Merck Sharp + Dohme Corp.

Merck Sharpe & Dohme Corp.

John Saunders

Raymond Baker

Christopher John Swain

Leslie Joseph Street

Kevin John Merchant

Graham A Showell

Angus M MaCleod

Janusz Jozef Kulagowski

Angus Murray MacLeod

Roger John Snow

Clare Octavia Kneen

Timothy M Willson

A class of novel oxadiazoles, substituted on one of the ring carbon atoms with a non-aromatic azacyclic or azabicyclic ring, and substituted on the other ring carbon atom with a substituent of low lipophilicity; are potent muscarinic agonists, and have good CNS penetrability. The compounds are therefore useful in the treatment of neurological and mental illnesses.

Oxadiazoles useful in the treatment of senile dementia

A class of novel thiadiazoles, substituted on one of the ring carbon atoms with a non-aromatic azacyclic or azabicyclic ring system, and substituted on the other ring carbon atom with a substituent of low lipophilicity, or a hydrocarbon substituent; are potent muscarinic agonists, and have good CNS penetrability. The compounds are therefore useful in the treatment of neurological and mental illnesses, and are also of benefit in the treatment of severe painful conditions.

Thiadiazoles useful in the treatment of senile dementia

Pyridines, substituted by a quinuclidine and a substituent of low lipophilicity or a hydrocarbon substituent, their salts and prodrugs, and formulations thereof are useful in the treatment of neurodegenerative disorders such as dementia. The compounds can be synthesized by methods analogous to these known in the art.

Substituted pyridines, their preparation, formulations and use in

1,3-Oxazole and 1,3-thiazole compounds of formula I, and their pharmaceutically acceptable salts and prodrugs: ##STR1## wherein X represents oxygen or sulphur;

Oxazoles and thiazoles for the treatment of senile dementia

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.

Pyrazines, pyrimidines and pyridazines useful in the treatment of senile

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.

Prodrugs for oxadiazole muscarinic agonists

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.

Five-membered ring systems with bonded imidazolyl ring substituents

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.

Novel substituted pyrazine, formulations thereof and use in medicine

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;

Pharmaceutically useful 3-(indol-3-yl)-1,2,4-oxa- and thiadiazoles

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.

Spiro-azabicyclic muscarinic agonists

Physiologically active 1,2,4,-oxa- and thiadiazoles

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;

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Bishops Stortford, United Kingdom

John Saunders