849934-95-8

Upstream product

• 849934-94-7 methyl 2-(4-bromo-2-chlorophenyl)acetate 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 59748-90-2 4-Bromo-2-chloro-benzoic Acid 
• 916516-89-7 2-(4-bromo-2-chlorophenyl)acetic acid 
• 185315-48-4 (4-bromo-2-chlorophenyl)methanol 
• 73183-34-3 bis(pinacol)diborane 
• 89720-77-4 4-bromo-1-bromomethyl-2-chlorobenzene 
• 89794-02-5 4-bromo-2-chlorotoluene 
• 67197-54-0 2-(4-bromo-2-chlorophenyl)acetonitrile 

Downstream Products

• 1433193-87-3 2-chloro-6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-8-ethylpyrido[2,3-d]pyrimidin-7(8H)-one 
• 1432908-05-8 6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-8-ethyl-2-((2-(1-methylpiperidin-4-yl)ethyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1432910-06-9 methyl 2-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)acetate 
• 1428759-62-9 C₃₃H₃₂ClN₇O₂ 
• 1428760-94-4 4-(3-chloro-4-(2-chloro-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-6-yl)phenyl)-N-methylpicolinamide 
• 1428760-95-5 [2-chloro-4-(2-methylcarbamoylpyridin-4-yl)phenyl]acetic acid methyl ester 

Relevant academic research and scientific papers

An optimized synthesis of the potent and selective Pak1 inhibitor FRAX-1036

FRAX-1036 is a p21-activated kinase I inhibitor of significant interest to cancer biologists yet no commercial providers or detailed procedures are available. In this Letter, we chronicle the optimized synthesis of FRAX-1036, one of the most specific Pak1

SERINE/THREONINE KINASE INHIBITORS

Compounds having the formula I wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety

Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (1) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing pKa and logP simultaneously. When positioned properly within the scaffold, this group conferred several benefits including potency, pharmacokinetics, and selectivity. Mouse xenograft PK/PD studies were carried out using an advanced compound, G-5555 (12), derived from this approach. These studies concluded that dose-dependent pathway modulation was achievable and paves the way for further in vivo investigations of PAK1 function in cancer and other diseases.

BENZENE COMPOUND HAVING 2 OR MORE SUBSTITUENTS

A superior LXR modulator is provided. A compound represented by the general formula (I): [wherein R1: -COR9 (wherein R9: alkyl, optionally substituted alkoxy or optionally substituted amino); R2: H, OH, alkoxy, optionally substituted amino, etc.; R3: H, optionally substituted alkyl, cycloalkyl, optionally substituted alkoxy, optionally substituted amino, halogeno, etc.; R4 and R5: H, optionally substituted alkyl, halogeno, etc.; R6 and R7: H, alkyl; R8: -X2R10 [wherein R10: -COR11 (wherein R11 : OH, optionally substituted alkoxy, optionally substituted amino, etc.), -SO2R12 (wherein R12: optionally substituted alkyl, optionally substituted amino, etc.), tetrazol-5-yl, etc.; X2: single bond, optionally substituted alkylene, etc.]; X1: -NH-, -O-, -S-, etc.; Y1: optionally substituted phenyl, optionally substituted 5- to 6-membered aromatic heterocyclyl; Y2: optionally substituted aryl, optionally substituted heterocyclyl, etc.] and the like is provided.

Modulators of LXR

Compounds of the invention, such as compounds of formula (I): where n, m, A, B, R1, R2, R3, R4 and R5 are defined herein, are useful as modulators of the activity of liver X receptors. Pharmaceutical compositions containing the compounds and methods of using the compounds are also disclosed.