ドキサゾシン
6,7-ジメトキシ-2-[4-[(2,3-ジヒドロ-1,4-ベンゾジオキシン-2-イル)カルボニル]-1-ピペラジニル]キナゾリン-4-アミン · 1-(4-アミノ-6,7-ジメトキシ-2-キナゾリニル)-4-[(2,3-ジヒドロ-1,4-ベンゾジオキシン-2-イル)カルボニル]ピペラジン · 2-[4-[(1,4-ベンゾジオキサン-2-イル)カルボニル]ピペラジノ]-6,7-ジメトキシ-4-キナゾリンアミン · 1-(4-アミノ-6,7-ジメトキシ-2-キナゾリニル)-4-[[(2,3-ジヒドロ-1,4-ベンゾジオキシン)-2-イル]カルボニル]ピペラジン · ドキサゾシン · 1-(4-アミノ-6,7-ジメトキシキナゾリン-2-イル)-4-[(2,3-ジヒドロ-1,4-ベンゾジオキシン-2-イル)カルボニル]ピペラジン · 4-(4-アミノ-6,7-ジメトキシキナゾリン-2-イル)-1-ピペラジニル(2,3-ジヒドロ-1,4-ベンゾジオキシン-2-イル)ケトン · 2-[4-(2,3-ジヒドロ-1,4-ベンゾジオキシン-2-カルボニル)ピペラジン-1-イル]-6,7-ジメトキシキナゾリン-4-アミン
識別子と物理属性
| CAS No. | 74191-85-8 |
|---|---|
| 分子式 | C23H25N5O5 |
| 平均分子量 | 451.5 g/mol |
| 単同位体質量 | 451.1855689 g/mol |
| SMILES | COc1cc2nc(N3CCN(C(=O)C4COc5ccccc5O4)CC3)nc(N)c2cc1OC |
| InChIKey | RUZYUOTYCVRMRZ-UHFFFAOYSA-N |
| PubChem CID | 3157 |
| ChEMBL | CHEMBL707 |
| ChEBI | CHEBI:4708 |
| EC No. | 616-059-6 |
| DTXSID | DTXSID7022964 |
| 現地名 | ドキサゾシン |
化学・物理的性質
| XLogP | 2.5 |
|---|---|
| 極性表面積 | 112 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 9 |
| 回転可能結合数 | 4 |
| 重原子数 | 33 |
| 形式電荷 | 0 |
| 複雑度 | 678 |
| 医薬品 | Pharmaceuticals -> Antihypertensives |
| LogP（分配係数） | 2.13.38 |
| 溶解度 | 0.8%7.90e-01 g/LSoluble in DMSO |
| Human Drugs | Breast FeedingLactationMilk, HumanAdrenergic alpha-AntagonistsAntihypertensive Agents |
| 融点 | 275-277289 - 290 °C289-290°C |
| Physical Description | Solid |
| Dissociation Constants | 6.52 |
| Collision Cross Section | 202.9 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]196.92 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| 沸点 | 718.0±70.0 °C(Predicted) |
| 密度 | 1.371±0.06 g/cm3(Predicted) |
| 貯蔵条件 | Store at -20°C |
| 外観・状態 | Powder |
| pKa（酸解離定数） | 6.52±0.50(Predicted) |
| 色 | White to off-white |
| CAS データベース | 74191-85-8(CAS DataBase Reference) |
安全性と法規制
| GHS 分類 | DangerH302 (20%): Harmful if swallowed [Warning Acute toxicity, oral]P260, P264, P270, P273, P280, P301+P317, P301+P330+P331, P302+P361+P354, P304+P340, P305+P354+P338, P316, P319, P321, P330, P363, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 5 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 規制情報 | Status: Active Update: 01-07-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/31210 |
| Hazard Classes and Categories | Skin Corr. 1B (80%) |
| Hepatotoxicity | Doxazosin has been associated with a low rate of serum aminotransferase elevations that in controlled trials was no higher than with placebo therapy. These elevations were transient and did not require dose modification. No instances of clinically apparent acute liver injury due to doxazosin have been published in the literature, but reports of cholestatic hepatitis have been received by the sponsor. Among the alpha adrenergic receptor antagonists, the most frequently implicated agent in causing liver injury has been alfuzosin with only single, and not well documented cases linked to other alpha blockers. Thus, acute symptomatic liver injury due to doxazosin is quite rare, and severe hepatotoxicity must be exceeding rare, if it occurs at all. |
| 有害作用 | Dose-related Adverse Effects |
| 毒性の概要 | Reports with overdosage and toxicity with the alpha-1 antagonists, including doxazosin, remain very limited in the literature. There is a report of one case of acute doxazosin overdose in 2005. The study found that the patient presented to the emergency department (ED) with drowsiness, decreased blood pressure, and reflex tachycardia but did not have orthostatic hypotension or any other abnormalities. This patient was able to fully awaken with supportive therapy in 8 hours and was discharged 48 hours after admission to the ED. Although there are limited works of literature for the toxicity of doxazosin, it appears to have low acute toxicity. |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)doxazosinDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
用途
説明
Doxazosin mesylate is a selective alpha, blocker indicated for the treatment of hypertension, reportedly of special benefit as a first-line agent in the most hypertonic patient population. Another advantage of doxazosin is its favorable effect on blood lipids; it significantly increases the HDL/total cholesterol ratio and decreases the total cholesterol as well as triglycerides levels.
使用
ACIPHEX therapeutic Erosive or Ulcerative Gastroesophageal Reflux Disease
一般的な説明
Doxazosin, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazine(Cardura), is a quinazoline compound that selectively inhibitsthe α1-subtype of α-adrenergic receptors. This agentis very useful in the management of hypertension associatedwith pheochromocytoma.