Abstract: A class of indole-substituted five-membered heteroaromatic compounds are specific agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.
Type:
Grant
Filed:
July 16, 1992
Date of Patent:
May 31, 1994
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Austin J. Reeve, Leslie J. Street
Abstract: A class of substituted imidazole, triazole and tetrazole derivatives are selective agonists of 5-HT.sub.1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated.
Type:
Grant
Filed:
January 28, 1993
Date of Patent:
March 29, 1994
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Victor G. Matassa, Leslie J. Street
Abstract: A class of 1,2,3,4,4a,5,6,10b-octahydrobenz[f]isoquinoline compounds and pharmaceutically acceptable salts of formula I: ##STR1## wherein, R.sup.1 represents hydrocarbon;R.sup.2 and R.sup.3 independently represent hydrogen, hydrocarbon, halogen, cyano, trifluoromethyl, nitro, --OR.sup.x, --SR.sup.x, --NR.sup.x R.sup.y, --CO.sub.2 R.sup.x or together represent methylenedioxy; andR.sup.x and R.sup.y independently represent hydrogen or hydrocarbon.The compounds disclosed herein are selective ligands at sigma recognition sites and are therefore useful in the treatment of psychiatric disorders.
Type:
Grant
Filed:
February 11, 1993
Date of Patent:
March 15, 1994
Assignee:
Merck Sharp & Dohme Limited
Inventors:
David C. Billington, Michael G. N. Russell
Abstract: Compounds of formula (I), and salts and prodrugs thereof: ##STR1## wherein Q is the residue of an optionally substituted azabicyclic ring system;X represents oxa or thia;Y represents H or hydroxy;R.sup.1 represents phenyl or thienyl, either of which groups may be optionally substituted by halo, trifluoromethyl or C.sub.1-3 alkoxy, or C.sub.5-7 cycloalkyl;R.sup.2 represents benzyl which may be substituted in the benzyl ring by halo, trifluoromethyl or C.sub.1-3 alkoxy, or C.sub.5-7 cycloalkyl; andR.sup.3, R.sup.4 and R.sup.5 independently represent H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, --OR.sup.a, SCH.sub.3, SOCH.sub.3, S0.sub.2 CH.sub.3, --NR.sup.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a C0.sub.2 R.sup.b, --C0.sub.2 R.sup.a or --CONR.sup.a R.sup.b ; andR.sup.a and R.sup.b independently represent H, C.sub.1-6 alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.
Type:
Grant
Filed:
June 16, 1992
Date of Patent:
February 22, 1994
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Christopher J. Swain, Martin R. Teall, Brian J. Williams
Abstract: 4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, and their pharmaceutically acceptable salts, are potent specific antagonists of N-methyl-D-aspartate (NMDA) receptors and are therefore useful in the treatment of neurodegenerative disorders. 4-Oxo-1,4-dihydroquinoline compounds having a 2-acidic group or a group convertible thereto in vivo, other than carboxy or C.sub.1-6 alkoxycarbonyl, are novel compounds, as also are compounds of formula II ##STR1## wherein R.sup.2 represents carboxy or a group convertible thereto in vivo, R.sup.6 is hydrogen and R.sup.5 and R.sup.7 represent C.sub.1-6 alkyl or halogen, provided that R.sup.5 and R.sup.7 are not simultaneously chlorine or simultaneously bromine; a process for preparing the novel compounds is described, as also are pharmaceutical compositions containing the novel compounds.
Abstract: A class of 2,4-dioxo-1,2,3,4-tetrahydroquinoline derivatives, substituted at the 3-position by a range of carbonyl-containing substituents 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 antagonist.
Type:
Grant
Filed:
January 22, 1992
Date of Patent:
December 7, 1993
Assignee:
Merck Sharp & Dohme, Limited
Inventors:
Raymond Baker, Paul D. Leeson, Michael Rowley, Graeme I. Sevenson
Abstract: The present invention provides pyrazines, pyridazines or pyrimidines, or salts or prodrugs thereof, substituted on one of the ring carbon atoms thereof with a non-aromatic azacyclic or azabicyclic ring system; and independently substituted on each of the other ring carbon atoms with a substituent of low lipophilicity or a hydrocarbon substituent; which compounds stimulate central muscarinic acetylcholine receptors and therefore are useful in the treatment of neurological and mental illnesses.
Type:
Grant
Filed:
October 10, 1991
Date of Patent:
November 9, 1993
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Leslie J. Street, John Saunders
Abstract: Compounds of formula (I), and salts and prodrugs thereof: ##STR1## wherein Q is the residue of an optionally substituted azabicyclic ring system;the dotted line represents an optional double bond;X represents H, --OH, .dbd.O or halo;R.sup.1 represents H, phenyl or thienyl, which phenyl or thienyl groups may be optionally substituted by halo or trifluoromethyl;R.sup.2 represents phenyl, thienyl or benzyl, any of which groups may be optionally substituted by halo or trifluoromethyl; andR.sup.3, R.sup.4 and R.sup.5 independently represent H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halo, cyano, nitro, trifluoromethyl, trimethylsilyl, --OR.sup.a, SR.sup.a, SOR.sup.a, SO.sub.2 R.sup.a, --NR.sup.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a CO.sub.2 R.sup.b, --CO.sub.2 R.sup.a or --CONR.sup.a R.sup.b ; andR.sup.a and R.sup.b independently represent H, C.sub.1-6 alkyl, phenyl or trifluoromethyl, are tachykinin receptor antagonists. They and compositions thereof are useful in therapy.
Type:
Grant
Filed:
June 29, 1992
Date of Patent:
October 26, 1993
Assignee:
Merck Sharp & Dohme, Limited
Inventors:
Tamara Ladduwahetty, Christopher J. Swain
Abstract: A class of 2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-c]pyridine and 2,3,4,4a,5,6,7,11b-octahydro-1H-benzo[3,4]cyclohepta[1,2-c]pyridine derivatives are selective ligands at sigma recognition sites and are therefore useful in the treatment and/or prevention of psychiatric and/or gastrointestinal disorders.
Type:
Grant
Filed:
June 18, 1991
Date of Patent:
October 19, 1993
Assignee:
Merck Sharp & Dohme Limited
Inventors:
David C. Billington, Michael G. N. Russell
Abstract: A class of 4-hydroxy-2(1H)-quinolone derivatives, substituted at the 3-position by an N-linked heteroaromatic ring system, 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.
Type:
Grant
Filed:
December 3, 1991
Date of Patent:
October 12, 1993
Assignee:
Merck Sharp & Dohme Limited
Inventors:
William R. Carling, Paul D. Leeson, Kevin W. Moore
Abstract: A class of novel oxadiazoles, substituted on one of the ring carbon atoms with a non-aromatic azacyclic or azabicyclic ring and on the other ring carbon atom with a substituent which is convertible in vivo to an amino group, are potent muscarinic agonists, and exhibit improved CNS penetrability and duration of action compared with the corresponding amino compounds. The compounds are therefore useful in the treatment of neurological and mental illnesses.
Type:
Grant
Filed:
July 18, 1988
Date of Patent:
September 7, 1993
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, John Saunders, Angus M. MaCleod, Graham A. Showell
Abstract: A class of spirocyclic piperidine derivatives are selective ligands at sigma recognition sites and are therefore useful in the treatment and/or prevention of psychiatric disorders.
Abstract: The compound (R)-3-[2-(6-chloropyrazin)yl]-1-azabicyclo[2.2.2]octane and its salts behave as M.sub.1, M.sub.3 muscarinic agonists and are useful in the treatment of neurological and mental disorders, preferably in a pharmaceutical formulation comprising the active compound in association with a pharmaceutically acceptable carrier. The compound can be prepared by via methods analogous to those known in the art and a chiral acid resolution.
Type:
Grant
Filed:
August 8, 1990
Date of Patent:
December 17, 1991
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Leslie J. Street, John Saunders
Abstract: The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted line represents an optional chemical bond in one of the two possible positions;A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, benzyloxy, hydroxy (C.sub.1-6)alkyl, halogen, amino, cyano, nitro, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, halogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl;R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl;V represents nitrogen, --CH or --C--; andW represents oxygen, sulphur or --NR.sup.8, in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.
Type:
Grant
Filed:
April 4, 1989
Date of Patent:
July 10, 1990
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, Clare O. Kneen, John Saunders, Christopher Swain
Abstract: The present invention provides a compound of formula I: ##STR1## or a salt thereof, wherein: the dotted lines represent optional double bonds;R.sup.1 represents hydrogen, hydroxy, alkenyl, alkyl, aminoalkyl or hydroxyalkyl;R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 independently represet hydrogen, hydroxy, fluoro, alkenyl, aryl, alkyl, or alkyl substituted with aryl, amino, hydroxy, carboxy or fluoro; andR.sup.7, R.sup.8, R.sup.9 and R.sup.10 independently represent hydrogen, hydrocarbon or a heterocyclic group provided that R.sup.7, R.sup.8, R.sup.9 and R.sup.10 are not simultaneously hydrogen; orR.sup.7 and R.sup.8 and/or R.sup.9 and R.sup.10 may complete a saturated or unsaturated C.sub.4-9 hydrocarbon or heterocyclic ring; which compounds are useful as anticonvulsant agents and in the treatment and/or prevention of neurodegenerative disorders.
Type:
Grant
Filed:
November 22, 1988
Date of Patent:
May 22, 1990
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Raymond Baker, William R. Carling, Kim James, Paul D. Leeson
Abstract: Specific N-methyl-D-aspartate receptor antagonists are useful in the prevention and treatment of neurodegeneration in various pathological states.
Type:
Grant
Filed:
December 24, 1986
Date of Patent:
December 19, 1989
Assignee:
Merck Sharp & Dohme Limited
Inventors:
Geoffrey N. Woodruff, Erik H. F. Wong, John A. Kemp