597544-21-3

Usage

Chemical structure

Long molecular structure containing a morpholine ring and a pyridin-4-ylpyrazolo ring

Functional groups

Various other functional groups present

Potential applications

Pharmaceuticals
Further research and testing required for specific uses and benefits

Upstream product

• 3240-94-6 N-(2-chlorethyl)morpholine 
• 515880-87-2 6-(4-hydroxyphenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine 
• 3647-69-6 4-(2-chloroethyl)morpholine hydrochride 
• 103851-89-4 3-(dimethylamino)-2-(4-pyridyl)prop-2-enenitrile 
• 92333-25-0 pyridin-4-ylacetonitrile hydrochloride 
• 216661-87-9 4-(4-pyridyl)-1H-pyrazol-3-amine 
• 1258311-28-2 C₁₈H₁₉BrN₄O₂ 
• 1692-15-5 4-pyridylboronic acid 
• 216661-58-4 3-(pyridin-4-yl)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine 
• 216661-87-9 5-amino-4-(pyridin-4-yl)-1H-pyrazole 
• 53868-40-9 2-(4-methoxyphenyl)-3-malonaldehyde 

Relevant academic research and scientific papers

The rational design of a novel potent analogue of the 5′-AMP- activated protein kinase inhibitor compound C with improved selectivity and cellular activity

We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5′-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK.

INHIBITORS OF THE BMP SIGNALING PATHWAY

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors

A structure-activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t1/2 = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition.

Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics.

We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements in physical properties result in marked increases in cellular activity and more favorable pharmacokinetics in rats. The synthesis and SAR of these compounds are described.