210421-74-2 Usage
Description
Sitaxentan sodium is a potent nonpeptide endothelin A (ETA) receptor antagonist that belongs to the sulfonamide class of endothelin receptor antagonists. It is characterized by its high selectivity for the ETA receptor over the ETB receptor (6,000-fold) and is used in the treatment of various conditions related to pulmonary hypertension and hypertension.
Uses
1. Used in Pulmonary Arterial Hypertension Treatment:
Sitaxentan sodium is used as a selective endothelin A (ETA) receptor antagonist for improving exercise capacity in patients with pulmonary arterial hypertension (PAH) classified as World Health Organization (WHO) functional class III. Its high selectivity for ETA receptors and once-daily oral treatment make it a preferred choice for PAH patients.
2. Used in Chronic Heart Failure Treatment:
Sitaxentan sodium is used as an antihypertensive agent for the treatment of chronic heart failure. Its ability to reduce blood pressure and inhibit phosphoinositol hydrolysis induced by endothelin-1 contributes to its effectiveness in managing heart failure.
3. Used in Hypertension Treatment:
Sitaxentan sodium is used as an antihypertensive agent in the treatment of hypertension. Its potent ETA receptor antagonist activity helps in reducing blood pressure and managing hypertension effectively.
4. Used in Acute Hypoxia-Induced Pulmonary Hypertension:
Sitaxentan sodium is used as a treatment for acute hypoxia-induced pulmonary hypertension in rat models. It has been shown to reduce blood pressure and improve lung mechanics in these models.
5. Used in Intraluminal Injury and Neointimal Lesion Treatment:
Sitaxentan sodium is used to reduce femoral artery neointimal lesion size in mouse models of intraluminal injury, demonstrating its potential in treating vascular injuries and related conditions.
6. Used in Bleomycin-Induced Lung Injury Treatment:
Sitaxentan sodium is used to decrease bronchoalveolar lavage fluid (BALF) pleocytosis, pulmonary collagen deposition, and fibrosis, as well as improve lung mechanics in mouse models of bleomycin-induced lung injury. This highlights its potential in treating lung injuries and related conditions.
Biochem/physiol Actions
Sitaxentan (Sitaxsentan) is a potent and selective endothelin ET(A) receptor antagonist once used in the treatment of pulmonary arterial hypertension (PAH), but removed from the market because of hepatotoxicity. It is over 6000-fold selective for the the ETA receptor subtype with an IC50 of 1 nM for ETA versus an IC50 of 9800 nM for ETB.
Synthesis
The synthesis
of sitaxentan is depicted in Scheme 12. 5-amino-3-
methylisoxazole 85 was treated with NCS in DCM at 0°C to
give chloroisoxazole 86 in 87% yield. The amine was then
coupled with the commercially available 2-(methoxycarbonyl)-
3-thiophenesulfonyl chloride (87) using sodium hydride
in THF at 0°C. The resulting ester was directly hydrolyzed in
1N NaOH to furnish acid 88 in 45% yield. The acid 88
was then coupled with N,O-dimethylhydroxylamine to give
Weinreb amide 89. The amide 89 was then treated with benzylic
Grignard reagent followed by acidic workup to give the
sitaxentan XII in 50% yield in two steps. The Grignard reagent
90 was prepared through the following sequence. The
5-methylbenzodioxole 91 was treated with aqueous formaldehyde
and concentrated HCl in ethyl ether to give the desired
benzyl chloride 93 and condensation product 92. The
mixture of 92 and 93 was used to form the Grignard reagent
without separation.
Check Digit Verification of cas no
The CAS Registry Mumber 210421-74-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,1,0,4,2 and 1 respectively; the second part has 2 digits, 7 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 210421-74:
(8*2)+(7*1)+(6*0)+(5*4)+(4*2)+(3*1)+(2*7)+(1*4)=72
72 % 10 = 2
So 210421-74-2 is a valid CAS Registry Number.
InChI:InChI=1/C18H14ClN2O6S2.Na/c1-9-5-13-14(26-8-25-13)7-11(9)6-12(22)17-15(3-4-28-17)29(23,24)21-18-16(19)10(2)20-27-18;/h3-5,7H,6,8H2,1-2H3;/q-1;+1/rC18H14ClN2NaO6S2/c1-9-5-13-14(27-8-26-13)7-11(9)6-12(23)17-15(3-4-29-17)30(24,25)21(22)18-16(19)10(2)20-28-18/h3-5,7H,6,8H2,1-2H3
