BENIDIPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C28H31N3O6
Molecular Weight	505.5622
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC(=O)C1=C(C)NC(C)=C([C@@H]1C2=CC(=CC=C2)[N+]([O-])=O)C(=O)O[C@@H]3CCCN(CC4=CC=CC=C4)C3

InChI

InChIKey=QZVNQOLPLYWLHQ-ZEQKJWHPSA-N

InChI=1S/C28H31N3O6/c1-18-24(27(32)36-3)26(21-11-7-12-22(15-21)31(34)35)25(19(2)29-18)28(33)37-23-13-8-14-30(17-23)16-20-9-5-4-6-10-20/h4-7,9-12,15,23,26,29H,8,13-14,16-17H2,1-3H3/t23-,26-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16565579

Benidipine is an orally triple L-, T-, and N-type calcium channel blocker for the treatment of hypertension and angina pectoris synthesized and developed by Kyowa Hakko Kogyo Co., Ltd. Benidipine, approved in Japan in November 1991, has become one of the three best selling CCBs and is highly useful as a potent, long-lasting antihypertensive and antianginal agent.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Voltage-gated L-type calcium channel 92 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2624603	Blocker 537	0.32 nM [Kd]
Voltage-gated N-type calcium channel alpha-1B subunit 12 Target ID: CHEMBL4478 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10525060	Blocker 537
Voltage-gated T-type calcium channel 17 Target ID: CHEMBL2362995 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15725949	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://kyowa-kirin.com/products/coniel/index.html	Primary		Approved 8429	CONIEL Approved Use CONIEL is a calcium channel blocker and extensive clinical testing has demonstrated the sustained efficacy and effectiveness of this agent. A large body of evidence including clinical data and analyses demonstrates that CONIEL protects the heart, kidneys and brain from the effects of hypertension and angina pectoris. Launch Date 6.8886718E11
Angina pectoris 106 Sources: http://kyowa-kirin.com/products/coniel/index.html	Primary		Approved 8429	CONIEL Approved Use CONIEL is a calcium channel blocker and extensive clinical testing has demonstrated the sustained efficacy and effectiveness of this agent. A large body of evidence including clinical data and analyses demonstrates that CONIEL protects the heart, kidneys and brain from the effects of hypertension and angina pectoris. Launch Date 6.8886718E11

PubMed

Title	Date	PubMed
[Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats].	1999 May	10480159
Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions.	2000 Feb-Mar	10805063
Interaction of digoxin with antihypertensive drugs via MDR1.	2002 Feb 15	11895100
A case of exercise-induced acute renal failure in a patient with idiopathic renal hypouricemia developed during antihypertensive therapy with losartan and trichlormethiazide.	2003 Jun	12862209
Benidipine, a long-acting calcium channel blocker, inhibits cardiac remodeling in pressure-overloaded mice.	2005 Mar 1	15721868
Subdepressor dose of benidipine ameliorates diabetic cardiac remodeling accompanied by normalization of upregulated endothelin system in rats.	2006 May	16387788
Renal-protective effect of T-and L-type calcium channel blockers in hypertensive patients: an Amlodipine-to-Benidipine Changeover (ABC) study.	2007 Sep	18037772
Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a dihydropyridine calcium channel blocker, inhibits aldosterone production in human adrenocortical cell line NCI-H295R.	2008 Apr 28	18331727

Patents

Sample Use Guides

In Vivo Use Guide

Orally, 4 mg/day

Route of Administration: Oral

In Vitro Use Guide

The oocytes expressing select Ca channels were cultured for 2 to 4 days and then subjected to electrophysiological measurement. The oocytes were placed in a small chamber perfused with extracellular solution , and Ba2+ currents through expressed channels were measured by the two-microelectrode voltageclamp method. The experimental chamber was 0.5 ml in volume, and it was perfused continuously with the extracellular solution. Typically, oocytes were clamped at a holding potential of 2100, 280, or 260 mV and depolarized to 110 mV for 200 ms every 15 s. Microelectrodes were filled with 3 M KCl, and those showing a resistance of 0.5 to 1.2 VM were used. Benidine was evaluated in concentration range of 0.1 - 100 uM, and demonstrated blocking effect with IC50 of 0.7 uM.

Name

Type

Language

BENIDIPINE

Official Name

English

Benidipine [WHO-DD]

Common Name

English

BENIDIPINE [MI]

Common Name

English

(±)-(R*)-3-((R*)-1-BENZYL-3-PIPERIDYL) METHYL 1,4-DIHYDRO-2,6-DIMETHYL-4-(M-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLATE

Systematic Name

English

(±)-2,6-DIMETHYL-4-(3-NITROPHENYL)-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLIC ACID-3-(1-BENZYL-3-PIPERIDYL) ESTER-5-METHYL ESTER

Common Name

English

benidipine [INN]

Common Name

English

(4R)-REL-1,4-DIHYDRO-2,6-DIMETHYL-4-(3-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLIC ACID METHYL (3R)-1-(PHENYLMETHYL)-3-PIPERIDINYL ESTER

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC08CA15