Centre National De La Recherche Scientifique

Université Joseph Fourier

Cnrs

Henri Joseph Vial

Michele Calas

Marie-Laure Ancelin

Valerie Vidal

Jean-Jacques Bourguignon

Eric Marechal

Cyrille Botte

Nadia Saidani

Marine Aimée Peuchmaur

Roger Escale

Eric Rubi

Novel polyspirane compounds used in the treatment of diseases involving parasites that belong to the phylum of apicomplexae, and a method for preparing the same.

Polyspirane compounds, application thereof in the treatment of malaria or toxoplasmosis and method for preparing same

The invention relates to compounds having an anti-parasitic, in particular antimalarial activity, characterized in that they correspond to general formula (I) Applications in particular as compounds with anti-parasitic activity.

Compounds with antiparasitic activity and medicines containing same

The invention concerns drug precursors with antimalarial effect, characterised in that it consists in quaternary bis-ammonium salts of general formula (I) wherein A and A', identical or different, are respectively either a group A1 and A&#x2032;1 of formula (1) wherein n=2 to 4; R&#x2032;1 is hydrogen, C1-C5 alkyl, optionally substituted by an aryl, a hydroxy, an alkoxy, wherein the alkyl comprises 1 to 5 C, or aryloxy and W is halogen or a nucleofuge group; or a group A2 which represents formyl-CHO, or acetyl-COCH3. B and B&#x2032;, identical or different, represent respectively either the group B1 and B&#x2032;1, if A and A&#x2032; respectively represent A1, A&#x2032;1, B1, B&#x2032;1 representing a group R1 which has the same definition as R&#x2032;1 above, but cannot be a hydrogen atom; or respectively the groups B2 and B&#x2032;2, if A and A&#x2032; represent A2, B2 or B&#x2032;2 being the group R1 as defined above, or a group of formula (2) wherein &#x2014;Ra is RS&#x2014; or RCO&#x2014;, wherein R is a C1-C6 alkyl, substituted if required, a phenyl or benzyl, wherein the phenyl is substituted if required, the latter being optionally substituted; R2 is hydrogen, C1-C5 alkyl, or a &#x2014;CH2-COO&#x2014; (C1-C5)alkyl group; and R3 is hydrogen, C1-C5 alkyl or alkenyl, substituted if required, a phosphate, an alkoxy wherein the alkyl is a C1-C3 alkyl, or aryloxy; or an alkyl (or arylcarbonyloxy; or R2 and R3 form together a cycle with 5 or 6 C; R and R3 can be bound to form a cycle. &#xb1; represents: either a single bond when A and A&#x2032; represent A1 and A&#x2032;1: or when A and A&#x2032; represent A2, and B2 and B&#x2032;2 Represent (3) either, when A and A&#x2032; are &#x2014;CHO or &#x2014;COCH3 and B2 and B&#x2032;2 are R1, a group of formula (4) or a group of formula (5) wherein (a) represents a bond towards Z and (b) a bond towards the nitrogen atom. Z is a C9-C21 alkyl, if required with insertion of one or several bonds, and/or one or several heteroatoms O and/or S and/or several aromatic cycles, and the pharmaceutically acceptable salts of said compounds. Said precursors and cyclized thiazolium derivatives are useful as antiparasitic medicines in particular antimalarial and antibabesiosis.

Quaternary bis-ammonium salt precursors and their uses as prodrugs having an antiparasitic activity

Growing community of inventors

Montpellier, France

Henri Joseph Vial