Merck + Co., Inc.

Merck Sharp + Dohme Corp.

Sunesis Pharmaceuticals, Inc.

Kenneth E Rittle

Ben E Evans

James C Barrow

Peter D Williams

Kevin F Gilbert

Mark G Bock

Harold G Selnick

J Christopher Culberson

Craig Alan Coburn

Melissa S Egbertson

Shaun R Stauffer

Wenjin Yang

Steven D Young

Philippe G Nantermet

Philip E Sanderson

Terry A Lyle

Donnette D Staas

Lou Anne Neilson

Jacob M Hoffman

Douglas J Pettibone

Catherine M Wiscount

Lekhanh O Tran

Zhiqiang Yang

Zhi-Qiang Yang

Melody McWherter

Georgia B McGaughey

Matthew M Morrissette

Kenneth J Stauffer

Joseph M Pawluczyk

Bruce Fahr

Wanli Lu

ZhiQiang Yang

Douglas W Hobbs

Phung Le Ngo

Rowena V Cube

Phung Le Bondiskey

Georgia B Mcgaughey

Melody A Mcwherter

The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease

The present invention is directed to imidazolidinone compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

Imidazolidinone compounds useful as &#x3b2;-secretase inhibitors for the treatment of Alzheimer's disease

The present invention is directed to quinazolinone compounds of the formula I: wherein R, R, R, X, XXare defined herein. These compounds are antagonists of T-type calcium channels, and are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

Quinazolinone T-type calcium channel antagonists

Thrombin 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

Tocolytic oxytocin receptor antagonists

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.

Peptides having the formula ##STR1## and their use as pharmaceuticals are disclosed.

Renin-inhibitory peptide analogs

Statine (Sta), a naturally-occurring amino acid and closely related derivatives, are prepared by a novel method involving an oxidative route to the requisite chiral .alpha.-aminoaldehyde intermediate, L-leucinal; the novel method may be illustrated by the following reaction scheme: ##STR1## .

Method of preparing statine and derivatives

Growing community of inventors

Green Lane, PA, United States of America

Kenneth E Rittle