7-Ethyl-10-Hydroxycamptothecin (HCID 104842)

Überblick

SN-38 is a member of the class of pyranoindolizinoquinolines that is (4S)-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione bearing two additional ethyl substituents at positions 4 and 11 as well as two additional hydroxy substituents at positions 4 and 9. It is the active metabolite of irinotecan and is ~1000 times more active than irinotecan itself. It has a role as an antineoplastic agent, a drug metabolite, an EC 5.99.1.2 (DNA topoisomerase) inhibitor and an apoptosis inducer. It is a delta-lactone, a tertiary alcohol, a member of phenols and a pyranoindolizinoquinoline.

Namen und Bezeichner

Bevorzugter Name: 7-Ethyl-10-Hydroxycamptothecin
IUPAC: (19S)-10,19-diethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione
Englischer Name: 7-Ethyl-10-hydroxycamptothecin
Summenformel: C22H20N2O5
Molmasse: 392.4

Namen und Synonyme

7-Ethyl-10-hydroxycamptothecin86639-52-3SN-38SN 38 lactoneSN 3810-Hydroxy-7-ethylcamptothecinNK-0127-Ethyl-10-hydroxy-20(S)-camptothecinNK 012NK0120H43101T0JCAMPTOTHECIN, 7-ETHYL-10-HYDROXY-

Weitere Namen anzeigen

SN387-ETHYL-10-HYDROXYCAMPTOTHECINE(S)-4,11-diethyl-4,9-dihydroxy-1,12-dihydro-14H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H)-dioneIrinotecan Related CoMpound B7-10-hydroxycamptothecin(S)-7-Ethyl-10-hydroxycamptothecin(S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dioneIrinotecan EP Impurity E/ Irinotecan Related Compound B (7-Ethyl-10-Hydroxy Camptothecin/ 11-Ethyl-9-Hydroxy Camptothecin)EHCPT

CHEBI:8988DTXSID4040399(4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione(4S)-4,11-diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione(19S)-10,19-diethyl-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(1S,2S,3R)-1-(3,4-dihydroxy-5-methoxy-phenyl)-2,3,7-trihydroxy-3-(hydroxymethyl)-6-methoxy-tetralin-2-carboxylic acid1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 4,11-DIETHYL-4,9-DIHYDROXY-, (4S)-H-Pyrano(3',4':6,7)indolizino(1,2-b)quinoline-3,14(4H,12H)-dione, 4,11-diethyl-4,9-dihydroxy-, (S)-

Datenbank-Bezeichner

CAS: 86639-52-3
PubChem CID: 104842
DTXSID: DTXSID4040399
ChEMBL: CHEMBL837
ChEBI: CHEBI:8988
UNII: 0H43101T0J
EC Number: 643-093-9
Nikkaji: J353.490A

Eigenschaften

Berechnete Struktureigenschaften

XLogP: 1,4
Polarare Oberfläche (TPSA): 100 Å²
H-Brücken-Donoren: 2
H-Brücken-Akzeptoren: 6
Frei drehbare Bindungen: 2
Schwere Atome: 29
Formalladung: 0
Komplexität: 820

Experimentelle und physikochemische Eigenschaften

DrugsPharmaceuticals -> Listed in ZINC15

Physikochemische Eigenschaften

Schmelzpunkt: 217 °C · 217 °C
Siedepunkt: 810.3 · 810.3±65.0 °C(Predicted)
Dichte: 1.51 · 1.51±0.1 g/cm3(Predicted)
Brechungsindex: 21.5 ° · 21.5 ° (C=0.2, THF)
storage temp.: 2 · 2-8°C
Löslichkeit: 1 mg/mL · DMSO: soluble1mg/mL
Aggregatzustand: powder
pka: 9.13 · 9.13±0.40(Predicted)
Farbe: Off-white
Stabilität: 2 years · Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.
InChI: InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1
InChIKey: FJHBVJOVLFPMQE-QFIPXVFZSA-N
SMILES: N1C2C(=CC(O)=CC=2)C(CC)=C2CN3C(C=12)=CC1[C@](CC)(O)C(=O)OCC=1C3=O
CAS Datenbank: 86639 · 86639-52-3(CAS DataBase Reference)

Sicherheit und Regulatorisches

GHS-Klassifizierung

GHS Classification · 4 Einträge

Danger

H301 (75%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 60 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Hazard Classes and CategoriesAcute Tox. 3 (75%)

Sicherheitsdaten

wgk: 3
ridadr: 2811
hs_code: 29399990
RTECS-Nr.: UQ0491000
risk_code: 25
hazard_code: T
safety_code: 45
hazard_class: 6.1
packing_group: Ⅲ
Speicherklasse: 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Hazard Classifications: Acute Tox. 4 OralRepr. 1BSTOT RE 1

Chemie und Industrie

Pharmakologische Informationen

Pharmacodynamics · 1 Eintrag

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of Irinotecan (CPT-11). Irinotecan is a topoisomerase I inhibitor commercially available as Camptosar®. SN-38 has been found to be 200–2000 times more cytotoxic than CPT-11, but has not been used as an anticancer drug due to its poor solubility in pharmaceutically acceptable solvents and low affinity to lipid membranes. SN-38 also undergoes a reversible conversion to an inactive open lactone ring structure at physiological pH. LE-SN-38 is a novel lipsome based formulation containing liposomes of uniform size distribution (<200 nm). Drug entrapment efficiency of the formulation is>95%.

Mechanism of Action · 1 Eintrag

The entrapment of SN-38 in lipsomes results in a more stable and more soluble form of the drug. This allows for increased affinity of SN-38 to lipid membranes and improved delivery of the drug to tumor sites. SN-38 is a highly effective cytotoxic topoisomerase I inhibitor.

MeSH Pharmacological ClassificationCompounds that inhibit the activity of DNA TOPOISOMERASE I.

Tissue LocationsKidney

Metabolite PathwaysIrinotecan Action Pathway

Anwendungen · 1 Eintrag

Verwenden7-ethyl-10-hydroxycamptothecin (SN 38) is a metabolite of Irinotecan, a DNA topoisomerase inhibitor. SN 38 has been used in trials studying the treatment of Cancer, Advanced Solid Tumors, Small Cell Lung Cancer, Metastatic Colorectal Cancer, and Triple Negative Breast Cancer, among others.

Darstellung · 1 Eintrag

synthetische7-Ethyl-10-hydroxycamptothecin (SN-38) was synthesized from 20(S)-camptothecin (1) as the starting material via a three-step route in 30–35% overall yield. first, 7-ethylation of 20(S)-camptothecin was carried out by adding hydrogen peroxide and freshly distilled propionaldehyde to an ice-cold sulfuric acid solution of the substrate in the presence of ferrous sulfate, giving 7-ethylcamptothecin (2) in 77% yield; second, N-oxidation of 2 with 30% H₂O₂ in acetic acid at 70–80 °C for 3.5 h afforded 7-ethylcamptothecin 1-oxide (3) in 78% yield; finally, photochemical 10-hydroxylation of 3 dissolved in dioxane containing an equimolar amount of sulfuric acid under irradiation with a 450 W high-pressure mercury lamp (Pyrex filter) for 30 min furnished compound 4 (SN-38) in 49% yield [5].

Vor- und nachgelagerte Produkte

Nachgelagerte Produkte

Irinotecan

Anbieter50 Anbieter

国药集团化学试剂有限公司86-21-63210123 · [email protected]

北京华美互利生物化工010-56205725 · [email protected]

梯希爱(上海)化成工业发展有限公司021-67121386 · [email protected]

上海阿拉丁生化科技股份有限公司400-6206333 13167063860 · [email protected]

INTATRADE GmbH+49 3493/605464 · [email protected]

Ergänzende Hinweise · 1 Eintrag

DefinitionChEBI: SN-38 (7-Ethyl-10-hydroxycamptothecin) is a member of the class of pyranoindolizinoquinolines that is (4S)-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione bearing two additional ethyl substituents at positions 4 and 11 as well as two additional hydroxy substituents at positions 4 and 9. It is the active metabolite of irinotecan and is ~1000 times more active than irinotecan itself. It has a role as an apoptosis inducer, an EC 5.99.1.2 (DNA topoisomerase) inhibitor, a drug metabolite and an antineoplastic agent. It is a pyranoindolizinoquinoline, a delta-lactone, a tertiary alcohol and a member of phenols.