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US 9,545,387 B2Granted
Composition and kit comprising piperazine derivatives and metformin, and use thereof in the treatment of diabetes
AssigneeMetabolys
InventorsGérard Moinet, Gabriel Baverel
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to a composition including, in combination, metformin or a salt thereof, a pharmaceutically acceptable carrier or excipient and at least one compound of formula (I), or the enantiomers, diastereoisomers or pharmaceutically acceptable salts thereof. Formula (I) is as follows: The present disclosure also relates to the use of this composition for the treatment of diseases associated with insulin resistance syndrome.
Claims20
A composition comprising metformin or a salt of metformin, a pharmaceutically acceptable carrier or excipient and at least one formula (I) compound and the enantiomers, diastereoisomers or pharmaceutically acceptable salts thereof:
- where:
- R1 is a group from among:
- —C(O)CR3R4CR5R6C(O)OH;
- —C(OH)(H)CR3R4CR5R6C(O)OH;
- —(CH2)4C(O)OH;
- or
- m is an integer ranging from 0 to 8;
- n is 0 or 1;
- L1 is a group from among —C(O)—;
- —C(O)O— or —S(O)2—;
- R2 is:
- a carbocycle group, 5-, 6 or 7-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- a polycarbocycle group, 8- to 14-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- a heterocycle group, 5-, 6- or 7-membered, substituted or unsubstituted, saturated, partly unsaturated or aromatic, optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur;
- a polyheterocycle group, 8- to 14-membered, substituted or unsubstituted, saturated, partly unsaturated or aromatic, optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur;
- -L2-carbocycle group, the carbocycle being 5-, 6- or 7-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- -L2-polycarbocycle group, the polycarbocycle being 8- to 14-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- -L2-heterocycle group, the heterocycle being 5-, 6- or 7-membered, substituted or unsubstituted, saturated, partly unsaturated or aromatic and optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur;
- -L2-polyheterocycle group, the polyheterocycle being 8- to 14-membered, substituted or unsubstituted, saturate, partly unsaturated or aromatic, and optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur;
- or
- hydrocarbon group, straight-chain or branched, C1 to C5;
- L2 being an alkyl, straight-chain or branched, C1 to C5;
- R3, R4, R5 and R6, the same or different, are:
- a hydrogen atom;
- an alkyl group, straight-chain or branched, C1 to C5;
- a carbocycle group, 5-, 6- or 7-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- or
- R3 and R4, together with the carbon atom to which they are attached, form a 5-, 6- or 7-membered carbocycle, substituted or unsubstituted, optionally saturated;
- or
- R5 and R6, together with the carbon atom to which they are attached, form a 5-, 6- or 7-membered carbocycle, substituted or unsubstituted, optionally saturated;
- R7, the same or different, are:
- an alkyl, straight-chain or branched, C1 to C5;
- -L2-carbocycle group, the carbocycle being 5-, 6- or 7-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- -L2-polycarbocycle group, the polycarbocycle being 8- to 14-membered, saturated, partly unsaturated or aromatic, substituted or unsubstituted;
- -L2-heterocycle group, the heterocycle being 5-, 6- or 7-membered, substituted or unsubstituted, saturated, partly unsaturated or aromatic and optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur;
- or
- -L2-polyheterocycle group, the polyheterocycle being 8- to 14-membered, substituted or unsubstituted, saturated, partly unsaturated or aromatic and optionally having 1, 2 or 3 heteroatoms, the same or different, selected from the group consisting of nitrogen, oxygen and sulfur.
34 more elements
A method for selecting a compound for the treatment of pathologies associated with insulin-resistance syndrome, having an additional effect adding to the effect of metformin, comprising the steps of:
- a) providing fasting, normal animals;
- b) measuring glycaemia in these animals;
- c) administering the compound to be tested to one portion of the animals, metformin to a second portion of the animals and an association of metformin and the compound to be tested to the last portion of the animals;
- d) administering a glycose load to the animals comprising 2 to 4 g/kg animal body weight;
- e) measuring glycaemia at different times;
- and
- f) determining whether the compound has an additive effect to the effect of metformin on lowering of glycaemia, comprising comparing the glycaemia area under curve obtained for each of the compounds administered, and determining whether the tested compound in association with metformin allowed a reduction in the glycaemia area under curve compared with metformin administered alone.
4 more elements
A method to select non-toxic or scarcely toxic compounds allowing the stimulation of complete lactate or glutamine oxidation and/or a reduction in ATP cell concentration, comprising the following steps:
- 1) determining the toxicity of the compound to be tested;
- 2) providing liver cells of fasting animals;
- 3) incubating these cells with lactate or glutamine;
- 4) adding the compound to be tested to the incubation medium;
- 5) performing enzymatic assay of the consumption of lactate or glutamine and/or of the production of glucose and/or assay of ATP cell concentration;
- 6) determining those non-toxic or scarcely toxic compounds allowing stimulation of complete lactate or glutamine oxidation and/or a reduction in ATP cell concentration.
3 more elements
Dependencies are inferred from the claim text.