Zibotentan

Base Information

• Chemical Name: Zibotentan
• CAS No.: 186497-07-4
• Molecular Formula: C19H16N6O4S
• Molecular Weight: 424.44
• European Community (EC) Number: 643-052-5
• UNII: 8054MM4902
• DSSTox Substance ID: DTXSID70870171
• Nikkaji Number: J2.959.694H
• Wikipedia: Zibotentan
• Wikidata: Q198371
• NCI Thesaurus Code: C48430
• Pharos Ligand ID: CQN1VURUL5MH
• Metabolomics Workbench ID: 149869
• ChEMBL ID: CHEMBL1628688
• Mol file: 186497-07-4.mol

Synonyms:trans,trans-2(4-methoxyphenyl)-4-(1-3-benzodiazol-5-yl)-1-(dibutylaminocarbonylmethyl)pyrrolidine-3-carboxylic acid;ZD4054;zibotentan

Chemical Property of Zibotentan

Chemical Property:

• Boiling Point: 636.996 °C at 760 mmHg
• PKA: 5.62±0.40(Predicted)
• Flash Point: 339.043 °C
• PSA: 141.37000
• Density: 1.423 g/cm³
• LogP: 3.86020
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility.: DMSO (Sparingly), Methanol (Slightly)
• XLogP3: 1.4
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 6
• Exact Mass: 424.09537419
• Heavy Atom Count: 30
• Complexity: 654

Purity/Quality:

98%,99%, ^*data from raw suppliers

Zibotentan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=CN=C(C(=N1)OC)NS(=O)(=O)C2=C(N=CC=C2)C3=CC=C(C=C3)C4=NN=CO4
• Recent ClinicalTrials: Precision Medicine With Zibotentan in Microvascular Angina
• Recent EU Clinical Trials: A Two Part Phase IIa/b Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose-ranging Study to Assess Efficacy, Safety, and Tolerability of the Combination of Zibotentan and Dapagliflozin, and Dapagliflozin Monotherapy Versus Placebo in Participants with Cirrhosis with Features of Portal Hypertension
• Recent NIPH Clinical Trials: A Phase 2b Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose-Ranging Study to Assess the Efficacy, Safety and Tolerability of Zibotentan and Dapagliflozin in Patients With Chronic Kidney Disease With Estimated Glomerular Filtration Rate (eGFR) Between 20 and 60 mL/Min/1.73 m^2
• Description: Zibotentan is a selective antagonist of the endothelin (ET) receptor type A (IC50s = 21 and >10,000 nM for human recombinant ETA and ETB, respectively). It inhibits growth of HEY, OVCA 433, SKOV3, and A2780 cells induced by endothelin 1 (ET-1; ) in vitro. Zibotentan reduces ET-1-induced expression of MMP-2, MMP-9, VEGF, COX-1 and COX-2, mediators of cell invasion and angiogenesis, in HEY cells. In vivo, zibotentan (10-50 mg/kg per day) reduces tumor growth in an HEY mouse xenograft model in a dose-dependent manner. Formulations containing zibotentan are under clinical investigation for the treatment of ovarian and castration-resistant prostate cancers.
• Uses: Zibotentan is a specific endothelin-A receptor antagonist that is a potential candidate in the treatment of prostate cancer, bone metastasis and various other types of cancer.

Technology Process of Zibotentan

There total 2 articles about Zibotentan 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: 86.7%

N-(isobutoxycarbonyl) N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide → [14C]-Zibotentan (186497-07-4)

Guidance literature:

N-(isobutoxycarbonyl) N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide; With ethanolamine; In water; isopropyl alcohol; toluene; at 42 ℃; for 1.5h;

With acetic acid; In water; at 20 - 50 ℃; for 1.66667h; Product distribution / selectivity;

Reference yield:

N-(isobutoxycarbonyl)-2-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide (186497-89-2) → [14C]-Zibotentan (186497-07-4)

Guidance literature:

With hydrazine hydrate; In methanol;

Reference yield: 81.6%

[14C]-Zibotentan (186497-07-4) + ethanolamine (141-43-5) → N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide ethanolamine salt (920524-16-9)

Guidance literature:

In ethanol; water; at 25 - 79 ℃; for 0.25h;

upstream raw materials:

N-(isobutoxycarbonyl)-2-(4-methoxycarbonylphenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulphonamide

Downstream raw materials:

N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide ethanolamine salt

N-(3-methoxy-5-methylpyrazin-2-yl)-2-(4-[1,3,4-oxadiazol-2-yl]phenyl)pyridine-3-sulphonamide ammonium salt

Refernces

• 1、 -. "Heterocyclic compounds". . . Retrieved 2008/06/13.