78686-84-7

Basic information

• Product Name: 5-bromo-6-chloronicotinoyl chloride
• Synonyms: 5-bromo-6-chloronicotinoyl chloride;3-PYRIDINECARBONYL CHLORIDE, 5-BROMO-6-CHLORO
• CAS NO: 78686-84-7
• Molecular Formula: C₆H₂BrCl₂NO
• Molecular Weight: 254.9
• Mol File: 78686-84-7.mol
• Article Data: 9

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 5-bromo-6-chloronicotinoyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 5-bromo-6-chloronicotinoyl chloride(78686-84-7)
• EPA Substance Registry System: 5-bromo-6-chloronicotinoyl chloride(78686-84-7)

Safety Data

• Hazardous Substances Data: 78686-84-7(Hazardous Substances Data)

Upstream product

• 29241-62-1 5-bromo-6-chloronicotinic acid 
• 41668-13-7 5-bromo-6-hydroxy-3-pyridinecarboxylic acid 
• 29241-64-3 5,6-Dibromnicotinsaeure 

Downstream Products

• 78686-77-8 5-bromo-6-chloro-3-pyridinecarboxylic acid methyl ester 

Relevant articles and documents

Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

Asciminib is a potent, specific BCR-ABL1 inhibitor being developed for the treatment of patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL). Here, we present the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. Asciminib was rapidly absorbed with a maximum plasma concentration at two hours post-dose. Total radioactivity and asciminib showed similar terminal half-lives in plasma. Oral asciminib absorption ranged between a minimum of 33%, and a maximum of 57% based on the metabolite profiles of late time-point feces collections. Asciminib was eliminated mainly through feces via unchanged asciminib excretion and metabolism. Direct glucuronidation and oxidation were major metabolic pathways in human that were catalyzed predominantly by UDP-glucuronosyltransferase (UGT)2B7 and cytochrome P450 (CYP)3A4, respectively. The relative contribution of the glucuronidation pathway to the total clearance of asciminib via metabolism is estimated to range ～28–58%, whereas the relative contribution of the oxidative pathway is estimated to range ～37–64%, based upon the maximum oral absorption in humans.

Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1

Chronic myelogenous leukemia (CML) arises from the constitutive activity of the BCR-ABL1 oncoprotein. Tyrosine kinase inhibitors (TKIs) that target the ATP-binding site have transformed CML into a chronic manageable disease. However, some patients develop drug resistance due to ATP-site mutations impeding drug binding. We describe the discovery of asciminib (ABL001), the first allosteric BCR-ABL1 inhibitor to reach the clinic. Asciminib binds to the myristate pocket of BCR-ABL1 and maintains activity against TKI-resistant ATP-site mutations. Although resistance can emerge due to myristate-site mutations, these are sensitive to ATP-competitive inhibitors so that combinations of asciminib with ATP-competitive TKIs suppress the emergence of resistance. Fragment-based screening using NMR and X-ray yielded ligands for the myristate pocket. An NMR-based conformational assay guided the transformation of these inactive ligands into ABL1 inhibitors. Further structure-based optimization for potency, physicochemical, pharmacokinetic, and drug-like properties, culminated in asciminib, which is currently undergoing clinical studies in CML patients.

THIADIAZOLE MODULATORS OF S1P AND METHODS OF MAKING AND USING

The invention is directed to compounds of the formula: wherein each of the variables are defined herein, as well as methods of making and using the compounds as agonists of S1P1 and/or S1P5 for instance treating an autoimmune disease.