Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C19H27ClN6O2 |
| Molecular Weight | 406.91 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(N)=C(Cl)C=C1C(=O)NCC2CCN(CCCN3C=CN=N3)CC2
InChI
InChIKey=AULLTYAISZREAX-UHFFFAOYSA-N
InChI=1S/C19H27ClN6O2/c1-28-18-12-17(21)16(20)11-15(18)19(27)22-13-14-3-8-25(9-4-14)6-2-7-26-10-5-23-24-26/h5,10-12,14H,2-4,6-9,13,21H2,1H3,(H,22,27)
| Molecular Formula | C19H27ClN6O2 |
| Molecular Weight | 406.91 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DA-6886 is an antagonist of the 5-HT4 receptor, discovered by the Korean Dong-A ST Research Institute. The drug binds with high activity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5 and 7.9 for the human 5-HT4a, 5-HT4b, and 5-HT4d, respectively. DA-886 induced relaxation of the rat esophagus preparation in a 5-HT4 receptor antagonist-sensitive manner. In the normal ICR mice, oral administration of the drug at 0.4 and 2 mg/kg resulted in a marked stimulation of colonic transit. DA-6886 was investigated in phase I clinical trial for the treatment of Irritable Bowel Syndrome.
Approval Year
| Substance Class |
Chemical
Created
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admin
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Sat Dec 16 11:31:18 GMT 2023
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Sat Dec 16 11:31:18 GMT 2023
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| Record UNII |
J6388YJ4YR
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| Record Status |
Validated (UNII)
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1342815-16-0
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54575171
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ACTIVE MOIETY |
Official Title: A Phase I, Dose Block-randomized, Double-blind, Placebo-controlled, Single/Multiple Dosing, Dose Escalation Clinical Trial With Open-labelled Food Effect Study of Single Dose to Investigate the Safety, Tolerability and Pharmacokinetics of DA-6886 After Oral Administration in Healthy Male Subjects
Purpose: DA-6886_IBS_I is a phase I, dose block-randomized, double-blind, placebo-controlled, single/multiple dosing, dose escalation clinical trial with open-labelled food effect study of single dose to investigate the safety, tolerability and pharmacokinetics of DA-6886 after oral administration in healthy male subjects.
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ACTIVE MOIETY |
DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit.
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ACTIVE MOIETY |
Originator: Dong-A Pharmaceutical; Developer: Dong-A ST; Class: Irritable bowel syndrome therapy; Mechanism of Action: Serotonin 4 receptor agonist; Orphan Drug Status: No; On Fast track: No; New Molecular Entity: Yes; Available For Licensing: Yes for Irritable bowel syndrome; Highest Development Phase: Phase I for Irritable bowel syndrome; Most Recent Events: 27 Apr 2016 Phase I development is ongoing in South Korea, 31 Dec 2013 Dong-A ST completes a phase I trial in Healthy volunteers in South Korea (NCT01633723), 31 Aug 2012 Phase-I clinical trials in Irritable bowel syndrome (in volunteers) in South Korea (PO)
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