138716-24-2

Upstream product

• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 2642-63-9 3',4'-dichloroacetophenone 

Downstream Products

• 1612217-74-9 C₁₆H₉Cl₄N₃ 
• 1612217-73-8 C₁₆H₁₀Cl₂N₄O₂ 
• 1612217-72-7 C₁₇H₁₃Cl₂N₃O 

Relevant academic research and scientific papers

Discovery of highly potent tubulin polymerization inhibitors: Design, synthesis, and structure-activity relationships of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines

By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.

Design and synthesis of a novel series of N,4-diphenylpyrimidin-2-amine derivatives as potent and selective PI3Kγ inhibitors

Due to the increasing evidence linking the PI3Kγ pathway to various disease states, PI3Kγ is becoming an important target for cancer treatment. Herein we designed and synthesized a novel series of N,4-diphenylpyrimidin-2-amine derivatives with low CDOCKER-INTERACTION-ENERGY and then evaluated their PI3Kγ in vitro inhibitory activities and in vitro antiproliferation assays against four human cancer cells. Among the compounds we synthesized, compound C8 (IC50 = 65 nM) demonstrated the most potent inhibitory activity against PI3Kγ kinase as well as at the cellular level, compared to the control drug TG100713 (IC50 = 127 nM). Moreover, molecular docking analysis was also performed to determine possible binding modes between PI3Kγ and the target compounds.

4,5-dihydro and 4,5,6,7-tetrahydropyrazolo(1,5-A)-pyrimidines

Novel compounds having the following structural formula: STR1 wherein - - - may represent the presence of a double bond between the C6 and C7 position, Ia, or the absence of a double bond between the C6 and C7 position, Ib; R1 is selected from the group consisting essentially of hydrogen, bromo, chloro, carbamoyl, carboxyl, carboxyalkoxyl where alkoxyl is (C1 -C3), cyano, --CO--CF3, COONa, STR2 --CO--C(CH3)3, and STR3 where X is hydrogen, cyano, halogen and nitro; R2, R4 and R5 may be hydrogen and lower alkyl (C1 -C3); R3 is hydrogen, alkyl (C1 -C3), STR4 where R7 and R8 may be the same or different and are selected from the group consisting essentially of hydrogen, halogen, alkyl (C1 -C3), nitro, alkoxy (C1 -C3), trifluoro-methyl, acetylamino or N-alkylacetylamino where alkyl is (C1 -C3), and R3 may also be selected from a monovalent radical selected from the class consisting essentially of 3-thienyl, 2-pyridinyl, 3-pyridinyl and 4-pyridinyl, either of said pyridinyl radicals being optionally substituted with an alkyl radical R9, where alkyl is (C1 -C4), and the structures of the monovalent 2-pyridinyl, 3-pyridinyl and 4-pyridinyl moieties are depicted respectively as: STR5 R6 is hydrogen or alkyl-(C1 -C3); pharmaceutical compositions of matter containing the above-defined compounds; methods for using the compounds as anxiolytic agents, antihypertensive agents or antidepressant agents in mammals; processes for the preparation of the compounds.