97682-44-5

Basic information

• Product Name: Irinotecan
• Synonyms: Irinotecan (free Base);Irinotecan(TECANS);1,4'-Bipiperidine-1'-carboxylic acid (S)-4,11-diethyl-3,4,12,14- tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl ester;DQ-2805;(4S)-4,11-Diethyl-4-hydroxy-9-[[(4-piperidinopiperidino)carbonyl]oxy]-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione;SN-38-11;(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate;(4S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl-[1,4'-bipiperidine]-1'-carboxylic acid
• CAS NO: 97682-44-5
• Molecular Formula: C₃₃H₃₈N₄O₆
• Molecular Weight: 623.14
• EINECS: 1806241-263-5
• Product Categories: Camptothecin series;APIs;Natural Anti-cancer Medical Materials and It's Derivatives;API's;API;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Camptosar, Campto;Anti-cancer&immunity;Anti cancer;Inhibitors
• Mol File: 97682-44-5.mol

Chemical Properties

• Melting Point: 222-223°
• Boiling Point: 873.4 °C at 760 mmHg
• Flash Point: 482 °C
• Appearance: /
• Density: 1.4 g/cm³
• Storage Temp.: 2-8°C
• Solubility: Acetonitrile (Slightly, Heated, Sonicated), DMSO (Slightly), Methanol (Slightly)
• PKA: 11.20±0.20(Predicted)
• CAS DataBase Reference: Irinotecan(CAS DataBase Reference)
• NIST Chemistry Reference: Irinotecan(97682-44-5)
• EPA Substance Registry System: Irinotecan(97682-44-5)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• RTECS: DW1061000
• Hazardous Substances Data: 97682-44-5(Hazardous Substances Data)

Usage

Uses

Used in Oncology:
Irinotecan is used as a chemotherapeutic agent for the treatment of various types of cancer. Its primary application is as a topoisomerase I inhibitor, which plays a crucial role in the management of cancer cells. By inhibiting topoisomerase I, Irinotecan disrupts the normal functioning of DNA replication and transcription, leading to the death of cancer cells.
Specifically, Irinotecan has demonstrated effectiveness in treating LoVo cells and HT-29 cells, with an IC50 of 15.8 μM and 5.17 μM, respectively. This indicates its potential use in targeting colorectal cancer cells, which are often associated with these cell lines. The ability of Irinotecan to selectively target cancer cells and inhibit their growth makes it a valuable tool in the fight against cancer and a promising candidate for further research and development in oncology.

Biological Activity

irinotecan (cpt-11), a prodrug for treating metastatic colorectal cancer, is a topoisomerase i inhibitor for lovo cells and ht-29 cells with ic50 of 15.8 μm and 5.17 μm, respectively [1].in vivo, irinotecan is converted to sn-38, its most active metabolite, by carboxylesterase converting enzyme (cce) [2].

in vitro

irinotecan induced similar amounts of cleavable complexes in lovocells and ht-29 cell lines with the ic50 of 15.8 μm and 5.17 μm, respectively [1].after addition of 157 mm irinotecan to plasma, sn-38 concentration showed linear increase during the first 60-min period, followed by a plateau.in the first 60 min, mean and standard deviation of the conversion rate were 515.9 ± 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097 [2]. irinotecan (cpt-11) was significantly more active in sclc than in nsclccelllines (p = 0.0036). ce activity appeared to be associated with higher sensitivity to cpt-11 in human lung cancercelllines and may partly explain the difference in the in vitro sensitivity to cpt-11 between sclc and nsclccells [3].in vitro, the sensitivity to cpt-11 and sn-38 was highest in ls174t and colo 320cells, intermediate in sw1398cellsand lowest in colo 205 and widr cells. the activity of sn-38 was 130 to 570 times than cpt-11[4].

in vivo

in colo 320 xenografts, irinotecan induced a maximum growth inhibition of 92% [4].a single dose of irinotecan significantly increased amounts of topoisomerase i covalently bound to dna in stomach, duodenum, colon and liver. concomitantly, the irinotecan-treated group exihibited significantly higher amounts of dna strand breaks in colon mucosa cells compared to the control group [5].

references

[1]. tobin p, clarke s, seale j p, et al. the in vitro metabolism of irinotecan (cpt‐11) by carboxylesterase and β‐glucuronidase in human colorectal tumours[j]. british journal of clinical pharmacology, 2006, 62(1): 122-129.[2]. shingyoji m, takiguchi y, watanabe‐uruma r, et al. in vitro conversion of irinotecan to sn‐38 in human plasma[j]. cancer science, 2004, 95(6): 537-540.[3]. van ark-otte j, kedde m a, van der vijgh w j, et al. determinants of cpt-11 and sn-38 activities in human lung cancer cells[j]. british journal of cancer, 1998, 77(12): 2171.[4]. jansen w j m, zwart b, hulscher s t m, et al. cpt-11 in human colon-cancer cell lines and xenografts: characterization of cellular sensitivity determinants[j]. international journal of cancer, 1997, 70(3): 335-340.[5]. na y s, jung k a, kim s m, et al. the histone deacetylase inhibitor pxd101 increases the efficacy of irinotecan in in vitro and in vivo colon cancer models[j]. cancer chemotherapy and pharmacology, 2011, 68(2): 389-398.

InChI:InChI=1/C33H38N4O6/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3/t33-/m0/s1

Upstream product

• 7693-46-1 4-Nitrophenyl chloroformate 
• 110351-94-5 (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione 
• 78287-27-1 7-ethylcamptothecin 
• 143254-82-4 4-piperidinopiperidine-1-carbonyl chloride hydrochloride 
• 86639-52-3 7-ethyl-10-hydroxycamptothecin 
• 4897-50-1 4-piperidinopiperidin 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 869097-09-6 (+/-)-4-ethyl-4-hydroxy-8-methoxy-6-(trimethylsilyl)-1,4-dihydro-3H-pyrano[3,4-c]pyridin-3-one 
• 202745-10-6 [1,4']Bipiperidinyl-1'-carboxylic acid 4-nitro-phenyl ester 
• 202745-11-7 [1,4']Bipiperidinyl-1'-carboxylic acid 4-aminophenylester 
• 174092-79-6 (S)-4-ethyl-4-hydroxy-6-iodo-8-methoxy-1,4-dihydro-pyrano[3,4-c]pyridin-3-one 
• 173442-34-7 (S)-4-ethyl-4-hydroxy-6-iodo-3-oxo-1H-pyrano[3,4-c]-8-pyridone 
• 16400-32-1 1-bromo-pent-2-yne 
• 174092-83-2 (S)-4-ethyl-4-hydroxy-6-iodo-7-(pent-2-yn-1-yl)-1,7-dihydro-3H-pyrano[3,4-c]pyridino-3,8(4H)-dione 

Downstream Products

• 86639-52-3 7-ethyl-10-hydroxycamptothecin 
• 4897-50-1 4-piperidinopiperidin 
• 181467-56-1 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin 
• 100286-90-6 irinotecan hydrochloirde 

Relevant articles and documents

Preparation method of irinotecan hydrochloride

The invention relates to a preparation method of irinotecan hydrochloride. The preparation method comprises the following steps: a) enabling 4-piperidylpiperidine and N, N'-carbonyldiimidazole to react with 7-ethyl-10-hydroxycamptothecine in an aprotic solvent containing a hemp and cotton resin compound to generate an irinotecan monomer, and b) adding water to dissolve the irinotecan monomer, adding a hydrochloric acid solution to adjust the pH value to 2-3, adding acetone of which the volume is 3-5 times that of the water, carrying out crystallizing, filtering and recrystallizing with a mixedsolvent of acetone and water, and carrying out vacuum drying to obtain the irinotecan hydrochloride finished product. Compared with the prior art, according to the invention, in preparatuion of irinotecan hydrochloride, no high-toxicity dangerous reagent is used, the N, N-dimethylformamide with relatively stable commercial easy-to-obtain property is used, a carbonyl group is introduced into N, N'-carbonyldiimidazole, an irinotecan monomer is obtained through a one-step reaction, the harsh condition that N, N'-carbonyldiimidazole needs to be anhydrous is avoided through cooperation with a hempand cotton resin compound, the reaction process is greatly simplified, the production period is shortened, and the preparation method has obvious industrial production advantages.

A preparation method of irinotecan hydrochloride (by machine translation)

The invention relates to a preparation method of irinotecan hydrochloride. Its steps are: parent ring to camptothecin as raw material generated by the reaction with the aldehyde 7 - ethyl camptothecin; hydrogen peroxide oxidation then N - oxide - 7 - ethyl camptothecin; by the illumination rearrangement 7 - ethyl - 10 - hydroxy camptothecin; 4 - piperidyl with dimethyl carbonate reaction to produce 4 - piperidyl carbonic acid methyl ester; 7 - ethyl - 10 - hydroxy camptothecin with 4 - piperidyl carbonic acid methyl ester reaction generating irinotecan monomer; irinotecan monomers with hydrochloric salt to obtain the finished product of the irinotecan hydrochloride. Compared with the prior art, the present invention avoid the use of phosgene in the reaction process, chloroform poisonous substance, in production with safe, convenient, less pollution and the like; in addition, the synthetic method avoids the need of the prior process in the defects of the chromatographic column separation and purification, reduces the production cost of the irinotecan, has great economic benefit. (by machine translation)

Irinotecan-cholesterol succinic acid simple lipid ion pair, liposome and preparation method and application thereof

The invention discloses an irinotecan-cholesterol succinic acid simple lipid ion pair, a liposome and a preparation method and application thereof. The cholesterol succinic acid simple lipid is used as a counter-ionic agent, and the active proton of carboxyl in the cholesterol succinic acid simple lipid structure transfers to the nitrogen of irinotecan amino group, a coordination bond is formed, an ion pair is formed with irinotecan, so that the lipid solubility of irinotecan is improved, and the simple preparation method is easily used for packaging the drug on a phospholipid layer of the liposome, and the drug loading and packaging efficiency are improved. According to the irinotecan-cholesterol succinic acid simple lipid ion pair, the liposome and the preparation method and applicationthereof, the hydrophobic ion pair technology is combined with the nano drug delivery system, the lipid solubility of the insoluble drugs is improved, nano-preparations are developed, the complexity ofthe preparation process is simplified, and the irinotecan-cholesterol succinic acid simple lipid ion pair, the liposome and the preparation method and application thereof is conducive to expanding the industrial production. In addition, irinotecan ion pair and the liposome releases faster in the meta-acid environment, certain pH sensitivity is achieved, good antitumor effect and safety are achieved, and good application is achieved.

Visible-Light-Induced Radical Cascade Cyclization: Synthesis of (20S)-Camptothecin, SN-38 and Irinotecan

(20S)-Camptothecin, irinotecan and SN-38 were successfully synthesized by a photocatalyzed radical cascade cyclization from an N-propargyl iodopyridinone and an arylisonitrile under visible light with a ruthenium catalyst. This synthetic method provided a useful entry into composing camptothecin family of antitumor agents in good yields under mild reaction conditions without the use of heavy metal reagents.

Method for producing irinotecan

PROBLEM TO BE SOLVED: To provide a novel method for producing irinotecan using amines.SOLUTION: A method of producing irinotecan represented by the chemical formula (1) includes reacting 7-ethyl-10-hydroxycamptothecin with 1-chlorocarbonyl-4-piperidinopiperidine or hydrochloride thereof in the presence of a nonaromatic tertiary amine having 5 or less carbon atoms.

Method for the synthesis of irinotecan

The present invention relates to a method for the synthesis of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (i.e. iriniotecan), comprising: (a) preparing 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptotecin; and (b) selectively ethylating the compound of step (a) at the 7-position, thus resulting in the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin. The present invention is further directed to a method for the synthesis of 10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (i.e. 7-des-ethyl-irinotecan) which is used as an intermediate in the synthesis of irinotecan.

Scalable synthetic route to 2-amino-5-hydroxypropiophenone: Efficient formal synthesis of irinotecan

2-Amino-5-hydroxypropiophenone, a key precursor in the total synthesis of irinotecan, has been synthesized. Regioselective nitration and a SNAr displacement are the key steps involved in this strategy, which is high yielding, is economical, and has been performed on a plant scale. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.

NOVEL POLYMORPH OF IRINOTECAN HYDROCHLORIDE

The present invention provides a novel crystalline form of irinotecan hydrochloride, process for its preparation and pharmaceutical compositions comprising it. Thus, for example, irinotecan hydrochloride trihydrate was dissolved in a mixture of methanol and methylene dichloride, the solvent was distilled off and then added acetone, and stirred for 18 hour at room temperature, filtered and dried to obtain irinotecan hydrochloride crystalline form H1.

PROCESS FOR THE MANUFACTURE OF IRINOTECAN HYDROCHLORIDE BY TOTAL SYNTHESIS

Disclosed herein is a highly safe and easily scalable process for the production of 7-Ethyl- 10-hydroxycamptothecin and its conversion to Irinotecan hydrochloride by total synthesis.

PROCESS FOR THE PREPARATION OF 7-ETHYL-10-[4- (1-PIPERIDINO)- 1-PIPERIDINO] CARBONYLOXY-CAMPTOTHECIN HYDROCHLORIDE TRIHYDRATE

The present invention relates to process for the preparation of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin hydrochloride trihydrate and process for the isolation of 1-chlorocarbonyl-4-piperidinopiperidine and novel crystalline form of 1-chlorocarbonyl-4-piperidinopiperidine and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin.