MEPERIDINE


Synonyms	IDS-NP-001 Isonipecaine Meperidine Meperidol Pethanol Pethidine Pethidine dbl Pethidineter Renaudin
Status
Molecule Category	Free-form
UNII	9E338QE28F
EPA CompTox	DTXSID9023253


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	XADCESSVHJOZHK-UHFFFAOYSA-N
Smiles	CCOC(=O)C1(c2ccccc2)CCN(C)CC1
InChI	InChI=1S/C15H21NO2/c1-3-18-14(17)15(9-11-16(2)12-10-15)13-7-5-4-6-8-13/h4-8H,3,9-12H2,1-2H3

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C15H21NO2
Molecular Weight	247.34
AlogP	2.21
Hydrogen Bond Acceptor	3.0
Hydrogen Bond Donor	0.0
Number of Rotational Bond	3.0
Polar Surface Area	29.54
Molecular species	NEUTRAL
Aromatic Rings	1.0
Heavy Atoms	18.0

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids: a conformation-activity study.

PubMed ID : 9873439

DOI : 10.1016/s0960-894x(98)00318-7

Year : 1998

Volume : 8

Issue : 14

First Page : 1813

Last Page : 1818

Authors : Tsai YC, Liou JP, Liao R, Cheng CY, Tao PL.

Abstract : Among a series of C-alkylated analogs of the weak mu opioid ligand spiro[benzofuran-3(2H),4'-1'-methylpiperidine-7-ol] (1), the 2-methyl, 2-ethyl, and cis 3'-methyl analogs, namely compounds (+/-)2, (+/-)-3, and (+/-)-4, showed much enhanced mu-affinities, with (+/-)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (+/-)-5 remained a weak mu-binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.

Reference

Journal : J. Med. Chem.

Title : Structure-affinity relationship studies on 5-HT1A receptor ligands. 1. Heterobicyclic phenylpiperazines with N4-alkyl substituents.

PubMed ID : 8410989

DOI : 10.1021/jm00071a006

Year : 1993

Volume : 36

Issue : 19

First Page : 2751

Last Page : 2760

Authors : van Steen BJ, van Wijngaarden I, Tulp MT, Soudijn W.

Abstract : Structure-affinity relationship (SAR) studies for 5-HT1A receptor site are presented for two series of heterobicyclic phenylpiperazines with N4-alkyl substituents: 4-alkyl derivatives of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine (3) and 1-(benzo[b]furan-7-yl)piperazine (4). The linear and branched hydrocarbon chain derivatives up to n-decyl were synthesized and evaluated for their ability to displace [3H]-2-(di-n-propylamino)-8-hydroxytetralin from its specific binding sites in rat frontal cortex homogenates. All compounds displayed a nanomolar affinity for the 5-HT1A receptor. In both series the N-ethyl and N-n-propyl substituted derivatives have similar affinities, being slightly but statistically significantly less active than the N-methyl-substituted derivatives. Elongation of the hydrocarbon chain increases the affinity for the central 5-HT1A receptor site, reaching a local maximum for the N-n-hexyl-substituted phenylpiperazines 23 (Ki = 0.50 nM) and 39 (Ki = 0.54 nM). Assuming that the arylpiperazine derivatives at the 5-HT1A binding site are in the ionic state, ionization constants were determined in order to evaluate the use of the local inhibition constant, Ki+, as a more convenient parameter to study the structure-affinity relationships. However, the Ki+ could not account for the specific N4-substituent effects found.

Reference

Journal : J. Med. Chem.

Title : Synthesis and biological activity of fluoroalkylamine derivatives of narcotic analgesics.

PubMed ID : 6106064

DOI : 10.1021/jm00183a005

Year : 1980

Volume : 23

Issue : 9

First Page : 985

Last Page : 990

Authors : Reifenrath WG, Roche EB, Al-Turk WA, Johnson HL.

Abstract : N-Ethyl-, N-(2-fluoroethyl)-, N-(2,2-difluoroethyl)-, and N-(2,2,2-trifluoroethyl)-substituted normeperidine (1b-e) and normetazocine (2b-e) derivatives were prepared. The analgesic activities of the compounds were determined in mice. Opiate receptor binding studies, in the presence and absence of sodium ion, were carried out. The antagonist activities of normetazocine derivatives were studied in monkeys. These were further examined in the isolated guinea pig ileum for relative agonist activity. The pKa values were measured; in vivo agonist acitivty was lost with weakly basic derivatives. For the normetazocine derivatives, opiate receptor binding data were consistent with guinea pig ileum agonist potency and mouse vas deferens antagonist potency but not with in vivo data. Opiate receptor binding was reduced for the less basic normetazocine derivatives. In the normeperidine series, there was no apparent direct relationship between pKa and opiate receptor binding. However, a relationship involving the hydrophobic character of the N-substituent is discussed. The N-(2-fluoroethyl) derivatives in both series were found to cause convulsions in rats at doses of 40-45 mg/kg ip. Elevated serum citrate levels were found in these rats, implicating in vivo oxidative deamination of the N-(fluoroalkyl) substituent to fluoroacetate.

Reference

Journal : J. Med. Chem.

Title : From hit to lead. Combining two complementary methods for focused library design. Application to mu opiate ligands.

PubMed ID : 11585443

DOI : 10.1021/jm010877o

Year : 2001

Volume : 44

Issue : 21

First Page : 3378

Last Page : 3390

Authors : Poulain R, Horvath D, Bonnet B, Eckhoff C, Chapelain B, Bodinier MC, Déprez B.

Abstract : Compound 1 obtained by random screening and displaying a micromolar activity on the mu opiate receptor was chosen as a starting point for optimization. Two complementary concepts of similarity were used for the design of analogues and compared. These are based, respectively, on a computer-aided comparison of pharmacophoric patterns and on topological similarity. The structure-activity relationships are discussed in light of both similarity concepts. Compound 40, an N-methyl-3-(4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decyl)acetamide derivative, designed by combining the structure-activity relationships enlightened by each method, has a subnanomolar affinity for mu (h) receptor (IC(50) = 0.9 nM). It is a promising lead, allowing the design of a new series of analogues substituted at the N-3 of the spirocycle moiety.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : Synthesis, dopamine and serotonin transporter binding affinities of novel analogues of meperidine.

PubMed ID : 10612583

DOI : 10.1016/s0960-894x(99)00606-x

Year : 1999

Volume : 9

Issue : 23

First Page : 3273

Last Page : 3276

Authors : Lomenzo SA, Izenwasser S, Gerdes RM, Katz JL, Kopajtic T, Trudell ML.

Abstract : A series of meperidine analogues was synthesized and the binding affinities for the dopamine and serotonin transporters were determined. The substituents on the phenyl ring greatly influenced the potency and selectivity of these compounds for the transporter binding sites. In general, meperidine (3) and its analogues were more selective for serotonin transporter binding sites and the esters 9 were more potent than the corresponding nitriles 8. The 3,4-dichloro derivative 9e was the most potent ligand of the series for dopamine transporter binding sites while the 2-naphthyl derivative 9g exhibited the most potent binding affinity and was highly selective for serotonin transporter binding sites.

Reference

Journal : Bioorg. Med. Chem. Lett.

Title : A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors.

PubMed ID : 15911273

DOI : 10.1016/j.bmcl.2005.03.080

Year : 2005

Volume : 15

Issue : 11

First Page : 2886

Last Page : 2890

Authors : Tobita M, Nishikawa T, Nagashima R.

Abstract : HERG attracts attention as a risk factor for arrhythmia, which might trigger torsade de pointes. A highly accurate classifier of chemical compounds for inhibition of the HERG potassium channel is constructed using support vector machine. For two test sets, our discriminant models achieved 90% and 95% accuracy, respectively. The classifier is even applied for the prediction of cardio vascular adverse effects to achieve about 70% accuracy. While modest inhibitors are partly characterized by properties linked to global structure of a molecule including hydrophobicity and diameter, strong inhibitors are exclusively characterized by properties linked to substructures of a molecule.

Reference

Journal : J. Med. Chem.

Title : N-(2-Cyanoethyl) derivatives of meperidine, ketobemidone, and a potent 6,7-benzomorphan.

PubMed ID : 109618

DOI : 10.1021/jm00193a028

Year : 1979

Volume : 22

Issue : 7

First Page : 889

Last Page : 890

Authors : Uwaydah IM, Waddle MK, Rogers ME.

Abstract : The N-(2-cyanoethyl)-9alpha-ethyl-5-methyl-6,7-benzomorphan (1c) is a more potent antinociceptive and has stronger receptor binding affinity than its N-methyl analogue 1b. The N-(2-cyanoethyl)-4-phenylpiperidine compounds 2b and 3b were almost inactive compared to their N-methyl congeners 2a and 3a, respectively. It appears that the pharmacological effect of the N-(2-cyanoethyl) moiety is dependent on the opioid on which it is substituted.

Assay Description	Organism	Bioactivity
Binding affinity against mu opioid receptor was determined in brain membrane preparations from male Hartley guinea-pigs	Cavia porcellus	451.0 nM
Tested for displacement of radioligand [3H]-Naloxone from opiate receptor	None	500.0 nM
Inhibition of Opioid receptors with [3H]naloxone binding in the absence of NaCl	Cavia porcellus	500.0 nM
Binding affinity against mu-opiate receptor (human) using [3H]DAMGO radioligand	None	315.0 nM
Displacement of [3H]paroxetine from serotonin transporter (SERT)	Rattus norvegicus	412.0 nM
Inhibitory concentration against potassium channel HERG	None	323.59 nM
Displacement of radiolabeled dihydromorphine from opioid receptor in rat brain homogenates	Rattus norvegicus	700.0 nM

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Cross References

Resources	Reference
ChEBI	6754
ChEMBL	CHEMBL607
DrugBank	DB00454
DrugCentral	1690
FDA SRS	9E338QE28F
Human Metabolome Database	HMDB0014597
Guide to Pharmacology	7221
KEGG	C07128
PharmGKB	PA450369
PubChem	4058
SureChEMBL	SCHEMBL25431
ZINC	ZINC000000001681

CONTENTS

Structure
Chemical and Physical Properties
Related Entries