871507-14-1

Basic information

• Product Name: Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-
• CAS NO: 871507-14-1
• Molecular Formula: C19H18N2O3
• Molecular Weight: 322.364
• Mol File: 871507-14-1.mol
• Article Data: 5

Chemical Properties

• CAS DataBase Reference: Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-(CAS DataBase Reference)
• NIST Chemistry Reference: Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-(871507-14-1)
• EPA Substance Registry System: Benzamide, N-methoxy-N-methyl-4-(2-quinolinylmethoxy)-(871507-14-1)

Safety Data

• Hazardous Substances Data: 871507-14-1(Hazardous Substances Data)

Upstream product

• 99-76-3 methyl 4-hydroxylbenzoate 
• 137426-86-9 4-(2-Quinolinylmethoxy)benzoic acid methyl ester 
• 123724-16-3 4-(quinolin-2-ylmethyloxy)benzoic acid 
• 4377-41-7 2-Chloromethylquinoline 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 134138-88-8 4-(quinolin-2-ylmethyloxy)benzoyl chloride 

Downstream Products

• 898562-94-2 2-({4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline 
• 898562-93-1 2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline 
• 871507-16-3 3-(dimethylamino)-2-(pyridin-4-yl)-1-(4-(quinolin-2-ylmethoxy)phenyl)prop-2-en-1-one 
• 871507-11-8 2-((4-(4-(pyridin-4-yl)-1H-pyrazol-5-yl)phenoxy)methyl)quinoline 
• 123724-16-3 4-(quinolin-2-ylmethyloxy)benzoic acid 
• 898563-16-1 2-(3-Methyl-isoxazol-5-yl)-1-[4-(quinolin-2-ylmethoxy)-phenyl]-ethanone 
• 898563-09-2 2-Pyridazin-4-yl-1-[4-(quinolin-2-ylmethoxy)-phenyl]-ethanone 
• 871507-15-2 2-pyridin-4-yl-1-[4-(quinolin-2-ylmethoxy)-phenyl]-ethanone 
• 956750-64-4 1-(4-((quinolin-2-yl)methoxy)phenyl)-2-(4-fluorophenyl)ethanone 

Relevant articles and documents

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.

PHOSPHODIESTERASE 10 INHIBITION AS TREATMENT FOR OBESITY-RELATED AND METABOLIC SYNDROME-RELATED CONDITIONS

The present invention provides methods to decrease body weight and/or body fat in animals, e.g., in the treatment of overweight or obese patients (e.g., humans or companion animals), or as a means to produce leaner meat in food stock animals (e.g., cattle, chickens, pigs), methods to treat non-insulin dependent diabetes (NIDDM), metabolic syndrome, or glucose intolerance, in patients in need thereof by administering a PDE10 inhibitor (alone or in combination with another therapeutic agent), kits for the above-identified therapeutic uses, and methods of identifying PDE10 inhibitors for the above-described therapeutic uses.