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BioAssay: AID 650198

Vasoconstrictive activity in human arteries assessed as inhibition of acetylcholine-induced vasorelaxation at 10 uM in presence of thromboxane A2 mimetic agent U46619

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)
 
 
Inactive(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Inactive(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 650198
Data Source: ChEMBL (807646)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-24

Data Table ( Complete ):           View All 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)
Comment
Putative Target:
ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Assay Data Source: Scientific Literature
BAO: Assay Format: tissue-based format
Assay Tissue: Artery
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50 activity commentIC50 activity commentString
2IC50 standard flagIC50 standard flagInteger
3IC50 qualifierIC50 qualifierString
4IC50 published valueIC50 published valueFloat
5IC50 standard valueIC50 standard valueFloat

Data Table (Concise)
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