898562-93-1

Basic information

• Product Name: 2-[4-(2-METHYL-4-PYRIDIN-4-YL-2H-PYRAZOL-3-YL)-PHENOXYMETHYL]-QUINOLINE
• Synonyms: 2-[4-(2-METHYL-4-PYRIDIN-4-YL-2H-PYRAZOL-3-YL)-PHENOXYMETHYL]-QUINOLINE
• CAS NO: 898562-93-1
• Molecular Formula: C25H20N4O
• Molecular Weight: 0
• Mol File: 898562-93-1.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 2-[4-(2-METHYL-4-PYRIDIN-4-YL-2H-PYRAZOL-3-YL)-PHENOXYMETHYL]-QUINOLINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[4-(2-METHYL-4-PYRIDIN-4-YL-2H-PYRAZOL-3-YL)-PHENOXYMETHYL]-QUINOLINE(898562-93-1)
• EPA Substance Registry System: 2-[4-(2-METHYL-4-PYRIDIN-4-YL-2H-PYRAZOL-3-YL)-PHENOXYMETHYL]-QUINOLINE(898562-93-1)

Safety Data

• Hazardous Substances Data: 898562-93-1(Hazardous Substances Data)

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 134138-88-8 4-(quinolin-2-ylmethyloxy)benzoyl chloride 
• 137426-86-9 4-(2-Quinolinylmethoxy)benzoic acid methyl ester 
• 123724-16-3 4-(quinolin-2-ylmethyloxy)benzoic acid 
• 871507-11-8 2-((4-(4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline 
• 60-34-4 methylhydrazine 
• 871507-15-2 2-pyridin-4-yl-1-[4-(quinolin-2-ylmethoxy)-phenyl]-ethanone 
• 871507-14-1 N-methoxy-N-methyl-4-(quinolin-2-ylmethoxy)-benzamide 
• 4377-41-7 2-Chloromethylquinoline 
• 871507-16-3 3-(dimethylamino)-2-(pyridin-4-yl)-1-(4-(quinolin-2-ylmethoxy)phenyl)prop-2-en-1-one 

Relevant articles and documents

METHODS FOR TREATING DISEASES OF THE RETINA

Disclosed herein is a method of treating disorders of the retina comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of Formula I as defined herein. These compounds are useful as PDE10 inhibitors.

Radiosynthesis and in vivo evaluation of [11C]MP-10 as a PET probe for imaging PDE10A in rodent and non-human primate brain

2-((4-(1-[11C]Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy) methyl)-quinoline (MP-10), a specific PDE10A inhibitor (IC50 = 0.18 nM with 100-fold selectivity over other PDEs), was radiosynthesized by alkylation of the desmethyl precursor with [11C]CH3I, ～45% yield, >92% radiochemical purity, >370 GBq/μmol specific activity at end of bombardment (EOB). Evaluation in Sprague-Dawley rats revealed that [11C]MP-10 had highest brain accumulation in the PDE10A enriched-striatum, the 30 min striatum: cerebellum ratio reached 6.55. MicroPET studies of [11C]MP-10 in monkeys displayed selective uptake in striatum. However, a radiolabeled metabolite capable of penetrating the blood-brain-barrier may limit the clinical utility of [11C]MP-10 as a PDE10A PET tracer.

Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3- yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia

By utilizing structure-based drug design (SBDD) knowledge, a novel class of phosphodiesterase (PDE) 10A inhibitors was identified. The structure-based drug design efforts identified a unique "selectivity pocket" for PDE10A inhibitors, and interactions within this pocket allowed the design of highly selective and potent PDE10A inhibitors. Further optimization of brain penetration and drug-like properties led to the discovery of 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920). This PDE10A inhibitor is the first reported clinical entry for this mechanism in the treatment of schizophrenia.

Heteroaromatic quinoline compounds

The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. In particular, the invention relates to said compounds which are selective inhibitors of PDE10. The invention also relates to intermediates for preparation of said compounds; pharmaceutical compositions comprising said compounds; and the use of said compounds in a method for treating certain central nervous system (CNS) or other disorders.