1439400-48-2

Upstream product

• 1439400-46-0 N-(6-chloropyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide 
• 203302-97-0 2-(3-(trifluoromethoxy)phenyl)acetic acid 
• 226570-68-9 (4-cyanobutyl)zinc(II) bromide 

Downstream Products

• 1439399-49-1 C₂₇H₂₄F₄N₆O₃S 
• 1439399-58-2 2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-^(3-)(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide 
• 1439399-63-9 C₂₅H₂₃F₃N₈O₃S 
• 1439399-78-6 C₃₅H₃₁F₃N₆O₆S 
• 1439399-45-7 N-(6-(4-(5-amino-1,3,4-thiadiazol-2-yl)butyl)pyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide 
• 2247127-79-1 2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)-acetamido)pyridazin-3-yl)butyl)-1,3,4-selenadiazol-2-yl)acetamide 

Relevant academic research and scientific papers

Inhibitors of kidney-type glutaminase mutant site containing oxadiazole or tetrazole structure (by machine translation)

The invention belongs to the field, and particularly relates to an inhibitor, which has better antitumor activity on tumors, especially liver cancer and pancreatic cancer, and is a broad-spectrum low-toxicity anti-tumor inhibitor, and is a broad-spectrum

Novel 1,3,4-Selenadiazole-Containing Kidney-Type Glutaminase Inhibitors Showed Improved Cellular Uptake and Antitumor Activity

Kidney-type glutaminase [KGA/isoenzyme glutaminase C (GAC)] is becoming an important tumor metabolism target in cancer chemotherapy. Its allosteric inhibitor, CB839, showed early promise in cancer therapeutics but limited efficacy in in vivo cancer models. To improve the in vivo activity, we explored a bioisostere replacement of the sulfur atom in bis-2-(5-phenylacetamido-1,2,4-thiadiazol)ethyl sulfide and CB839 analogues with selenium using a novel synthesis of the selenadiazole moiety from carboxylic acids or nitriles. The resulting selenadiazole compounds showed enhanced KGA inhibition, more potent induction of reactive oxygen species, improved inhibition of cancer cells, and higher cellular and tumor accumulation than the corresponding sulfur-containing molecules. However, both CB839 and its selenium analogues show incomplete inhibition of the tested cancer cells, and a partial reduction in tumor size was observed in both the glutamine-dependent HCT116 and aggressive H22 liver cancer xenograft models. Despite this, tumor tissue damage and prolonged survival were observed in animals treated with the selenium analogue of CB839.

CRYSTAL FORMS OF GLUTAMINASE INHIBITORS

The invention relates to crystalline salts of a compound having the structure of formula (I), methods for their preparation, and related pharmaceutical compositions comprising the crystalline salt. The invention further relates to methods of treating or preventing cancer or an immunological or neurological disease comprising administering a crystalline salt of the invention.

HETEROCYCLIC INHIBITORS OF GLUTAMINASE

The invention relates to the heterocyclic compounds of Formula (I) as defined further herein, and pharmaceutical preparations thereof. The invention further relates to methods of treating cancer, immunological or neurological diseases using the heterocyclic compounds of the invention.