885693-15-2

Upstream product

• 214360-73-3 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)aniline 
• 138647-49-1 4-Trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 885693-01-6 4-(4-amino-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 885693-00-5 4-(4-amino-3-bromophenyl)piperidine-1-carboxylic acid tert-butyl ester 
• 170011-57-1 tert-butyl 4-(4-aminophenyl)piperidin-1-carboxylate 
• 873454-43-4 4-(4-aminophenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 885693-02-7 (4-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbon-yl]-amino}-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester 
• 76-05-1 trifluoroacetic acid 

Downstream Products

• 885693-03-8 4-cyano-1-(2-trimethylsilanylethoxymethyl)-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(2-morpholin-4-yl-ethyl)piperidin-4-yl]phenyl}amide 
• 885693-16-3 4-(4-{[4-cyano-1-(2-trimethylsilanylethoxymethyl)-1H-imidazole-2-carbonyl]amino}-3-cyclohex-1-enylphenyl)piperidine-1-carboxylic acid (2-hydroxyethyl)amide 

Relevant academic research and scientific papers

Optimization of a potent class of arylamide colony-stimulating factor-1 receptor inhibitors leading to anti-inflammatory clinical candidate 4-cyano-N -[2-(1-cyclohexen-1-yl)-4-[1-[(dimethylamino)acetyl]-4-piperidinyl]phenyl]-1 H -imidazole-2-carboxamide (JNJ-28312141)

A class of potent inhibitors of colony-stimulating factor-1 receptor (CSF-1R or FMS), as exemplified by 8 and 21, was optimized to improve pharmacokinetic and pharmacodynamic properties and potential toxicological liabilities. Early stage absorption, distribution, metabolism, and excretion assays were employed to ensure the incorporation of druglike properties resulting in the selection of several compounds with good activity in a pharmacodynamic screening assay in mice. Further investigation, utilizing the type II collagen-induced arthritis model in mice, culminated in the selection of anti-inflammatory development candidate JNJ-28312141 (23, FMS IC50 = 0.69 nM, cell assay IC50 = 2.6 nM). Compound 23 also demonstrated efficacy in rat adjuvant and streptococcal cell wall-induced models of arthritis and has entered phase I clinical trials.

METHOD OF INHIBITING C-KIT KINASE

A method of reducing or inhibiting kinase activity of C-KIT in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to C-KIT using a compound of the present invention: or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

METHOD OF INHIBITING FLT3 KINASE

A method of reducing or inhibiting kinase activity of FLT3 in a cell or a subject, and the use of such compounds for preventing or treating in a subject a cell proliferative disorder and/or disorders related to FLT3 using a compound of the present invention (I), or a solvate, hydrate, tautomer or pharmaceutically acceptable salt thereof. The present invention is further directed to methods for treating conditions such as cancers and other cell proliferative disorders.

INHIBITORS OF C-FMS KINASE

The invention is directed to compounds of Formula (I): wherein A, X, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, colon cancer, stomach cancer, hairy cell leukemia and non-small lung carcinoma; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including arthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula (I), are also provided.

SYNERGISTIC MODULATION OF FLT3 KINASE USING A FLT3 INHIBITOR AND A FARNESYL TRANSFERASE INHIBITOR

The invention is directed to a method of inhibiting FLT3 tyrosine kinase activity or expression or reducing FLT3 kinase activity or expression in a cell or a subject comprising the administration of a farnesyl transferase inhibitor and a FLT3 kinase inhibitor selected from compounds of Formula I′: Included within the present invention is both prophylactic and therapeutic methods for treating a subject at risk of (or susceptible to) developing a cell proliferative disorder or a disorder related to FLT3.