Papers by Claude Monneret
3-(amino-or aminoalkyl) pyridinone derivatives and their use for the treatment of HIV related diseases
Stereocontrolled route to 3-amino-2,3,6-trideoxy-hexopyranoses. K-10 Montmorillonite as a glycosidation reagent for acosaminide synthesis
Journal of the Chemical Society, Chemical Communications, 1987
ABSTRACT A stereoselective synthesis of methyl (or benzyl) 3-azido-2,3,6-trideoxy-α-L-arabino-hex... more ABSTRACT A stereoselective synthesis of methyl (or benzyl) 3-azido-2,3,6-trideoxy-α-L-arabino-hexopyranoside from di-O-acetyl-L-rhamnal is reported; it proceeds via addition of hydrazoic acid to a hex-2-enopyranose, followed by acetylation and glycosidation with the appropriate alcohol, in the presence of K-10 montmorillonite as catalyst.
ChemInform Abstract: Prodrugs of Natural Anthracyclines Suited for Antibody-Directed Enzyme Prodrug Therapy (ADEPT) and Prodrug Monotherapy (PMT)
ChemInform, 2000
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Anthracyclinones. Part 9. Enantioselective Synthesis of 9- Alkylanthracyclinone via Highly Diastereocontrolled Alkylation of 4- Cyanofurano Sugars
ChemInform, 1993
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Synthesis and study of a dipyridamole prodrug: application of the ADEPT strategy to the MDR resistance in cancer chemotherapy
Comptes Rendus de l Académie des Sciences - Series IIC - Chemistry
Synthesis of self-immolative glucuronide-based prodrugs of a phenol mustard
Anti-cancer drug design
The design and synthesis of the mustard pro-prodrugs which can be used in ADEPT is reported. Prod... more The design and synthesis of the mustard pro-prodrugs which can be used in ADEPT is reported. Prodrugs 1 and 2 include a glucuronide group which is connected to the drug via an aromatic and/or aliphatic bis-carbamate spacer. The design of these new prodrugs takes advantage of a spontaneous 1,6-elimination and/or an intramolecular cyclization reaction after enzymatic cleavage. Thus, enzymatic-catalyzed hydrolysis of the glucuronyl moiety of 1 by Escherichia coli beta-glucuronidase results in the liberation of the parent mustard drug 20 with formation of CO2, 2-nitro-4-hydroxymethylphenol 19 and dimethylimidazolidinone 21. Surprisingly, prodrug 2 was not cleaved under the same conditions. According to in vitro experiments, prodrugs 1 and 2 were approximately 50- and 80-fold less cytotoxic than the parent drug and, when treated with beta-glucuronidase, the level of cytotoxic activity of 1 became comparable to that of the drug. Stability of 1 in phosphate buffer was satisfactory. These r...
Synthesis of self-immolative glucuronide spacers based on aminomethylcarbamate. Application to 5-fluorouracil prodrugs for antibody-directed enzyme prodrug therapy
Journal of the Chemical Society Perkin Transactions 1
The synthesis of three novel potential glucuronide-based prodrugs for antibody-directed enzyme pr... more The synthesis of three novel potential glucuronide-based prodrugs for antibody-directed enzyme prodrug therapy (ADEPT) is described. These prodrugs were designed to be activated at the tumour site by β-glucuronidase to afford the corrresponding anticancer agent, 5-FU. The structural pattern of these compounds includes a self-immolative spacer between the glucuronyl residue and the N1 of 5-FU. Three types of spacers have been elaborated which, after enzymic hydrolysis, spontaneously decompose to deliver an unstable N1 aminal 5-FU derivative and, from there, the cytotoxic drug. All potential prodrugs were stable and proved to be excellent substrates of E. coli in in vitro experiments.
Prodrugs of natural anthracycleves suited for antibody directed enzyme prodrug therapy (ADEPT) and prodrug monotherapy (PMT)
The chemical efficacy of most anticancer agents, including anthracyclines such as daunorubicin an... more The chemical efficacy of most anticancer agents, including anthracyclines such as daunorubicin and doxorubicin, is severely hampered by general toxicity and by the appearance of acquired resistance. The Antibody Directed-Enzyme Prodrug Therapy (ADEPT) concept aims at modifying the distribution of such drugs. It entails the use of an enzyme-antibody conjugate targeted towards the tumor cell surface, in conjunction with a non-cytotoxic prodrug, which can be converted upon enzyme activation, into the cytotoxic species. By this way, high local concentration of drug can be specifically obtained at the tumor site, resulting in decreased general toxicity, when compared with classical chemotherapy.We report here the synthesis and biological behaviour of triparte prodrugs in which an osidic specifier is linked to the primary amino function of an thracycline through a self-immolative ortho-or para-hydroxybenzyl connector. This spacer can undergo spontaneous 1,4- or 1,6-elimination, after enzy...
Anti-cancer drug design
Topoisomerase II represents the main target for the antitumour drugs etoposide and amsacrine, whi... more Topoisomerase II represents the main target for the antitumour drugs etoposide and amsacrine, which are both used clinically. Previous studies have shown that the glycoside moiety of etoposide is not necessary for cytotoxicity or DNA topoisomerase II inhibition. For this reason, we designed two epipodophyllotoxin derivatives for which the dispensable sugar moiety of etoposide has been replaced by a m-methoxy-methane-sulfonamide-anilino group analogous to the topoisomerase II-targeted domain of amsacrine. We report the synthesis of the hybrid molecules that have the epipodophyllotoxin and anilino groups directly linked (ICP-114) or connected by an ethylene spacer (ICP-147). Plasmid DNA relaxation and kinetoplast DNA decatenation assays were used to evaluate the effects of the drug on the catalytic activity of human topoisomerase II. We found that the hybrid ICP-147 was significantly more potent than both etoposide and amsacrine at stimulating DNA cleavage by the enzyme, whereas the h...
ChemInform Abstract: Enantioselective Synthesis of 12-Amino Alkylidenecyclopentenone Prostaglandins
The Journal of Organic Chemistry
An enantioselective synthesis of new 12-amino alkylidenecyclopentenone prostaglandins is reported... more An enantioselective synthesis of new 12-amino alkylidenecyclopentenone prostaglandins is reported. The key step of the synthesis involved a [3.3] sigmatropic rearrangement of an asymmetric allylic cyanate to elaborate an asymmetric 5-amino-1,6-diene which was further transformed into cyclopentenone by successive ring-closing metathesis reaction catalyzed by the Grubbs reagent and one-pot oxidation. A palladium-catalyzed cross-coupling reaction on a 5-iodo-1,5-diene allowed the synthesis of prostanoids with variable Rw side chains. These new compounds exhibit high cytotoxic activities.
ChemInform Abstract: Synthesis of a Highly Functionalized γ-Lactone (VI) as a Precursor of 9Pentyl Anthracyclines
ChemInform
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform
The principles of Xkyaoo-hydroxylation of olefm were applied to the preparation of l,Zcyano-amine... more The principles of Xkyaoo-hydroxylation of olefm were applied to the preparation of l,Zcyano-amines. The dipole component of this cycloaddition was nihile imines, which formed pynv..olines with olefins. Ring cleavage was accomplished by thennolysis of 3-cacboxypyrazolines, which gave 1,2-cyano-amiues and subsequent hydrolysis gave p-amino acids. The syntheses of the tide reagents were described. Ethyl 2-cNom-2-ethoxy-ace&k. gave selectively oximes, hydrazones. n&ones. and phos&oni~ salts with hydroxylamine, hydrasines. &.ubstituted hydmxylamines and uiphenylphosphine nspedively. The p&sph&ium salt-was used ga Wittig reaction w&h aldehydes to give a-ketoesters. Treatment of the acid chloride with ally1 alcohols and subsequently with a monosubstituted hydroxylamine gave the allylic ester &one. which underwent ikamoleculsx cyclization. Similarly, intramolecular cyclizations were carried out with the allylic ester -nibile oxide and allylic ester -niuile imine systems.
ChemInform Abstract: Synthesis and Biological Evaluation of 5-Arylfuro[2,3-d]pyrimidines as Novel Dihydrofolate Reductase Inhibitors
CHEMICAL & PHARMACEUTICAL BULLETIN
A series of about fifty novel 5-arylfuro[2,3-d]pyrimidine derivatives were synthesized as potenti... more A series of about fifty novel 5-arylfuro[2,3-d]pyrimidine derivatives were synthesized as potential inhibitors of dihydrofolate reductase (DHFR) arising from different species. Weak enzyme inhibition was observed for most of the compounds, with only a few reaching IC50 values less than 30 microM. With regards to antibacterial and anti-malarial potency, only seven compounds showed a modest in vitro activity against some bacteria strains and only three products proved significantly active against P. falciparum.
ChemInform Abstract: Synthesis and Antitumor Activity of a New Series of Nitrosoureido Sugars
ChemInform
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: p-Nitrophenyl β-D-Glucopyranosiduronic Analogues as Potential Substrates for β-Glucuronidase
ChemInform
ChemInform Abstract: Isosaccharino- and Glucosaccharino-Lactones as Chirons for the Syntheses of Natural Compounds and Analogs of Biological Relevance
ChemInform
ChemInform Abstract: Anthracyclinones. Part 7. Total Synthesis of 4-Demethoxyfeudomycinone C (I)
ChemInform, 1991
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Synthesis of Novel Angular Heterocyclic Lignans by an InCl 3 -Catalyzed Friedel-Crafts-Type Cyclization
ChemInform, 2008
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Anthracyclinones. Part 5. Glucosaccharino-1,4-lactone as a Chiral Template for the Synthesis of New Anthracyclinones
ChemInform, 1991
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
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Papers by Claude Monneret