Day: October 13, 2022

Kaplan, Anna; Gaschler, Michael M.; Dunn, Denise E.; Colligan, Ryan; Brown, Lewis M.; Palmer, Arthur G. III; Lo, Donald C.; Stockwell, Brent R. published the artcile< Small molecule-induced oxidation of protein disulfide isomerase is neuroprotective>, Synthetic Route of 21725-69-9, the main research area is protein disulfide isomerase oxidation neuroprotective pharmacokinetics; drug; inhibitor; neuroprotection; protein disulfide isomerase; small molecule.

Protein disulfide isomerase (PDI) is a chaperone protein in the endoplasmic reticulum that is up-regulated in mouse models of, and brains of patients with, neurodegenerative diseases involving protein misfolding. PDI’s role in these diseases, however, is not fully understood. Here, the authors report the discovery of a reversible, neuroprotective lead optimized compound I, that acts as a modulator of PDI. I was identified using a high-throughput screen of ∼10,000 lead-optimized compounds for potent rescue of viability of PC12 cells expressing mutant huntingtin protein, followed by an evaluation of compounds on PDI reductase activity in an in vitro screen. Isothermal titration calorimetry and fluorescence experiments revealed that binding to PDI was reversible with a Kd of 62 nM, suggesting I to be the most potent PDI inhibitor reported to date. Using 2D heteronuclear single quantum correlation NMR experiments, the authors were able to map the binding site of I as being adjacent to the active site and to observe that binding of I forces PDI to adopt an oxidized conformation. Furthermore, the authors found that I-induced oxidation of PDI has a neuroprotective effect not only in cell culture, but also in corticostriatal brain slice cultures. I exhibited high stability in mouse liver microsomes and blood plasma, low intrinsic microsome clearance, and low plasma-protein binding. These results suggest that I is a promising lead compound to evaluate the potential therapeutic effects of modulating PDI in animal models of disease.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Homo sapiens. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Synthetic Route of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Yang, Yutao; Huo, Fangjun; Yin, Caixia; Xu, Ming; Hu, Ying; Chao, Jianbin; Zhang, Yongbin; Glass, Timothy E.; Yoon, Juyoung published the artcile< A novel method for the synthesis of 1,2-benzisoxazoline-3-one and its application to hypochlorite recognition>, Electric Literature of 21725-69-9, the main research area is benzisoxazolineone synthesis hypochlorite determination imaging.

The reaction of salicylhydroxamic acid with hypochlorite produces 1,2-benzisoxazoline-3-one, a heterocycle that contains a fluorophore. As a result, this reaction was used as the basis for a new, selective and sensitive fluorescence system for the recognition of hypochlorite. The effectiveness of the method was demonstrated by its use to detect hypochlorite in a disinfectant solution as well as to image hypochlorite in cells.

Journal of Materials Chemistry B: Materials for Biology and Medicine published new progress about Biological imaging. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Electric Literature of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Ueda, Mitsuru; Oikawa, Hideaki published the artcile< 1,2-Benzisoxazol-3-yl diphenyl phosphate: a new, reactive activating agent for the synthesis of amides, esters, and peptides via condensation>, SDS of cas: 21725-69-9, the main research area is benzisoxazolyl phosphate preparation condensation agent; amidation agent benzisoxazolyl phosphate; esterification agent benzisoxazolyl phosphate; peptide coupling agent benzisoxazolyl phosphate.

Title agent I was prepared and used to activate carboxylic acids (e.g., benzoic, hexanoic, and cinnamic acids) prior to amidation or esterification. One- and two-step procedures are given. I was also shown to be useful as a peptide-forming reagent; eleven protected dipeptides esters were prepared

Journal of Organic Chemistry published new progress about Amidation. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, SDS of cas: 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Yevich, Joseph P.; New, James S.; Smith, David W.; Lobeck, Walter G.; Catt, John D.; Minielli, Joseph L.; Eison, Michael S.; Taylor, Duncan P.; Riblet, Leslie A.; Temple, Davis L. Jr. published the artcile< Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents>, Related Products of 21725-69-9, the main research area is antipsychotic benzisothiazolylpiperazine benzisoxazolylpiperazine preparation; piperazine benzisothiazolyl benzisoxazolyl.

The title compounds e.g. I [R = H, 2-benzothiazolyl, 4-(7,9-dioxo-8-azaspiro[4.5]decane-8-yl)butyl, p-FC6H4CO(CH2)3; X = S, O], were prepared and exhibited potential antipsychotic activity on the basis of their potent affinity for dopaminergic rat membrane sites labeled with [3H]spiperone and their attenuation of conditioned avoidance responding and apomorphine-induced stereotypy in rats. Thus, 3-chloro-1,2-benzisoxazole was treated with piperazine to give I (R = H, X = S), which was treated with 8-(4-chlorobutyl)-8-azaspiro[4.5]decane-7,9-dione to give I [R = 4-(7,9-dioxo-8-azaspiro[4.5]decane-8-yl)butyl, X = S] (II). Structure-activity relationships within the series are discussed. II was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound’s lack of typical neuroleptic-like effects in the rat catalepsy test coupled with its failure to produce dopamine receptor supersensitivity following chronic administration suggests that it should not cause the movement disorders commonly associated with antipsychotic therapy. II is currently undergoing clin. evaluation in schizophrenic patients.

Journal of Medicinal Chemistry published new progress about Antipsychotics. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Related Products of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

He, Jie; Li, Dongdong; Xiong, Kun; Ge, Yongjie; Jin, Hongwei; Zhang, Guozhou; Hong, Mengshi; Tian, Yongliang; Yin, Jin; Zeng, Huihui published the artcile< Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy>, Category: isoxazole, the main research area is anticancer thioredoxin reductase inhibitor benzisoselenazolone preparation SAR.

Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an important target for anticancer drugs. Selective inhibition of TrxR by 1,2-(bis-1,2-benzisoselenazol-3(2H)-one)ethane (4a) prevents proliferation of several cancer cell lines both in vivo and in vitro. Using the structure of 4a as a starting point, a series of novel bis-1,2-benzisoselenazol-3(2H)-ones was designed, prepared and tested to explore the structure-activity relationships (SARs) for this class of inhibitor and to improve their potency. Notably, 1,2-(5,5′-dimethoxybis(1,2-benzisoselenazol-3(2H)-one))ethane (12) was found to be more potent than 4a in both in vitro and in vivo evaluation. Its binding sites were confirmed by biotin-conjugated iodoacetamide assay and a SAR model was generated to guide further structural modification.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Category: isoxazole.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Bertaccini, G.; Impicciatore, M.; Vitali, T. published the artcile< Pharmacological activities of benzisothiazolone and benzisoxazolone>, Safety of Benzo[d]isoxazol-3-ol, the main research area is benzisoxazolinone antiinflammatory analgesic antipyretic; benzisothiazolinone antiinflammatory analgesic antipyretic; toxicity benzisothiazolinone benzisoxazolinone.

1,2-Benzisoxazolin-3-one (I) [21725-69-9] and 1,2-benzisothiazolin-3-one (II) [2634-33-5] were more potent antiinflammatory, analgesic, and antipyretic agents than salicylamide and less potent than phenylbutazone when tested in rats, mice, and rabbits; II was generally more potent than I. The acute oral LD50 values for I and II in mice were 2,650 and 1,020 mg/kg, resp.

Pharmacological Research Communications published new progress about Analgesics. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Safety of Benzo[d]isoxazol-3-ol.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Tomita, Kazuo; Sugai, Soji; Kobayashi, Tomiko; Murakami, Tadashi published the artcile< Studies on isoxazoles. VIII. Versatile syntheses and chemical properties of 3-chloroisoxazolium chlorides>, Quality Control of 21725-69-9, the main research area is isoxazolinone chlorination; chloroisoxazolium chloride preparation pyrolysis; isoxazolinethione; acid esterification amidation isoxazolium chloride.

The reaction of 4-isoxazolin-3-ones with COCl2 or ClCO2CCl3 gave 3-chloroisoxazolium chlorides in good yields, and these were converted to 4-isoxazoline-3-thiones on treatment with NaSH. Pyrolysis of 3-chloro-2-methylisoxazolium chlorides afforded 3-chloroisoxazoles. In the presence of Bu3N, 3-chloro-2-methyl-5-phenylisoxazolium chloride condensed carboxylic acids with alcs. or amines to give the corresponding esters or amides in high yields, together with 2-methyl-5-phenyl-4-isoxazolin-3-one.

Chemical & Pharmaceutical Bulletin published new progress about Amidation. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Quality Control of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Slawik, Tomasz; Paw, Beata published the artcile< Synthesis of 3-(3-oxo-1,2-benzisoxazol-2-yl)propionic acids derivatives>, Computed Properties of 21725-69-9, the main research area is oxo benzisoxazolepropanamide preparation; hydroxy benzisoxazolepropanamide preparation.

In the reaction of 3-hydroxy-1,2-benzisoxazole (1,2-benzisoxazol-3(2H)-one) and its derivatives with 3-bromopropionic acid only N-substituted products were obtained. Esters and amides of these acids and N-dibenzylaminomethyl- and N-hydroxymethylamides were also synthesized.

Acta Poloniae Pharmaceutica published new progress about 21725-69-9. 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Computed Properties of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Jin, Wen Bin; Xu, Chen; Cheung, Qipeng; Gao, Wei; Zeng, Ping; Liu, Jun; Chan, Edward W. C.; Leung, Yun-Chung; Chan, Tak Hang; Wong, Kwok-Yin; Chen, Sheng; Chan, Kin-Fai published the artcile< Bioisosteric investigation of ebselen: Synthesis and in vitro characterization of 1,2-benzisothiazol-3(2H)-one derivatives as potent New Delhi metallo-β-lactamase inhibitors>, Synthetic Route of 21725-69-9, the main research area is benzoisothiazolone preparation metallo beta lactamase inhibitor SAR; 1,2-benzisothiazol-3(2H)-one; Bioisosteric replacement; Carbapenem-resistant Enterobacteriaceae; Ebselen; New Delhi metallo-β-lactamase inhibitors.

In the present study, by employing the concept of bioisosteric replacement of the selenium moiety of ebselen, a small compound library of 2-substituted 1,2-benzisothiazol-3(2H)-ones, compounds I [R = 4-lCC6H4, 4-HOCH2C6H4, cyclohexyl, etc.] were designed, synthesized and evaluated their cytotoxicity and synergistic activity in combination with meropenem against the E. coli Tg1 (NDM-1) strain. The most promising compound I [R = 4-lCC6H4] demonstrated potent synergistic activity against a panel of clin. isolated NDM-1 pos. CRE strains with FICI as low as 0.09. Moreover, its IC50 value and inhibition mechanism were also confirmed by using the enzyme inhibition assay and the ESI-MS anal. resp. Importantly, compound I [R = 4-lCC6H4] has acceptable toxicity and is not a PAINS. Because of its structural simplicity and potent synergistic activity in combination with meropenem, we propose that compound 3a may be a promising meropenem adjuvant and a new series of such compounds may worth further investigations.

Bioorganic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Synthetic Route of 21725-69-9.

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem