Day: November 10, 2022

Inagaki, Masanao published the artcileHighly E-Selective and Effective Synthesis of Antiarthritic Drug Candidate S-2474 Using Quinone Methide Derivatives, Application In Synthesis of 73343-04-1, the main research area is ditertbutylhydroxybenzylideneethylisothiazolidine dioxide preparation; isothiazolidine ditertbutylhydroxybenzylideneethyl dioxide preparation.

We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474), in which α-methoxy-p-quinone methide is used as a key intermediate. α-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with α-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.

Journal of Organic Chemistry published new progress about ditertbutylhydroxybenzylideneethylisothiazolidine dioxide preparation; isothiazolidine ditertbutylhydroxybenzylideneethyl dioxide preparation. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Application In Synthesis of 73343-04-1.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Inagaki, Masanao published the artcileNovel Antiarthritic Agents with 1,2-Isothiazolidine-1,1-dioxide (γ-Sultam) Skeleton: Cytokine Suppressive Dual Inhibitors of Cyclooxygenase-2 and 5-Lipoxygenase, Formula: C5H11NO2S, the main research area is antiarthritic isothiazolidine dioxide sultam preparation; structure activity antiarthritic isothiazolidine dioxide sultam.

Various 1,2-isothiazolidine 1,1-dioxide (γ-sultam) derivatives containing an antioxidant moiety, 2,6-di-tert-butylphenol substituent, were prepared Some compounds, which have a lower alkyl group at the 2-position of the γ-sultam skeleton, showed potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), as well as production of interleukin (IL)-1 in in vitro assays. They also proved to be effective in several animal arthritic models without any ulcerogenic activities. Among these compounds, (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474) (I) was selected as an antiarthritic drug candidate and is now under clin. trials. The structure-activity relationships (SAR) examined and some pharmacol. evaluations are described.

Journal of Medicinal Chemistry published new progress about Antiarthritics. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Formula: C5H11NO2S.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Oda, Katsuo published the artcileDevelopment of One-Pot Synthesis of New Antiarthritic Drug Candidate S-2474 with High E-Selectivity, Product Details of C5H11NO2S, the main research area is antiarthritic drug candidate S2474 high E selectivity preparation.

A one-pot synthesis of S-2474 was developed to overcome the problems of a large number of steps, low stereoselectivity, low yield, a large amount of waste, and severe reaction conditions. Aldol-type condensation of 3,5-di-tert-butyl-4-hydroxybenzaldehyde and N-ethyl-γ-sultam was carried out with LDA and then quenched with water. Dehydration proceeded under basic conditions, providing S-2474 directly as a single isomer on the benzylidene double bond. The reaction mechanism appears to involve a quinone methide intermediate. Environmental assessment of the development of this compound is also discussed.

Organic Process Research & Development published new progress about Antiarthritics. 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Product Details of C5H11NO2S.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Kocevar, Marjan published the artcileNeighboring group participation in formation of condensed azines. Formation of pyrazolo[3,4-b]pyrazines, isoxazolo[4,5-b]pyrazines and isothiazolo[5,4-b]pyridine. Heterocycles. CCX, Synthetic Route of 56891-64-6, the main research area is neighboring group participation cyclization; azine condensed; pyrazine pyrazolo isoxazolo; pyrazolopyrazine; oxazolopyrazine; isothiazolopyridine; pyridine isothiazolo.

Pyrazine- and pyridinecarboxamidoximes with an amino or potentially tautomeric hydroxy or mercapto group in the ortho position were transformed into condensed azines. Representative pyrazolo[3,4-b]pyrazines, isoxazolo[4,5-b]pyrazines and isothiazolo[5,4-b] pyridine ring systems were synthesized and some transformations investigated.

Monatshefte fuer Chemie published new progress about Cyclocondensation reaction. 56891-64-6 belongs to class isothiazole, name is Isothiazolo[5,4-b]pyridin-3-amine, and the molecular formula is C6H5N3S, Synthetic Route of 56891-64-6.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

Inagaki, Masanao published the artcileShort Synthesis of tert-Butyl-Hydroxylated 3,5-Di-tert-butyl-4-hydroxybenzaldehyde: Synthesis of tert-Butyl-Hydroxylated S-2474, Formula: C5H11NO2S, the main research area is hydroxybenzaldehyde hydroxybutyl preparation; oxidizing agent hydrobromic acid DMSO; antiarthritic drug S2474 metabolite preparation.

We have developed a very short synthesis of tert-butyl-hydroxylated di-tert-butyl-4-hydroxybenzaldehyde (I) in which the HBr-DMSO system is used as an effective oxidant (overall yield of 45% for the entire four-step process from 2-tert-butyl-p-cresol). We also accomplished the synthesis of a major metabolite (II) of the antiarthritic drug candidate S-2474.

Journal of Organic Chemistry published new progress about Oxidizing agents (hydrobromic acid-DMSO). 73343-04-1 belongs to class isothiazole, name is 2-Ethylisothiazolidine 1,1-dioxide, and the molecular formula is C5H11NO2S, Formula: C5H11NO2S.

Referemce:
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com