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Topotecan hydrochloride

Topotecan hydrochloride 구조식 이미지
카스 번호:
119413-54-6
상품명:
Topotecan hydrochloride
동의어(영문):
108563;Hycamtin;NSC 609669;SKF-104864A;Levulan-13C;SKFS 104864A;HYDROCHLORIDE;TOPOTECAN HCL;Nogitecan HCl;5-ALA HCl-13C
CBNumber:
CB3361775
분자식:
C23H24ClN3O5
포뮬러 무게:
457.91
MOL 파일:
119413-54-6.mol

Topotecan hydrochloride 속성

녹는점
213-218°C
저장 조건
Sealed in dry,Room Temperature
물리적 상태
Light yellow to greenish powder.
CAS 데이터베이스
119413-54-6(CAS DataBase Reference)

안전

위험품 표기 T
위험 카페고리 넘버 25-36/37/38-46
안전지침서 26-36/37/39-45
HS 번호 29420000

Topotecan hydrochloride C화학적 특성, 용도, 생산

화학적 성질

White Crystalline Solid

Originator

Hycamtin,SmithKline Beecham Pharmaceuticals,UK

용도

Naturally occurring amino acid; precursor of tetrapyrroles in the biosynthesis of chlorophyll and heme. Antineoplastic (photosensitizer)

용도

antineoplastic; topoisomerase I inhibitor

용도

A DNA topoisomerase I inhibitor; semisynthetic analog of Camptothecin. Antineoplastic. Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase 1 inhibitor.

Manufacturing Process

Camptothecin (CPT) - a compound isolated from the bark, leaves and fruit of Camptotheca acuminate (Wall M. E. et al., J. Am. Chem. Soc. 88, 3888, 1966).
10-Hydroxycamptothecin (10-HCPT) was prepared by subjecting CPT (3.2 g 0.0092 mol), 0.8 g of Pt0 (prepared by pre-reduction of 8 g of amorphous PtO2 in 80 ml of acetic acid for 1.5 h under 1 atm hydrogen pressure) and acetic acid to 1 atm of H2 for 8.5 h after which theoretical amount of H2 absorbed (slightly more than 0.4 L) and uptake of H2 gets slowed down. The reaction mixture was degassed under steam of helium and filtered through celite and washed with acetic acid (20 ml). The resulting solution was treated immediately with Pb(OAc)4 (6.4 g 0.014 mol) in portions and reaction mixture, stirred vigorously under helium for 30 min. Gumy residue was obtained on evaporation of solvent which was triturated with cold water (100 ml) to produce light brown solid. The solid was collected, washed with cold water and air dried overnight when a mixture of 10-HCPT (44%), acetyl 10- hydroxycamptothecin (10-AcHCPT, 26%) and unreacted CPT (32%) on HPLC basis was obtained. This crude mixture was combined with 150 ml of 50% acetic acid and heated under reflux conditions overnight. The reaction mixture was cooled, concentrated to 20 ml and treated with cold water (100 ml) to produce precipitate, which is filtered, washed with more cold water and dried to afford 2.1 g of solid containing 10-HCPT (70%), 10-AcCPT (1.2%) and CPT (21.3%) on the basis HPLC. Mixture was triturating with 0.5% aq HCl to dissolve the water-soluble. When insoluble CPT was removed by filtration. Water-soluble was extracted with chloroform and crystallized from boiling solution of 20% of MeOH in CHCl3 by adding EtOAC dropwise until turbidity appeared to obtain pure yellow 10-(HCPT), melting point 268°-270°C. 10-HCPT (0.364 g 0.01 mmol) and 40% aqueous dimethylamine (12 ml) was added in dichloromethane (50 ml) in which anhydrous potassium carbonate (2.17 g, 15 mmol) has been suspended. The reaction mixture was stirred at room temperature for 5 h, then filtered and solid extracted with ethylacetate (20 ml). The solvent is evaporated in vacuo giving a residue. The residue was triturated with 0.5% aq HCl (50 ml) to dissolve the water-soluble adduct. Water-soluble were partitioned with petroleum ether (3 times 50 ml) and followed by ethylacetate (3 times 50 ml). The aqueous layer was lyophilized as an off white hydrochloride salt of 9-[(dimethylamino)methyl]10- hydroxy(20S)-camptothecin (topotecan hydrochloride) yield 0.236 g (65%).

상표명

Topotecan is INN and BAN.

Therapeutic Function

Antineoplastic

일반 설명

Topotecan is supplied in 4-mg vials and administered IV forthe treatment of ovarian cancer, cervical cancer, and smallcell lung cancer in those patients who did not respond tofirst-line therapy. Following IV administration, the drug iswidely distributed with 10% to 35% of the agent bound toplasma proteins. There is evidence that the agent may crossthe blood-brain barrier to some extent. In plasma, an equilibriumis established between the lactone and the less activehydroxy acid with 20% of the drug present as the lactone 1hour after the infusion is complete. In contrast to irinotecan,both the lactone and the hydroxy acid bind equally well tohuman serum albumin. N-Demethylation of the tertiaryamine to give the secondary amine is mediated by CYP3A4and represents a minor route of metabolism. Glucuronidationof the parent and the phase I metabolites also occurs to a limited(10%) extent.Elimination occurs primarily in theurine, with 30% of the dose being recovered as unchangeddrug. The terminal elimination half-life is 2 to 3 hours. Themajor toxicity seen for topotecan is dose-limiting myelosuppression.Nausea and vomiting are seen in most (70%–80%)patients, along with diarrhea and abdominal pain. Other toxicitiesinclude headache myalgias, alopecia and elevation ofserum transaminases, alkaline phosphatases, and bilirubin.Microscopic hematuria (blood in the urine) may also be seen.

Pharmacokinetics

Topotecan elimination is biphasic, with a terminal half-life of 2.0 to 3.5 hours. Lactone hydrolysis is rapid, and binding to serum proteins is limited to between 25 and 40%. CYP3A4-mediated N-dealkylation to mono?and didealkylated metabolites occurs to a limited extent, and the O-glucuronides that form at multiple points along the metabolic path are excreted via the kidney.

Clinical Use

This active camptothecin analogue is used by the IV route in the treatment of ovarian and small cell lung cancer that has not responded to first-line therapy.

Topotecan hydrochloride 준비 용품 및 원자재

원자재

준비 용품


Topotecan hydrochloride 공급 업체

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Xi'an ZB Biotech Co.,Ltd
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Henan Tianfu Chemical Co.,Ltd.
0371-55170693
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Shanghai Time Chemicals CO., Ltd.
+8618017249410 +86-021-57951555
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Hangzhou FandaChem Co.,Ltd.
008615858145714
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Nanjing Finetech Chemical Co., Ltd.
025-85710122 17714198479
025-85710122 sales@fine-chemtech.com CHINA 890 55
Shanghai Zheyan Biotech Co., Ltd.
18017610038
zheyansh@163.com CHINA 3623 58
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 29954 58
Chengdu GLP biotechnology Co Ltd
13350802083 028-87075086
scglp@glp-china.com CHINA 1824 58
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 968 58
Jinan Carbotang Biotech Co.,Ltd.
+86 15866703830
figo.gao@foxmail.com CHINA 2778 58

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