90349-23-8

Usage

Uses

Used in Pharmaceutical Industry:
5,7-DIMETHYL-PYRAZOLO[1,5-A]PYRIMIDINE-3-CARBOXYLIC ACID is used as a reactant for the synthetic preparation of noninhibitory small molecule chaperones of glucocerebrosidase, which are essential for the treatment of lysosomal storage disorders such as Gaucher disease. These chaperones help in stabilizing and enhancing the activity of the enzyme glucocerebrosidase, thereby improving the therapeutic outcomes for patients suffering from these disorders.

InChI:InChI=1/C9H9N3O2/c1-5-3-6(2)12-8(11-5)7(4-10-12)9(13)14/h3-4H,1-2H3,(H,13,14)

Upstream product

• 43024-16-4 5,7-dimethylpyrazolo<1,5-a>pyrimidine-3-carbonitrile 
• 123-54-6 acetylacetone 
• 41680-34-6 5-amino-1H-pyrazole-4-carboxylic acid 
• 52664-01-4 ethyl 5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylate 

Downstream Products

• 1380716-06-2 N-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]-pyrimidine-3-carboxamide 

Relevant academic research and scientific papers

Synthesis of pyrazolo[1,5-α]pyrimidine ring as a possible bioisosteric replacement of the 5-(1H-pyrrol-1-yl)pyrazole scaffold

Reaction of 3-amino-1H-pyrazole-4-carbonitrile with 2,4-pentanedione yielded 5,7-dimethylpyrazolo[1,5-α]pyrimidine-3-carbonitrile, which was easily and efficiently transformed into a small library of amido derivatives. This procedure opens the way to new compounds potentially endowed with interesting biological activities.

CRYSTALLINE SUBSTITUTED CYCLOHEXYL PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUND AND THERAPEUTIC USES THEREOF

The invention provides crystalline 5,7-dimethyl-N-((1S*,4S)-4-(pentyloxy)cyclohexyl) pyrazolo[1,5-a]pyrimidine-3-carboxamide, compositions containing the crystalline compound, methods for making the crystalline compound, medical kits, and methods for usin

Design, Synthesis, and Evaluation of the Anticancer Properties of a Novel Series of α-(Benzoylamino)-β-substituted Acrylic Amide Derivatives of Pyrazolo[1,5-a]pyrimidine

A novel series of α-(benzoylamino)-β-substituted acrylic amide derivatives of pyrazolo[1,5-a]pyrimidine has been synthesized using a convergent multistep synthesis. The synthesized compounds were characterized by 1H NMR, 13C NMR, ESI-MS, and IR analyses. Those new compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of nine derivatives synthesized in the current study, compounds 13g, 13d, 13h, and 13i exhibited the greatest anticancer activities in HeLa and HepG2 cell lines. The in vitro anticancer activity of compound 13g against HeLa, HepG2, and MCF-7 cell lines is superior to the marketed drugs paclitaxel and SAHA.

Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders

Herein, we describe the discovery of a potent, selective, brain-penetrating, in vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high-quality leads suitable for optimization and enable validation of the physiological function of PDE2A in vivo, structural modifications of the high-throughput screening hit 18 were performed. Our lead generation efforts revealed three key potency-enhancing functionalities with minimal increases in molecular weight (MW) and no change in topological polar surface area (TPSA). Combining these structural elements led to the identification of 6-methyl-N-((1R)-1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a molecule with the desired balance of preclinical properties. Further characterization by cocrystal structure analysis of 38a bound to PDE2A uncovered a unique binding mode and provided insights into its observed potency and PDE selectivity. Compound 38a significantly elevated 3′,5′-cyclic guanosine monophosphate (cGMP) levels in mouse brain following oral administration, thus validating this compound as a useful pharmacological tool and an attractive lead for future optimization.

Design, synthesis, and evaluation of the anticancer properties of a novel series of carboxamides, sulfonamides, ureas, and thioureas derived from 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl substituted with pyrazolo[1,5-a]pyrimidine derivatives

Abstract: A series of novel carboxamides, sulfonamides, ureas, and thioureas derived from 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl substituted with pyrazolo[1,5-a]pyrimidine analog were designed and synthesized. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, ESI–MS, and IR and were tested for their in vitro antiproliferative activity by MTT assay. Out of these twenty derivatives, five compounds showed good anticancer activity against HeLa cell line. These are superior with less than 10?μg/cm3 of IC50 when compared to the marketed anticancer drug paclitaxel with 30?μg/cm3 of IC50 against Hela cell line. Graphical abstract: [Figure not available: see fulltext.]

SUBSTITUTED PYRAZOLO(1,5-A)PYRIMIDINES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS

The invention provides substituted pyrazolo[l,5-a]pyrimidine and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[l,5-a]pyrimidine compounds described herein include 5,7- dimethyl-N-phenylpyrazolo[l,5-a]pyrimidine-3-carboxamide compounds and variants thereof.

SUBSTITUTED PYRAZOLOPYRIMIDINES AS GLUCOCEREBROSIDASE ACTIVATORS

Substituted pyrazolopyrimidines and dihydropyrazolopyrimidines and related compounds, their methods of manufacture, compositions containing these compounds, and methods of use of these compounds in treating lysosomal storage disorders such as Gaucher disease are described herein. The compounds are of general Formula (I) in which variables R1-R7 and X are described in the application.

Discovery, structure - Activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase

A major challenge in the field of Gaucher disease has been the development of new therapeutic strategies including molecular chaperones. All previously described chaperones of glucocerebrosidase are enzyme inhibitors, which complicates their clinical development because their chaperone activity must be balanced against the functional inhibition of the enzyme. Using a novel high throughput screening methodology, we identified a chemical series that does not inhibit the enzyme but can still facilitate its translocation to the lysosome as measured by immunostaining of glucocerebrosidase in patient fibroblasts. These compounds provide the basis for the development of a novel approach toward small molecule treatment for patients with Gaucher disease. This article not subject to U.S. Copyright. Published 2012 by the American Chemical Society.