1,2,3-Thiadiazole substituted pyrazolones as potent KDR/VEGFR-2 kinase inhibitors was written by Tripathy, Rabindranath;Ghose, Arup;Singh, Jasbir;Bacon, Edward R.;Angeles, Thelma S.;Yang, Shi X.;Albom, Mark S.;Aimone, Lisa D.;Herman, Joseph L.;Mallamo, John P.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2007.Safety of 1,4-Dimethyl-1H-indole-3-carbaldehyde This article mentions the following:
KDR kinase inhibition is considered to play an important role in regulating angiogenesis, which is vital for the survival and proliferation of tumor cells. Recently we disclosed a structure-based kinase inhibitor design strategy which led to the identification of a new class of VEGFR-2/KDR kinase inhibitors bearing heterocyclic substituted pyrazolones as the core template. Instability in a rat S9 preparation and poor iv PK profiles for most of these inhibitors necessitated exploration of new pyrazolones to identify new analogs with improved metabolic stability. Optimization of the heterocyclic moiety led to the identification of the thiadiazole series of pyrazolones (D) as potent VEGFR-2/KDR kinase inhibitors. SAR modifications, kinase selectivity profiling, and structural elements for improved PK properties were explored. Oral bioavailability up to 29% was achieved in the rat. Modeling results based on the Glide XP docking approach supported our postulation regarding the interaction of the lactam segment of the pyrazolones with the hinge region of the KDR kinase. In the experiment, the researchers used many compounds, for example, 1,4-Dimethyl-1H-indole-3-carbaldehyde (cas: 170489-16-4Safety of 1,4-Dimethyl-1H-indole-3-carbaldehyde).
1,4-Dimethyl-1H-indole-3-carbaldehyde (cas: 170489-16-4) belongs to indole derivatives. Indole, first isolated in 1866, and it is commonly synthesized from phenylhydrazine and pyruvic acid, although several other procedures have been discovered. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Safety of 1,4-Dimethyl-1H-indole-3-carbaldehyde
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles