Name | Doxazosin Mesylate |
Synonyms | ALFADIL CARDURA CARDENALIN UK-33274-27 DOXAZOSIN MEYLATE Doxazosin Mesylate DOXAZOSIN MESYLATE Doxazosin Mesilate Doxazosin, Mesylate DOXAZOSIN METHANESULFONATE Mesylate sandy azole lamictal 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate 1-(4-AMINO-6,7-DIMETHOXY-2-QUINAZOLINYL)-4-[4-(1,4-BENZODIOXAN-2-YL)CARPIPERAZIN-1-YL)]-6,7-DIMETHOXYQUINAZOLINE MESYLATE |
CAS | 77883-43-3 |
EINECS | 1308068-626-2 |
InChI | InChI=1/C23H25N5O5.CH4O3S/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20;1-5(2,3)4/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26);1H3,(H,2,3,4) |
InChIKey | VJECBOKJABCYMF-UHFFFAOYSA-N |
Molecular Formula | C24H29N5O8S |
Molar Mass | 547.58 |
Melting Point | 275-277°C |
Solubility | Slightly soluble in water, soluble in a mixture of 15 volumes of water and 35 volumes of tetrahydrofuran, slightly soluble in methanol, practically insoluble in acetone. It shows polymorphism (5.9), some forms may be hygroscopic |
Appearance | powder |
Color | white |
Storage Condition | 2-8°C |
Stability | Protect from light |
MDL | MFCD00216023 |
Physical and Chemical Properties | Appearance: white or white crystalline powder related substances: less than or equal to 1.0% Loss on drying: less than or equal to 1.0% ignition residue: less than or equal to 0.1% heavy metals: less than or equal to 10ppm content: more than or equal to 99.0% |
Use | This product is for scientific research only and shall not be used for other purposes. |
Hazard Symbols | Xi - Irritant |
Risk Codes | 36/37/38 - Irritating to eyes, respiratory system and skin. |
Safety Description | S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36/37 - Wear suitable protective clothing and gloves. S24/25 - Avoid contact with skin and eyes. |
WGK Germany | 2 |
RTECS | TK8044000 |
HS Code | 29349990 |
Overview | Doxazosin mesylate is a new generation of the alpha 1 receptor blocker, its long half-life, by blocking a 1 receptor to dilate blood vessels, reduce vascular resistance, lower blood pressure, selective blocking prostate smooth muscle matrix, capsule and bladder neck a 1 adrenergic receptor, to improve the symptoms of patients with benign prostatic hyperplasia, and has a good effect on the dysuria caused by simple prostatic hyperplasia. In 1988, Doxazosin was listed in Denmark as a drug for the treatment of hypertension. In 1995, the US FDA approved it for the treatment of benign prostatic hyperplasia, it provides a new choice for the drug treatment of benign prostatic hyperplasia in China, and has been recommended as the first-line drug for anti-hypertension and prostate disease in foreign clinic. [Pharmacological action] This product is a new type of highly selective alpha 1 receptor blocker, which has a significant effect on lowering blood pressure and improving blood lipid metabolism, can significantly reduce serum triglycerides and total cholesterol; Other selective blocking prostate smooth muscle matrix, capsule and bladder neck a 1 adrenergic receptor, improve the symptoms of benign prostatic hyperplasia patients, significantly slow down the role of benign prostatic hyperplasia, in particular, it has a good effect on dysuria caused by simple prostatic hyperplasia, and its half-life is long. |
synthesis | 1. Catechol and sodium hydroxide solution were added to the reaction flask, stirred evenly, and epichlorohydrin was added dropwise at 50 ° C. For 0.5 h. After dropping and refluxing at 85 °c for 2.5 h, the solution turned from dark green to brown yellow oil. The mixture was extracted with chloroform, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure, and the residue was cooled to crystallize. The filter cake was filtered and washed with a small amount of cold carbon tetrachloride and dried below 50 °c to give compound 2 as a white solid. 2. Potassium permanganate and potassium hydroxide solution were added to the reaction flask, and the pyridine solution of intermediate 2 was added dropwise at 0-10 °c. The reaction time was 24 h at room temperature. The filtrate was filtered, adjusted to pH = 7 with concentrated aqueous ammonia, concentrated to half, cooled, and added with chloroform. Under stirring, concentrated hydrochloric acid was added dropwise to adjust pH = 1. Then it was extracted with chloroform. The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give compound 3 as a pale yellow solid. 3. The reaction flask was added with intermediate 3, toluene solution, DMF, heated to 50 ° C., stirred and dissolved, then thionyl chloride was added dropwise and refluxed Dropwise for 4 h. The toluene and the remaining thionyl chloride were distilled off under reduced pressure to obtain a crude compound 4. 4. After adding piperazine, methanol and water to the reaction flask and stirring evenly, the ethyl acetate solution of intermediate 4 was added dropwise at 10-20 ℃, and the reaction was continued for 2 h. The reaction mixture was extracted with dichloromethane, and the aqueous phase was separated, the organic phase was extracted twice with water, the aqueous phase was combined, adjusted to pH = 10 with concentrated ammonia, extracted three times with dichloromethane, the organic phase was combined, washed twice with water, dried over anhydrous sodium sulfate, filtered, methylene chloride was distilled off under reduced pressure to give compound 5 as a pale yellow solid. 5.2-chloro-4-amino-6, 7-dimethoxyquinazoline, intermediate 5 and n-butanol were added to the reaction flask, and the mixture was stirred and refluxed for 4H. After the reaction was completed, crystals were cooled and precipitated, washing with n-butanol and drying gave compound 6 as a white crystalline powder. 6.6 put it in a beaker, adjust pH = 10 with ammonia, extract with dichloromethane, separate the aqueous layer, wash the organic phase once with water, slowly add methanesulfonic acid, gradually precipitate white crystals, cool down and crystallize, after filtration and drying, the crude product 1 was obtained. 7.1 The crude product was added to methanol, heated to dissolve all the product, cooled and crystallized, filtered, washed once with cold methanol, and dried to obtain fine product 1. Figure 1 is the synthesis of Doxazosin mesylate |
Use | primary mild to moderate hypertension, and hypertension patients with benign prostatic hypertrophy. For patients who have difficulty controlling blood pressure with a single drug, doxothiazide can be used in combination with thiazide diuretics and beta-blockers, calcium antagonists, or angiotensin-converting enzyme inhibitors. (2016-04-09) treatment of hypertension. |
usage and dosage | 1. Adult usual dose of oral, starting dose of 1mg once a day, 1-2 weeks after the clinical response and tolerance to adjust the dose; The first dose and adjust the dose should be taken before going to bed. The maintenance dose is 1-8mg once a day, but more than 4mg is easy to cause orthostatic hypotension. Foreign research data suggest that the maximum dose of this product to 16mg/day. The pediatric dose has not been determined. |
pharmacokinetics | The oral bioavailability is 62%-69%, the protein binding rate was 98% ~ 99%, and the peak time was 1. 7~3. 6 hours, the elimination half-life of 16~22 hours, in the liver metabolism, about 65% of the drug metabolites to fecal elimination, only about 5% to the prototype by the urine exclusion. |
adverse reactions | there may be dizziness, dry mouth, Head Pain, palpitations, Fatigue, and the symptoms are mild and tolerable, it disappeared in about 1 week without special treatment. No orthostatic hypotension occurred. |
note | is contraindicated for those allergic to this product. In the post-marketing experience of treating hypertension, there are reports of tachycardia, palpitations, chest pain, angina pectoris, myocardial infarction, cerebrovascular accident and arrhythmia, but in general, this is indistinguishable from the symptoms that may occur in those who do not use doxothiazide. The application of this product may affect the ability of drivers and mechanical operators, especially in the initial stage of medication. |
toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |