Grapiprant

Base Information

• Chemical Name: Grapiprant
• CAS No.: 415903-37-6
• Molecular Formula: C26H29N5O3S
• Molecular Weight: 491.61
• UNII: J9F5ZPH7NB
• ChEMBL ID: CHEMBL3039498
• DSSTox Substance ID: DTXSID60194419
• Metabolomics Workbench ID: 153744
• NCI Thesaurus Code: C124131
• Pharos Ligand ID: GPRB8HN92T4U
• Wikidata: Q27077852
• Wikipedia: Grapiprant
• Mol file: 415903-37-6.mol

Synonyms:1-(2-(4-(2-ethyl-4,6-dimethylimidazo(4,5-c)pyridin-1-yl)phenyl)ethyl)-3-(4-methylphenyl)sulfonylurea;AAT-007;CJ 023,423;CJ 023423;CJ-023;CJ-023,423;CJ-023423;grapiprant;MR-10A7;MR10A7;N-(((2-(4-(2-ethyl-4,6-dimethyl-1H-imidazo(4,5-c)pyridin-1-yl) phenyl)ethyl)amino)carbonyl)-4-methylbenzenesulfonamide;RQ-00000007;RQ-7

Chemical Property of Grapiprant

Chemical Property:

• PKA: 5.19±0.10(Predicted)
• PSA: 114.36000
• Density: 1.29±0.1 g/cm3(Predicted)
• LogP: 6.00130
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: Soluble in DMSO (up to at least 10 mg/ml)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 491.19911098
• Heavy Atom Count: 35
• Complexity: 802

Purity/Quality:

99% ^*data from raw suppliers

Grapiprant >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

• Canonical SMILES: CCC1=NC2=C(N1C3=CC=C(C=C3)CCNC(=O)NS(=O)(=O)C4=CC=C(C=C4)C)C=C(N=C2C)C
• Recent ClinicalTrials: Grapiprant and Eribulin for the Treatment of Metastatic Inflammatory Breast Cancer
• Description: Prostaglandin E2 (PGE2) activates four E prostanoid (EP) receptors, EP1-4. EP4 is a Gs protein-coupled receptor that, by elevating the second messenger cAMP, plays important roles in bone formation and resorption, cancer, and atherosclerosis. CJ-023423 is a potent and selective antagonist of the EP4 receptor (Ki = 13 and 20 nM for human and rat EP4, respectively). It inhibits PGE2-evoked elevation in intracellular cAMP in cells and, in vivo, reduces thermal hyperalgesia induced by intraplantar injection of PGE2. CJ-023423 reduces acute and chronic inflammatory pain in different mouse models.
• Uses: CJ-023423 is a potent and selective antagonist of E prostanoid 4 (EP4) receptor.
• Biological Functions: Grapiprant (CJ-023423) is an orally available, a potent and selective EP4 receptor antagonist that exhibits significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. Grapiprant is highly selective for the human EP4 receptor over other human prostanoid receptor subtypes. It also inhibits PGE2-evoked elevation in intracellular cAMP at the human and rat EP4 receptors with pA2 of 8.3 and 8.2 nM, respectively. In vivo, oral administration of grapiprant significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE2 (ED50 = 12.8 mg/kg). It is also effective in models of acute and chronic inflammatory pain. Grapiprant significantly reduces mechanical hyperalgesia in the carrageenan model. Furthermore, it significantly reverses complete Freund′s adjuvant-induced chronic inflammatory pain response. It produces antihyperalgesic effects in animal models of inflammatory pain. Grapiprant is approved and widely used for treatment of osteoarthritis related pain in dogs. Grapiprant is classify as a non-cyclooxygenase inhibiting non-steroidal anti-inflammatory drug (NSAID).

Technology Process of Grapiprant

There total 19 articles about Grapiprant 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: 83.4%

Tosyl isocyanate (4083-64-1) → CJ-023423 (415903-37-6)

Guidance literature:

2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenyl]ethylamine hydrochloride; With sodium hydroxide; In dichloromethane; water; at 30 ℃; for 1.5h;

Tosyl isocyanate; In dichloromethane; at 10 - 25 ℃; for 1h; Product distribution / selectivity;

Reference yield: 9.8%

2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenyl]ethylamine (415908-96-2) + Tosyl isocyanate (4083-64-1) → CJ-023423 (415903-37-6)

Guidance literature:

In dichloromethane; at 10 - 25 ℃; for 1 - 1.5h; Product distribution / selectivity;

Reference yield:

Tosylurethane (5577-13-9) + 2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenyl]ethylamine (415908-96-2) → CJ-023423 (415903-37-6)

Guidance literature:

With triethylamine; In toluene; at 80 - 90 ℃; for 4h;

upstream raw materials:

2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenyl]ethylamine

Tosyl isocyanate

2-[4-(2-Ethyl-4,6-dimethyl-1H-imidazo[4,5-c]pyridin-1-yl)phenyl]ethanol

p-Aminophenethylamine

Refernces

• 1、 -. "EP4 INHIBITORS AND SYNTHESIS THEREOF". Paragraph 00529. . Retrieved 2020/02/06.
• 2、 -. "EP4 INHIBITORS AND USE THEREOF". Paragraph 0875-0882. . Retrieved 2019/10/29.