G.d. Searle & Company

Pharmacia Corporation (of Pfizer, Inc.)

Donald E Korte

John Jeffrey Talley

Matthew James Graneto

Balekudru Devadas

David Louis Brown

Srinivasan Raj Nagarajan

Suzanne S Metz

Stephen R Bertenshaw

Jeffery S Carter

Cindy L Ludwig

Mark G Obukowicz

Cathleen Elizabeth Hanau

Donald J Rogier

Susan J Hartmann

Kevin A Babiak

Donald W Hansen, Jr

Barnett S Pitzele

Timothy J Hagen

E Ann Hallinan

Sofya Tsymbalov

Karen B Peterson

Srinivasan Babu

James R Behling

Sean T Nugent

John R Medich

Daniel R Pilipauskas

Payman N Farid

Mark L Boys

Vlasdislav Orlovski

Jung M Park

Glenn L Stahl

Kimberly J Cain-Janicki

Wendel W Doubleday

Donald J Rogier, Jr

Claire A Przybyla

Kathleen T McLaughlin

Pierre-Jean Colson

Lisa M Seaney

Bruce Eric Wise

Susan J Hartman

Kathleen T Mc Laughlin

A class of benzopyrans, benzothiopyrans, dihydroquinolines, dihydronaphthalenes, and analogs thereof, is described for use in treating cyclooxygenase-2 mediated disorders. Compounds of particular interest are defined by Formula I' wherein X, A, A, A, A, R, R&#x2033;, Rand Rare as described in the specification.

Substituted benzopyran derivatives for the treatment of inflammation

A class of benzopyran, derivatives is described for use in treating cyclooxygenase-2 mediated disorders. Compounds of particular interest are defined by Formula I' wherein X, A, A, A, A, R, R&#x2033;, Rand Rare as described in the specification.

Substituted benzopyran derivatives for the treatment

Substituted benzopyran analogs for the treatment of inflammation

A class of benzopyrans, benzothiopyrans, dihydroquinolines, dihydronaphthalenes, and analogs thereof, is described for use in treating cyclooxygenase-2 mediated disorders. Compounds of particular interest are defined by Formula I&prime;

A class of benzopyrans, benzothiopyrans, dihydroquinolines, dihydronaphthalenes, and analogs thereof, is described for use in treating cyclooxygenase-2 mediated disorders. Compounds of particular interest are defined by Formula I'wherein X, A.sup.1, A.sup.2, A.sup.3, A.sup.4, R, R', R.sup.1 and R.sup.2 are as described in the specification.

A process for producing a lactam of the formula ##STR1## wherein 2-bromo-4 chloro butyryl bromide or 2,4-dibromo butyryl bromide is coupled with 4-aminobenzonitrile to produce 4-(2,4-bromobutyrylamino)-benzonitrile, which is combined with sodium hydroxide, potassium hydroxide or potassium carbonate to produce 4-(3-bromo-2-oxopyrrolidin-1-yl)benzonitrile which is subjected to an excess of ammonium hydroxide to produce compounds of the formula (I).

Process for the preparation of a 2-oxopyrrolidine compound

The present invention relates to a novel process for the preparation of ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentyno ate and pharmaceutically acceptable acid addition salt thereof.

Process for the preparation of ethyl

The present invention relates to a novel process for the preparation of ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentyno ate and pharmaceutically acceptable acid addition salt thereof which comprises treating (trimethylsilyl)acetylene sequentially with n-butyllithium and 4-formylmorpholine followed by acid hydrolysis to give 3-(trimethylsilyl)-2-propynal; treating 3-(trimethylsilyl)-2-propynal with lithium bis(trimethylsilyl)amide to give in situ N,3-bis(trimethylsilyl)-2-propyn-1-imine; condensation of N,3-bis(trimethylsilyl)-2-propyn-1-imine with lithium t-butyl acetate to give (.+-.)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; treating (.+-.)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate- with p-toluenesulfonic acid to give (.+-.)1,1-dimethylethyl 3-amino-5-(trimethylsilyl)-4-pentynoate, mono p-toluenesulfonic acid salt, treatment of resulting salt with ethanol in the presence of p-toluenesulfonic acid to give (.+-.)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate; desilylation of (.+-.)ethyl 3-amino-5-(trimethylsilyl)-4-pentynoate to give in situ (.+-.)ethyl 3-amino-4-pentynoate; resolution of (.+-.)ethyl 3-amino-4-pentynoate using (R)-(-)-mandelic acid and treatment of the resolved product with gaseous hydrochloric acid to give ethyl 3S-amino-4-pentynoate, monohydrochloride; coupling the ethyl 3S-amino-4-pentynoate, monohydrochloride to 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid, monohydrochloride in the presence of isobutyl chloroformate and N-methylmorpholine to give ethyl 3S-[[4-[[4-(aminoiminomethyl)phenyl]amino]-1,4-dioxobutyl]amino]-4-pentyno ate, monohydrochloride.

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Mundelein, IL, United States of America

Donald E Korte