Manidipine

Manidipine
Clinical data
Trade names	Manyper, Caldine, etc.
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	C08CA11 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name (±)-2-[4-(Diphenylmethyl)piperazin-1-yl]ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate;
CAS Number	89226-50-6 120092-68-4;
PubChem CID	4008;
ChemSpider	3868;
UNII	6O4754US88;
CompTox Dashboard (EPA)	DTXSID2043745 ;
Chemical and physical data
Formula	C35H38N4O6
Molar mass	610.711 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES [O-][N+](=O)c1cccc(c1)C5C(/C(=O)OC)=C(\N\C(=C5\C(=O)OCCN4CCN(C(c2ccccc2)c3ccccc3)CC4)C)C;
	InChI InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3;

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

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

^ Cheer SM, McClellan K (2001). "Manidipine: a review of its use in hypertension". Drugs. 61 (12): 1777–1799. doi:10.2165/00003495-200161120-00010. PMID 11693466. S2CID 260814599. Archived from the original on 2013-01-17. Retrieved 2009-06-20.
^ McKeage K, Scott LJ (2004). "Manidipine: a review of its use in the management of hypertension". Drugs. 64 (17): 1923–1940. doi:10.2165/00003495-200464170-00011. PMID 15329044. S2CID 195689527. Archived from the original on 2013-01-16. Retrieved 2009-06-20.
^ Roca-Cusachs A, Triposkiadis F (2005). "Antihypertensive effect of manidipine". Drugs. 65 (Suppl 2): 11–19. doi:10.2165/00003495-200565002-00003. PMID 16398058. S2CID 25854593. Archived from the original on 2013-01-16. Retrieved 2009-06-20.
^ Otero ML (2007). "Manidipine-delapril combination in the management of hypertension". Vascular Health and Risk Management. 3 (3): 255–263. PMC 2293964. PMID 17703633.
^ Mizuno K, Haga H, Takahashi M, Fukuchi S (August 1992). "Evaluation of manidipine hydrochloride, a new calcium antagonist, in the treatment of hypertensive patients with renal disorders". Current Therapeutic Research. 52 (2): 248–253. doi:10.1016/S0011-393X(05)80475-8.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 465. ISBN 9783527607495.
^ 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.
^ EP0094159 idem Kanji Meguro & Akinobu Nagaoka, US4892875 (1990 to Takeda Pharmaceutical Co Ltd).
^ Dharmaraj Ramachandra Rao, Rajendra Narayanrao Kankan, Maruti Ganpati Ghagare, WO20110203954 (2011 to Cipla Limited, Curtis, Philip Anthony).
^ 刘玉海, et al. CN105924382 (2018).
^ 金晓峰, et al. CN102875451 (2014 to CHANGZHOU PHARMACEUTICAL FACTORY CO LTD).
^ 刘忠春, CN107337632 (2017).
^ 谷志勇, et al. CN104292150 (2015).
^ , CN103351362 (2013 to).
^ http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZHOU200402000.htm