Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Robert M DiPardo

Mark G Bock

Roger M Freidinger

Scott D Kuduk

Douglas C Beshore

John J Baldwin

Daniel F Veber

David C Remy

Michael A Patane

Ben E Evans

Joshua S Boger

Linda S Payne

Jacob M Hoffman

The present invention is directed to quinolinone-pyrazolone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor. 

Quinolinone-pyrazolone M1 receptor positive allosteric modulators

The present invention is directed to fused pyridone compounds of formula (I) (I) that are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Fused pyridone M1 receptor positive allosteric modulators

Arylhydantoin derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1a adrenergic receptor antagonists is also described. One application of these compounds is in the treatment of benign prostatic hyperplasia. These compounds are typically selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia can be achieved.

Arylhydantoin derivatives and uses thereof

Imidazolinobenzodiazepines

Imidazobenzo-(1,5)-diazepine derivatives with an amide or urea function in the 3-position are useful in the treatment of arrhythmia. The compounds have structural formulae: ##STR1##

Antiarrhythmic benzodiazepines

Benzodiazepine analogs of the formula: ##STR1## are disclosed which are antagonists of gastrin and cholecystokinin (CCK).

Cholecystokinin antagonists

Peptide compounds of formula I are antagonists of oxytocin and are useful in the treatment of preterm labor and dysmenorrhea, and for the stoppage of labor prepatory to Caesarian delivery. ##STR1##

Peptide oxytocin antagonists

Renin inhibitory peptides of the formula ##STR1## and analogs thereof inhibit renin and are useful for treating various forms of renin-associated hypertension and hyperaldosteronism.

Renin inhibitory peptides having improved solubility

The present invention provides an improved process for producing 3-acylamino benzodiazepines of the formula: ##STR1## wherein: R is loweralkyl of from 1-6 carbon atoms, aryl such as phenyl and halophenyl, aralkyl, alkyloxy, aralkyloxy, indolyl or substituted indolyl;

Process for 3-acylamino benzodiazepines

4-Amino-3-hydroxy-2,4-(disubstituted)pentanoic acids of the formula: ##STR1## useful as intermediates in preparing antibacterial compounds, are synthesized enantiospecifically by acylation of a chiral enolate with an optically active acylating agent. The resulting product is reduced stereospecifically to afford a protected form of the desired product, which contains three adjacent asymmetric centers of known configuration. The synthesis may be illustrated as follows: ##STR2##

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Lansdale, PA, United States of America

Robert M DiPardo