MONATEPIL

Details

Stereochemistry	RACEMIC
Molecular Formula	C28H30FN3OS
Molecular Weight	475.621
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC1=CC=C(C=C1)N2CCN(CCCC(=O)NC3C4=C(CSC5=C3C=CC=C5)C=CC=C4)CC2

InChI

InChIKey=WFNRNNUZFPVBSM-UHFFFAOYSA-N

InChI=1S/C28H30FN3OS/c29-22-11-13-23(14-12-22)32-18-16-31(17-19-32)15-5-10-27(33)30-28-24-7-2-1-6-21(24)20-34-26-9-4-3-8-25(26)28/h1-4,6-9,11-14,28H,5,10,15-20H2,(H,30,33)

HIDE SMILES / InChI

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/7826563
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/7496051

Monatepil is a calcium antagonist that, as do existing calcium antagonists, inhibits the influx of extracellular Ca 2 + through voltage-dependent Ca 2 + channels. It is a new type of antihypertensive agent. Its unique chemical structure was specially designed with intrinsic calcium antagonist and a1 -adrenoceptor-blocking moieties, creating a dual mechanism of action. Positive effects on plasma lipid metabolism are derived from the a1 -adrenoceptor-blocking activity and the antiatherosclerotic effect derives from the calcium antagonist properties. The novel structure of monatepil produces a slow onset of action and a long-lasting antihypertensive effect in experimental animals.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acyl-CoA:cholesterol acyltransferase (Macaca fuscata) 2 Target ID: Acyl-CoA:cholesterol acyltransferase (Macaca fuscata) Sources: http://www.ncbi.nlm.nih.gov/pubmed/9234833	Inhibitor 8297
artery smooth muscle contraction 2 Target ID: GO:0014824 Sources: http://www.ncbi.nlm.nih.gov/pubmed/7509897	Inhibitor 8297	20.8 nM [IC50]
calcium ion import 8 Target ID: GO:0070509 Sources: http://www.ncbi.nlm.nih.gov/pubmed/2002473	Inhibitor 8297	16.0 nM [IC50]
Adrenergic receptor alpha-1 169 Target ID: CHEMBL2094251 Sources: http://adisinsight.springer.com/drugs/800001558	Antagonist 2778
Lipid hydroperoxidation of low density lipoprotein 2 Target ID: Lipid hydroperoxidation of low density lipoprotein Sources: http://www.ncbi.nlm.nih.gov/pubmed/8740082	Inhibitor 8297	28.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Atherosclerosis 74 Sources: http://www.ncbi.nlm.nih.gov/pubmed/7826566	Primary		Preclinical	Unknown Approved Use Unknown
Hypertension 567 Sources: http://www.ncbi.nlm.nih.gov/pubmed/7826567	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Inhibition of vasoconstriction by AJ-2615, a novel calcium antagonist with alpha(1)-adrenergic receptor blocking activity in human conduit arteries used as bypass grafts.	2001 Sep	11560560

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of essential hypertension: The initial dose of monatepil was 30 mg/day in monotherapy and 15 mg/day in combination therapy; the daily dose was titrated to 60 mg/day according to the antihypertensive response.

Route of Administration: Oral

In Vitro Use Guide

Treatment of human skin fibroblasts with 2 x 10(-5) M of monatepil for 6 hours resulted in an increase in LDL receptor mRNA to 163% of the control level

Name

Type

Language

MONATEPIL

Official Name

English

1-PIPERAZINEBUTANAMIDE, N-(6,11-DIHYDRODIBENZO(B,E)THIEPIN-11-YL)-4-(4-FLUOROPHENYL)

Common Name

English

monatepil [INN]

Common Name

English

MONATEPIL [MI]

Common Name

English

(±)-N-(6,11-DIHYDRODIBENZO(B,E)THIEPIN-11-YL)-4-(P-FLUOROPHENYL)-1-PIPERAZINEBUTYRAMIDE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C333