2-{[(1S,2S,3aR,9aR)-2-hydroxy-1-[(3R)-3-hydroxyoctyl]-1H,2H,3H,3aH,4H,9H,9aH-cyclopenta[b]naphthalen-5-yl]oxy}acetic acid

• ChemBase编号: 258
• 分子式: C23H34O5
• 平均质量: 390.51306
• 单一同位素质量: 390.24062419
• SMILES: O[C@@H]1[C@H]([C@H]2[C@@H](C1)Cc1c(C2)cccc1OCC(=O)O)CC[C@H](O)CCCCC
• Canonical SMILES: CCCCC[C@H](CC[C@@H]1[C@@H](O)C[C@@H]2[C@H]1Cc1cccc(c1C2)OCC(=O)O)O
• InChI: InChI=1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m1/s1
• InChIKey: PAJMKGZZBBTTOY-YRIDSSQKSA-N

名称和登记号

名称

• IUPAC标准名: 2-{[(1S,2S,3aR,9aR)-2-hydroxy-1-[(3R)-3-hydroxyoctyl]-1H,2H,3H,3aH,4H,9H,9aH-cyclopenta[b]naphthalen-5-yl]oxy}acetic acid
• IUPAC传统名: viveta
• 商标名: Remodulin; Viveta
• 别名: treprostinil; Treprostinil

登记号

• CAS号: 81846-19-7
• PubChem SID: 160963721
• PubChem CID: 54786

理论计算性质

JChem

• Acid pKa: 3.760436
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): 2.2637904
• LogD (pH = 7.4): 0.7241018
• Log P: 4.0042095
• 摩尔折射率: 108.0016 cm^3
• 极化性: 42.45696 Å^3
• 极化表面积: 86.99 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.53
• LOG S: -4.73
• 溶解度: 7.31e-03 g/l

分子性质

理化性质

• 溶解度: Insoluble at 25°C
• 疏水性(logP): 4.1

详细说明

DrugBank - DB00374

• Drug Groups: approved; investigational
• Description: Treprostinil is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. Treprostinil is marketed as Remodulin®. [Wikipedia]
• Indication: For use as a continuous subcutaneous infusion or intravenous infusion (for those not able to tolerate a subcutaneous infusion) for the treatment of pulmonary arterial hypertension in patients with NYHA Class II-IV symptoms to diminish symptoms associated with exercise.
• Pharmacology: Pulmonary arterial hypertension (PAH) is a disease in which blood pressure is abnormally high in the arteries between the heart and lungs. PAH is characterized by symptoms of shortness of breath during physical exertion. The condition can ultimately lead to heart failure. Treprostinil is a potent oral antiplatelet agent. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed.
• Toxicity: Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of treprostinil.
• Affected Organisms: Humans and other mammals
• Biotransformation: Substantially metabolized by the liver, but the precise enzymes responsible are unknown. Five metabolites have been described (HU1 through HU5) however, the biological activity and metabolic fate of these are unknown. The chemical structure of HU1 is unknown. The metabolite HU5 is the glucuronide conjugate of treprostinil. The other metabolites are formed by oxidation of the 3-hydroxyoctyl side chain (HU2) and subsequent additional oxidation (HU3) or dehydration (HU4). Study results of in vitro human hepatic cytochrome P450 demonstrates that treprostinil does not inhibit CYP-1A2, 2C9, 2C19, 2D6, 2E1, or 3A. Whether treprostinil induces these enzymes has not been studied.
• Absorption: Relatively rapid and complete after subcutaneous infusion, with an absolute bioavailability approximately 100%. In patients with mild (n=4) or moderate (n=5) hepatic insufficiency and portopulmonary hypertension following a subcutaneous dose of 10 ng per kg of body weight per min for 150 mins the AUC 0-∞ was increased 3-fold and 5-fold respectively.
• Half Life: Terminal elimination half-life is approximately 2 to 4 hours. Plasma half-life is 34 and 85 minutes for intravenous and subcutaneous infusion of the drug, respectively.
• Protein Binding: Human plasma protein binding is approximately 91% in in vitro concentrations ranging from 330 to 10,000 µ/L.
• Distribution: * 14 L/70 kg
• External Links: Wikipedia; RxList; Drugs.com