17693-17-3

Upstream product

• 15761-38-3 L-N-Boc-Ala 
• 107960-04-3 pentachlorophenyl 1,2,2,2-tetrachloroethyl carbonate 
• 87-86-5 Pentachlorophenol 
• 47541-47-9 N,N'-Dicyclohexyl-O-pentachlorphenyl-isoharnstoff 

Downstream Products

• 110523-35-8 tert.-butyloxycarbonylalanyl-N^ε-benzyloxycarbonyllysyl-serine 
• 110523-41-6 tert.-butyloxycarbonylalanyl-N^ε-benzyloxycarbonyl-lysyl-seryl-glutaminyl-glycyl-glycyl-seryl-asparagine 4-nitrobenzyl ester 
• 79069-13-9 (S)-2-t-butoxycarbonylaminopropan-1-ol 
• 84983-67-5 tert.-butyloxycarbonylalanyl-N^ε-benzyloxycarbonyllysyl-serine methyl ester 

Relevant academic research and scientific papers

New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment

Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptidase N (APN, EC 3.4.11.2). Selective and efficient inhibitors of both enzymes, designated enkephalinases, have been designed that markedly increase extracellular concentrations and half-lives of enkephalins, inducing potent antinociceptive effects. Several chemical families of Dual ENKephalinase Inhibitors (DENKIs) have previously been developed but devoid of oral activity. We report here the design and synthesis of new pro-drugs, derived from co-drugs combining a NEP and an APN inhibitor through a disulfide bond with side chains improving oral bioavailability. Their pharmacological properties were assessed in various animal models of pain targeting central and/or peripheral opioid systems. Considering its efficacy in acute and neuropathic pain, one of these new DENKIs, 19-IIIa, was selected for clinical development.

AMINOACID DERIVATIVES CONTAINING A DISULFANYL GROUP IN THE FORM OF MIXED DISULFANYL AND AMINOPEPTIDASE N INHIBITORS

The invention relates to novel compounds of formula (I): H2N-CH(R1)-CH2-S-S-CH2-CH(R2)-CONH-R5, wherein R1 is a hydrocarbon chain, phenyl or benzyl radical, methylene radical substituted by a 5 or 6 atom heterocycle; R2 is a phenyl or benzyl radical, a 5 or 6 atom aromatic heterocycle, methylene group substituted by a 5 or 6 atom heterocycle; R5 is a CH(R3)-COOR4 radical, wherein R3 is hydrogen, an OH or OR group, a saturated hydrocarbon group, a phenyl or benzyl radical and OR4 is hydrophile ester, or 5 or 6 membered heterocycle comprising several heteroatoms selected from a group consisting of nitrogen, sulphur and oxygen, with at least two nitrogene atoms, wherein said heterocycle is substitutable by an alkyl C1-C6, phenyl or benzyl radical. The use of the inventive compounds in the form of drugs, a pharmaceutical composition comprising said compounds, a pharmaceutically acceptable excipient, the use in conjunction of at least one type of cannabinoid derivative for potentiating the analgesic and antidepressant effect of the novel compounds of formula (I) and/or morphine or the derivatives thereof are also disclosed.

Process for synthesizing active esters of carboxylic acids

The invention relates to a new process for preparing active esters or carboxylic acids, which consists in reacting a carboxylic acid, in the presence of an agent for binding hydrohalic acid, with a carbonate of formula: STR1 in which R1 denotes either a radical of formula STR2 in which R3 and R4, which may be identical or different, are not hydrogen atoms and denote organic radicals which may be substituted or unsubstituted and saturated or unsaturated, and may be or may not be bound to a polymer, and which can be joined together to form a hetero-cyclic system with the nitrogen atom, or a substituted or unsubstituted aryl radical which may or may not be bound to a polymer, R2 denotes a hydrogen atom, an aliphatic or cycloaliphatic radical which may be substituted or unsubstituted and saturated or unsaturated, or a substituted or unsubstituted aromatic radical, and X denotes a halogen atom. This process is especially useful for the synthesis of active esters of N-protected amino acids. The invention also relates to the new carbonates described above and the method of producing them, which consists in reacting an alpha-halogenated chloroformate of formula: with an alcohol of formula R1 OH in an inert solvent medium of the presence of an organic or inorganic base.

Novel Preparation of N-Protected Amino Acid Active Esters Using 1,2,2,2-Tetrachloroethyl Carbonates

1,2,2,2-Tetrachloroethyl chloroformate reacts with substituted phenols or N-hydroxy imides to yield crystalline and stable mixed aryl or oximido tetrachloroethyl carbonates.When allowed to react with an N-protected amino acid derivative, these compounds proved to be efficient for the syntheses of the corresponding active esters.A series of active esters including p-nitrophenol, trichlorophenol, pentafluorophenol, and N-hydroxysuccinimide derivatives were prepared by this new procedure.