16082-27-2

Usage

Synthesis Reference(s)

Chemical and Pharmaceutical Bulletin, 10, p. 620, 1962 DOI: 10.1248/cpb.10.620

InChI:InChI=1/C7H6ClN3/c1-5-4-6(8)11-7(10-5)2-3-9-11/h2-4H,1H3

Upstream product

• 29274-35-9 5-methyl-4H-pyrazolo<1,5-a>pyrimidin-7-one 
• 16082-26-1 5-methyl-7-hydroxy-pyrazolo[1,5-a]pyrimidine 

Downstream Products

• 167371-60-0 4'-<(5-methylpyrazolo<1,5-a>pyrimidin-7-yl)aminomethyl>biphenyl-2-carbonitrile 

Relevant academic research and scientific papers

BAX INHIBITORS AND USES THEREOF

A compound having formula (I) or (II) for use inhibiting Bax mediated cell death and/or apoptosis.

Structural Insights into the Inhibition of Undecaprenyl Pyrophosphate Synthase from Gram-Positive Bacteria

The polyprenyl lipid undecaprenyl phosphate (C55P) is the universal carrier lipid for the biosynthesis of bacterial cell wall polymers. C55P is synthesized in its pyrophosphate form by undecaprenyl pyrophosphate synthase (UppS), an essentialcis-prenyltransferase that is an attractive target for antibiotic development. We previously identified a compound (MAC-0547630) that showed promise as a novel class of inhibitor and an ability to potentiate β-lactam antibiotics. Here, we provide a structural model for MAC-0547630’s inhibition of UppS and a structural rationale for its enhanced effect on UppS fromBacillus subtilisversusStaphylococcus aureus. We also describe the synthesis of a MAC-0547630 derivative (JPD447), show that it too can potentiate β-lactam antibiotics, and provide a structural rationale for its improved potentiation. Finally, we present an improved structural model of clomiphene’s inhibition of UppS. Taken together, our data provide a foundation for structure-guided drug design of more potent UppS inhibitors in the future.

Picolinamide compound and preparation method and application thereof

The invention discloses a picolinamide compound. The structural general formulas of the picolinamide compound are shown as formulas (I) and (II). The invention also discloses a preparation method of the picolinamide compound and application of the picolinamide compound in preparation of anti-tumor drugs. The picolinamide compound can effectively inhibit a variety of tumor cells, including human breast cancer cells, human lung cancer cells, human liver cancer cells and the like, has good anti-tumor active substances and can be used for preparing the anti-tumor drugs.

Design, synthesis and antitumor evaluation of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives as potential c-Met inhibitors

A series of novel 5-methylpyrazolo[1,5-a]pyrimidine derivatives (10a–10x) were designed, synthesized, and evaluated for their in vitro inhibitory activities against c-Met kinase and antiproliferative activities against the SH-SY5Y, MDA-MB-231, A549, and HepG2 cell lines. Most of the compounds remarkably inhibited c-Met kinase and showed moderate to good cytotoxicity and selectivity toward the four cancer cell lines. Among them, compounds 10b and 10f were the two most potent selective c-Met inhibitors with half-maximal inhibitory concentration (IC50) values of 5.17 ± 0.48 nM and 5.62 ± 0.78 nM, respectively, and suppression abilities comparable with the positive control cabozantinib. Cell proliferation assay further demonstrated that the two most promising compounds 10a and 10b also showed good cytotoxicity and selectivity toward MDA-MB-231 cells, with IC50 values of 26.67 ± 2.56 μM and 26.83 ± 2.41 μM, respectively. Compounds 10f and 10g showed cytotoxicity and selectivity toward A549 cells, with IC50 values of 20.20 ± 2.04 μM and 21.65 ± 1.58 μM, respectively. All antiproliferative activities were within the range of those of cabozantinib. Notably, these compounds presented relatively low hepatotoxicity compared with reference drugs. Moreover, the preliminary structure–activity relationship and docking studies revealed that replacement of a nitrogen-containing heterocycle on the R2 (block A) group might improve the c-Met kinase inhibitory and antiproliferative effects in MDA-MB-231 cells, whereas displacement by a substituted benzene ring, especially for the p-fluorophenyl or 4-fluoro-3-methoxyphenyl moiety, on the R2 group enhanced cytotoxicity toward A549 cells. Together, these results suggest that 10b and 10f are promising compounds and provide a basis for their development as new antitumor agents.

SPIRO COMPOUNDS AS GLYCOSIDASE INHIBITORS

Compounds of formula (I) wherein A, R, L, Z, Q1, Q2 and n have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.

Development of Highly Potent, Selective, and Cellular Active Triazolo[1,5- a]pyrimidine-Based Inhibitors Targeting the DCN1-UBC12 Protein-Protein Interaction

The cullin-RING ubiquitin ligases (CRLs) are responsible for about 20% of cellular protein degradation and regulate diverse cellular processes, and the dysfunction of CRLs is implicated in human diseases. Targeting the CRLs has become an emerging strategy for the treatment of human diseases. Herein, we describe the discovery of a hit compound from our in-house library and further structure-based optimizations, which have enabled the identification of new triazolo[1,5-a]pyrimidine-based inhibitors targeting the DCN1-UBC12 interaction. Compound WS-383 blocks the DCN1-UBC12 interaction (IC50 = 11 nM) reversibly and shows selectivity over selected kinases. WS-383 exhibits cellular target engagement to DCN1 in MGC-803 cells. WS-383 inhibits Cul3/1 neddylation selectively over other cullins and also induces accumulation of p21, p27, and NRF2. Collectively, targeting the DCN1-UBC12 interaction would be a viable strategy for selective neddylation inhibition of Cul3/1 and may be of therapeutic potential for disease treatment in which Cul3/1 is dysregulated.

Pyrazolopyrimidine-type compound, and preparation method and application thereof

The invention discloses a pyrazolopyrimidine-type compound. The structural general formula of the pyrazolopyrimidine-type compound is shown as formula (I). The invention further discloses a preparation method of the pyrazolopyrimidine-type compound and application of the pyrazolopyrimidine-type compound in preparation of antitumor drugs. The provided pyrazolopyrimidine-type compound can effectively inhibit multipletumor cells, including human breast cancer cells, human lung cancer cells, human hepatoma carcinoma cells, human neuroblastoma cells and the like, has high antitumor activity and canbe applied to preparation of the antitumor drugs.

Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization

Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with p

Bioisosteric transformations and permutations in the triazolopyrimidine scaffold to identify the minimum pharmacophore required for inhibitory activity against plasmodium falciparum dihydroorotate dehydrogenase

Plasmodium falciparum causes approximately 1 million deaths annually. However, increasing resistance imposes a continuous threat to existing drug therapies. We previously reported a number of potent and selective triazolopyrimidine-based inhibitors of P.

Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor

We describe a novel 7-aminopyrazolo[1,5-a]pyrimidine (7-APP) derivative as a potent hepatitis C virus (HCV) inhibitor. A series of 7-APPs was synthesized and evaluated for inhibitory activity against HCV in different cell culture systems. The synthesis and preliminary structure-activity relationship study of 7-APP are reported.