Tag: 476.89

A review of sitaxsentan sodium in patients with pulmonary arterial hypertension was written by Waxman, Aaron B.. And the article was included in Vascular Health and Risk Management in 2007.Electric Literature of C18H14ClN2NaO6S2 This article mentions the following:

Pulmonary arterial hypertension (PAH) is a life threatening, progressive condition which eventually leads to fatal right heart failure. Endothelin-1 (ET-1), a potent vasoconstrictor peptide, is increased in the pulmonary arteries of patients with pulmonary hypertension. Endothelin-1 acts through the stimulation of 2 subtypes of receptors (endothelin receptor subtypes A [ET_A] and B [ET_B]). In PAH patients, ETRAs block the deleterious vasoconstrictor effects of ET-1, and ETRA treatment in PAH patients has been shown to be safe and efficacious. Sitaxsentan is an orally active, highly ET_A selective ETRA that, in clin. trials, has demonstrated improvements in exercise capacity, functional class and hemodynamics in PAH patients. Sitaxsentan has been shown to be safe, well tolerated, and associated with a lower incidence of liver toxicity than other approved ETRAs. In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Electric Literature of C18H14ClN2NaO6S2).

Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives. Isoxazoles present in various natural products and synthetic compounds of biological importance like antibacterial, antagonists, antiinflammatory, analgesics, and also show the applications in functional materials. Some alternative routes for the synthesis of isoxazoles have also been developed and reported. The 2-benzoyl-2-halo-2H-azirines provide 4-haloisoxazoles in good yields after heating in toluene at reflux temperature.Electric Literature of C18H14ClN2NaO6S2

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Endothelin Receptor Antagonists are an Effective Long Term Treatment Option in Pulmonary Arterial Hypertension Associated with Congenital Heart Disease With or Without Trisomy 21 was written by Kermeen, F. D.;Franks, C.;O’Brien, K.;Seale, H.;Hall, K.;McNeil, K.;Radford, D.. And the article was included in Heart, Lung and Circulation in 2010.Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide This article mentions the following:

Traditionally, treatment options for patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) are limited. Bosentan has been shown to improve pulmonary haemodynamics and exercise tolerance short term but long term clin. studies are lacking. To report long term efficacy and safety data with endothelin receptor antagonists (ERA) in patients with PAH associated CHD. Prospective, open label, uncontrolled, single center study of 53 patients (33 females, 17 Trisomy 21, mean age 34 ± 12 years) prescribed ERA (48 bosentan, 5 sitaxentan) from 2003 to August 2009. Outcome measurements of oxygen saturation (SaO2), WHO functional class, 6-min walk test distance (6MWD) and adverse events were analyzed. Mean duration of therapy was 15 ± 13 mo in 53 patients with CHD. Four patients failed ERA, seven died (five progressive RHF) and one delisted from transplantation. No abnormal liver transaminases occurred on bosentan, with one case on sitaxentan. After 3, 6, 12, 18 and 24 mo of treatment a significant improvement was seen in WHO functional class (mean 3.15 vs 2.8 vs 2.5 vs 2.5 vs 2.4 vs 2.4; p < 0.01) and 6MWD (344 ± 18 vs 392 ± 17 vs 411 ± 17 vs 420 ± 17 vs 442 ± 18 vs 417 ± 23: p < 0.0005, p < 0.01) compared with baseline. The Trisomy 21 and PAH-CHD showed a significant improvement in 6MWD at 6 and 12 mo (263 ± 24 vs 348 ± 29 vs 360 ± 32, p < 0.01, p < 0.05) resp. No changes in SaO2, BNP, RV or LV function were demonstrated during follow-up. This large single center study demonstrates that endothelin receptor antagonism is an effective and safe treatment in PAH associated CHD with or without Trisomy 21. The improvements in exercise tolerance are similar to reported benefits in other forms of PAH. In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide).

Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives. Isoxazole rings are found in some natural products, such as ibotenic acid and muscimol. The electrophilic cyclization of various 2-alkynone O-methyl oximes with a wide range of substrates such as ICl, I2, Br2, PhSeBr, etc. provides a variety of 3,4,5-trisubstituted isoxazoles in good to excellent yields.Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

An overview of the preclinical toxicity and potential carcinogenicity of sitaxentan (Thelin), a potent endothelin receptor antagonist developed for pulmonary arterial hypertension was written by Owen, Keith;Cross, David M.;Derzi, Mazin;Horsley, Elizabeth;Stavros, Fiona L.. And the article was included in Regulatory Toxicology and Pharmacology in 2012.Related Products of 210421-74-2 This article mentions the following:

Sitaxentan (Thelin), an endothelin receptor antagonist with a long duration of action and high specificity for the endothelin receptor A subtype, was used to treat pulmonary arterial hypertension. It was withdrawn from the market due to an idiosyncratic risk of drug-induced liver injury identified from emerging clin. trial data and clin. case reports. The preclin. safety profile of sitaxentan is presented, including single- and repeat-dose toxicity in mice, rats, and dogs and carcinogenicity in mice and rats. Sitaxentan-related adverse effects included coagulopathy in rats and dogs, increased serum alk. phosphatase activity in mice and dogs, and hepatic hypertrophy in all species. Decreased albumin, erythrocyte count, Hb concentration and hematocrit, and increased coagulation times and liver weight were also noted. These effects generally occurred at systemic exposures (AUC_0-24) that were substantially greater than those seen in humans. Twice-daily (vs. once daily) dosing resulted in increased toxicity, which correlated with increased trough plasma sitaxentan concentrations Sitaxentan appeared to have a low potential for testicular and hepatic toxicity and was not carcinogenic. These studies suggested that sitaxentan would have a reasonable margin of safety when used as directed in humans and supported a pos. benefit:risk assessment at the time of marketing approval. In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Related Products of 210421-74-2).

Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives. Isoxazoles are aromatic heterocycles containing an N–O bond. Isoxazoles are commonly used as enaminoketone or β-diketone surrogate. Some alternative routes for the synthesis of isoxazoles have also been developed and reported. The 2-benzoyl-2-halo-2H-azirines provide 4-haloisoxazoles in good yields after heating in toluene at reflux temperature.Related Products of 210421-74-2

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Evaluation of carcinogenicity studies of medicinal products for human use authorised via the European centralised procedure (1995-2009) was written by Friedrich, Anita;Olejniczak, Klaus. And the article was included in Regulatory Toxicology and Pharmacology in 2011.Application of 210421-74-2 This article mentions the following:

Carcinogenicity data of medicinal products for human use that have been authorized via the European centralized procedure (CP) between 1995 and 2009 were evaluated. Carcinogenicity data, either from long-term rodent carcinogenicity studies, transgenic mouse studies or repeat-dose toxicity studies were available for 144 active substances contained in 159 medicinal products. Out of these compounds, 94 (65%) were pos. in at least one long-term carcinogenicity study or in repeat-dose toxicity studies. Fifty compounds (35%) showed no evidence of a carcinogenic potential. Out of the 94 compounds with pos. findings in either carcinogenicity or repeat-dose toxicity studies, 33 were pos. in both mice and rats, 40 were pos. in rats only, and 21 were pos. exclusively in mice. Long-term carcinogenicity studies in two rodent species were available for 116 compounds Data from one long-term carcinogenicity study in rats and a transgenic mouse model were available for eight compounds For 13 compounds, carcinogenicity data were generated in only one rodent species. One compound was exclusively tested in a transgenic mouse model. Six compounds were tumorigenic in repeat-dose toxicity studies in rats. The majority of tumor findings observed in rodent carcinogenicity studies were considered not to be relevant for humans, either due to a rodent-specific mechanism of carcinogenicity, a high safety margin between exposures at the NOAEL (No Observed Adverse Effect Level) in rodents and recommended therapeutic doses in humans, or based on historical control data, a small effect size and lack of dose-response relationship and tumors typically observed in rodent strains used, or were considered not to be relevant for humans based on literature and clin. data or likely differences in metabolism/local concentrations between rodents and humans. Due to the high number of rodent tumor findings with unlikely relevance for humans, the value of the currently used testing strategy for carcinogenicity appears questionable. A revision of the carcinogenicity testing paradigm is warranted. In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Application of 210421-74-2).

Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives.Synthetically, isoxazoles serve as valuable precursors for the construction of diverse molecules, including many natural products. Fe(CO)5 efficiently cleaves the N–O bond of fused isoxazolo-1,4-quinones to give the corresponding imines.All the common reducing reagents failed to open the isoxazole ring.Application of 210421-74-2

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Phosphate binder for dialysis patients was written by Becker, Conny;Gensthaler, Brigitte M.;Grafe, Kerstin A.;Morck, Hartmut. And the article was included in Pharmazeutische Zeitung in 2007.Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide This article mentions the following:

Characteristics, pharmacodynamics, and pharmacokinetics are discussed of a new Ca-free phosphate binder, lanthanum carbonate (Fosrenol), for dialysis patients with terminal nephrotic insufficiency to avoid hyperphosphatemia. 4 New drugs are characterized: oxytocin analog carbetocin (Pabal), Tyr kinase inhibitor dasatinib (Sprycel), cyclooxygenase (COX)-2 inhibitor lumiracoxib (Prexige), and endothelin-A-receptor inhibitor sitaxentan (Thelin). In the experiment, the researchers used many compounds, for example, Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide).

Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide (cas: 210421-74-2) belongs to isoxazole derivatives. An isoxazolyl group is found in many beta-lactamase-resistant antibiotics, such as cloxacillin, dicloxacillin and flucloxacillin. As with isoxazolines, isoxazoles may be cleaved using low-valent titanium obtained from the Kulinkovich reaction.This procedure affords enaminoketones from 2,4-substituted isoxazoles.Application In Synthesis of Sodium (4-chloro-3-methylisoxazol-5-yl)((2-(2-(6-methylbenzo[d][1,3]dioxol-5-yl)acetyl)thiophen-3-yl)sulfonyl)amide

Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem