170570-84-0

Upstream product

• 4392-54-5 4-aminosulfonylphenylhydrazine 
• 6296-54-4 ethyl 2,4-dioxo-4-phenylbutyrate 
• 88330-79-4 2-hydroxy-4-oxo-4-phenylbut-2-enoic acid ethyl ester 
• 20577-73-5 methyl 4-phenyl-2,4-dioxobutanoate 
• 98-86-2 acetophenone 
• 88330-79-4 ethyl-(Z)-2-hydroxy-4-oxo-4-phenyl-but-2-enoate 
• 781663-70-5 5-phenyl-1-(4-sulfamoylphenyl)-1H-pyrazole-3-carboxylic acid ethyl ester 
• 170570-83-9 Methyl 1-(4-aminosulfonylphenyl)-5-phenyl-1H-pyrazole-3-carboxylate 

Downstream Products

• 781663-80-7 1-(4-aminosulfonylphenyl)-3-bromomethyl-5-phenyl-1H-pyrazole 
• 1287761-04-9 4-(3-azidomethyl-5-phenyl-pyrazol-1-yl)-benzenesulfonamide 
• 1287760-90-0 4-{5-phenyl-3-[3-(3-trifluoromethylphenyl)-ureidomethyl]-pyrazol-1-yl}-benzenesulfonamide 
• 1287761-13-0 4-[3-((E)-2-nitro-vinyl)-5-phenyl-pyrazol-1-yl]-benzenesulfonamide 
• 1287761-14-1 4-[3-(2-aminoethyl)-5-phenyl-pyrazol-1-yl]-benzenesulfonamide 
• 1287760-92-2 4-(5-phenyl-3-{2-[3-(3-trifluoromethylphenyl)-ureido]-ethyl}-pyrazol-1-yl)-benzenesulfonamide 

Relevant academic research and scientific papers

LOCALLY BIOAVAILABLE DRUGS

Drugs have been designed and developed with a structural motif allowing local bioavailability in the target organ but that are not broadly distributed at a concentration sufficient to illicit toxic side effects in non-targeted organs. The structural motif

PYRAZOLE INHIBITORS OF COX-2 AND SEH

The present invention provides compounds and compositions, e.g., a series of compounds wherein a 1,5-biarylpyrazole group is conjugated to a urea group by a non-cleavable covalent chain, that are useful as dual COX-2/sEH inhibitors. The compounds disclosed herein have activity associated with the arachidonate cascade. The activity of these compounds was demonstrated using a lipopolysaccharide (LPS) induced model of pain in the rat. The compounds of the present invention demonstrated superior anti-allodynic activity as compared to the same dose of celecoxib, i.e., a COX-2 inhibitor, also as compared to the same dose of t-AUCB, i.e., a sEH inhibitor, and also as compared to the co-administered same dose of both celecoxib and t-AUCB. The dual inhibitors of the present invention demonstrate enhanced in vivo anti-allodynic activity in a nociceptive behavioral assay. In addition, the compounds of the present invention also demonstrated to have potent anti-angiogenic effects toward endothelial cells (HUVEC) and inhibit angiogenesis in vitro, ex vivo and in vivo. The dual inhibitors of the present invention also demonstrate anti-angiogenic effect to slow breast tumor growth in vivo.

New selective carbonic anhydrase IX inhibitors: Synthesis and pharmacological evaluation of diarylpyrazole-benzenesulfonamides

Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been proposed as a therapeutic target since it has been associated with poor prognosis, tumor progression and pH regulation. We report the synthesis and the pharmacological evaluation

Synthesis and structure-activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase

A series of dual inhibitors containing a 1,5-diarylpyrazole and a urea were designed, synthesized, and evaluated as novel COX-2/sEH dual inhibitors in vitro using recombinant enzyme assays and in vivo using a lipopolysaccharide (LPS) induced model of pain in rats. The best inhibition potencies and selectivity for sEH and COX-2 over COX-1 were obtained with compounds (21b, 21i, and 21j) in which both the 1,5-diaryl-pyrazole group and the urea group are linked with a three-methylene group. Compound 21i showed the best pharmacokinetic profiles in both mice and rats (higher AUC and longer half-life). Following subcutaneous administration at 10 mg/kg, compound 21i exhibited antiallodynic activity that is more effective than the same dose of either a COX-2 inhibitor (celecoxib) or a sEH inhibitor (t-AUCB) alone, as well as coadministration of both inhibitors. Thus, these novel dual inhibitors exhibited enhanced in vivo antiallodynic activity in a nociceptive behavioral assay.

New COX-2/5-LOX inhibitors: Apoptosis-inducing agents potentially useful in prostate cancer chemotherapy

The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.

Substituted pyrazolyl benzenesulfonamides for use in veterinary therapies

A method of using pyrazolyl benzenesulfonamide compounds in treating inflammation and inflammation-related disorders in companion animals is disclosed.

Substituted pyrazolyl benzenesulfonamides for the treatment of inflammation

A class of pyrazolyl benzenesulfonamide compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula II: STR1 or a pharmaceutically-acceptable salt thereof.

Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: Identification of 4-[5-(4-methylphenyl)- 3(trifluoromethyl)-1h-pyrazol-1-yl]benzenesulfonamide (sc-58635, celecoxib)

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC- 236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3- (trifluoromethyl)-1H-pyrazol-1-y1]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.