Quinolone derivatives
AssigneeMerck Sharp & Dohme Corp.
InventorsWilliam R. Carling, Paul D. Leeson, Michael Rowley
Life of this patent
Estimating the term…
Abstract
A class of 2(1H)-quinolone derivatives, substituted at the 3-position by a range of carbonyl-containing substitutients or by a five- or six-membered heteroaromatic moiety, are selective non-competitive antagonists of NMDA receptors and/or are antagonists of AMPA receptors, and are therefore of utility in the treatment of conditions, such as neurodegenerative disorders, convulsions or schizophrenia, which require the administration of an NMDA and/or AMPA receptor antagonist.
Claims8
A method for the treatment of conditions which require the administration of a selective non-competitive antagonist of NMDA receptors, which comprises administering to a patient in need of such treatment an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof or a prodrug thereof:
- ##STR17## wherein:
- R represents a hydrogen atom or an amino group,
- R.sup.1 is carboxy or tetrazolyl,
- one of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 represents halogen, and the other three of R.sup.2, R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen or halogen.
A pharmaceutical composition comprising a compound of formula IA or a pharmaceutically acceptable salt thereof or a prodrug thereof:
- ##STR18## wherein:
- R.sup.10 represents a hydrogen atom or an amino group,
- R.sup.11 is carboxy or tetrazolyl,
- one of R.sup.12, R.sup.13, R.sup.14 and R.sup.15 represents halogen, and the other three of R.sup.12, R.sup.13, R.sup.14 and R.sup.15 independently represent hydrogen or halogen;
- provided that, when R.sup.11 represents carboxy, one of the substituents R.sup.12 to R.sup.15 represents chloro or bromo and the other three substituents R.sup.12 to R.sup.15 are hydrogen, then R.sup.10 does not represent amino;
- provided also that, when R.sup.10 represents hydrogen, one or two of R.sup.12 to R.sup.15 represent halogen, and the remainder of the substituents R.sup.12 to R.sup.15 represent hydrogen, then R.sup.11 does not represent a .sup.1 H-tetrazol-5-yl group;
- in association with one or more pharmaceutically acceptable carriers and/or excipients.
A compound of formula IB or a pharmaceutically acceptable salt or prodrug thereof:
- ##STR19## wherein:
- R.sup.20 represents a hydrogen atom or an amino group,
- R.sup.21 is carboxy or tetrazolyl,
- one of R.sup.22, R.sup.23, R.sup.24 and R.sup.25 represents halogen, and the other three of R.sup.22, R.sup.23, R.sup.24 and R.sup.25 independently represent hydrogen or halogen;
- provided that, when R.sup.21 represents carboxy, one of the substituents R.sup.22 to R.sup.25 represents chloro or bromo and the other three substituents R.sup.22 to R.sup.25 are hydrogen, then R.sup.20 does not represent amino;
- provided also that, when R.sup.20 represents hydrogen, one or two of R.sup.22 to R.sup.25 represent halogen, and the remainder of the substituents R.sup.22 to R.sup.25 represent hydrogen, then R.sup.21 does not represent a 1 H-tetrazol-5-yl group.
A compound selected from:
- 4-amino-3-carboxy-7-chloro-2(1H)-quinolone;
- 7-chloro-3-(1H-tetrazol-5-yl)-2(1H)-quinolone;
- and salts and prodrugs thereof.
Dependencies are inferred from the claim text.