of compounds from these two series of compounds for the vascular 5-HT_1B receptor is discussed as well as a proposed mode of binding to the receptor pharmacophore.

European Journal of Medicinal Chemistry published new progress about 92-36-4. 92-36-4 belongs to thiazole, auxiliary class Organic Pigment, name is 2-(4-Aminophenyl)-6-methylbenzothiazole, and the molecular formula is C14H12N2S, Recommanded Product: 2-(4-Aminophenyl)-6-methylbenzothiazole.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

He, Wei-Bao published the artcileVisible-light-initiated malic acid-promoted cascade coupling/cyclization of aromatic amines and KSCN to 2-aminobenzothiazoles without photocatalyst, Quality Control of 95-24-9, the publication is Chinese Chemical Letters (2020), 31(7), 1895-1898, database is CAplus.

By using ambient air as the oxidant and malic acid as the promoter, a practical method for the preparation of 2-aminobenzothiazoles through visible-light-initiated cascade reaction of aromatic amines and KSCN in eco-friendly bis(methoxypropy)ether under metal-, hazardous additive-, photocatalyst-free conditions was established.

Chinese Chemical Letters published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C7H5ClN2S, Quality Control of 95-24-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Chanon, Michel published the artcileAlkylation reactions of thiazoles. II. Comparative study of the pK(sub a) values of various 2-(methylthio)thiazoles and of their kinetic constants in the reaction with methyl iodide, Product Details of C4H5NS2, the publication is Bulletin de la Societe Chimique de France (1968), 2885-9, database is CAplus.

The 4- (I) and 5-di-Me derivatives (II) of 2-(methylthio)thiazole were treated with MeI in Me2CO at 20, 25, and 30° and the reaction site, order of reaction, and the magnitude of activation determined The pKa values of the bases were measured. The pKa values were lowered by the influence of the methylthio group; the protonation reaction on N was less sensitive to steric effects than acylation; the methylthio group withdrew the electrons in the thiazole ring and sterically hindered the reaction site; and the Me substituent increased the rate constants

Bulletin de la Societe Chimique de France published new progress about 5053-24-7. 5053-24-7 belongs to thiazole, auxiliary class Thiazole,sulfides, name is 2-(Methylthio)thiazole, and the molecular formula is C4H5NS2, Product Details of C4H5NS2.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

HajKacem, Sihem published the artcileBioreactor Membranes for Laccase Immobilization Optimized by Ionic Liquids and Crosslinking Agents, Category: thiazole, the publication is Applied Biochemistry and Biotechnology (2020), 190(1), 1-17, database is CAplus and MEDLINE.

A novel concept of membrane bioreactor based on polymeric ionic liquids laccase membrane has been implemented in batch process for decolorization of the anthraquinonic dye Remazol Brillant Blue R (RBBR). New laccase immobilization strategy has been optimized by casting the enzyme into a polymeric inclusion membrane (PIM) using ionic liquids (ILs) and polyvinyl chloride (PVC) leading to laccase polymeric IL membrane (PILM). Four different ILs (1-octyl-3-metylimidazolium bis(trifluoromethylsulfonyl)imide, [OMIM][NTF₂]; cholinium bis(trifluoromethylsulfonyl)imide, [Ch ol][NTF₂]; cholinium dihydrogenphosphate, [Chol][H₂PO₄] and hydroxyethylammonium formate, [HEA][Fo]) have been screened and mixed to constitute the active phase of the support of PIM. This strategy has been fully succeeded since high laccase immobilization rates were recorded (about 98%) when using the optimal mixture containing three ILs (45% [OMIM][NTf₂]/5% [Chol][NTf₂]/2.5% [HEA][Fo]) and supplemented by 0.5% glutaraldehyde. It was found that such mixture contributes to increase the stability and reusability of laccase-PILM during eight successive assays in a batch discontinued stirred reactor. Decolorization rate of 75% has been reached in the batch decolorization process of RBBR with high reusability yield.

Applied Biochemistry and Biotechnology published new progress about 30931-67-0. 30931-67-0 belongs to thiazole, auxiliary class Salt,Hydrazine,Amine,Benzothiazole, name is Ammonium 2,2′-(hydrazine-1,2-diylidene)bis(3-ethyl-2,3-dihydrobenzo[d]thiazole-6-sulfonate), and the molecular formula is C18H24N6O6S4, Category: thiazole.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Li, Jun published the artcileComparison of fruit quality and characteristics at different growth stages of kumquat from Rongan, Recommanded Product: Ammonium 2,2′-(hydrazine-1,2-diylidene)bis(3-ethyl-2,3-dihydrobenzo[d]thiazole-6-sulfonate), the publication is Xiandai Shipin Keji (2021), 37(2), 138-146, database is CAplus.

A study on the dynamic change of the physicochem. properties and the active ingredients of kumquat fruits at different growth stages was carried out with Guangxi Rongan specialty Fortunella margarita (Lour.) ′Youpi′ (YP) and Fortunella margarita (Lour.) ′Cuipi′ (CP). The results showed that from Sept. to Dec., the phys. and chem. indexes such as single fruit weight, juice yield, pH value, soluble solids, and sugar-acid ratio of kumquat increased, and the fruit seed rate and titratable acid content decreased. The main sugar content rose from 39.04 and 32.38 mg/g to 111.23 and 137.11 mg/g, resp. The main organic acids were ascorbic acid, malic acid and oxalic acid, and the ascorbic acid content increased first and then decreased. In Oct., kumquat ascorbic acid content peaked (48.23 and 23.20 mg/g, resp.). While malic acid and oxalic acid contents continued to decline. Compared with Sept., the total flavonoid contents of YP and CP kumquat decreased from 3.45 and 2.14 mg RE/g to 1.21 and 0.76 mg RE/g resp. in Dec., in which the characteristic flavonoid fortunellin content increased significantly. The total phenol content and antioxidant activity decreased significantly. Between the two varieties, there were no significant differences in mature single fruit weight, titratable acid, TFs, and hesperidin content, and the fruit seed rate, ascorbic acid, fortunellin, TPs content, and total antioxidant capacity of YP were significantly higher than those of CP. While the juice yield, fruit juice pH, soluble solids, sugar-acid ratio, fructose, glucose, sucrose, malic acid, oxalic acid, and rutin content of YP were significantly lower than those of CP. This study clarifies the fruit quality characteristics of the two kinds of kumquat at different growth stages and provides a theor. basis for the development and utilization of kumquat fruit.

Xiandai Shipin Keji published new progress about 30931-67-0. 30931-67-0 belongs to thiazole, auxiliary class Salt,Hydrazine,Amine,Benzothiazole, name is Ammonium 2,2′-(hydrazine-1,2-diylidene)bis(3-ethyl-2,3-dihydrobenzo[d]thiazole-6-sulfonate), and the molecular formula is C18H24N6O6S4, Recommanded Product: Ammonium 2,2′-(hydrazine-1,2-diylidene)bis(3-ethyl-2,3-dihydrobenzo[d]thiazole-6-sulfonate).

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Li, Yudong published the artcileProton Transfer Can Govern Regioselectivity Assisted by Iron Catalysis, Application of 5-Chlorobenzo[c][1,2,5]thiadiazol-4-amine, the publication is iScience (2020), 23(6), 101214, database is CAplus and MEDLINE.

Ortho-selective aromatic C-H functionalization is frequently used in organic synthesis and chem./pharmaceutical industries. However, this reaction relies heavily on the use of directing groups suffering from limited substrate scope and extra steps to put on and remove the directing/protecting groups. Herein authors present the previously neglected concept that enables good to nearly complete selective ortho position. Proton transfer was utilized to tune the electron d. on the aryl ring and determine the positional selectivity of electrophilic substitution. Consistently with deuteration experiments and DFT studies, this work demonstrates that acid-promoted proton transfer directs accelerated ortho-selective halogenation of NH/OH contained aromatic amines/phenols with excellent selectivity (>40 examples; up to 98:2 ortho/para selectivity). The application potential of this Fe-catalyzed method is demonstrated by the convenient synthesis of three alkaloids and tizanidine. This report raises the possibility that proton transfer could serve as the basis of developing new selective C-H functionalization reactions.

iScience published new progress about 30536-19-7. 30536-19-7 belongs to thiazole, auxiliary class Other Aromatic Heterocyclic,Chloride,Amine, name is 5-Chlorobenzo[c][1,2,5]thiadiazol-4-amine, and the molecular formula is C6H4ClN3S, Application of 5-Chlorobenzo[c][1,2,5]thiadiazol-4-amine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Marcantonio, Karen M. published the artcileA practical preparation of 5-(ketoaryl)thiazoles, Synthetic Route of 5053-24-7, the publication is Tetrahedron Letters (2002), 43(49), 8845-8848, database is CAplus.

This article describes a facile synthesis of 2-substituted-5-(ketoaryl)thiazoles, which are important intermediates for the synthesis of biol. active compounds A variety of 2-substituted thiazole anions were added to aryl nitriles to provide the desired ketones after aqueous hydrolysis.

Tetrahedron Letters published new progress about 5053-24-7. 5053-24-7 belongs to thiazole, auxiliary class Thiazole,sulfides, name is 2-(Methylthio)thiazole, and the molecular formula is C4H5NS2, Synthetic Route of 5053-24-7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica

Hoveyda, Hamid R. published the artcileOptimization of Novel Antagonists to the Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part II), Name: 3-Methyl-1,2,4-thiadiazole-5-carbohydrazide, the publication is ACS Medicinal Chemistry Letters (2015), 6(7), 736-740, database is CAplus and MEDLINE.

Further lead optimization on N-acyl-triazolopiperazine antagonists to the neurokinin-3 receptor (NK₃R) based on the concurrent improvement in bioactivity and ligand lipophilic efficiency (LLE) is reported. Overall, compound I (LLE > 6) emerged as the most efficacious in castrated rat and monkey to lower plasma LH, and it displayed the best off-target safety profile that led to its clin. candidate nomination for the treatment of sex-hormone disorders.

ACS Medicinal Chemistry Letters published new progress about 1375066-73-1. 1375066-73-1 belongs to thiazole, auxiliary class Thiadiazole,Hydrazine,Amine,Hydrazide,Amide, name is 3-Methyl-1,2,4-thiadiazole-5-carbohydrazide, and the molecular formula is C4H6N4OS, Name: 3-Methyl-1,2,4-thiadiazole-5-carbohydrazide.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica