213819-48-8 Usage
Description
Camtobell hydrochloride, also known as belotecan, is a DNA topoisomerase I inhibitor and an analog of camptothecin. It is a novel camptothecin-derivative anti-tumor agent that has been developed to improve the solubility and reduce the toxicity associated with camptothecin. Camtobell hydrochloride is prepared through a two-step semi-synthesis process and has demonstrated potent antineoplastic activity against various human cancer cell lines.
Uses
Used in Oncology:
Camtobell hydrochloride is used as an antineoplastic agent for the treatment of ovarian and small cell lung cancer. It inhibits topoisomerase I with approximately equal potency as camptothecin and about 3-fold higher potency than topotecan. In clinical studies, it has shown an overall response rate of 45% in patients with recurrent or refractory ovarian cancer when administered intravenously.
Used in Drug Development:
Camtobell hydrochloride serves as a basis for the development of new synthetic and semi-synthetic analogs of camptothecin with improved water solubility and lower toxicity. These analogs aim to enhance the clinical application of camptothecin derivatives in cancer treatment.
Used in Pharmacokinetic Research:
Camtobell hydrochloride is utilized in pharmacokinetic studies to understand its dose-dependent behavior, clearance, distribution, and elimination half-life. This information is crucial for determining the optimal dosing regimen and evaluating the drug's safety and efficacy in clinical settings.
Used in Clinical Trials:
Camtobell hydrochloride is employed in Phase I clinical trials to assess its safety, tolerability, and pharmacokinetics in human subjects. These trials provide valuable data on the drug's renal clearance, protein-binding fraction, and hepatobiliary excretion, which are essential for guiding further clinical development and application.
Brand Name:
Camtobell
Originator
CKD Pharmaceuticals (S. Korea)
Synthesis
The total synthesis route is depicted in the Scheme. The
known pyridinone 7 was converted to the bicyclic
pyridinone 8 by treatment with methyl acrylate and K2CO3
in DMF. Hydrolysis and decarboxylation of 8 to ketone 9
was effected by refluxing in a mixture of HOAc and conc.
HCl under nitrogen. Ketalization was performed in a two
phase system of toluene and ethylene glycol to provide ketal
10 in 90% yield. Functionalization of the methyl group in
10 using diethyl carbonate in the presence of KH furnished
the ester 11 in 76% yield. Ethylation of 11 was
accomplished by use of KOBut and EtI in DME. Catalytic
hydrogenation of 12 using Raney Ni in a mixture of Ac2O
and HOAc gave the amide 13. Removal of the catalyst by
filtration followed by addition of NaNO2 to the filtrate gave
the N-nitroso amide. Decomposition of the nitroso amide by heating in an inert solvent (CCl4) gave the acetate 14.
The diester 14 was lactonized by LiOH in MeOH/H2O to
give lactone 15 in 92% yield. The carbonyl group in 15
was then reduced with DIBAL-H in THF to give lactol,
which was dehydrated via its mesylate to afford 16. The
asymmetric dihydroxylation of 16 gave diasteromeric
mixtures in favor of the desired isomer 17 (81% d.e.).
Compound 16 was then oxidized directly with iodine in the
presence of CaCO3 to give a-hydroxy lactone 18. The
deketalization was accomplished by HCl in THF/H2O to
provide the ketone 19. Condensation of ketone 19 and
the amine 20 in the presence of p-TSA followed by
hydrolytic removal of Cbz group provided the free base
Which was convert to its corresponding HCl salt as
belotecan hydrochloride (II).
Check Digit Verification of cas no
The CAS Registry Mumber 213819-48-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,1,3,8,1 and 9 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 213819-48:
(8*2)+(7*1)+(6*3)+(5*8)+(4*1)+(3*9)+(2*4)+(1*8)=128
128 % 10 = 8
So 213819-48-8 is a valid CAS Registry Number.
InChI:InChI=1/C25H27N3O4.ClH/c1-4-25(31)19-11-21-22-17(12-28(21)23(29)18(19)13-32-24(25)30)15(9-10-26-14(2)3)16-7-5-6-8-20(16)27-22;/h5-8,11,14,26,31H,4,9-10,12-13H2,1-3H3;1H/t25-;/m0./s1
