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BioAssay: AID 650195

Inhibition of human CYP3A4

A series of 3,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). Various guanidine isosteric groups were explored at the 5-position of the indole ring, while keeping the basic amine side chain such as N-methylpiperidine ring, fixed at the 3-position of the indole ring. Compounds having 2-thiophene amidine and 2-furanyl more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 650195
Data Source: ChEMBL (807643)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-24

Data Table ( Complete ):           View All Data
Target
Sequence: RecName: Full=Cytochrome P450 3A4; AltName: Full=1,8-cineole 2-exo-monooxygenase; AltName: Full=Albendazole monooxygenase; AltName: Full=Albendazole sulfoxidase; AltName: Full=CYPIIIA3; AltName: Full=CYPIIIA4; AltName: Full=Cytochrome P450 3A3; AltName: Full=Cytochrome P450 HLp; AltName: Full=Cytochrome P450 NF-25; AltName: Full=Cytochrome P450-PCN1; AltName: Full=Nifedipine oxidase; AltName: Full=Quinine 3-monooxygenase; AltName: Full=Taurochenodeoxycholate 6-alpha-hydroxylase
Description ..   
Protein Family: Cytochrome P450
Comment ..   

Gene:CYP3A4     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: 3,5-Disubstituted indole derivatives as selective human neuronal nitric oxide synthase (nNOS) inhibitors.

Abstract: A series of 3,5-disubstituted indole derivatives was designed, synthesized and evaluated as inhibitors of human nitric oxide synthase (NOS). Various guanidine isosteric groups were explored at the 5-position of the indole ring, while keeping the basic amine side chain such as N-methylpiperidine ring, fixed at the 3-position of the indole ring. Compounds having 2-thiophene amidine and 2-furanyl amidine groups (7, 8, 10 and 12) showed increased activity for human neuronal NOS and good selectivity over endothelial and inducible NOS isoforms. Compound 8 was shown to reverse (10mg/kg, ip) thermal hyperalgesia in the L(5)/L(6) spinal nerve ligation (neuropathic pain) model and was devoid of any significant drug-drug interaction potential due to cytochrome P450 inhibition or cardiovascular liabilities associated with the inhibition of endothelial NOS.
(PMID: 22318159)
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View All Data
Classification
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