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【结 构 式】 
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【药物名称】Pentacaine hydrochloride, Trapencaine hydrochloride, K-1902, Anulcen 【化学名称】(±)-trans-3-(n-Pentyloxy)carbanilic acid 2-(1-pyrrolidinyl)cyclohexyl ester monohydrochloride 【CA登记号】77656-21-4, 104485-01-0 (free base) 【 分 子 式 】C22H35ClN2O3 【 分 子 量 】410.98885 |
【开发单位】Slovak Acad. Sci. (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Anesthetic Drugs, Anti-Helicobacter Pylori Agents, Antispasmodics, Antiulcer Drugs, GASTROINTESTINAL DRUGS, Local Anesthetics |
合成路线1
Trapencaine is prepared from 3-(n-pentyloxy)phenylisocyanate and (+)-trans-2-(1-pyrrolidinyl)cyclohexanol in dry benzene or some other inert solvent. Stereochemically pure isomer is obtained by treatment of the pure base with hydrochloric acid, yielding the corresponding salt.
| 【1】 Benes, L.; Trapencaine Hydrochloride. Drugs Fut 1991, 16, 7, 627. |
| 【2】 Benes, L.; Borovansky, A.; Kopácová, L.; Alkoxycarbanilic acid esters with high local anaesthetic activity. Arzneim-Forsch Drug Res 1969, 19, 1902-3. |
合成路线2
By refluxing a solution of equimolecular quantities of 3-pentyloxyphenyl isocyanate (I) and trans-2-(1-pyrrolidinyl)cyclohexanol (II) in toluene. The obtained pentacaine base is transformed to the hydrochloride by treatment of an ether solution of anhydrous hydrogen chloride (1,2). The starting amino-alcohol (II) is prepared from cyclohexanol (III), which is first dehydrated to cyclohexene (IV). The following addition of HClO gives trans-2-chlorocyclohexanol (V), which, in turn is dehydrochlorinated to 1,2-epoxycyclohexane (VI). Final addition of pyrrolidine (A) yields the required intermediate (II).
| 【1】 Castaner, J.; Pentacaine. Drugs Fut 1976, 1, 8, 379. |
| 【2】 Subert, J.; et al.; Studies on local anesthetics. XLVIII. Preliminary analytical evaluation of the substance K-1902 (pentacaine). Cesk Farm 1975, 24, 5. |
| 【3】 Benes, L.; Borovansky, A.; Kopácová, L.; Basische trans- und cis-Cyklohexylester substituierter Alkoxycarbanilsäuren. XLI. Studien über Lokalanästhetika. Arch Pharm 1972, 305, 648. |
| 【4】 Benes, L.; Borovansky, A.; Kopácová, L.; Alkoxycarbanilic acid esters with high local anaesthetic activity. Arzneim-Forsch Drug Res 1969, 19, 1902-3. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (I) | 14636 | 3-(pentyloxy)phenyl isocyanate; 1-isocyanato-3-(pentyloxy)benzene | C12H15NO2 | 详情 | 详情 | |
| (II) | 14637 | (1R,2R)-2-(1-pyrrolidinyl)cyclohexanol | C10H19NO | 详情 | 详情 | |
| (III) | 11306 | Cyclohexanol | 108-93-0 | C6H12O | 详情 | 详情 |
| (IV) | 40446 | 1-cyclohexene | 110-83-8 | C6H10 | 详情 | 详情 |
| (V) | 40447 | (1R,2R)-2-chlorocyclohexanol | 1561-86-0 | C6H11ClO | 详情 | 详情 |
| (VI) | 40448 | (1R,6R)-7-oxabicyclo[4.1.0]heptane | C6H10O | 详情 | 详情 |