CID 11751756

Base Information

• Chemical Name: CID 11751756
• CAS No.: 213819-48-8
• Molecular Formula: C25H27 N3 O4 . Cl H
• Molecular Weight: 469.968
• Mol file: 213819-48-8.mol

Synonyms:

Chemical Property of CID 11751756

Chemical Property:

• Vapor Pressure: 4.21E-25mmHg at 25°C
• Boiling Point: 772.4°Cat760mmHg
• Flash Point: 420.9°C
• PSA: 93.45000
• Density: g/cm³
• LogP: 3.81300
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility.: DMSO (Slightly), Methanol (Slightly, heated), Water (Slightly)
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 5
• Exact Mass: 469.1768341
• Heavy Atom Count: 33
• Complexity: 865

Purity/Quality:

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

Belotecanhydrochloride(CKD-602) >98% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CC[NH2+]C(C)C)O.[Cl-]
• Isomeric SMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=C(C5=CC=CC=C5N=C4C3=C2)CC[NH2+]C(C)C)O.[Cl-]
• Description: Camtobell hydrochloride, a DNA topoisomerase I inhibitor, is an analog of camptothecin. It was launched in the Republic of Korea as an injectable formulation for the treatment of ovarian and small cell lung cancer. Although camptothecin exhibits potent antineoplastic activity in vitro, its clinical application is hampered by severe toxicity and poor water solubility. Several synthetic and semi-synthetic analogs of camptothecin with improved solubility and lower toxicity have been developed over the past two decades. Two drugs from this class, topotecan and irinotecan, have been launched in previous years and belotecan is the newest member to reach the market. Camtobell hydrochloride is prepared by a two-step semi-synthesis starting from camptothecin, first by converting to 7-methylcamptothecin via a free-radical methylation reaction using a combination of acetic acid, tert-butylhydroperoxide, ferrous sulfate and sulfuric acid, and subsequently, in the second step, a Mannich reaction with isopropylamine hydrochloride and dimethylsulfoxide. A total synthesis of belotecan in seventeen steps starting from ethyl acetopyruvate is also reported. Belotecan inhibits topoisomerase I with approximately equal potency as camptothecin and about 3-fold higher potency than topotecan, with respective IC50 values of 0.119, 0.123 and 0.33 μg/mL. Its cytotoxic activity is comparable to that of camptothecin, with IC50 values ranging from 2 ng/mL to 2 μg/mL against 26 different human cancer cell lines. In studies using human tumor xenografts in nude mice, 80-100 mg/ kg of belotecan dosed every four days for four doses produced 67 to 94% tumor regression rates against HT-29, WIDR and CX-1 colon, LX-1 lung, MX-1 breast and SKOV-3 ovarian carcinomas. Pharmacokinetic studies of camtobell hydrochloride in rats at intravenous doses of 2.6–8.9 mg/kg demonstrated that both Cmax and AUC increased in a dose-dependent manner. Total clearances, volumes of distribution and mean residence times did not change significantly with increasing doses. The elimination half-life ranged between 9.2 to 11.2 hours. In a Phase I study of camtobell hydrochloride, the fraction of renal clearance was found to be 33.1 to 50.3%, and the protein-binding fraction was 53 to 87%. Approximately 9.5% of the administered dose was excreted via the hepatobiliary system. In clinical studies involving 20 patients with recurrent or refractory ovarian cancer, intravenous administration of 0.5 mg/m2/day of belotecan for 5 days every 3 weeks over a median of six dosing cycles resulted in an overall response rate of 45%. All patients had grade 3 or 4 neutropenia as the most significant adverse event.
• Uses: A novel camptothecin-derivative anti-tumor agent. CKD-602-related toxicities induced by IV infusion administration have not yet been evaluated, although the drug is more widely used in clinical settings.

Technology Process of CID 11751756

There total 2 articles about CID 11751756 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: 47.0%

(S)-7-methylcamptothecin (78287-26-0) + isopropylamine (75-31-0) + dimethyl sulfate (77-78-1) → Belotecan hydrochloride (213819-48-8)

Guidance literature:

With hydrogenchloride; at 140 ℃; for 1h;

Reference yield:

camptothecin (7689-03-4,91926-09-9) → Belotecan hydrochloride (213819-48-8)

Guidance literature:

Multi-step reaction with 2 steps

1: 86 percent / ferrous sulfate heptahydrate; tert-butylhydroperoxide; conc. H₂SO₄ / H₂O / 60 h / 20 °C

2: 47 percent / conc. HCl / 1 h / 140 °C

With hydrogenchloride; tert.-butylhydroperoxide; sulfuric acid; iron(II) sulfate; In water; 1: Methylation / 2: Mannich reaction;

Reference yield:

methanesulfonyl chloride (124-63-0) + Belotecan hydrochloride (213819-48-8) → (S)-N-(2-(4-ethyl-4-hydroxyl-3,14-dione-3,4,12,14-tetrahydro-1H-pyrano[3',4',6,7]indolizino[1,2-b]quinolin-11-yl)ethyl)-N-isopropylmethanesulfonamide

Guidance literature:

With triethylamine; In dichloromethane; at 20 ℃; for 2h;

upstream raw materials:

(S)-7-methylcamptothecin

isopropylamine

dimethyl sulfate

camptothecin