G.d. Searle & Company

Roger A Nosal

Daniel L Flynn

Daniel Paul Becker

Clara I Villamil

Alan E Moormann

Norman A Abood

Lori A Schretzman

Richard M Weier

Scott A Laneman

Ish K Khanna

Hui Li

Alan E Moorman

Brian M Bax

Dale P Spangler

Robert L Shone

Michael S Dappen

Daniel L Zabrowski

Michael A Stealey

Kirk T Lentz

Richard M Weiser

Ish K Khannal

Richard Mathias Weier

2-Amino-benzoxazinones for the treatment of viral infections

2-amino benzoxazinones for the treatment of viral infections

A class of compounds for the treatment of viral infections. Compounds of particular interest are defined by Formula II ##STR1## wherein R.sup.28 is selected from (a) amino substituted with one or two radicals selected from alkyl, aralkyl, heterocycoalkyl, heterocyclo, and aryl, and (b) amino acid residues and derivatives thereof; wherein R.sup.29 is selected from hydrido, alkyl, halo, ##STR2## wherein R.sup.30 is selected from alkyl, alkoxy, alkylamino, carboxyalkyl, alkoxyalkyl, alkylaminoalkyl, cycloalkyl, heterocyclo, heterocycloalkyl, heterocycloalkoxy, alkylaminoalkoxy, alkylaminoalkylamino, heterocycloalkylamino, and N-aralkylamino; wherein R.sup.31 is alkyl; wherein R.sup.32 is alkyl and aryl; or a pharmaceutically-acceptable salt thereof.

2-amino-benzoxazinones for the treatment of viral infections

A method is described for synthesis of N-Boc-L-propargylglycine, a key intermediate used in the preparation of high-potency, orally-active renin inhibitors. This method involves reaction of an organic halide with a glycine cation equivalent, such as methyl N-Boc-2-acetoxyglycine, in the presence of zinc dust to give Boc-protected amino acid derivatives in high yield. Typically useful organic halides are allylic, benzylic and propargylic halides. Resolution of methyl N-Boc-propargylglycine with .alpha.-chymotrypsin provides N-Boc-L-propargylglycine in high yield.

Synthesis of chiral N-protected-.alpha.-substituted-glycine free acids

The invention herein is directed to a process for producing a lactam of the formula ##STR1## from a methionine analog of the formula ##STR2## by treating the methionine analog with trimethylsulfonium halide or trimethylsulfoxonium halide in the presence of a base in a suitable aprotic solvent. The invention herein is further directed to the preparation of amidinophenyl pyrrolidinyl .beta.-alanine urea analogs using such methionine and lactam compounds as intermediates, which .beta.-alanine urea analogs are useful as antithrombotics.

Intermediates for amidino phenyl pyrrolidine .beta.-alanine urea analogs

The meso-azacyclic aromatic acid amides and esters of the present invention are useful in the treatment of the central nervous system and gastrointestinal motility disorders such as gastroesophageal reflux, non-ulcer dyspepsia, delayed gastric emptying, ileus, irritable bowel syndrome, and the like. Additionally, the compounds of the present invention find utility as antagonists of serotonin 5-HT.sub.3 receptors. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and/or withdrawal, irritable bowel syndrome, emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Meso-azacyclic aromatic acid amides and esters as novel serotonergic

Process for the preparation of amidino phenyl pyrrolidine beta-alanine

The imidazopyridines compounds of the present invention are serotonergic 5-HT.sub.3 antagonists. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, gastric stasis, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Imidazopyridines as serotonergic 5-HT.sub.3 antagonists

The imidazopyridines compounds of the present invention are serotonergic 5-HT.sub.3 antagonists. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and withdrawal, gastrointestinal motility disturbances (including esophageal reflux, dyspepsia, gastric stasis, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

Imidazopyridines as serotonergic 5-HT.sub.3 -antagonists

Process for the preparation of amidino phenyl pyrrolidine .beta.-alanine

Benzimidazole compounds

This invention relates to compounds useful in treating HT.sub.4 and/or HT.sub.3 mediated, conditions of the formula ##STR1## or a pharmaceutically acceptable salt thereof.

New meso-azacyclic aromatic acid amides and esters as novel serotonergic

Synthesis of N-protected-.alpha.-substituted-glycine racemic esters by

Growing community of inventors

Buffalo Grove, IL, United States of America

Roger A Nosal