Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C21H24FN5O5S |
| Molecular Weight | 477.509 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)OC(=O)N1CCC(CC1)OC2=NC=NC3=C2C=NN3C4=C(F)C=C(C=C4)S(C)(=O)=O
InChI
InChIKey=XTRUQJBVQBUKSQ-UHFFFAOYSA-N
InChI=1S/C21H24FN5O5S/c1-13(2)31-21(28)26-8-6-14(7-9-26)32-20-16-11-25-27(19(16)23-12-24-20)18-5-4-15(10-17(18)22)33(3,29)30/h4-5,10-14H,6-9H2,1-3H3
| Molecular Formula | C21H24FN5O5S |
| Molecular Weight | 477.509 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
APD668 is a novel, highly potent and orally active glucose-dependent insulinotropic receptor (GDIR) agonist intended to more efficiently stimulate insulin release by beta cells in response to elevated blood glucose levels, and to avoid hypoglycemia. Ortho-McNeil's initial clinical studies evaluated healthy volunteers and patients with type 2 diabetes in randomized, double-blind, placebo-controlled trials evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple (14 day) escalating doses of APD668. Based on the data from those studies, Ortho-McNeil has decided to put APD668 on hold and has advanced a potentially more potent Arena discovered GDIR agonist into preclinical development.
Approval Year
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:31:13 GMT 2023
by
admin
on
Sat Dec 16 11:31:13 GMT 2023
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| Record UNII |
JC77BCH2AP
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| Record Status |
Validated (UNII)
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11705608
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JC77BCH2AP
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DTXSID701025686
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832714-46-2
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APD-668
Created by
admin on Sat Dec 16 11:31:13 GMT 2023 , Edited by admin on Sat Dec 16 11:31:13 GMT 2023
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PRIMARY | JNJ-28630368: GPR119, a glucose-dependent insulinotropic receptor, is a G protein-coupled receptor that is expressed in pancreatic .BETA.-cells and intestinal L-cells.1 Activation of GPR119 by the endogenous ligands lyso-phosphatidylcholine (Item No. 10172) and oleoyl ethanolamide (Item No. 90265) increases intracellular cAMP levels and promotes glucose-stimulated insulin secretion.1,2 APD668 is a potent agonist of GPR119 (EC50s = 2.7 and 33 nM for human and rat forms, respectively).3 Chronic dosing with APD668 in Zucker diabetic fatty rats over several weeks significantly reduces blood glucose and glycated hemoglobin levels. |
| Related Record | Type | Details | ||
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ACTIVE MOIETY |
We herein outline the design of a new series of agonists of the pancreatic and GI-expressed orphan G-protein coupled receptor GPR119, a target that has been of significant recent interest in the field of metabolism, starting from our prototypical agonist AR231453. A number of key parameters were improved first by incorporation of a pyrazolopyrimidine core to create a new structural series and secondly by the introduction of a piperidine ether group capped with a carbamate. Chronic treatment with one compound from the series, 3k, showed for the first time that blood glucose and glycated hemoglobin (HbA1c) levels could be significantly reduced in Zucker Diabetic Fatty (ZDF) rats over several weeks of dosing. As a result of these and other data described here, 3k (APD668, JNJ-28630368) was the first compound with this mechanism of action to be progressed into clinical development for the treatment of diabetes.
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ACTIVE MOIETY |
Class: Anti-hyper-glycaemic, Small molecule; Mechanism of Action: G protein-coupled receptor agonist; Highest Development Phase: Discontinued for Type 2 diabetes mellitus; Most Recent Events: 07 Sep 2010 Discontinued - Phase-I for Type-2 diabetes mellitus in USA (PO), 07 Jan 2008 Suspended - Phase-I for Type-2 diabetes mellitus in USA (PO), 28 Sep 2006 Data presented at the 232nd American Chemical Society National Meeting (232nd-ACS-2006) have been added to the Diabetes pharmacodynamics section
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