APD-668

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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

Structure of APD-668

Structure Search

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

HIDE SMILES / InChI

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

Approval Year

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:31:13 UTC 2023` Edited by `admin` on `Sat Dec 16 11:31:13 UTC 2023`
Record UNII	JC77BCH2AP
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

APD-668

Code

English

4-((1-(2-FLUORO-4-METHYLSULFONYLPHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-YL)OXY)PIPERIDINE-1-CARBOXYLIC ACID ISOPROPYL ESTER

Systematic Name

English

PROPAN-2-YL 4-(1-(2-FLUORO-4-METHYLSULFONYLPHENYL)PYRAZOLO(4,5-E)PYRIMIDIN-4-YL)OXYPIPERIDINE-1-CARBOXYLATE

Systematic Name

English

1-PIPERIDINECARBOXYLIC ACID, 4-((1-(2-FLUORO-4-(METHYLSULFONYL)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-YL)OXY)-, 1-METHYLETHYL ESTER

Systematic Name

English

ISOPROPYL 4-((1-(2-FLUORO-4-(METHYLSULFONYL)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-YL)OXY)-1-PIPERIDINECARBOXYLATE

Systematic Name

English

APD668

Code

English

1-METHYLETHYL 4-((1-(2-FLUORO-4-(METHYLSULFONYL)PHENYL)-1H-PYRAZOLO(3,4-D)PYRIMIDIN-4-YL)OXY)-1-PIPERIDINECARBOXYLATE

Systematic Name

English

JNJ-28630368

Code

English

Code System Code Type Description

PUBCHEM

11705608

Created by admin on Sat Dec 16 11:31:13 UTC 2023 , Edited by admin on Sat Dec 16 11:31:13 UTC 2023

PRIMARY

FDA UNII

JC77BCH2AP

Created by admin on Sat Dec 16 11:31:13 UTC 2023 , Edited by admin on Sat Dec 16 11:31:13 UTC 2023

PRIMARY

EPA CompTox

DTXSID701025686

Created by admin on Sat Dec 16 11:31:13 UTC 2023 , Edited by admin on Sat Dec 16 11:31:13 UTC 2023

PRIMARY

CAS

832714-46-2

Created by admin on Sat Dec 16 11:31:13 UTC 2023 , Edited by admin on Sat Dec 16 11:31:13 UTC 2023

PRIMARY

MANUFACTURER PRODUCT INFORMATION

APD-668

Created by admin on Sat Dec 16 11:31:13 UTC 2023 , Edited by admin on Sat Dec 16 11:31:13 UTC 2023

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


					JC77BCH2AP

APD-668

ACTIVE MOIETY

Comments:

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.


					JC77BCH2AP

APD-668

ACTIVE MOIETY

Comments:

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