Home > Compound List > Compound details
119413-54-6 molecular structure
click picture or here to close

(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione

ChemBase ID: 902
Molecular Formular: C23H23N3O5
Molecular Mass: 421.44582
Monoisotopic Mass: 421.16377085
SMILES and InChIs

SMILES:
O1Cc2c([C@@](O)(CC)C1=O)cc1n(Cc3c1nc1c(c3)c(CN(C)C)c(O)cc1)c2=O
Canonical SMILES:
CC[C@@]1(O)C(=O)OCc2c1cc1c3nc4ccc(c(c4cc3Cn1c2=O)CN(C)C)O
InChI:
InChI=1S/C23H23N3O5/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20/h5-8,27,30H,4,9-11H2,1-3H3/t23-/m0/s1
InChIKey:
UCFGDBYHRUNTLO-QHCPKHFHSA-N

Cite this record

CBID:902 http://www.chembase.cn/molecule-902.html

Collapse All Expand All

NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
IUPAC Traditional name
topotecan
Brand Name
Hycamptamine
Hycamptin
Hycamtin
Synonyms
TPT
TTC
Topotecanum [INN-Latin]
Topotecane [INN-French]
Topotecan Lactone
Topotecan Hydrochloride
Topotecan Hcl
topotecan
Topotecan
9-[(dimethylamino)methyl]-10-hydroxy-(20S)-camptothecin hydrochloride hydrate
NSC-609669 hydrochloride hydrate
SKF-104864A hydrochloride hydrate
hycamptamine hydrochloride hydrate
Topotecan hydrochloride hydrate
CAS Number
119413-54-6
123948-87-8(freebase)
123948-87-8
MDL Number
MFCD00870670
PubChem SID
46505204
160964365
PubChem CID
60700

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 7.999574  H Acceptors
H Donor LogD (pH = 5.5) -2.4005558 
LogD (pH = 7.4) -0.9559677  Log P -0.35709506 
Molar Refractivity 115.0161 cm3 Polarizability 44.844234 Å3
Polar Surface Area 103.2 Å2 Rotatable Bonds
Lipinski's Rule of Five true 
Log P 1.84  LOG S -2.69 
Solubility (Water) 8.61e-01 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Product Information Bioassay(PubChem)
Solubility
1 mg/ml expand Show data source
DMSO: ≥20 mg/mL expand Show data source
Apperance
yellow powder expand Show data source
Hydrophobicity(logP)
0.8 expand Show data source
Storage Condition
desiccated expand Show data source
protect from light expand Show data source
UN Number
2811 expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Hazard Class
6.1 expand Show data source
Packing Group
3 expand Show data source
Risk Statements
46-48 expand Show data source
Safety Statements
22-36 expand Show data source
GHS Pictograms
GHS08 expand Show data source
GHS Signal Word
Warning expand Show data source
GHS Hazard statements
H341 expand Show data source
GHS Precautionary statements
P281 expand Show data source
RID/ADR
UN 2811 6.1/PG 3 expand Show data source
Storage Temperature
-20°C expand Show data source
Purity
≥98% (HPLC and enzymatic) expand Show data source
95+% expand Show data source
Empirical Formula (Hill Notation)
C23H23N3O5 · xHCl · yH2O expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Sigma Aldrich Sigma Aldrich
DrugBank - DB01030 external link
Item Information
Drug Groups approved; investigational
Description An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA topoisomerases, type I. [PubChem]
Indication For the treatment of advanced ovarian cancer in patients with disease that has recurred or progressed following therapy with platinum-based regimens. Also used as a second-line therapy for treatment-sensitive small cell lung cancer, as well as in combination with cisplatin for the treatment of stage IV-B, recurrent, or persistent cervical cancer not amenable to curative treatment with surgery and/or radiation therapy.
Pharmacology Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.
Toxicity The primary anticipated complication of overdosage would consist of bone marrow suppression.
Affected Organisms
Humans and other mammals
Biotransformation Topotecan undergoes a reversible pH dependent hydrolysis of its lactone moiety; it is the lactone form that is pharmacologically active.
Half Life 2-3 hours
Protein Binding 35%
Elimination Renal clearance is an important determinant of topotecan elimination. In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Fecal elimination of total topotecan accounted for 9 ± 3.6% while fecal elimination of N-desmethyl topotecan was 1.7 ± 0.6%.
References
Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. [Pubmed]
Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. [Pubmed]
Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Sigma Aldrich - T2705 external link
Biochem/physiol Actions
Topotecan is a topoisomerase I inhibitor and an apoptosis inducer. It is a potent antineoplastic agent.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • • Kollmannsberger C, Mross K, Jakob A, Kanz L, Bokemeyer C: Topotecan - A novel topoisomerase I inhibitor: pharmacology and clinical experience. Oncology. 1999;56(1):1-12. Pubmed
  • • Herben VM, ten Bokkel Huinink WW, Beijnen JH: Clinical pharmacokinetics of topotecan. Clin Pharmacokinet. 1996 Aug;31(2):85-102. Pubmed
  • • Dennis MJ, Beijnen JH, Grochow LB, van Warmerdam LJ: An overview of the clinical pharmacology of topotecan. Semin Oncol. 1997 Feb;24(1 Suppl 5):S5-12-S5-18. Pubmed
  • Searching...Please wait...

PATENTS

PATENTS

PubChem iconPubChem Patent Google Patent Search IconGoogle Patent

INTERNET

INTERNET

Baidu iconBaidu google iconGoogle