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Innovative therapeutic potential of cannabinoid receptors as targets in alzheimer?s disease and less well-known diseases

The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG). The endogenous cannabinoid system is a complex signalling system that comprises transmembrane endocannabinoid receptors, their endogenous ligands (the endocannabinoids), the specific uptake mechanisms and the enzymatic systems related to their biosynthesis and degradation. The endocannabinoid system has been implicated in a wide diversity of biological processes, in both the central and peripheral nervous systems, including memory, learning, neuronal development,32 stress and emotions, food intake, energy regulation, peripheral metabolism, and the regulation of hormonal balance through the endocrine system. In this context, this article will review the current knowledge of the therapeutic potential of cannabinoid receptor as a target in Alzheimer?s disease and other less well-known diseases that include, among others, multiple sclerosis, bone metabolism, and Fragile X syndrome. The therapeutic applications will be addressed through the study of cannabinoid agonists acting as single drugs and multi-target drugs highlighting the CB2 receptor agonist. 32.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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4,6-Dinitrobenzo[c]isothiazole: Synthesis and 1,3-dipolar cycloaddition to azomethine ylide

1,3-Dipolar cycloaddition of 4,6-dinitrobenzo[c]isothiazole to (N-methyl-N-methylideneammonio)methanide (2 equiv.) gives 5,8-dimethyl-3b,6b- dinitrodecahydroisothiazolo[3,4-e]pyrrolo[3,4-g]isoindole, whose structure was confirmed by X-ray diffraction analysis.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Fluorine in medicinal chemistry: A review of anti-cancer agents

In this review those fluorinated compounds which have found a role as anti-cancer agents are summarized. The emphasis is to highlight the important drugs but also to highlight the latest developments on emerging compounds. This has been done as comprehensively as possible with the objective of informing readers of some of the latest developments in this area.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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PDE7-selective and dual inhibitors: Advances in chemical and biological research

Phosphodiesterase 7 (PDE7) is an intracellular enzyme that specifically hydrolyzes the second messenger, cyclic-3?,5?-adenosine monophosphate (cAMP), into inactive noncyclic nucleotide, 5?-AMP. To date, many structurally diverse compounds with PDE7 inhibitory properties have been described, including selective PDE7 inhibitors, dual PDE4/PDE7, PDE7/PDE8, and PDE7/GSK-3 inhibitors, and non-selective PDE inhibitors with high affinity for PDE7. Inhibitors of PDE7 have provided beneficial effects in animal models of inflammatory and neurological disorders, including Alzheimer?s disease, Parkinson?s disease, multiple sclerosis, and many others. This review is a comprehensive summary of the current state-of-the-art in the field of design and synthesis of PDE7 inhibitors, their physicochemical properties, biological evaluation, and structure-activity relationships as well as it highlights the updated evidence for a potential therapeutic utility of these compounds. Moreover, new approaches to obtain more effective and safer PDE7 inhibitors than those available now are presented.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Privileged Structural Motif Detection and Analysis Using Generative Topographic Maps

Identification of “privileged structural motifs” associated with specific target families is of particular importance for designing novel bioactive compounds. Here, we demonstrate that they can be extracted from a data distribution represented on a two-dimensional map obtained by Generative Topographic Mapping (GTM). In GTM, structurally related molecules are grouped together on the map. Zones of the map preferentially populated by target-specific compounds were delineated, which helped to capture common substructures on the basis of which these compounds were grouped together by GTM. Such privileged structural motifs were identified across three major target superfamilies including proteases, kinases, and G protein coupled receptors. Traditionally, the search for privileged structural motifs focused on scaffolds, whereas motifs were detected here without prior knowledge of compound classification in GTMs. This alternative way of navigating medicinal chemistry space further extends the classical, scaffold-centric approach. Importantly, detected motifs might also comprise fuzzy sets of similar scaffolds, pharmacophore-like patterns, or, by contrast, well-defined scaffolds with specific substituent patterns.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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It is a common heterocyclic compound, the isothiazole compound, Isothiazole, cas is 288-16-4 its synthesis route is as follows.

Under nitrogen protection, compound 1 was added(20 g, 0.235 mol) was added to dry 100 ml of ether and stirred to dissolve,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After completion of the dropwise addition, the temperature was gradually raised to room temperature, and after stirring for half an hour, the reaction was quenched by adding thereto a hydrochloric acid solution (2N, 500 ml). (100ml * 2), dried over anhydrous sodium sulfate, filtered and concentrated to dryness. After drying, the aqueous phase was washed with diethyl ether (200ml * 3) and extracted.To give the yellow oily compound 2.

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Reference£º
Patent; Tianjin Jinyao Group Co., Ltd.; Li Jing; He Guangjie; Yang Xinyi; Wang Shuli; Chen Liying; Hu Xiaoyun; Sun Liang; (37 pag.)CN106890175; (2017); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

 

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Name is Isothiazole, as a common heterocyclic compound, it belongs to isothiazole compound, and cas is 288-16-4, its synthesis route is as follows.

EXAMPLE 15 6-Cyano-1-hydroxy-1-(5-isothiazolyl)-1,2,3,4-tetrahydronaphthalene Analogously to Example 12, the crude title compound is obtained starting from 353 mg of isothiazole, 0.632 ml of diisopropylamine, 3 ml of 1.6M n-butyllithium in hexane and 546 mg of 6-cyano-1-tetralone in 38 ml of THF. It is purified by column chromatography (SiO2, hexane/ethyl acetate 4:1) and crystallisation from hexane; m.p. 182-184; 1 H-NMR (d6 -DMSO): delta(ppm)=1.76 and 1.97 (2m,4H), 2.9 (t,2H), 6.65 (s,1H), 6.93 (d,1H), 7.37 (dd,1H), 7.59 (dd,1H), 7.7 (d,1H), 8.39 (d,1H).

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Reference£º
Patent; Ciba-Geigy Corporation; US5246952; (1993); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

 

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As a common heterocyclic compound, it belongs to isothiazole compound, name is Isothiazole, and cas is 288-16-4, its synthesis route is as follows.,288-16-4

To a solution of isothiazole (5 g, 0.06 mol) in anhydrous THF (50 mL) was added n- BuLi (28.2 mL, 0.07 mol) dropwise at -70 oC over 1 h. After stirring at -70 oC for 1 h, Br2 (6 mL, 0.12 mol) was added dropwise over 30 min and the resulting mixture was allowed to warm to RT and poured into an excess of cold 2N HCl solution. The organic layer was separated and the aqueous layer was extracted with Et2O (200 mL x 3). The combined organic extracts were washed with saturated sodium dithionite solution (200 mL x 2), dried over anhydrous Na2SO4, and filtered. The filtrate was concentrated in vacuo, and the resulting residue was distilled to afford 5-bromoisothiazole (2 g, 21%) as yellow oil.1H NMR (400 MHz, CDCl3) delta 8.33 (d, J = 1.6 Hz, 1H), 7.28 (d, J = 1.6 Hz, 1H).

With the complex challenges of chemical substances, we look forward to future research findings about 288-16-4,belong isothiazole compound

Reference£º
Patent; LYSOSOMAL THERAPEUTICS INC.; SKERLJ, Renato, T.; BOURQUE, Elyse Marie Josee; LANSBURY, Peter, T.; GREENLEE, William, J.; GOOD, Andrew, C.; (309 pag.)WO2017/176961; (2017); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

 

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As a common heterocyclic compound, it belongs to quinuclidine compound,Quinuclidine-4-carboxylic acid hydrochloride,40117-63-3,Molecular formula: C8H14ClNO321,mainly used in chemical industry, its synthesis route is as follows.,288-16-4

To a solution of isothiazole (5.0 g, 58.82 mmol) in AcOH (37 mL) was added Br2 (12.5 g, 78.12 mmol) dropwise at 95 oC over 20 min and the mixture was stirred for 6 h at 95 oC, then cooled to RT, and poured into ice water (100 mL). The resulting mixture was extracted with Et2O (200 mL x 2). The organic phases were washed with 6N NaOH to pH at 7~8, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo, and the resulting residue was purified by distillation to afford 4-bromoisothiazole as a white solid (1.5 g, 15%).

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Reference£º
Patent; LYSOSOMAL THERAPEUTICS INC.; SKERLJ, Renato, T.; BOURQUE, Elyse Marie Josee; LANSBURY, Peter, T.; GREENLEE, William, J.; GOOD, Andrew, C.; (309 pag.)WO2017/176961; (2017); A1;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com

 

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With the complex challenges of chemical substances, we look forward to future research findings about Isothiazole

Name is Isothiazole, as a common heterocyclic compound, it belongs to isothiazole compound, and cas is 288-16-4, its synthesis route is as follows.,288-16-4

Compound 1 (20 g, 0.235 mol) was added under stirring with nitrogen to dry 100 ml of ether and stirred to dissolve,And then cooled to below 0 ,To this was added n-butyllithium (0.24 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, the incubation reaction was carried out until no compound 1 was added.To the reaction solution was added bromine (0.5 mol)During the dropping process, the temperature was kept below 0 C,After the dropwise addition, slowly raise to room temperature,After stirring for half an hour, the reaction was quenched by the addition of hydrochloric acid solution (2N, 500 ml).The aqueous phase was extracted with ether (200 ml * 3) and discarded.The combined organic phase, sodium dithionite solution (100 ml * 2)Dried over anhydrous sodium sulfate, filtered and concentrated to dryness,A yellow oily compound was prepared.

With the complex challenges of chemical substances, we look forward to future research findings about Isothiazole

Reference£º
Patent; Tianjin Jinyao Group Co., Ltd.; Ge Yu; Li Yanfeng; (38 pag.)CN106892911; (2017); A;,
Isothiazole – Wikipedia
Isothiazole – ScienceDirect.com