1062368-49-3

Basic information

• Product Name: 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a]
• Synonyms: 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a];ML-347(LDN-193719);5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline;LDN 193719;Quinoline, 5-[6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]-;5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline ML-347(LDN-193719);LDN 193719 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline;ML347(DN193719)
• CAS NO: 1062368-49-3
• Molecular Formula: C₂₂H₁₆N₄O
• Molecular Weight: 352.38864
• Product Categories: Inhibitors
• Mol File: 1062368-49-3.mol
• Article Data: 3

Chemical Properties

• Melting Point: 209-210℃
• Appearance: /
• Solubility: insoluble in H2O; insoluble in EtOH; ≥5.87 mg/mL in DMSO with gentle warming
• CAS DataBase Reference: 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a](CAS DataBase Reference)
• NIST Chemistry Reference: 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a](1062368-49-3)
• EPA Substance Registry System: 5-[6-(4-Methoxyphenyl)pyrazolo[1,5-a](1062368-49-3)

Safety Data

• RIDADR: 3077
• Hazardous Substances Data: 1062368-49-3(Hazardous Substances Data)

Usage

Uses

LDN 193719 is a selective bone morphogenetic protein receptor (BMP) inhibitor for ALK2.

Biological Activity

ml347 is a potent and selective inhibitor of bone morphogenetic protein (bmp) receptor with ic50 value of 32nm against alk2 [1].ml347 is discovered as a selective inhibitor of bmp type-i receptor alk2 versus alk3 and is identified as a probe molecule. in the in vitro kinase assay, ml347 shows potent inhibitory activities against alk1 and alk2 with ic50 values of 46 and 32 nm, respectively. the ic50 value of it for alk3 is more than 10μm, demonstrating that ml347 is 300-fold more potent against alk2. besides that, ml347 exerts no inhibition effect on other related kinases such as alk6 and kdr. moreover, ml347 also shows effective inhibition with ic50 value of 152nm in the bmp4 cell based assay using c2c12bra cells [1].

references

[1] engers d w, frist a y, lindsley c w, et al. synthesis and structure–activity relationships of a novel and selective bone morphogenetic protein receptor (bmp) inhibitor derived from the pyrazolo [1.5-a] pyrimidine scaffold of dorsomorphin: the discovery of ml347 as an alk2 versus alk3 selective mlpcn probe. bioorganic & medicinal chemistry letters, 2013, 23(11): 3248-3252.

Upstream product

• 705263-10-1 6-bromo-pyrazolo[1,5-α]pyrimidine 
• 4964-71-0 5-bromoquinoline 
• 1062368-61-9 C₁₃H₁₁N₃O 
• 709631-61-8 3-iodo-6-(4-methoxyphenyl)pyrazolo[1,5-a]pyrimidine 
• 355386-94-6 quinolin-5-ylboronic acid 
• 65192-28-1 2-(4-methoxyphenyl)malondialdehyde 
• 216661-83-5 3-(bromo)-6-(4-methoxyphenyl)-pyrazolo(1,5-A)pyrimidine 

Relevant articles and documents

A synthetic bone morphogenetic protein receptor inhibitors

The invention discloses a method for synthesizing a bone morphogenetic protein receptor inhibitor, and solves the problem of long inhibitor synthesis route in the prior art. The method comprises the following steps: 1, obtaining an intermediate represented by formula (III) shown in the specification, wherein R1 in the formula (III) can be a first formula or a second formula also shown in the specification; 2, adding 5-bromoquinoline to the intermediate represented by formula (III), adding potassium acetate and palladium acetate, adding N,N-dimethyl acetamide, reacting, and cooling to room temperature; and 3, adding water to precipitate a solid when the R1 is the first formula, drying, and separating to obtain a product 1; and extracting the above obtained reaction solution by ethyl acetate when the R1 is the second formula, drying the obtained organic phase to remove a solvent, separating to obtain the product 1, dissolving the product 1 in methanol, adding concentrated hydrochloric acid, reacting to precipitate a solid, carrying out pumping filtration, washing, and drying to obtain a product 2. The method has the advantages of short preparation steps, low price of adopted raw materials, and high yield of target products.

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.