958646-47-4

Upstream product

• 215800-05-8 2-(4-bromo-2-methylphenyl)acetonitrile 
• 74-88-4 methyl iodide 
• 67-56-1 methanol 
• 853796-39-1 2-(4-bromo-2-methyl-phenyl)acetic acid 
• 24078-15-7 4-bromo-1-(chloromethyl)-2-methylbenzene 
• 156001-49-9 4-bromo-2-methylbenzyl bromide 
• 17100-58-2 4-bromo-2-methylbenzyl alcohol 
• 99548-55-7 4-bromo-2-methyl-benzoic acid methyl ester 
• 68837-59-2 4-bromo-2-methylbenzoic acid 

Downstream Products

• 1261653-82-0 (4-cyano-2-methylphenyl)acetic acid methyl ester 
• 1428761-11-8 [4-(N-hydroxycarbamimidoyl)-2-methylphenyl]acetic acid methyl ester 
• 1428761-12-9 [2-methyl-4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl]acetic acid methyl ester 
• 1415960-54-1 methyl 2-(2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate 
• 1432909-72-2 methyl 2-(2-methyl-4-(3-methylpyrazin-2-yl)phenyl)acetate 
• 1432907-30-6 8-ethyl-6-(2-methyl-4-(3-methylpyrazin-2-yl)phenyl)-2-(tetra hydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one 
• 1432909-74-4 2-chloro-8-ethyl-6-(2-methyl-4-(3-methylpyrazin-2-yl)phenyl)pyrido[2,3-d]pyrimidin-7(8H)-one 

Relevant academic research and scientific papers

Discovery of carboxyl-containing biaryl ureas as potent RORγt inverse agonists

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76percent inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1, exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model.

BIARYL UREA DERIVATIVE OR SALT THEREOF, AND MANUFACTURING AND APPLICATION OF SAME

The present invention discloses a biaryl urea RORγt inhibitor, and specifically relates to a biaryl urea derivative, as represented by formula I, with an RORγt inhibiting activity, and a preparation process thereof, and a pharmaceutical composition comprising the compound. Further disclosed is use of the compound for treating an RORγt-related disease.

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.

8-ETHYL-6-(ARYL)PYRIDO [2,3-D]PYRIMIDIN-7(8H) -ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER

Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.

BENZENE COMPOUND HAVING 2 OR MORE SUBSTITUENTS

Disclosed is an excellent LXR modulator. Specifically disclosed is a compound represented by the general formula (I) below or the like. (I) [In the formula, R1 represents a -COR9 (wherein R9 represents an alkyl, optionally substituted alkoxy or optionally substituted amino); R2 represents an H, OH, alkoxy, optionally substituted amino or the like; R3 represents an H, optionally substituted alkyl, cycloalkyl, optionally substituted alkoxy, optionally substituted amino, halogeno or the like; R4 and R5 respectively represent an H, optionally substituted alkyl, halogeno or the like; R6 and R7 respectively represent an H or alkyl; R8 represents a -X2R10 [wherein R10 represents a -COR11 (wherein R11 represents an OH, optionally substituted alkoxy, optionally substituted amino or the like), -SO2R12 (wherein R12 represents an optionally substituted alkyl, optionally substituted amino or the like), tetrazole-5-yl or the like; and X2 represents a single bond, optionally substituted alkylene or the like]; X1 represents an -NH-, -O-, -S- or the like; Y1 represents an optionally substituted phenyl or optionally substituted 5-membered or 6-membered aromatic heterocyclyl; and Y2 represents an optionally substituted aryl, substituted heterocyclyl or the like.]

SUBSTITUTED INDOLE COMPOUND

Disclosed is an excellent LXR modulator. A compound represented by the general formula (I): (I) wherein R1, R2, R3 and R4: H, an alkyl which may be substituted, OH, an alkoxy which may be substituted, an amino which may be substituted, a halogeno, a phenyl or the like; R5: H or an alkyl; R6: -COR8 (wherein R8: an alkoxy which may be substituted, a phenyloxy which may be substituted, an amino which may be substituted, or the like), -SO2R9 (wherein R9: an alkyl which may be substituted, a phenyl which may be substituted or a heterocyclyl which may be substituted), or an alkyl which may be substituted; R7: -X2R10 [wherein R10: -COR11 (where R11: OH, an alkoxy which may be substituted or an amino which may be substituted), -SO2R12 (where R12: an alkyl which may be substituted or amino which may be substituted), -N(R13)COR14 (where R13: H or an alkyl which may be substituted; R14: H or an alkyl which may be substituted), -N(R13)SO2R15 (where R13: as defined above; R15: an alkyl which may be substituted) or tetrazol-5-yl; and X2: a single bond or an alkylene which may be substituted]; X1: a methylene which may be substituted; Y1: a phenyl which may be substituted or a heterocyclyl which may be substituted; and Y2: an aryl which may be substituted, a heterocyclyl which may be substituted or the like], or the like.