Manidipine

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Manidipine is a calcium channel blocker (dihydropyridine type) that is used clinically as an antihypertensive.[1][2][3][4][5]

It was patented in 1982 and approved for medical use in 1990.[6]

Synthesis

File:Manidipine synthesis.svg
Thieme Synthesis:[7] Patent:[8] Sino:[9][10][11][12][13][14][15]

The alkylation between N-(2-hydroxyethyl)piperazine [103-76-4] (1) and Benzhydryl Bromide [776-74-9] (2) gives 2-(4-benzhydrylpiperazin-1-yl)ethanol [10527-64-7] (3). The reaction with Diketene [674-82-8] (4) gives 2-(4-benzhydryl-1-piperazinyl)ethyl acetoacetate [89226-49-3] (5). The reaction with 3-nitrobenzaldehyde [99-61-6] (6) and Methyl 3-aminocrotonate [14205-39-1] (7) completed the synthesis of Manidipine (8).

References

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  7. Meguro, Kanji; Aizawa, Masahiro; Sohda, Takashi; Kawamatsu, Yutaka; Nagaoka, Akinobu (1985). "New 1,4-dihydropyridine derivatives with potent and long-lasting hypotensive effect.". CHEMICAL & PHARMACEUTICAL BULLETIN. 33 (9): 3787–3797. ISSN 0009-2363. doi:10.1248/cpb.33.3787.
  8. EP0094159 idem Kanji Meguro & Akinobu Nagaoka, US4892875 (1990 to Takeda Pharmaceutical Co Ltd).
  9. Dharmaraj Ramachandra Rao, Rajendra Narayanrao Kankan, Maruti Ganpati Ghagare, WO20110203954 (2011 to Cipla Limited, Curtis, Philip Anthony).
  10. 刘玉海, et al. CN105924382 (2018).
  11. 金晓峰, et al. CN102875451 (2014 to CHANGZHOU PHARMACEUTICAL FACTORY CO LTD).
  12. 刘忠春, CN107337632 (2017).
  13. 谷志勇, et al. CN104292150 (2015).
  14. , CN103351362 (2013 to).
  15. http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZHOU200402000.htm Template:Bare URL inline

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