1082743-70-1

Basic information

• Product Name: PDE-9
• Synonyms: PDE-9;1,5-Dihydro-6-[(3S,4S)-4-methyl-1-(phenylmethyl)-3-pyrrolidinyl]-1-(tetrahydro-2H-pyran-4-yl)-4H-pyrazolo[3,4-d]pyrimidin-4-one;PDE-9 inhibitor;4H-Pyrazolo[3,4-d]pyriMidin-4-one, 1,5-dihydro-6-[(3S,4S)-4-Methyl-1-(phenylMethyl)-3-pyrrolidinyl]-1-(tetrahydro-2H-pyran-4-yl)-
• CAS NO: 1082743-70-1
• Molecular Formula: C₂₂H₂₇N₅O₂
• Molecular Weight: 393.48208
• Mol File: 1082743-70-1.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 584.8±60.0 °C(Predicted)
• Appearance: /
• Density: 1.39
• PKA: 7.99±0.60(Predicted)
• CAS DataBase Reference: PDE-9(CAS DataBase Reference)
• NIST Chemistry Reference: PDE-9(1082743-70-1)
• EPA Substance Registry System: PDE-9(1082743-70-1)

Safety Data

• Hazardous Substances Data: 1082743-70-1(Hazardous Substances Data)

Usage

General Description

PDE-9, also known as Phosphodiesterase 9, is a type of enzyme that plays a crucial role in cellular functions by breaking down cyclic guanosine monophosphate (cGMP), a molecule that transmits signals inside the cell. Scientists have found high levels of PDE-9 in the brain, indicating its involvement in various neurological processes. In fact, inhibitors of PDE-9 are being studied for their potential use in treating neurological and psychological disorders such as Alzheimer's disease and schizophrenia. Furthermore, PDE-9 has also been found to be involved in the regulation of the immune system and could be a target for autoimmune diseases.

Upstream product

• 29943-42-8 Tetrahydro-4H-pyran-4-one 
• 693287-79-5 N’-(tetrahydropyran-4-yl)hydrazinecarboxylic acid tert-butyl ester 
• 1082745-49-0 5-amino-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carbonitrile 
• 1082745-50-3 5-amino-1-(tetrahydropyran-4-yl)-1H-pyrazole-4-carboxylic acid amide 
• 181114-98-7 (3S,4S)-methyl 1-benzyl-4-methylpyrrolidine-3-carboxylate 
• 93102-05-7 N-benzyl-N-(methoxymethyl)-N-[(trimethylsilyl)methyl]amine 

Downstream Products

• 1082743-98-3 6-((3S,4S)-1-(3-fluorobenzyl)-4-methylpyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 1082744-05-5 6-((3S,4S)-1-(4-fluorobenzyl)-4-methylpyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 1082744-10-2 6-((3S,4S)-1-(4-methoxybenzyl)-4-methylpyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 
• 1082744-20-4 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one 

Relevant articles and documents

Design and discovery of 6-[(3 s,4 s)-4-methyl-1-(pyrimidin-2-ylmethyl) pyrrolidin-3-yl]-1-(tetrahydro-2 h -pyran-4-yl)-1,5-dihydro-4 h -pyrazolo[3,4- d ]pyrimidin-4-one (PF-04447943), a selective brain penetrant pde9a inhibitor for the treatment of cognitive disorders

6-[(3S,4S)-4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl] -1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic site. The physicochemical properties of the series were optimized to provide excellent in vitro and in vivo pharmacokinetics properties in multiple species including humans. It has been reported to elevate central cGMP levels in the brain and CSF of rodents. In addition, it exhibits procognitive activity in several rodent models and synaptic stabilization in an amyloid precursor protein (APP) transgenic mouse model. Recent disclosures from clinical trials confirm that it is well tolerated in humans and elevates cGMP in cerebral spinal fluid of healthy volunteers, confirming that it is a quality pharmacological tool for testing clinical hypotheses in disease states associated with impairment of cGMP signaling or cognition.

AMINO-HETEROCYCLIC COMPOUNDS

The invention provides PDE9-inhibiting compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R, R1, R2 and R3 are as defined herein. Pharmaceutical compositions containing the compounds of Formul