惕格列定

化学物质

惕格列定(英文:tigloidine)是一种托品烷生物碱,化学式:C13H21NO2,其作为一种生物碱广泛分布于茄科植物中,包括软木茄(学名:Duboisia myoporoides[1],灯笼果(学名:Physalis peruviana[2]曼陀罗等。为惕格酸与3β-托品醇的。临床上常作抗胆碱剂,用于治疗帕金森等神经退行疾病[3]。商品名为托品林(Tropigline)[4]

惕格列定
Tigloidine
臨床資料
商品名英语Drug nomenclature托品林
Tropigline
其他名稱巴豆酰莨菪碱、惕格酰莨菪碱、惕格酰假托品(3β-tigloyloxytropane)
识别信息
  • (8-Methyl-8-azabicyclo[3.2.1]octan-3-yl) (E)-2-methylbut-2-enoate
CAS号495-83-0  checkY
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.007.101 編輯維基數據鏈接
化学信息
化学式C13H21NO2
摩尔质量223.32 g·mol−1
3D模型(JSmol英语JSmol
  • CC=C(C)C(=O)OC1CC2CCC(C1)N2C
  • InChI=1S/C13H21NO2/c1-4-9(2)13(15)16-12-7-10-5-6-11(8-12)14(10)3/h4,10-12H,5-8H2,1-3H3/b9-4+
  • Key:UVHGSMZRSVGWDJ-RUDMXATFSA-N

生物合成

惕格列定作为茄科植物次级代谢产物托品烷生物碱的一种[5],其生物合成主要由托品酮经还原酶还原成3β-托品醇(假托品醇),然后与惕格酰假托品合成酶催化3β-托品醇与惕格酰辅酶A(tigloyl-CoA)发生酯化反应得到[6]

医学用途

1950年Trautner和McCallum发现惕格列定使反复刺激的牛蛙缝匠肌产生疲劳,60年代报道其对帕金森病、亨廷顿舞蹈症、痉挛性截瘫有效果[7]。1968年美国批准其用于治疗帕金森病[8]

惕格列定是阿托品的替代药物,用于治疗帕金森。与阿托品相比,其头痛、喉咙干燥、瞳孔扩大等不良反应率更低[6]

参考文献

  1. ^ Barger G, Martin WF, Mitchell W. 383. The minor alkaloids of Duboisia myoporoides. Journal of the Chemical Society (Resumed). 1937: 1820. doi:10.1039/JR9370001820. hdl:1842/35366 . 
  2. ^ Beresford PJ, Woolley JG. Biosynthesis of ticloidine in Physalis peruviana. Phytochemistry. 1974, 13 (10): 2143–2144. Bibcode:1974PChem..13.2143B. doi:10.1016/0031-9422(74)85016-8. 
  3. ^ Approved Names. British Medical Journal. 1958, 1 (5080): 1175. PMC 2028565 . doi:10.1136/bmj.1.5080.1175. 
  4. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000: 1663–. ISBN 978-3-88763-075-1. 
  5. ^ S Rodriguez, U Uria, E Reyes, L Prieto, M Rodríguez-Rodríguez, L Carrillo, JL Vicario. Enantioselective construction of the 8-azabicyclo [3.2. 1] octane scaffold: application in the synthesis of tropane alkaloids. Organic & Biomolecular Chemistry. 2021, (19): 3763–3775. PMID 33949549. doi:10.1039/d1ob00143d. 
  6. ^ 6.0 6.1 Junlan Zeng, Xiaoqiang Liu, Zhaoyue Dong; et al. Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane. Nature Communications. 2024, (15): 3623. doi:10.1038/s41467-024-47968-0. 
  7. ^ I Sanghvi, E Bindler, S Gershon. Pharmacology of a potential anti-parkinson agent: tigloidine. European Journal of Pharmacology. 1968, 4 (3): 246–253. doi:10.1016/0014-2999(68)90091-5. 
  8. ^ Parkinson's Disease Information and Research Center (New York, N.Y.). Parkinson's Disease & Related Disorders; Cumulative Bibliography: 1800-1970: Subject index. National Institute of Neurological Diseases and Stroke. 1971: 1988.