1229583-72-5

Upstream product

• 875639-15-9 5-bromo-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridine 
• 757978-18-0 3-iodo-5-bromo-1H-pyrrolo[2,3-b]-pyridine 
• 183208-35-7 5-bromo-1H-pyrrolo[2,3-b]pyridine 
• 98-59-9 p-toluenesulfonyl chloride 
• 1229583-70-3 5-bromo-3-(1H-indol-5-yl)-1-(p-toluenesulfonyl)-1H-pyrrolo[2,3-b]pyridine 
• 87199-17-5 4-formylphenylboronic acid, 

Downstream Products

• 1351477-73-0 4-(3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzaldehyde 
• 1351476-74-8 5-(4-((4,4-difluoropiperidin-1-yl)methyl)phenyl)-3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridine 
• 1351476-73-7 4-(4-(3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzyl)morpholine 
• 1351477-77-4 tert-butyl 4-(4-(3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzyl)-2-methylpiperazine-1-carboxylate 
• 1351477-78-5 tert-butyl 4-(4-(3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)benzyl)piperazine-1-carboxylate 
• 1229582-33-5 3-(1H-indol-5-yl)-5-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridine 
• 1351476-76-0 3-(1H-indol-5-yl)-5-(4-((3-methylpiperazin-1-yl)methyl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine 
• 1351476-77-1 1-(4-(4-(3-(1H-indol-5-yl)-1H-pyrrolo [2,3-b]pyridin-5-yl)benzyl)-2-methylpiperazin-1-yl)ethananone 
• 1351476-78-2 5-(4-((3,4-dimethylpiperazin-1-yl)methyl)phenyl)-3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridine 
• 1351477-80-9 3-(1H-indol-5-yl)-5-(4-(piperazin-1-ylmethyl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine 
• 1351476-81-7 C₃₁H₃₃N₅O 
• 1351476-91-9 C₂₉H₂₉N₅O₂ 
• 1351476-97-5 3-(1H-indol-5-yl)-5-(4-((4-(2,2,2-trifluoroethyl)piperazin-1-yl)methyl)phenyl)-1H-pyrrolo[2,3-b]pyridine 
• 1351477-79-6 C₃₅H₃₂F₃N₅O₂S 

Relevant academic research and scientific papers

MIXED LINEAGE KINASE INHIBITORS FOR HIV/AIDS THERAPIES

Disclosed are methods for treating an individual infected with a retrovirus that comprise administering to the individual effective amounts of a mixed lineage kinase inhibitor and antiretroviral drug. In further aspects, disclosed are methods for treating an individual infected with a retrovirus that comprises administering an antiretroviral drug formulated into a crystalline nanoparticle comprising a surfactant, and a MLK inhibitor. Still further disclosed are methods for treating an individual infected with a retrovirus that comprises administering a composition comprising both an antiretroviral and MLK inhibitor formulated into a crystalline nanoparticle, which comprises a surfactant. Still further disclosed are compositions that comprise an antiretroviral drug, a MLK inhibitor, and a surfactant, wherein the composition is a crystalline nanoparticle. Compostions comprising MLK inhibitors with other drugs in nanoparticulate form, and methods of there use, are also disclosed.

Discovery, synthesis, and characterization of an orally bioavailable, brain penetrant inhibitor of mixed lineage kinase 3

Inhibition of mixed lineage kinase 3 (MLK3) is a potential strategy for treatment of Parkinson's disease and HIV-1 associated neurocognitive disorders (HAND), requiring an inhibitor that can achieve significant brain concentration levels. We report here URMC-099 (1) an orally bioavailable (F = 41%), potent (IC50 = 14 nM) MLK3 inhibitor with excellent brain exposure in mouse PK models and minimal interference with key human CYP450 enzymes or hERG channels. The compound inhibits LPS-induced TNFα release in microglial cells, HIV-1 Tat-induced release of cytokines in human monocytes and up-regulation of phospho-JNK in Tat-injected brains of mice. Compound 1 likely functions in HAND preclinical models by inhibiting multiple kinase pathways, including MLK3 and LRRK2 (IC50 = 11 nM). We compare the kinase specificity and BBB penetration of 1 with CEP-1347 (2). Compound 1 is well tolerated, with excellent in vivo activity in HAND models, and is under investigation for further development.

BICYCLIC HETEROARYL KINASE INHIBITORS AND METHODS OF USE

Provided are compounds having an inhibitory effect on kinases including Mixed Lineage Kinases. Also provided are pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by Mixed Lineage Kinase inhibition. Also provided are methods of treatment of neuropsychiatric disorders that comprise the inhibition of Mixed Lineage Kinases.

MLK INHIBITORS AND METHODS OF USE

Provided are compounds having an inhibitory effect on Mixed Lineage Kinases. Also provided are pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by Mixed Lineage Kinase inhibition. Also provided are methods of treatment of neuropsychiatric disorders which comprise the inhibition of Mixed Lineage Kinases.