2587-10-2

Upstream product

• 2555-37-5 3-acetyl-4-hydroxychromen-2-one 
• 59-88-1 phenylhydrazine hydrochloride 
• 100-63-0 phenylhydrazine 
• 1076-38-6 4-hydroxy[1]benzopyran-2-one 

Downstream Products

• 86100-07-4 3-methyl-2-phenylchromeno[4,3-c]pyrazol-4(2H)-one 
• 30241-63-5 (5-Hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-(2-hydroxy-phenyl)-methanone 
• 2764-19-4 3-methyl-1-phenyl-1H,4H-chromeno[4,3-c]pyrazol-4-(1H)one 
• 30241-53-3 3-methyl-1-phenylchromeno[2,3-c]pyrazol-4(1H)-one 

Relevant academic research and scientific papers

Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins

Inhibitors of muscle myosin ATPases are needed to treat conditions that could be improved by promoting muscle relaxation. The lead compound for this study ((3-(N-butylethanimidoyl)ethyl)-4-hydroxy-2H-chromen-2-one; BHC) was previously discovered to inhibit skeletal myosin II. BHC and 34 analogues were synthesized to explore structure-activity relationships. The properties of analogues, including solubility, stability, and toxicity, suggest that the BHC scaffold may be useful for developing therapeutics. Inhibition of actin-activated ATPase activity of fast skeletal and cardiac muscle myosin II, inhibition of skeletal muscle contractility ex vivo, and slowing of in vitro actin-sliding velocity were measured. Several analogues with aromatic side arms showed improved potency (half-maximal inhibitory concentration (IC50) 1 μM) and selectivity (≥12-fold) for skeletal myosin versus cardiac myosin compared to BHC. Several analogues blocked neurotransmission, suggesting that they are selective for nonmuscle myosin II over skeletal myosin. Competition and molecular docking studies suggest that BHC and blebbistatin bind to the same site on myosin.

Structural investigations on coumarins leading to chromeno[4,3-c]pyrazol-4-ones and pyrano[4,3-c]pyrazol-4-ones: New scaffolds for the design of the tumor-associated carbonic anhydrase isoforms IX and XII

Human carbonic anhydrases (hCAs, EC 4.2.1.1) IX and XII are overexpressed in a wide variety of cancers and are considered available drug targets for anti-tumor therapy since their inhibition has been shown to reduce tumor growth and metastasis. A set of coumarin derivatives (1–10) and several 1-aryl and 2-aryl-substituted chromeno[4,3-c]pyrazol-4-ones (11–37) and pyrano[4,3-c]pyrazol-4-ones (38–39) were synthesized and tested against the tumor-associated hCAs IX and XII and the cytosolic isoforms hCAs I and II. Several compounds were potent (Ki i = 5.6–9.6 nM), while none were effective against the off-target cytosolic hCAs I and II. Some selected inhibitors (6, 11, 13, 19, 21, 25, 31 and 39) showed activity as antiproliferative agents on HT-29 colon cancer cell lines both in normoxic and hypoxic conditions. This finding led us to hypothesize for these derivatives more than one mechanism of action, involving hCAs IX and XII inhibition in hypoxia and other not identified target(s) in normoxia.

Ring closure reactions of 3-arylhydrazonoalkyl-quinolin-2-ones to 1-aryl-pyrazolo[4,3-c]quinolin-2-ones

4-Hydroxy-3-arylhydrazonoalkyl-2-quinolones 6 or reactive derivatives such as 3-arylhydrazonoalkyl-4-tosyloxy-2-quinolones 7 or 4-chloro-3- arylhydrazonoalkyl-2-quinolones 14, which are obtained via 3-acyl-4- hydroxyquinolones 4, 10 or 3-phenylaminomethylene-quinoline-2,4-diones 12, cyclize in excellent yields to 1-aryl-pyrazolo[4,3-c]quinolin-4-ones (11). The cyclization conditions were investigated by differential scanning calorimetry (DSC).