Cycloalkanedione derivatives, method for the production thereof and their pharmacological applications
AssigneeSchwarz Pharma S.L.
InventorsJoaquin Del Río Zambrana, Diana Frechilla Manso, M. Luz López Rodríguez, Bellinda Benhamú Salama, José Ángel Fuentes Cubero, Mercedes Delgado Wallace
Life of this patent
Estimating the term…
Abstract
New cycloalkanedione derivatives that are serotonin (5-hydroxytriptamine, 5-HT) 5-HT1A receptor subtype agonists and, consequently, they are useful in the treatment of pathological states for which an agonist of these receptors is indicated. They are particularly useful as neuroprotective agents, of special interest in the treatment and prophylaxis of cerebral damage produced by traumatic or ischemic stroke. In general terms, said cycloalkanedione derivatives correspond to formula I:
Claims23
A compound, a stereochemical isomer of the compound, or a solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I:
- wherein:
- R2 is selected from the group consisting of N, NH and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—,—(CH2)4—,—CH2SCH2, and —SCH2CH2—;
- if R2 is S or NH, then R1 is absent;
- if R2 is NH, then n is 1;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynyl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- W is selected from the group consisting of S and NH.
A process to prepare a compound, a stereochemical isomer of the compound, or a solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I:
- wherein:
- R2 is selected from the group consisting of N, NH and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—, —(CH2)4—, —CH2SCH2, and —SCH2CH2—;
- if R2 is S or NH, then R1 is absent;
- if R2 is NH, then n is 1;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynyl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- and
- W is selected from the group consisting of S and NH comprising:
- reacting compounds according to Formula II with compounds according to Formula III according to scheme I:
- or
- reacting the compounds of Formula IV with the compounds of Formula V according to scheme II:
- wherein:
- L is selected from the group consisting of Cl and Br;
- and
- the definitions of R1, R2, n, Z, m, R4 and R5 are identical to those in Formula I.
A pharmaceutical composition comprising a therapeutically effective quantity of a compound, a stereochemical isomer of the compound, or a solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I
- wherein:
- R2 is selected from the group consisting of N, NH and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—, —(CH2)4—, —CH2SCH2, and —SCH2CH2—;
- if R2 is S or NH, then R1 is absent;
- if R2 is NH, then n is 1;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynyl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- W is selected from the group consisting of S and NH;
- and one or more pharmaceutically acceptable carriers or excipients.
A method for the treatment of a pathological state in a subject in need of such treatment, wherein the method comprises administering to the subject a compound, a stereochemical isomer of the compound, or a solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I:
- wherein:
- R2 is selected from the group consisting of N, NH and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—, —(CH2)4—, —CH2SCH2, and —SCH2CH2—;
- if R2 is S or NH, then R1 is absent;
- if R2 is NH, then n is 1;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- W is selected from the group consisting of S and NH;
- wherein a 5-HT1A agonist is indicated in the pathological state and the pathological state is selected from the group consisting of an anxiety disorder, depression and a mixed disorder of anxiety and depression.
A method to provide neuroprotection to a subject in need thereof comprising administering to the subject a neuroprotective amount of a compound, a stereochemical isomer of the compound, or solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I:
- wherein:
- R2 is selected from the group consisting of N, NH and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—, —(CH2)4—, —CH2SCH2, and —SCH2CH2—;
- if R2 is S or NH, then R1 is absent;
- if R2 is NH, then n is 1;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynyl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- W is selected from the group consisting of S and NH.
A compound, a stereochemical isomer of the compound, or a solvate or pharmaceutically acceptable salt of the compound or isomer, wherein the compound corresponds in structure to Formula I:
- wherein:
- R2 is selected from the group consisting of N and S;
- wherein
- if R2 is N, then R1 is selected from the group consisting of —(CH2)3—, —(CH2)4—, —CH2SCH2, and —SCH2CH2—;
- if R2 is S, then R1 is absent;
- n has a value of zero or 1;
- Z is selected from the group consisting of C2-C10-alkyl, C2-C10-alkenyl, and C2-C10-alkynyl;
- R3 is selected from the group consisting of H, C1-C10-alkyl, aryl, and aralkyl;
- m has a value of zero, 1, or 2;
- R4 is selected from the group consisting of O and CH2;
- R5 is selected from the group consisting of
- wherein:
- R6 is selected from the group consisting of H, C1-C5-alkyl, C1-C5-alkoxyl, OH, F, Cl, Br, and I;
- X is selected from the group consisting of O, S, NH, and NCH3;
- Y is selected from the group consisting of O and NH;
- W is selected from the group consisting of S and NH.
Dependencies are inferred from the claim text.