PROADIFEN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H31NO2
Molecular Weight	353.4977
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCC(C(=O)OCCN(CC)CC)(C1=CC=CC=C1)C2=CC=CC=C2

InChI

InChIKey=SNTQPLDRUZOSDP-UHFFFAOYSA-N

InChI=1S/C23H31NO2/c1-4-17-23(20-13-9-7-10-14-20,21-15-11-8-12-16-21)22(25)26-19-18-24(5-2)6-3/h7-16H,4-6,17-19H2,1-3H3

HIDE SMILES / InChI

Molecular Formula	C23H31NO2
Molecular Weight	353.4977
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/mesh/68011335 | https://www.ncbi.nlm.nih.gov/pubmed/3532206

Proadifen is an inhibitor of drug metabolism and cytochrome P450 enzyme system activity. It stimulated the release of prostacyclin (PGI2) from the rabbit aorta, bovine aorta and human umbilical vein in vitro, but had no effect on cultured smooth muscle from the bovine aortic media. In human platelets, proadifen inhibited prostaglandin and thromboxane production induced by A23187, thrombin, and ADP. Proadifen might thus constitute the prototype of a new class of antiplatelet drugs.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Pregnane X receptor 35 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20966043	Activator 1410		25.1 µM [EC50]
Cytochrome P450 3A4 126 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20966043	Modulator 822		12.6 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2565

PubMed

Title	Date	PubMed
Acute cytogenetic effect of benzene on rat bone marrow cells in vivo and the effect of inducers or inhibitors of drug-metabolizing enzymes.	1992 Dec	1282215
Understanding channel blocking in the nicotinic acetylcholine receptor.	2001	11697233
Low-density lipoprotein induced actin cytoskeleton reorganization in endothelial cells: mechanisms of action.	2001	11577705
Anti-apoptotic and apoptotic action of (-)-deprenyl and its metabolites.	2001	11261744
The role of enzyme induction and inhibition on cypermethrin hepatotoxicity.	2001 Jul	11428908
Perinatal development influences mechanisms of bradykinin-induced relaxations in pulmonary resistance and conduit arteries differently.	2001 Jul	11399256
Site-specific charge interactions of alpha-conotoxin MI with the nicotinic acetylcholine receptor.	2001 Jun 29	11323431
Phosphoinositide 3-kinase regulates crosstalk between Trk A tyrosine kinase and p75(NTR)-dependent sphingolipid signaling pathways.	2001 Mar	11238738
Microsomal metabolism of ciprofloxacin generates free radicals.	2001 May 15	11369501
Possible mechanisms for the suppressing action of 17beta-estradiol on beta-adrenoceptor-mediated vasorelaxation in rat aorta.	2001 Sep 7	11553364
Inhibition of vascular smooth muscle cell migration by cytochrome p450 epoxygenase-derived eicosanoids.	2002 May 17	12016269
Involvement of NO in the endothelium-independent relaxing effects of N(omega)-hydroxy-L-arginine and other compounds bearing a C=NOH function in the rat aorta.	2002 Nov	12388669
The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to hepatocytes.	2002 Nov	12388641
In vivo detection of aflatoxin-induced lipid free radicals in rat bile.	2002 Oct 10	12383942
Effects of gap junction uncoupling in the gerbil cochlea.	2002 Sep	12352678
Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cells.	2003 Dec	12970580
Role of metabolism by flavin-containing monooxygenase in thioacetamide-induced immunosuppression.	2003 Jan 13	12505269
Assessment of mazindane, a pro-drug form of mazindol, in assays used to define cocaine treatment agents.	2003 Jan 5	12504782
11,12-epoxyeicosatrienoic acid attenuates synthesis of prostaglandin E2 in rat monocytes stimulated with lipopolysaccharide.	2003 Jul	12876297
A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic aromatic hydrocarbons in LNCaP human prostate carcinoma cells.	2003 Jun	12799773
In vivo identification of aflatoxin-induced free radicals in rat bile.	2003 Nov 15	14607532
Metabolism of medroxyprogesterone acetate (MPA) via CYP enzymes in vitro and effect of MPA on bleeding time in female rats in dependence on CYP activity in vivo.	2003 Nov 7	14561525
Effect of ketamine on cocaine-induced immunotoxicity in rats.	2003 Sep-Oct	14555406
Lipoxygenase-dependent superoxide release in skeletal muscle.	2004 Aug	15107407
Chlorpropham induces mitochondrial dysfunction in rat hepatocytes.	2004 Aug 5	15212809
Skf 525-A induces cocaine N-demethylase, ethoxyresorufin O-deethylase, and pentoxyresorufin O-dealkylase activities by induction of cytochrome p-450 2B in female B6C3F1 mice.	2004 Dec	15513895
Hyperosmolar solution effects in guinea pig airways. III. Studies on the identity of epithelium-derived relaxing factor in isolated perfused trachea using pharmacological agents.	2004 Jan	14566001
Gas chromatographic determination of cocaine and its metabolites in blood and urine from cocaine users in northwestern Spain.	2004 Jul-Aug	15300716
Role of endothelium-derived hyperpolarizing factor in ACE inhibitor-induced renal vasodilation in vivo.	2004 Mar	14769805
Relaxant effect of oxime derivatives in isolated rat aorta: role of nitric oxide (NO) formation in smooth muscle.	2004 Mar 15	15006555
Pharmacokinetics of baicalin in rats and its interactions with cyclosporin A, quinidine and SKF-525A: a microdialysis study.	2004 Nov	15549664
In vitro confirmation of selegiline N-oxidation by flavin-containing monooxygenase in rat microsome using LC-ESI MS.	2004 Oct	15467197
Mechanisms of hydroxyl radical-induced contraction of rat aorta.	2004 Sep 19	15363964
Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications.	2005 Apr	15869481
Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3-buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.	2005 Aug	15863696
Excretion and metabolism of DA-7867, a new oxazolidinone, in rats.	2005 Mar	15617136
Effect of potassium channel and cytochrome P450 inhibition on transient hypotension and survival during lipopolysaccharide-induced endotoxic shock in the rat.	2005 Mar	15499226
Properties and regional expression of a CYP3A-like protein in channel catfish intestine.	2005 May 15	15848255
Role of nitric oxide during coronary endothelial dysfunction after myocardial infarction.	2005 May 23	15923002
Increased cell-cell adhesion, a novel effect of R-(-)-deprenyl.	2005 Nov	15785858
Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of acrylonitrile.	2005 Oct	15864551
Involvement of phenobarbital and SKF 525A in the hepatotoxicity of antifungal drugs itraconazole and fluconazole in rats.	2006	16777703
Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth.	2006 Dec	16980726
[Analysis of the interaction between nicotinic acetylcholine receptor and Na+,K(+)-ATPase in the rat skeletal muscle and the Torpedo electric organ membrane preparation].	2006 Feb	16739652
Site specificity of agonist-induced opening and desensitization of the Torpedo californica nicotinic acetylcholine receptor.	2006 Jan 10	16388595
Participation of epoxygenase activation in saikogenin D-induced inhibition of prostaglandin E(2) synthesis.	2006 Jun	16734988
Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling.	2006 Mar 15	16540563
Metabolism of pyrene by aquatic crustacean, Daphnia magna.	2006 Nov 16	16973224
Analytical approach to determine ticlopidine in post-mortem blood.	2006 Oct 16	16859849
Clozapine bioactivation induces dose-dependent, drug-specific toxicity of human bone marrow stromal cells: a potential in vitro system for the study of agranulocytosis.	2006 Sep 14	16844094

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Effects of local anesthetics-related drugs, proadifen, and quinacrine, on glibenclamide-sensitive K+ currents, were investigated using native Xenopus oocytes. Proadifen and quinacrine suppressed cromakalim-induced/glibenclamide-sensitive K+ currents with IC50 values of 9.8 microM and 4.4 microM, respectively. Inhibitors of either cytochrome P450 or phospholipase A2, which are structurally unrelated to local anesthetics, however, did not affect the K+ currents. Similar results were obtained for Y-26763-induced/glibenclamide-sensitive K+ currents. Proadifen and quinacrine block the glibenclamide-sensitive K+ currents by a mechanism irrelevant to the inhibition of cytochrome P450 or phospholipase A2 in oocytes.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:46:46 UTC 2023` Edited by `admin` on `Wed Jul 05 23:46:46 UTC 2023`
Record UNII	A510CA4CBT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROADIFEN

Official Name

English

BENZENEACETIC ACID, .ALPHA.-PHENYL-.ALPHA.-PROPYL-, 2-(DIETHYLAMINO)ETHYL ESTER

Common Name

English

2-(DIETHYLAMINO)ETHYL-2,2-DIPHENYLVALERATE

Systematic Name

English

proadifen [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29574