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特拉唑嗪
降压宁 · 特拉唑嗪 · 盐酸四喃唑嗪 · 哌唑嗪四氢杂质 · 特拉唑嗪标准品 · 哌唑嗪四氢化杂质 · 哌嗪四氢呋喃杂质 · 化合物 TERAZOSIN
标识与物理属性
| CAS No. | 63590-64-7 |
|---|---|
| 分子式 | C19H25N5O4 |
| 平均分子量 | 387.4 g/mol |
| 单同位素质量 | 387.19065428 g/mol |
| SMILES | COc1cc2nc(N3CCN(C(=O)C4CCCO4)CC3)nc(N)c2cc1OC |
| InChIKey | VCKUSRYTPJJLNI-UHFFFAOYSA-N |
| PubChem CID | 5401 |
| ChEMBL | CHEMBL611 |
| ChEBI | CHEBI:9445 |
| EC No. | 613-265-8 |
| DTXSID | DTXSID3023639 |
| 中文名 | 特拉唑嗪 |
化学与物理性质
| XLogP | 1.4 |
|---|---|
| 极性表面积 | 103 |
| 氢键供体 | 1 |
| 氢键受体 | 8 |
| 可旋转键 | 4 |
| 重原子 | 28 |
| 形式电荷 | 0 |
| 复杂度 | 544 |
| 药物 | Pharmaceuticals -> Antihypertensives |
| LogP（油水分配系数） | 11.14 |
| 溶解性 | 1.50e+00 g/LH2O: 25 mg/mL30.6mg/L(22.5 ºC) |
| Human Drugs | Breast FeedingLactationMilk, HumanAdrenergic alpha-AntagonistsAntihypertensive AgentsPharmaceuticals |
| 熔点 | 271-274273 °C281-283°C |
| Physical Description | Solid |
| Collision Cross Section | 189.79 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| 沸点 | 664.5±65.0 °C(Predicted) |
| 密度 | 1.332±0.06 g/cm3(Predicted) |
| 储存条件 | -20°C Freezer |
| 形态 | powder |
| pKa（酸度系数） | pKa (0.1N NaOH): 7.1(at 25℃) |
| 颜色 | white to off-white |
| BCS Class | 1/3 |
| InChIKey | VCKUSRYTPJJLNI-UHFFFAOYSA-N |
| CAS 数据库 | 63590-64-7(CAS DataBase Reference) |
化学性质
细微白色结晶，无臭无味，熔点272.6～174℃。25℃的溶解度(mg/m1)：甲醇33.7，水29.7，95%乙醇4.1，0.1mol/L盐酸3,8，氯仿1.2，丙酮0.01。几不溶于己烷。UV最大吸收(0.005%水)：212，245，330nm(a 65.7，127.5，24.0)。pKa(0.1mol/L氢氧化钠)7.1。盐酸特拉唑嗪(Terazosin Hydrochloride)：C19H25N5O4HCl。从异丙醇结晶，有吸湿性。熔点278～279℃。溶于水：761.2mg/ml。急性毒性LD50小鼠(mg/kg)：259.3静脉注射。盐酸特拉唑嗪二水合物：C19H25N5O4HCl2H2O。[70024-40-7]。熔点271～274℃。溶于水：24.2mg/ml。急性毒性LD50雄、雌大鼠(mg/kg)：277，293静脉注射。
安全与法规
| GHS 分类 | This chemical does not meet GHS hazard criteria for 2.3% (1 of 44) of reports.WarningH302 (97.7%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 44 reports by companies from 3 notifications to the ECHA C&L Inventory. |
|---|---|
| 法规信息 | Status: Active Update: 25-07-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/25502 |
| Hazard Classes and Categories | Acute Tox. 4 (97.7%) |
| Treatment | Should overdosage of Terazosin lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Terazosin is highly protein boundtherefore, dialysis may not be of benefit. (L1712) |
| 健康影响 | Hypotension, palpitations, postural hypotension, syncope, peripheral edema, weight gain, dyspnea, nasal congestion/rhinitis, impotence. |
| Hepatotoxicity | Terazosin 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. Instances of serum enzyme elevations, but no instances of clinically apparent acute liver injury with jaundice due to terazosin, have been published. Furthermore, product labels do not include discussion of hepatic toxicity. Cholestatic hepatitis and jaundice have been reported with other alpha-adrenergic blockers. Thus, acute symptomatic liver injury due to terazosin must be exceedingly rare if it occurs at all. |
| 不良影响 | Terazosin is generally well-tolerated. Many adverse effects of terazosin are explainable due to its blockade of alpha-1 adrenergic receptors. |
| 暴露途径 | Oral. Essentially completely absorbed in man (90% bioavailability). |
| 毒性概述 | Overdose of terazosin may lead to hypotension, and standard life-support protocols should be in place for instances of hemodynamic instability. There are no specific antidotes for terazosin toxicity. Vasopressors may be used to support physiologic blood pressure parameters in the event of terazosin overdose. Terazosin is long-acting, with an elimination half-life of approximately 12 hours, and is highly protein-bound. Elimination is via renal excretion (40%) and excretion of feces (60%).Terazosin selectively and competitively inhibits vascular postsynaptic alpha(1)-adrenergic receptors, resulting in peripheral vasodilation and a reduction of vascular resistance and blood pressure. Unlike the nonselective alph-adrenergic blockers phenoxybenzamine and phentolamine, terazosin does not block presynaptic alpha(2)-receptors and, hence, does not cause reflex activation of norepinephrine release to produce reflex tachycardia. |
| Signs and Symptoms | Asthenia, postural hypotension, dizziness, somnolence, nasal congestion/rhinitis. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)terazosinDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| Toxicity Data | LD50: 259.3mg/kg (parental-intravenous, Mouse) (A308) |
| 水危害等级（WGK） | 3 |
| RTECS 号 | TK8044925 |
| 安全说明（S） | 26-36 |
| 危险品标志 | Xn,Xi |
| 危险类别码（R） | 22-36/37/38 |
用途与应用
用途
抗高血压药。
用途
为喹唑啉衍生物，α1-受体阻滞剂，具有良好的降压作用。用于肾性，原发性轻、中度高血压和由细胞瘤引起的高血压。
制备与合成方法
生产方法
以糠酸为原料，用氯化亚砜氯化生成糠酰氯，再对哌嗪进行单酰化，单酰化产物还原后与4-氨基-2-氯-6，7-二甲氧基喹唑啉在三乙胺存在下缩合，即得特拉唑嗪。在乙醇中用盐酸酸化可得含两个结晶水的盐酸特拉唑嗪。