Abstract: A class of pyrazine, pyrimidine and pyridazine derivatives, substituted by a non-aromatic azabicyclic ring system and optionally by up to two further substituents, is of use in the preparation of medicaments, especially formulations adapted for topical administration to the eye, suitable for the treatment of glaucoma and/or for reducing intraocular pressure.
Abstract: A class of indazole-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, 1991
Date of Patent:
May 4, 1993
Assignee:
Merck Sharpe & Dohme, Ltd.
Inventors:
Raymond Baker, Mark S. Chambers, Leslie J. Street
Abstract: A class of substituted cyclic sulphamide 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.
Abstract: Benzenes, substituted by a non-aromatic, non-fused 1-azabicycle and a substituent of low lipophilicity or a hydrocarbon substituent, their salts and prodrugs are useful in medicine, for example, in treating dementia. Some formulations of such benzenes are novel as are some of the compounds per se. They can be synthesized by methods analogous to those known in the art.
Abstract: A sterile packaging assembly (100) for dispensing a liquid in drops comprises a main body (101) of plastic material, having a top portion (103) with an outside thread for receiving a screw cap (104), the top portion ending in an elongate neck, constituting a dispensing portion which is surmounted by a closure head (110) that can be torn off in order to define a dispensing orifice (111) on first utilization of the packaging assembly. The invention is particularly applicable to sterile packaging of pharmaceutical substances such as eye drops.
Abstract: A sterile packaging assembly (100) for dispensing a liquid in drops comprises a main body (101) of plastic material, having a top portion (103) with an outside thread for receiving a screw cap (104), and containing a flow rate restriction system (105) for controlling drop formation. The flow rate restriction system is positioned substantially on the axis of the main body and is held in position by a constricted portion (106) of the top portion (103) of the main body. The invention is particularly applicable to sterile packaging of pharmaceutical substances such as eye drops.
Abstract: A class of 5-membered heterocyclic compounds having at least one heteroatom, substituted on the heterocyclic ring by an imidazolyl moiety, are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal or dependence; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; movement disorders; and presenile and senile dementia.
Type:
Grant
Filed:
March 8, 1990
Date of Patent:
August 18, 1992
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Christopher Swain, John Saunders
Abstract: A process for preparing a substantially pure enantiomer of a compound formula (I) ##STR1## wherein X is O or S; andR.sup.2 represents hydrogen, --CF.sub.3, --OR.sup.7, --SR.sup.7, --NR.sup.7 R.sup.8, --CN, --COOR.sup.7, --CONR.sup.7 R.sup.8, or a saturated or unsaturated, substituted or unsubstituted hydrocarbon group, wherein R.sup.7 and R.sup.8 are independently selected from hydrogen and C.sub.1-2 alkyl provided that --NR.sup.7 R.sup.8 is other than NH.sub.2 ;which process comprises cyclization of a compound of formula (10) or salt thereof: ##STR2## wherein X and R.sup.2 are as defined in formula (I); and R.sup.4 is a labile leaving group and optionally epimerizing the endo-diastereomer so prepared to produce the corresponding exo-diastereomer.
Abstract: The compound (3R, 4R)-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane and its salts behave as a functionally selective muscarinic agonist 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 methods analogous to those known in the art via suitable chiral intermediates and cyclopropyl carboxamide oxime.
Abstract: A process for preparing substantially pure enantiomers of formula (I) ##STR1## where the * represents a chiral center, x is 0 or 1, in exo-, endo- or a mixture of exo- and endo- forms; and R is hydrogen, alkyl or aralkyl, via diastereomers of formula (IIA) or (IIB); ##STR2##
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: This invention provides the 4-mono-anion of myo-inositol orthoformate, and describes a process for preparing this anion as well as the use of this anion in the preparation of a variety of mono- and poly-phosphate derivatives of myo-inositol.
Abstract: The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring;X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen;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, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --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, 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 alkylcarobnyl;V represents nitrogen, ##STR3## W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.
Type:
Grant
Filed:
July 13, 1990
Date of Patent:
August 20, 1991
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, John Saunders, Christopher Swain
Abstract: The present invention concerns a pharmaceutical and/or cosmetic composition designed to be applied on the skin or the mucosae, characterized in that it contains Rhamsan gum.
Abstract: The present invention provides a compound of formula (I): ##STR1## or a pharmaceutically acceptable salt thereof, wherein one of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 represents a hydrocarbon or hydrocarbyloxycarbonyl group and the remaining groups R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent hydrogen, hydrocarbon, hydrocarbyloxycarbonyl, halogen, hydroxy or C.sub.1-6 alkoxy, or R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 may together represent the residue of a carbocyclic ring; R.sup.5 and R.sup.6 independently represent hydrogen, hydrocarbon, hydroxy or fluoro; R.sup.7 represents hydrogen or C.sub.1-3 alkyl; and R.sup.8 represents methyl or ethyl; which compounds are useful as anticonvulsant agents and in the treatment of neurodegenerative diseases.
Type:
Grant
Filed:
August 12, 1988
Date of Patent:
February 26, 1991
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, Paul D. Leeson, Susan F. Britcher
Abstract: The present invention provides a spiro-azabicyclic compound or a salt or prodrug thereof, said compound comprising a saturated or unsaturated 5-membered heterocyclic ring containing two heteroatoms selected from oxygen, nitrogen and sulphur, no more than one of said heteroatoms being nitrogen; said heterocyclic ring having a spiro attachment to an optionally substituted azabicyclo[2.2.1]heptane or azabicyclo[3.2.1]octane ring system; which compounds are useful for the treatment of neurological and mental disorders.
Type:
Grant
Filed:
June 29, 1989
Date of Patent:
February 12, 1991
Assignee:
Merck Sharp & Dohme, Ltd.
Inventors:
Raymond Baker, Leslie J. Street, John Saunders
Abstract: Compounds of formula III: ##STR1## wherein R.sup.1 is a 5- or 6-membered aromatic heterocyclic group; and R.sup.4 and R.sup.5 each idependently signify hydrogen, halogen, trifluoromethyl, cyano, nitro, amino or lower alkyl; are useful intermediates in a novel process for the preparation of a class of pharmacologically active compounds of formula I: ##STR2## wherein R.sup.1, R.sup.4 and R.sup.5 are as defined above; and R.sup.3 represents hydrogen or lower alkyl.
Type:
Grant
Filed:
September 29, 1989
Date of Patent:
December 11, 1990
Assignee:
Merck, Sharp & Dohme Ltd.
Inventors:
Peter G. Houghton, Stanley H. B. Wright
Abstract: The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring;X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen;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, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --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, 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, ##STR3## and W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.
Type:
Grant
Filed:
February 3, 1989
Date of Patent:
August 28, 1990
Assignee:
Merck Sharp & Dohme Ltd.
Inventors:
Raymond Baker, John Saunders, Christopher Swain
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: A packaging and dispensing system provides for separate packaging of two ingredients of which at least one is a liquid and for extemporaneous mixing of the two ingredients at the time of first use. The system comprises a first bottle (2) containing the liquid or solid first ingredient and the neck of which is stoppered by a plug (5, 8). It further comprises a second bottle (9) containing the liquid second ingredient and assembled to the first bottle (2) at its neck. There is also an internal coupling member (11) carried by the second bottle (9) and the end of which is coupled to the plug (8). This coupling is obtained automatically when the two bottles are assembled together. A cap (13)screwed onto the second bottle (9) is coupled to the coupling member (11) so that at the time of first use unscrewing the cap (13) initially displaces the plug (8) and establishes automatically the communication between the two bottles without compromising any sterile conditions that may apply.