Polmacoxib

Base Information

• Chemical Name: Polmacoxib
• CAS No.: 301692-76-2
• Deprecated CAS: 1427301-99-2
• Molecular Formula: C18H16FNO4S
• Molecular Weight: 361.394
• UNII: IJ34D6YPAO
• DSSTox Substance ID: DTXSID901029389
• Wikipedia: Polmacoxib
• Wikidata: Q19598695
• NCI Thesaurus Code: C170335
• Pharos Ligand ID: KNAP6JD4X9L2
• Metabolomics Workbench ID: 153392
• ChEMBL ID: CHEMBL166863
• Mol file: 301692-76-2.mol

Synonyms:CG100649;polmacoxib

Chemical Property of Polmacoxib

Chemical Property:

• Melting Point: 155-156 °C
• Boiling Point: 527.7±60.0 °C(Predicted)
• PKA: 10.21±0.10(Predicted)
• PSA: 94.84000
• Density: 1.361±0.06 g/cm3(Predicted)
• LogP: 4.50040
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 3
• Exact Mass: 361.07840733
• Heavy Atom Count: 25
• Complexity: 672

Purity/Quality:

97% ^*data from raw suppliers

Polmacoxib ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1(C(=O)C(=C(O1)C2=CC=C(C=C2)S(=O)(=O)N)C3=CC(=CC=C3)F)C
• Recent ClinicalTrials: Phase III Study of CG100649 in Osteoarthritis Patients
• Recent EU Clinical Trials: Double-blind, placebo controlled Phase II repeat dose study of the safety and efficacy of three parallel loading and maintenance dose regimens of CG100649 versus placebo for the treatment of primary osteoarthritis in male subjects
• Description: Polmacoxib, also known as (CG-100649), is a first-in-class NSAID which is a dual inhibitor of COX-2 and carbonic anhydrase (CA). The drug, which was approved in South Korea for the treatment of colorectal cancer (CRC) in 2015 and whose discovery has been described by workers at AmorePacific R&D, interacts with CA in red blood cells, providing a novel “tissue-specific” transport mechanism that is designed to deliver sustained levels of drug to inflamed tissues while maintaining low systemic exposure. Although the unique dual COX-2/CA inhibition is designed to provide potentially superior safety to cardiovascular, renal, and gastrointestinal tissues compared to traditional NSAIDs or COX-2 inhibitor drugs, the long-term safety profile of the drug, particularly cardiovascular risks notoriously associated with inhibition of COX-2, has yet to be determined, and the drug is currently not approved for use in any other country outside of South Korea. Polmacoxib is an inhibitor of cyclooxygenase 2 (COX-2) and the carbonic anhydrase subtypes I (CAI) and CAII. It inhibits COX-2 in the absence of carbonic anhydrase II with an IC50 value of 40 nM, which increases by approximately 4- and 17-fold in the presence of a CAII at a molar ratio of 1:1 and 1:5, respectively. It also inhibits CAI and CAII (IC50s = 210 and 95 nM, respectively). Polmacoxib prevents >95 and 90% of prostaglandin E2 (PGE2) production in HCA-7 and HT-29 human colon cancer cells, respectively, using concentrations of 0.01 and 0.001 μg/ml. It inhibits polyp formation in a transgenic mouse model of intestinal polyp formation and tumor growth in human colorectal carcinoma mouse xenograft models when used at a dose of 7 mg/kg. The inhibition of COX-2 and CAII by polmacoxib has the potential for fewer serious systemic adverse effects, including cardiovascular events associated with COX-2 selective inhibitors such as celecoxib . Formulations containing polmacoxib have been used in the treatment of osteoarthritis.
• Uses: Polmacoxib is a nonsteroidal anti-inflammatory drug that inhibits both cyclooxygenase-2 (COX-2) and carbonic anhydrase enzymes.

Technology Process of Polmacoxib

There total 9 articles about Polmacoxib which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 86.0%

C18H14FO4S(1-)*Na(1+) → polemacoxib (301692-76-2)

Guidance literature:

With sodium acetate; hydroxylamine-O-sulfonic acid; In methanol; water; dimethyl sulfoxide; for 5h; Cooling;

Reference yield:

3-fluorophenylboronic acid (768-35-4) + 5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)furanone (301699-02-5) → polemacoxib (301692-76-2)

Guidance literature:

With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate; In ethanol; toluene; at 95 ℃;

DOI:10.1021/jm020545z

Reference yield:

2-methyl-but-3-yn-2-ol (115-19-5) → polemacoxib (301692-76-2)

Guidance literature:

Multi-step reaction with 7 steps

1.1: BuLi / tetrahydrofuran; hexane / 0.33 h / -78 °C

1.2: 724 mg / tetrahydrofuran; hexane / -78 - 20 °C

2.1: 120 g / MnO₂ / CH₂Cl₂ / 20 h / 20 °C

3.1: 90 mg / Et₂NH / ethanol / 1 h / 20 °C

4.1: 7.5 g / m-chloroperoxybenzoic acid / CH₂Cl₂ / 2 h / 0 °C

5.1: 4.5 g / [bis(trifluoroacetoxy)iodo]benzene; I₂ / CCl₄; CHCl₃ / 4 h / 20 °C

6.1: Pd(PPh₃)4; aq. Na₂CO₃ / toluene; ethanol / 95 °C

With manganese(IV) oxide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; n-butyllithium; iodine; sodium carbonate; diethylamine; 3-chloro-benzenecarboperoxoic acid; bis-[(trifluoroacetoxy)iodo]benzene; In tetrahydrofuran; tetrachloromethane; ethanol; hexane; dichloromethane; chloroform; toluene; 7.1: Suzuki coupling;

DOI:10.1021/jm020545z

upstream raw materials:

3-fluorophenylboronic acid

5-{4-(aminosulfonyl)phenyl}-2,2-dimethyl-4-iodo-3(2H)furanone

2-methyl-but-3-yn-2-ol

4-(Methylthio)benzaldehyde

Downstream raw materials:

5-[4-{(Acetylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone

5-[4-{(Butyrylamino)sulfonyl}phenyl]-2,2-dimethyl-4-(3-fluorophenyl)-3(2H)-furanone