Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Msd Italia S.r.l.

Kevin F Gilbert

Ben E Evans

Mark G Bock

Peter D Williams

Kenneth E Rittle

Dansu Li

Mark E Layton

Lianyun Zhao

Scott E Wolkenberg

Michael J Kelly, Iii

James J Mulhearn

Michael A Rossi

Joseph E Pero

Doug W Hobbs

J Christopher Culberson

Pablo De Leon

Scott D Kuduk

Nigel J Liverton

Daniel F Veber

Roger M Freidinger

John A McCauley

Michael T Rudd

Vincenzo Summa

Marco Ferrara

Anthony J Roecker

John W Butcher

M Katharine Holloway

Zhijian Zhao

Steven Harper

Charles J McIntyre

Joseph J Romano

Jacob M Hoffman

Douglas J Pettibone

George F Lundell

Hannah D Fiji

James B Hoffman

Marco Pompei

Hannah D G F Lehman

Swati I P Mercer

Michael J Iii Kelly

Swati Pal Mercer

Hannah Fiji

Charles J Mcintyre

Maria Emilia Di Francesco

Alessia Petrocchi

John A Mccauley

Disclosed are compounds of Formula A: Formula A, or a salt thereof, wherein 'Het', R, and Rare defined herein, which have properties for blocking Na1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating neuropathic pain disorders using the same. 

Benzoxazolinone compounds with selective activity in voltage-gated sodium channels

Disclosed are compounds of Formula (A) or a salt thereof, wherein 'Het', R, and Rare defined herein, which have properties for blocking Na1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula (A) or their salts, and methods of treating neuropathic pain disorders using the same. 

The present invention is directed to tetrahydroquinoline amide compounds of formula (I) (Formula should be inserted here) 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. 

Tetrahydroquinoline amide M1 receptor positive allosteric modulators

The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections. 

HCV NS3 protease inhibitors

Spirotricyclic azacycloalkyl compounds and pharmaceutically acceptable salts thereof are disclosed. The synthesis of these compounds is also described. One application of these compounds, which are alpha 1a adrenergic receptor antagonists, is in the treatment of benign prostatic hyperplasia. These compounds are 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.

Spirotricyclic substituted azacycloalkane derivatives and uses thereof

Lactam and cyclic urea derivatives and their pharmaceutically acceptable salts are disclosed. The synthesis of these compounds and their use as alpha 1,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 1,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.

Lactam and cyclic urea derivatives useful as alpha 1a adrenoceptor antagonists

Tocolytic oxytocin receptor antagonists

Hydantoin and succinimide-substituted derivatives of

Compounds of the formula X--Y--R, or the pharmaceutically acceptable salts and esters thereof, wherein X is ##STR1## Y is --SO.sub.2 --, --(CH.sub.2).sub.p -- or --CO--(CH.sub.2).sub.p --; R is unsubstituted or substituted phenyl where said substitutents are one or more of R.sup.5, R.sup.6 or R.sup.7 ; R.sup.1 is hydrogen, cyano, phenyl,--CONHR.sup.2, --CONR.sup.2 R.sup.2, --(CH.sub.2).sub.m --OR.sup.2, --(CH.sub.2).sub.p --S(O).sub.r --R.sup.2, --(CH.sub.2).sub.m --CO.sub.2 R.sup.2, --(CH.sub.2).sub.m --N.sub.3, --(CH.sub.2).sub.m --NH.sub.2 or --(CH.sub.2).sub.m --NR.sup.2 R.sup.2 ; R.sup.2 is hydrogen, C.sub.3-8 cycloalkyl or C.sub.1-5 alkyl; R.sup.5 and R.sup.6 are each independently selected from hydrogen, C.sub.1-5 alkoxy, halogen or --(CH.sub.2).sub.n --N(R.sup.2)--C(O)--R.sup.18 ; R.sup.7 is hydrogen or ##STR2## R.sup.11 is selected from hydrogen, C.sub.1-5 alkylcarbonyl, ##STR3## or substituted C.sub.1-5 alkyl wherein said alkyl substituent is unsubstituted, mono-, di- or tri-substituted pyridyl wherein said substitutents on said pyridyl are independently selected from halogen, C.sub.1-5 alkyl or C.sub.1-5 alkoxyl; R.sup.13 is unsubstituted or substituted C.sub.1-10 alkyl wherein the substituent is selected from --N(R.sup.2).sub.2, --NHR.sup.2 or imidazolyl; R.sup.14 and R.sup.15 are each independently selected from C.sub.1-5 alkyl, C.sub.1-5 alkoxy or halogen; R.sup.16 is hydrogen or oxo; R.sup.18 is C.sub.1-5 alkoxyl, unsubstituted or substituted C.sub.1-5 alkyl where said substituent is Het, unsubstituted or substituted C.sub.2-5 alkenyl where said subsituent is Het or Het; Het is benzimidazolyl, carboxymethyl-substituted benzimidazolyl or indolyl; m is an integer of from 1 to 5; p is an integer of from 1 to 3; and r is an integer of from 0 to 2. Such compounds as useful as oxytocin and vasopressin receptor antagonists.

Compounds of the formula: ##STR1## where R.sup.1 is hydrogen or hydroxy and R.sup.2 is a substituted amino group, a substituted heterocyclic ring or a substituted alkyl. These compounds are oxytocin and vasopressin antagonists useful in the treatment of preterm labor, dysmenorrhea and for the stoppage of labor preparatory to cesarean delivery, timing of parturition, uterine hyperactivity, endometriosis, hypertension, congestive heart failure, hyponatremia and cognitive disorders. Also disclosed are pharmaceutical compositions containing these compounds, methods of their use and methods of their preparation.

Amide-substituted derivatives of spiroindanylcamphorsulfonyl oxytocin

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Barto, PA, United States of America

Kevin F Gilbert