1206482-69-0

Basic information

• Product Name: 2-(4-{[(4-iodophenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
• Synonyms: 2-(4-{[(4-iodophenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
• CAS NO: 1206482-69-0
• Molecular Weight: 564.407
• Mol File: 1206482-69-0.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: 2-(4-{[(4-iodophenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(4-{[(4-iodophenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid(1206482-69-0)
• EPA Substance Registry System: 2-(4-{[(4-iodophenyl)amino]carbonothioyl}-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid(1206482-69-0)

Safety Data

• Hazardous Substances Data: 1206482-69-0(Hazardous Substances Data)

Upstream product

• 2059-76-9 4-iodophenyl isothiocyanate 
• 51940-44-4 pipedimic acid 

Relevant articles and documents

PIPEMIDIC ACID DERIVATIVE AUTOTAXIN INHIBITORS

Novel and optimized classes of pipemidic acid derivative compounds that exhibit effective inhibition of autotaxin enzymes are provided. Such classes of compounds exhibit exhibit reactivity with autotaxin to ultimately reduce the size of the reactive sites thereon to prevent conversion of lysophosphatidyl choline to lysophophatidic acid. Furthermore, such compounds can be incorporated within delivery forms for human ingestion. As such, these compounds accord an excellent manner of potentially reducing generation of certain cancers attributable to the presence of naturally occurring autotaxin within the human body. Methods of inactivating autotaxin to certain degrees therewith such compounds are encompassed within invention as well.

Optimization of a pipemidic acid autotaxin inhibitor

Autotaxin (ATX, NPP2) has recently been shown to be the lysophospholipase D responsible for synthesis of the bioactive lipid lysophosphatidic acid (LPA). LPA has a well-established role in cancer, and the production of LPA is consistent with the cancer-promoting actions of ATX. Increased ATX and LPA receptor expression have been found in numerous cancer cell types. The current study has combined ligand-based computational approaches (binary quantitative structure-activity relationship), medicinal chemistry, and experimental enzymatic assays to optimize a previously identified small molecule ATX inhibitor, H2L 7905958 (1). Seventy prospective analogs were analyzed via computational screening, from which 30 promising compounds were synthesized and screened to assess efficacy, potency, and mechanism of inhibition. This approach has identified four analogs as potent as or more potent than the lead. The most potent analog displayed an IC50 of 900 nM with respect to ATX-mediated FS-3 hydrolysis with a Ki of 700 nM, making this compound approximately 3-fold more potent than the previously described lead.