Wyeth

American Home Products Corporation

Other

Thomas Joseph Caggiano

Amedeo A Failli

Jay Scott Shumsky

Kevin Anthony Memoli

Eugene John Trybulski

John P Dusza

Craig E Caufield

Anthony Frank Kreft

Anthony F Kreft, Iii

Dennis Michael Kubrak

Joseph Peter Sabatucci

Koi Morris

Mark A Ashwell

Alexander A Greenfield

John H Sellstedt

Panolil C Raveendranath

Koji Nakanishi

Donna Mary Huryn

Jehan F Bagli

Anita Wai-Yin Chan

Katherine L Molnar-Kimber

Joan E Sabalski

Lynn Resnick

Gloria Cheal

Dennis Martin Kubrak

Razzak Noureldin

David K Williams

Joshua D Berkowitz

Yanqiu Chen

Joseph Prol, Jr

Boyd Lynn Harrison

Jay Donald Albright

Mark Anthony Ashwell

Robert J Steffan

Scott Christian Mayer

Surendra N Sehgal

Eugene J Trybulski

George Diamantidis

William Sanders

Charles William Mann

Albert John Molinari

Molly Hoke

Diane Barbara Hauze

Laurel M Adams

Albert J Molinari

Alexander Michael Porte

Antony Aldo Brazzale

William L Baeder

Peter S Chan

David Cheng Hu

A method of selectively preparing a chiral 2S-amino alcohol useful in preparation of an amide sulfonated or acylated with alkyl, substituted aryl or substituted heteroaryl is described. The method involves reacting a di-tert-butyl diazene-1,2-dicarboxylate with a (4S)-4-benzyl-3-[(S)-trifluoromethyl-alkyl substituted alkanoyl]-1,3-oxazolidin-2-one to afford a di-tert-butyl 1-(1S,2S)-([(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-yl]-carbonyl}-trifluoromethyl-alkyl substituted alkyl)hydrazine-1,2-dicarboxylate. This dicarboxylate is then reduced to yield di-tert-butyl 1-(1S,2S)-[trifluoromethyl-alkyl substituted alkyl]hydrazine-1-(hydroxymethyl)-1,2-dicarboxylate. The resulting product is deblocked with an acid to yield the acid addition salt of (2S,3S)-trifluoro-hydrazino-methyl alkan-1-ol. The acid addition salt of (2S,3S)-trifluoro-2-hydrazino-methyl alkan-1-ol is hydrogenated in the presence of a suitable metal catalyst to yield the amino alcohol (2S,3S)-2-amino-trifluoro-methyl alkan-1-ol HCl.

Production of chirally pure amino alcohol intermediates, derivatives thereof, and uses thereof

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: wherein, Ris lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SOR; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; Ris lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; Ris hydrogen, lower alkyl, or substituted lower alkyl; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; Ris hydrogen, lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CRor N; and Ris hydrogen, halogen, lower alkyl, or substituted lower alkyl.

Heterocyclic sulfonamide inhibitors of beta amyloid production containing an azole

A method of selectively preparing a chiral 2S-amino alcohol useful in preparation of an amide sulfonated or acylated with alkyl, substituted aryl or substituted heteroaryl is described. The method involves reacting a di-tert-butyl diazene-1,2-dicarboxylate with a (4S)-4-benzyl-3-[(S)-trifluoromethyl-alkyl substituted alkanoyl]-1,3-oxazolidin-2-one to afford a di-tert-butyl 1-(1S,2S)-([(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-yl]-carbonyl}-trifluoromethyl-alkyl substituted alkyl)hydrazine-1,2-dicarboxylate. This dicarboxylate is then reduced to yield di-tert-butyl 1-(1S,2S)-[trifluoromethyl-alkyl substituted alkyl]hydrazine-1-(hydroxymethyl)-1,2-dicarboxylate. The resulting product is deblocked with an acid to yield the acid addition salt of (2S,3S)-trifluoro-hydrazino-methyl alkan-1-ol. The acid addition salt of (2S,3S)-trifluor-2-hydrazino-methyl alkan-1-ol is hydrogenated in the presence of a suitable metal catalyst to yield the amino alcohol (2S,3S)-2-amino-trifluoro-methyl alkan-1-ol HCl.

A compound of Formula (I), or pharmaceutically acceptable salts and/or hydrates or prodrugs thereof, wherein Formula (I) has the structure: is provided, wherein R-Rare defined herein. These compounds are useful in medicaments for treating a disease selected from the group consisting of Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome, in a subject.

Trifluoromethyl-containing phenylsulfonamide beta amyloid inhibitors

A compound of the formulae (I) or (II): wherein:Y is a moiety selected from NR or &#x2014;(CH);wherein R is hydrogen or (C-C) lower alkyl,and n is 1;  (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C-C) lower alkyl, halogen, cyano, CF, hydroxy, (C-C) lower alkoxy, (C-C) lower alkoxy carbonyl, carboxy, &#x2014;CONH, &#x2014;CONH[(C-C) lower alkyl], &#x2014;CON[(C-C) lower alkyl]; or (2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C-C) lower alkyl, halogen or (C-C) lower alkoxy; represents: (1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C-C) lower alkyl, halogen, cyano, CF, hydroxy, (C-C) lower alkoxy, or (C-C) lower alkoxy carbonyl, carboxy, &#x2014;CONH, &#x2014;CONH[(C-C) lower alkyl], &#x2014;CON[(C-C) lower alkyl]; or (2) a 5-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C-C) lower alkyl, (C-C) lower alkoxy, or halogen; or (3) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C-C) lower alkyl, halogen, or (C-C) lower alkoxy; represents a 5-membered aromatic (unsaturated) heterocyclic ring having one sulfur atom, optionally substituted by (C-C) lower alkyl, halogen, or (C-C) lower alkoxy; Ris a moiety of the formula and R, R, R, Rand Rare, independently, selected from a group consisting of hydrogen, (C-C) lower alkyl, OCH, halogen, CF, &#x2014;SCH, OCF, SCF, or CN;or a pharmaceutically acceptable salt, or pro-drug form thereof.

Biphenyl vasopressin agonists

The present invention concerns compounds of formula: where R, R, Rand Rare defined in the specification.

(Diaryl-methyl)-malononitriles and their use as estrogen receptor ligands

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: 

The present invention provides compounds of the general formulas: wherein Y is NR or &#x2014;(CH); R is H or alkyl; 'Z' represents optionally substituted phenyl or a 6-membered aromatic ring having one nitrogen atom; 'W' represents a optionally substituted phenyl or 5-membered aromatic ring having one nitrogen atom; &#x201c;X&#x201d; represents an optionally substituted 5-membered aromatic ring having one sulfur atom; as well as methods and pharmaceutical compositions utilizing these compounds for the inducing temporary delay of urination or treatment of disorders remedied by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, or bleeding and coagulation disorders.

Cyclohexylphenyl vasopressin agonists

A compound of the formulae (I) or (II): wherein: represents: represents: represents a 5-membered aromatic (unsaturated) heterocyclic ring having one sulfur atom, optionally substituted by (C&#x2013;C) lower alkyl, halogen, or (C&#x2013;C) lower alkoxy; and R, R, R, Rand Rare, independently, selected from a group consisting of hydrogen, (C&#x2013;C) lower alkyl, OCH, halogen, CF, &#x2014;SCH, OCF, SCF, or CN;or a pharmaceutically acceptable salt, or pro-drug form thereof.

This invention provides novel tricyclic diazepine compounds as well as methods and pharmaceutical compositions utilizing these compounds for the treatment and/or prevention and/or suppression of disorders which may be remedied or alleviated by oxytocin antagonist activity, including treatment of preterm labor, dysmenorrhea, endometritis, and for suppressing labor prior to caesarean delivery. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

Tricyclic diazepines tocolytic oxytocin receptor antagonists

This invention provides novel substituted tricyclic pyridyl carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea, endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

Tricyclic pyridyl carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists

The present invention provides compounds of the general formulas: wherein Y is NR or &#x2014;(CH); R is H or alkyl 'Z' represents optionally substituted phenyl or a 6-membered aromatic ring having one nitrogen atom; 'W' represents a optionally substituted phenyl or 5-membered aromatic ring having one nitrogen atom; &#x201c;X&#x201d; represents an optionally substituted 5-membered aromatic ring having one sulfur atom; as well as methods and pharmaceutical compositions utilizing these compounds for the inducing temporary delay of urination or treatment of disorders remedied by vasopressin agonist activity, including diabetes insipidus, nocturnal enuresis, nocturia, urinary incontinence, or bleeding and coagulation disorders.

A compound of the formulae (I) or (II):wherein:

This invention provides novel substituted tricyclic carboxamides which act as oxytocin receptor competitive antagonists, as well as methods of their manufacture, pharmaceutical compositions and methods of their use in treatment, inhibition, suppression or prevention of preterm labor, dysmenorrhea and endometritis, suppression of labor at term prior to caesarean delivery, and to facilitate antinatal transport to a medical facility. These compounds are also useful in enhancing fertility rates, enhancing survival rates and synchronizing estrus in farm animals; and may be useful in the prevention and treatment of disfunctions of the oxytocin system in the central nervous system including obsessive compulsive disorder (OCD) and neuropsychiatric disorders.

Tricyclic hydroxy carboxamides and derivatives thereof tocolytic oxytocin receptor antagonists

This invention comprises novel Rapamycin-FKBP12 binding proteins of mammalian origin for identification, design and synthesis of immunomodulatory, anti-restenosis or anti-tumor agents, as well as fragments of the proteins and the DNA, cDNA, antisense RNA and DNA segments corresponding to the proteins. This invention also comprises methods for isolating the proteins and therapeutic uses related to the proteins.

Effector proteins of Rapamycin

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Morrisville, PA, United States of America

Thomas Joseph Caggiano