(1S,5R,13R,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one

• ChemBase编号: 212
• 分子式: C17H19NO3
• 平均质量: 285.33766
• 单一同位素质量: 285.13649347
• SMILES: O1[C@@H]2[C@]34[C@H]([C@H](N(CC3)C)Cc3c4c1c(O)cc3)CCC2=O
• Canonical SMILES: O=C1CC[C@@H]2[C@@]34[C@H]1Oc1c4c(C[C@H]2N(CC3)C)ccc1O
• InChI: InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19H,3,5-8H2,1H3/t10-,11+,16-,17-/m0/s1
• InChIKey: WVLOADHCBXTIJK-YNHQPCIGSA-N

名称和登记号

名称

• IUPAC标准名: (1S,5R,13R,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^{1,13}.0^{5,17}.0^{7,18}]octadeca-7(18),8,10-trien-14-one; (1S,5R,13R,17R)-10-hydroxy-4-methyl-12-oxa-4-azapentacyclo[9.6.1.0^1,^1^3.0^5,^1^7.0^7,^1^8]octadeca-7,9,11(18)-trien-14-one
• IUPAC传统名: hydromorphone
• 商标名: DiMo; Dilaudid; Dilaudid Oros; Dilaudid-hp; Dimorphone; Hymorphan; Idromorfone; Laudacon; Laudicon; Novolaudon; Palladone; Paramorphan
• 别名: Dihydromorfinon [Czech]; Dihydromorphinone; Hidromorfona [INN-Spanish]; Hydromorfona [Spanish]; Hydromorphon; Hydromorphone HCL; Hydromorphonum [INN-Latin]; Hydromorphone

登记号

• CAS号: 466-99-9
• PubChem SID: 160963675; 46508700
• PubChem CID: 5284570
• CHEBI ID: 5790
• ATC码: N02AA03
• CHEMBL: 398707
• Chemspider ID: 4447624
• DrugBank ID: DB00327
• KEGG ID: D08047
• 美国药典/FDA物质标识码: Q812464R06
• 维基百科标题: Hydromorphone
• Medline Plus: a682013

理论计算性质

JChem

• Acid pKa: 10.107628
• 质子受体: 4
• 质子供体: 1
• LogD (pH = 5.5): -1.1500992
• LogD (pH = 7.4): 0.57617587
• Log P: 1.6227497
• 摩尔折射率: 78.2624 cm^3
• 极化性: 30.4739 Å^3
• 极化表面积: 49.77 Å^2
• 可自由旋转的化学键: 0
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.69
• LOG S: -1.81
• 溶解度: 4.39e+00 g/l

分子性质

理化性质

• 溶解度: HCl: 333 mg/mL (20°C)
• 疏水性(logP): 0.9

药理学性质

• 给药途径: oral, intramuscular, intravenous, subcutaneous, intranasal, rectal, sublingual, transmucosal, buccal, transdermal (experimental)
• 生物利用度: Oral: 30–35%, Intranasal: 52–58%
• 排泄: Renal
• 半衰期: 2–3 hours
• 代谢: Hepatic
• 蛋白结合率: 20%
• 法定药品分级: Class A—Non-Clinical use—and Schedule II—Clinical use (UK), ; DEA Schedule II (USA), S8 (AU)
• 妊娠期药物分类: C

详细说明

DrugBank - DB00327

• Drug Groups: illicit; approved
• Description: An opioid analgesic derived from morphine and used mainly as an analgesic. It has a shorter duration of action and is more potent than morphine. [PubChem]
• Indication: For the relief of moderate to severe pain such as that due to surgery, cancer, trauma/injury, or burns.
• Pharmacology: Hydromorphone is a hydrogenated ketone derivative of morphine that acts as a narcotic analgesic. It has a shorter duration of action than morphine. Hydromorphone is approximately 8 times more potent on a milligram basis than morphine. In addition, hydromorphone is better absorbed orally than is morphine. In clinical settings, Hydromorphone exerts its principal pharmacological effect on the central nervous system and gastrointestinal tract. Its primary actions of therapeutic value are analgesia and sedation. Hydromorphone appears to increase the patient's tolerance for pain and to decrease discomfort, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Opioids also produce respiratory depression by direct action on brain stem respiratory centers.
• Toxicity: Hydromorphone is a schedule II narcotic which can lead to physical dependence or addiction. High doses lead to respiratory depression, nausea, and vomiting. Overdoses lead to extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic. After absorption hydromorphone is metabolized by the liver to the glucuronide conjugate which is then excreted in the urine. Hydromorphone is metabolized to the major metabolites hydromorphone-3-glucuronide, hydromorphone-3-glucoside and dihydroisomorphine-6-glucuronide.
• Absorption: Better absorbed orally than morphine
• Half Life: 2.6 hours (oral); 18.6 hours for sustained release Palladone
• Protein Binding: 20%
• Elimination: Only a small amount of the hydromorphone dose is excreted unchanged in the urine. ; Most of the dose is excreted as hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.
• Clearance: * 1.96 L/min
• References: Coda BA, Rudy AC, Archer SM, Wermeling DP: Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2003 Jul;97(1):117-23, table of contents. [Pubmed] ; Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL: Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol. 1981 Apr;21(4):152-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

参考文献

• Coda BA, Rudy AC, Archer SM, Wermeling DP: Pharmacokinetics and bioavailability of single-dose intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2003 Jul;97(1):117-23, table of contents. Pubmed
• Vallner JJ, Stewart JT, Kotzan JA, Kirsten EB, Honigberg IL: Pharmacokinetics and bioavailability of hydromorphone following intravenous and oral administration to human subjects. J Clin Pharmacol. 1981 Apr;21(4):152-6. Pubmed