91421-43-1

Basic information

• Product Name: 9-Aminocamptothecin
• Synonyms: 4':6,7)indolizino(1,2-B)quinoline-3,14(4H,12H)-dione;4':6,7)indolizino(1,2-B)quinoline-3,14(4H,12H)-dione, 10-amino-4-ethyl-4-hydroxy-, (S)-;CAMPTOTHECIN, 9-AMINO-(RG);(S)-10-AMino-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione;AMinocaMptothecin;(S)-10-Amino-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinoline-3,14(4H,12H)-di;CAMPTOTHECIN, 9-AMINO-;9-AMINO-CAMPTOTHECIN
• CAS NO: 91421-43-1
• Molecular Formula: C₂₀H₁₇N₃O₄
• Molecular Weight: 363.37
• Product Categories: Pharmaceutical Raw Materials;Alkaloids;Natural Anti-cancer Medical Materials and It's Derivatives
• Mol File: 91421-43-1.mol

Chemical Properties

• Melting Point: 142.0-145.0 °C
• Boiling Point: 819.6 °C at 760 mmHg
• Flash Point: 449.5 °C
• Appearance: /
• Density: 1.55 g/cm³
• Vapor Pressure: 2.01E-28mmHg at 25°C
• Refractive Index: 1.771
• Storage Temp.: 2-8°C(protect from light)
• Solubility: ≤1mg/ml in DMSO;1mg/ml in dimethyl formamide
• PKA: 11.23±0.20(Predicted)
• Merck: 14,431
• CAS DataBase Reference: 9-Aminocamptothecin(CAS DataBase Reference)
• NIST Chemistry Reference: 9-Aminocamptothecin(91421-43-1)
• EPA Substance Registry System: 9-Aminocamptothecin(91421-43-1)

Safety Data

• RTECS: UQ0490500
• Hazardous Substances Data: 91421-43-1(Hazardous Substances Data)

Usage

Uses

9-Amino Camptothecin is a derivative of Camptothecin (C175150), as antitumor agent.

Biological Activity

9-amino camptothecin is a topoisomerase i inhibitor [1][2].dna topoisomerases relax dna torsional strain generated during replication, transcription, recombination, repair, and chromosome condensation. the relaxation of dna supercoiling by topoisomerase i is enabled by a mechanism of controlled rotation around a transient dna single-strand break. camptothecin (cpt) is isolated from the bark of the chinese tree camptotheca accuminata [3].9-amino camptothecin, a water-soluble camptothecin analogue, is a topoisomerase i inhibitor. in human ht-29 colon adenocarcinoma, 9-amino camptothecin (9-ac) exhibited cytotoxicity with ic50 value of 19 nm. 9-ac also induced dna damage in whole cells and nuclei at a concenstration of 85 nm and 21 nm, respectively [1].9-amino camptothecin had greater activity than camptothecin against human tumour xenografts, including lewis lung carcinoma and b16 melanoma. 9-ac had entered phase ii trials. in patients with advanced solid tumours, 9-amino camptothecin exhibited anti-tumor activity [1][2].

references

[1]. rothenberg, m.l. topoisomerase i inhibitors: review and update. annals of oncology 8(9), 837-855 (1997).[2]. dancey j, eisenhauer ea. current perspectives on camptothecins in cancer treatment. br j cancer. 1996 aug;74(3):327-38.[3]. drwal mn1, agama k, wakelin lp, et al. exploring dna topoisomerase i ligand space in search of novel anticancer agents. plos one. 2011;6(9):e25150.

InChI:InChI=1/C20H17N3O4/c1-2-20(26)13-7-16-17-10(6-11-14(21)4-3-5-15(11)22-17)8-23(16)18(24)12(13)9-27-19(20)25/h3-7,26H,2,8-9,21H2,1H3/t20-/m0/s1

Upstream product

• 164159-93-7 Methanesulfonic acid (S)-4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester 
• 7689-03-4 camptothecin 
• 606-31-5 2,6-dinitrobenzaldehyde 
• 151585-78-3 2-amino-6-nitrobenzaldehyde ethylene acetal 
• 130133-53-8 2-amino-6-nitrobenzaldehyde 
• 110351-94-5 (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 
• 104267-73-4 9-nitro-10-hydroxy-20(S)-camptothecin 
• 19685-09-7 (S)-10-hydroxycamptothecin 
• 164159-99-3 9-nitro-10-(p-toluenesulfonyl)camptothecin 
• 172917-95-2 Naphthalene-1-sulfonic acid (S)-4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester 
• 172917-94-1 Benzenesulfonic acid (S)-4-ethyl-4-hydroxy-10-nitro-3,13-dioxo-3,4,12,13-tetrahydro-1H-2-oxa-6,12a-diaza-dibenzo[b,h]fluoren-9-yl ester 
• 91421-42-0 rubitecan 
• 151585-77-2 2,6-dinitrobenzaldehyde ethylene acetal 

Downstream Products

• 67656-30-8 10-hydroxycamptothecin 
• 7689-03-4 camptothecin 
• 39026-92-1 9-methoxycamptothecin 
• 246032-59-7 methyl N-[9-(β-D-glucuronyl)benzyloxycarbonyl]aminocamptothecin 
• 189311-99-7 (S)-4-Ethyl-4-hydroxy-10-((E)-styryl)-1,12-dihydro-4H-2-oxa-6,12a-diaza-dibenzo[b,h]fluorene-3,13-dione 

Relevant articles and documents

A practical regiospecific synthesis of 9-nitrocamptothecin

9-Nitrocamptothecin has shown potent antitumor activity against many types of human cancers. A practical scale-up procedure for this compound is reported by selective reduction of corresponding sulfonate. Georg Thieme Verlag Stuttgart.

Integrin-Mediated drug targeting

The present invention relates to cytostatics which have a tumour-specific action as a result of linkage to αvβ3 integrin antagonists via preferred linking units. The preferred linking units guarantee serum stability of the conjugate of cytostatic and αvβ3 integrin antagonist and at the same time the desired intracellular action in tumour cells as a result of their enzymatic or hydrolytic cleavability with release of the cytostatic.

Radiosynthesis of carbon-11-labeled camptothecin derivatives as potential positron emission tomography tracers for imaging of topoisomerase I in cancers

Four carbon-11-labeled camptothecin derivatives, 9-[11C]methoxy- 20(S)-camptothecin ([11C]5), 10-[11C]methoxy-20(S)- camptothecin ([11C]7), 9-nitro-10-[11C]methoxy-20(S)- camptothecin ([11C]9), and 9-[([11C]trimethylamino)methyl] -10-hydroxy-20(S)-camptothecin ([11C]11), have been synthesized as potential positron emission tomography tracers for imaging of topoisomerase I in cancers.

Antiangiogenic combination therapy for the treatment of cancer

The present invention provides combinations of a DNA topoisomerase I inhibiting agent and a selective COX-2 inhibiting agent for preventing, treating, and/or reducing the risk of developing a neoplasia disorder in a mammal.

Process for the preparation of 9-amino camptothecin

9-Amino-20(S)-camptothecin (I) is prepared by reducing 12-nitro-20(S)-camptothecin (II); converting the resulting 12-amino-20(S)-camptothecin (III) into a compound of formula (IV) wherein X is a group which can be reductively removed; reacting the compound of formula (IV) with a nitrating agent, to obtain thereby the corresponding 9-nitro-20(S)-camptothecin compound of formula (V) substituted at the 12-position by the group X; reducing in a single step the compound of formula (V), so obtaining the 9-amino-20(S)-camptothecin of formula (I); or reducing the compound of formula (V), so obtaining the corresponding 9-amino-20(S)-camptothecin compound of formula (VI) substituted at the 12-position by the group X and reductively removing the X group from the compound of formula (VI), so obtaining 9-amino-20(S)-camptothecin.

Polymeric derivatives of camptothecins

The invention relates to polymeric conjugates of 20-O-[glycyl-aminoacyl-glycyl]-camptothecins and a process for producing the same.

PROCESS FOR THE PREPARATION OF 9-AMINO CAMPTOTHECIN

A process for preparing the 9-amino camptothecin of formula (I) said process comprising: (1) reacting a compound of formula (III) wherein the hydroxy group on ring A is in the 10- or 12-position, with a nitrating agent, so obtaining a corresponding compound of formula (IV) (2) converting the compound of formula (IV) into a corresponding compound of formula (V) wherein XO is a group that can be removed reductively; and (3) reductively removing the said XO group and reducing the nitro group of the compound of formula (V), so obtaining the 9-amino camptothecin of formula (I), a known antitumor compound. The present invention includes also in its scope compounds having the above reported formula (V) and compound of formula (VII) which are endowed with antitumor activity.p

Method for the preparation of 9-amino camptothecin

9-Amino camptothecin of formula (I) STR1 is prepared by: 1) reducing a compound of formula (II): STR2 wherein Hal is 10- or 12-halogen, in a single step to the 9-amino-camptothecin of formula (I) or, alternatively, 2a) reductively removing the Hal group from a compound of formula (II) so obtaining the compound of formula (III): STR3 and 2b) reducing the compound of formula (III) so obtaining the 9-amino camptothecin of formula (I); the said steps 1 and 2a) and, optionally, step 2b) each being carried out in the presence of a catalytic amount of a compound of formula PdL2 wherein L is acetate or halogen and, additionally, in the presence of an ammonium formate as a hydrogen source. The 9-amino camptothecin of formula (I) is useful as inhibitor of the enzyme topoisomerase I. It is useful in the treatment of cancers, in particular leukaemia, colon and rectal tumours.

Process for the preparation of 9-amino camptothecin

A process for preparing 9-amino camptothecin comprising the steps of: (1) reacting a compound of formula (III) STR1 wherein the hydroxy group on ring A is in the 10- or 12-position, with a nitrating agent, to form the corresponding 9-nitro compound; (2) converting the 9-nitro compound into a corresponding compound of formula (V) STR2 wherein XO is a group that can be removed reductively; and (3) reductively removing the XO group and reducing the nitro group of the compound of formula (V), to form the 9-amino camptothecin, a known antitumor compound. The present invention also includes compound having the above formula (V) and their 9-amino analogs, which have antitumor activity.

Synthesis and antitumor activity of a new class of water soluble camptothecin derivatives

A new family of water soluble camptothecin derivatives is described. Their synthesis, in vitro cytotoxicity, and in vivo antitumor activity is reported. Compounds 5a and 5c displayed excellent in vivo antitumor activity both ip and iv.