Patents Assigned to Merck Sharp
  • Patent number: 5668153
    Abstract: Compounds of formula (I) ##STR1## exemplified by formulae (Ia) and (Ib) ##STR2## are tachykinin receptor antagonists useful in the treatment of disorders associated with the presence of an excess of tachykinins such as pain, inflammation, migraine, emesis and post herpetic neuralgia.
    Type: Grant
    Filed: August 4, 1995
    Date of Patent: September 16, 1997
    Assignee: Merck Sharp & Dohme, Ltd.
    Inventors: Richard Thomas Lewis, Angus Murray MacLeod
  • Patent number: 5668280
    Abstract: The present invention provides a process for the preparation of substantially pure N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one which comprises:(i) contacting racemic N-benzyl-3-(4-fluorophenyl)-1,4-oxazin-2-one with (-)-3-bromocamphor-8-sulphonic acid (hereinafter referred to as (-)-3-BCS) in the presence of a racemising agent;(ii) collecting the resultant crystalline (-)-3-BCS salt of N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one; and(iii) liberating the free base of N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one by treatment of the (-)-3-BCS salt collected in step (ii) with aqueous base.
    Type: Grant
    Filed: May 23, 1996
    Date of Patent: September 16, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Ramon John Alabaster, Ian Frank Cottrell, Andrew William Gibson, Simon Adrian Johnson
  • Patent number: 5665722
    Abstract: A class of chemical compounds comprising a benzo [b] furan moiety and a substituted heterocyclic moiety, linked via the 3-position of the benzo [b] furan moiety by a methylene group, are antagonists of dopamine receptor subtypes within the brain, being extremely potent antagonists of the human dopamine D.sub.4 subtype over other dopamine receptor subtypes, and are accordingly of benefit in the treatment and/or prevention of psychotic disorders such as schizophrenia while manifesting fewer side-effects than those associated with classical neuroleptic drugs.
    Type: Grant
    Filed: October 18, 1996
    Date of Patent: September 9, 1997
    Assignee: Merck, Sharp & Dohme, Ltd.
    Inventors: Janusz Jozef Kulagowski, Paul David Leeson, Ian Michael Mawer
  • Patent number: 5665883
    Abstract: The present invention relates to compounds of formula (I) wherein n is 3 and where any carbon atom of (CH.sub.2).sub.n may be substituted by R.sup.4 and/or R.sup.5 ; X represents O or S; R.sup.1 represents (CH.sub.2).sub.q phenyl, wherein q is 0, 1 , 2 or 3 which may be optionally substituted in the phenyl ring; R.sup.2 represents aryl selected from phenyl and naphthyl; heteroaryl selected from indazolyl, thienyl, furyl, pyridyl, thiazolyl, tetrazolyl and quinolyl; benzhydryl; or benzyl; wherein each aryl or heteroaryl moiety may be substituted; R.sup.4 and R.sup.5 each independently represent H, halo, C.sub.1-6 alkyl, oxo, CO.sub.2 R.sup.a or CONR.sup.a R.sup.b ; R.sup.6 represents H or C.sub.1-6 alkyl; R.sup.7 represents trifluoromethyl, C.sub.2-6 alkenyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, (CH.sub.2).sub.p NR.sup.9 R.sup.10, CO.sub.2 R.sup.16, CONR.sup.9 R.sup.10, (CH.sub.2).sub.p CO.sub.2 R.sup.16, (CH.sub.2).sub.p CONR.sup.9 R.sup.10, (CH.sub.2).sub.p NR.sup.9 COR.sup.16, (CH.sub.
    Type: Grant
    Filed: September 26, 1996
    Date of Patent: September 9, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Raymond Baker, Angus Murray MacLeod, Eileen Mary Seward, Christopher John Swain
  • Patent number: 5665732
    Abstract: A class of chemical compounds comprising a 1-H-indazole moiety and a substituted heterocyclic moiety, linked via the 3-position of the indazole moiety by a methylene group, are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment and/or prevention of disorders of the dopamine system, in particular schizophrenia. In formula (I) R represents hydrogen or C.sub.1-6 alkyl, Q represents a moiety of formula Qa, Qb, or Qc.
    Type: Grant
    Filed: September 8, 1995
    Date of Patent: September 9, 1997
    Assignee: Merck, Sharp & Dohme Ltd.
    Inventors: Raymond Baker, Janusz Jozef Kulagowski, Paul David Leeson, Adrian Leonard Smith
  • Patent number: 5663352
    Abstract: The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts and prodrugs thereof, wherein X represents a propylene or propenylene chain optionally substituted by one or more of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 ; m is 2, 3 or 4; n is 0, 1 or 2 when m is 2 or 3, and n is 0 or 1 when m is 4; R.sup.1 represents optionally substituted phenyl; R.sup.2 represents optionally substituted phenyl, heteroaryl, benzhydryl or benzyl; R.sup.3 represents H, COR.sup.9, CO.sub.2 R.sup.10, COCONR.sup.10 R.sup.11, COCO.sub.2 R.sup.10, SO.sub.2 R.sup.15, CONR.sup.10 SO.sub.2 R.sup.15, C.sub.1-6 alkyl optionally substituted by a group selected from (CO.sub.2 R.sup.10, CONR.sup.10 R.sup.11, hydroxy, cyano, COR.sup.9, NR.sup.10 R.sup.11, C(NOH)NR.sup.10 R.sup.11, CONHphenyl(C.sub.1-4 alkyl), COCO.sub.2 R.sup.10, COCONR.sup.10 R.sup.11, SO.sub.2 R.sup.15, CONR.sup.10 SO.sub.2 R.sup.15 and optionally substituted phenyl), Y--R.sup.8 or CO--Z--(CH.sub.2).sub.q --R.sup.12 ; R.sup.4 and R.sup.
    Type: Grant
    Filed: January 19, 1996
    Date of Patent: September 2, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Angus Murray MacLeod, Kevin John Merchant, Graeme Irvine Stevenson
  • Patent number: 5661162
    Abstract: The present invention is directed to compounds of the formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8, m, n and X are defined herein, and pharmaceutically acceptable salts thereof, which are useful as tachykinin antagonists.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: August 26, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Angus Murray MacLeod, Graeme Irvine Stevenson
  • Patent number: 5641787
    Abstract: The present invention accordingly provides the use of a compound of formula I, or a pharmaceutically acceptable salt thereof or a prodrug thereof: ##STR1## wherein R.sup.1 represents hydrogen or C.sub.1-6 alkyl;Z represents --CH.sub.2 -- or --CH.sub.2 CH.sub.2 --;R.sup.2 represents hydrogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, aryl(C.sub.1-6)alkyl or halogen;R.sup.3, R.sup.4 and R.sup.5 independently represent hydrogen, hydrocarbon, a heterocyclic group, halogen, cyano, trifluoromethyl, nitro, --OR.sup.a, --SR.sup.a, --SOR.sup.a, --SO.sub.2 R.sup.a, --SO.sub.2 NR.sup.a R.sup.b, --NR.sub.a R.sup.b, --NR.sup.a COR.sup.b, --NR.sup.a CO.sub.2 R.sup.b, --COR.sup.a, --CO.sub.2 R.sup.a or --CONR.sup.a R.sup.b ; andR.sup.a and R.sup.b independently represent hydrogen, hydrocarbon or a heterocyclic group;for the manufacture of a medicament for the treatment and/or prevention of psychotic disorders such as schizophrenia.
    Type: Grant
    Filed: September 12, 1995
    Date of Patent: June 24, 1997
    Assignee: Merck, Sharp & Dohme Ltd.
    Inventors: Ian Michael Mawer, Howard Barff Broughton, Janusz Jozef Kulagowski, Paul David Leeson
  • Patent number: 5633281
    Abstract: Compounds of formula (I), or a salt or prodrug thereof, wherein R.sup.1 represents H, C.sub.1-4 alkyl or CH.sub.2 COOH; R.sup.2 represents H or C.sub.1-4 alkyl, with the proviso that R.sup.1 and R.sup.2 are not both H; R.sup.3 and R.sup.4 each independently rely resent H, C.sub.1-, alkyl. C.sub.2-6 alkenyl C.sub.1-6 alkoxy, halo or trifluoromethyl; A.sup.1, A.sup.2, A.sup.3, and A.sup.4 each independently represent H, C.sub.1-6 alkyl, C.sub.1-6 alkenyl, C.sub.1-6 alkoxy, halo or trifluoromethyl; and A.sup.5 and A.sup.6 each independently represent H or C.sub.
    Type: Grant
    Filed: December 8, 1995
    Date of Patent: May 27, 1997
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Martin R. Teall, Brian J. Williams
  • Patent number: 5633266
    Abstract: The present invention relates to compounds of formula (I), and salts and prodrugs thereof, wherein n is 1 , 2 or 3 and where any carbon atom of (CH.sub.2).sub.n may be substituted by R.sup.4 and/or R.sup.5 ; X represents O or S; R.sup.1 represents optionally substituted (CH.sub.2).sub.q phenyl, wherein q is 0, 1, 2 or 3; R.sup.2 represents optionally substituted aryl, heteroaryl, benzhydryl or benzyl; R.sup.4 and R.sup.5 each independently represent H, halo, C.sub.1-6 alkyl, oxo, CO.sub.2 R.sup.a or CONR.sup.a R.sup.b ; R.sup.6 represents H or C.sub.1-6 alkyl; R.sup.7 represents C.sub.1-6 alkyl or optionally substituted phenyl; R.sup.8 represents H, COR.sup.a, CO.sub.2 R.sup.a, COCONR.sup.a R.sup.b, COCO.sub.2 R.sup.a, C.sub.1-6 alkyl optionally substituted by a variety of substituents, or C.sub.1-6 alkyl, optionally substituted by oxo, substituted by an optionally substituted aromatic heterocycle. The compounds are tachykinin antagonists useful for treating pain or inflammation, migraine or emesis.
    Type: Grant
    Filed: July 26, 1995
    Date of Patent: May 27, 1997
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Raymond Baker, Christopher J. Swain, Brian J. Williams
  • Patent number: 5631269
    Abstract: Compounds of formula (I) ##STR1## wherein one of X and Y represents nitrogen, and the other of X and Y represents oxygen, sulphur or N--R.sup.2 ; Q represents a substituted five- or six- membered monocyclic heteroaliphatic ring which contains one nitrogen atom as the sole heteroatom and is linked to the five-membered heteroatomic ring containing the moieties X and Y via a carbon atom; as well as substituted 1,3-dioxopropane precursors thereto, are ligands for dopamine receptor subtypes within the body and are therefore useful in the treatment of disorders of the dopamine system, in particular schizophrenia.
    Type: Grant
    Filed: April 20, 1995
    Date of Patent: May 20, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Howard B. Broughton, Ian J. Collins, Raymond Baker, Paul D. Leeson, Michael Rowley
  • Patent number: 5629347
    Abstract: Compounds of formula (I), and salts and prodrugs thereof, wherein Q is R.sup.9 CR.sup.10 R.sup.11 or CH.sub.2 R.sup.9 CR.sup.10 R.sup.11 where R.sup.9 is H or OH and R.sup.10 and R.sup.11 are optionally substituted phenyl, optionally substituted benzyl, C.sub.5-7 cycoalkyl or (C.sub.5-7 cycloalkyl)methyl; R.sup.1 and R.sup.2 are H, optionally substituted C.sub.1-6 alkyl, optionally substituted phenyl(C.sub.1-4 alkyl), C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, COR.sup.a, COOR.sup.a, COC.sub.1-6 alkylhalo, COC.sub.1-6 alkylNR.sup.a R.sup.b, CONR.sup.12 C.sub.1-6 alkylCONR.sup.a R.sup.b, CONR.sup.a R.sup.b, or SO.sub.2 R.sup.a, or R.sup.1 and R.sup.2 together form a chain (CH.sub.2).sub.q optionally substituted by oxo where one methylene group may optionally be replaced by O or NR.sup.x ; R.sup.3 is H, C.sub.1-6 alkyl or C.sub.2-6 alkenyl; R.sup.4 is optionally substituted phenyl(C.sub.1-3 alkyl); X and Y are H, or X and Y together are .dbd.O; and Z is O, S, or NR.sup.7 ; are tachykinin antagonists.
    Type: Grant
    Filed: December 22, 1993
    Date of Patent: May 13, 1997
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: Christopher J. Swain, Martin R. Teall, Brian J. Williams
  • Patent number: 5629336
    Abstract: Compounds capable of interacting with the strychnine-insensitive glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor are active in preventing or reducing dependence on dependence-inducing agents such as morphine, but lack the undesirable side-effects of agents hitherto employed for this purpose.
    Type: Grant
    Filed: February 22, 1994
    Date of Patent: May 13, 1997
    Assignee: Merck, Sharp & Dohme Ltd.
    Inventor: Peter H. Hutson
  • Patent number: 5627211
    Abstract: Compounds of formula (I), and salts and prodrugs thereof wherein X, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.7 and R.sup.8 are defined herein, are tachykinin receptor antagonists.
    Type: Grant
    Filed: March 13, 1995
    Date of Patent: May 6, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventor: Martin R. Teall
  • Patent number: 5624947
    Abstract: Compounds of formula (I), or a salt or prodrug thereof are tachykinin antagonists.
    Type: Grant
    Filed: June 20, 1995
    Date of Patent: April 29, 1997
    Assignee: Merck, Sharp & Dohme Ltd.
    Inventors: Linda E. Keown, Tamara Ladduwahetty, Monique B. Van Niel
  • Patent number: 5622950
    Abstract: A class of pyrrolo[2,3-b]pyridine derivatives, substituted at the 3-position by a substituted piperazinylmethyl moiety, are antagonists of dopamine receptor subtypes within the brain, having a selective affinity for the dopamine D.sub.4 receptor subtype over other dopamine receptor subtypes, and are accordingly of benefit in the treatment and/or prevention of psychotic disorders such as schizophrenia whilst manifesting fewer side-effects than those associated with classical neuroleptic drugs.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: April 22, 1997
    Assignee: Merck, Sharp & Dohme Ltd.
    Inventors: Raymond Baker, Neil R. Curtis, Janusz J. Kulagowski, Paul D. Leeson, Mark P. Ridgill, Adrian L. Smith
  • Patent number: 5620972
    Abstract: Benzapines of the formula (I) ##STR1## and salts and prodrugs thereof useful as CCK antagonists.
    Type: Grant
    Filed: June 20, 1995
    Date of Patent: April 15, 1997
    Assignee: Merck Sharp & Dohme Ltd.
    Inventor: Monique B. van Niel
  • Patent number: 5620989
    Abstract: The present invention is directed to compounds of the formula (I) ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and R.sup.
    Type: Grant
    Filed: April 13, 1995
    Date of Patent: April 15, 1997
    Assignee: Merck Sharp & Dohme Limited
    Inventors: Timothy Harrison, Angus M. MacLeod, Graeme I. Stevenson, Brian J. Williams
  • Patent number: 5618812
    Abstract: Compounds of Formula (I), and salts and prodrugs thereof, wherein R.sup.1 represents H, optionally substituted C.sub.1-6 alkyl or C.sub.3-7 cycloalkyl; R.sup.2 is NHR.sup.12 or (CH.sub.2).sub.s R.sup.13 where 5 is 0, 1 or 2; R.sup.3 represents C.sub.1-6 alkyl, halo or NR.sup.6 R.sup.7 ; R.sup.4 and R.sup.5 are H, C.sub.1-12 alkyl optionally substituted by NR.sup.9 R.sup.9' or an azacyclic or azabicyclic group, optionally substituted C.sub.4-9 cycloalkyl, C.sub.4-9 cycloalkyl C.sub.1-4 alkyl, aryl, arylC.sub.1-6 alkyl or azacyclic or azabicyclic groups, or R.sup.4 and R.sup.5 together form the residue of an optionally substituted azacyclic or azabicyclic ring system; x is 0, 1, 2 or 3; R.sup.12 is optionally substituted phenyl or pyridyl; R.sup.13 represents a group (A) wherein R.sup.14 is H or C.sub.1-6 alkyl; R.sup.15 is H, C.sub.1-6 alkyl, halo or NR.sup.6 R.sup.7 ; and the dotted line is an optional covalent bond; are CCK and/or gastrin antagonists useful in therapy.
    Type: Grant
    Filed: January 26, 1995
    Date of Patent: April 8, 1997
    Assignee: Merck Sharp & Dohme, Ltd.
    Inventors: Jose L. Castro Pineiro, William R. Carling, Mark S. Chambers, Stephen R. Fletcher, Sarah C. Hobbs, Victor G. Matassa, Kevin W. Moore, Graham A. Showell, Michael G. Russell
  • Patent number: 5614524
    Abstract: A class of substituted piperazine derivatives of formula I ##STR1## 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 conditions, for which a selective agonist of these receptors is indicated.
    Type: Grant
    Filed: May 19, 1995
    Date of Patent: March 25, 1997
    Assignee: Merck Sharp & Dohme Ltd.
    Inventors: V. G. Matassa, L. J. Street, A. J. Reeve