In 2017,Bhattarai, Deepak; Jung, Joo Hyun; Han, Seunghyeon; Lee, Hankyu; Oh, Soo Jin; Ko, Hyuk Wan; Lee, Kyeong published 《Design, synthesis, and biological evaluation of structurally modified isoindolinone and quinazolinone derivatives as hedgehog pathway inhibitors》.European Journal of Medicinal Chemistry published the findings.Application of 76006-33-2 The information in the text is summarized as follows:
The Hedgehog (Hh) signaling pathway is associated with diverse aspects of cellular events, such as cell migration, proliferation, and differentiation throughout embryonic development and tissue patterning. An abnormal Hh signaling pathway is linked to numerous human cancers, including basal cell carcinoma (BCC), medulloblastoma (MB), lung cancer, prostate cancer, and ovarian cancer, and it is therefore a promising target in cancer therapy. Using a structure-hopping approach, we designed new Hh signaling pathway inhibitors with isoindolinone or quinazolinone moieties, which were synthesized and biol. evaluated using an 8xGli-luciferase (Gli-Luc) reporter assay in NIH3T3 cells. Compounds with isoindolinone scaffolds demonstrated moderate Hh inhibitory activity; whereas quinazolinone derivatives exhibited good potency with submicromolar IC50 values and the analog I showed nanomolar IC50 value. Although sonidegib shows a decrease in inhibitory effect on vismodegib resistance-conferring Smo mutants, the structurally modified new compounds not only possess the pharmacophoric properties of Hh pathway inhibition but also preserve the suppressive potency in drug-resistant Smo mutants. Mechanistically, quinazolinone derivatives I and II suppress Hh signaling by blocking Smo and Gli translocation into the cilia, similar to vismodegib and sonidegib. Addnl., the human microsomal stability of the representative analogs I and II were determined to be comparable to that of the reference compound sonidegib. Thus, these new scaffolds can serve as a platform for the development of novel cancer therapeutics targeting the Hh pathway. The results came from multiple reactions, including the reaction of 3-Bromo-2-methylbenzoic acid(cas: 76006-33-2Application of 76006-33-2)
3-Bromo-2-methylbenzoic acid(cas: 76006-33-2) belongs to organobromine compounds.Depending on the type of carbon to which the bromine is bonded, organic bromide could be alkyl, alkenyl, alkynyl, or aryl. Application of 76006-33-2 Due to the reactivity of bromide, they are used as potential precursors or important intermediates in organic synthesis.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary