Pfizer Corporation

Masaya Ikunaka

Nakao Kojima

Hiroyuki Nishida

Nobuji Yoshikawa

Katsuomi Ichikawa

Masami Nakane

Hiroaki Wakabayashi

John Adams Lowe, Iii

Brian Thomas O'Neill

Fumitaka Ito

Terry J Rosen

Harry R Howard, Jr

Yuji Shishido

Kunio Satake

This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the terpenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.

Oidiodendron strain for the production of terpenoid lactone compounds

Substituted benzolactam compounds as substance P antagonists

This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating,FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the terpenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.

Terpenoid lactone compounds and their production process

This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating,FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the teipenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.

A compound of the chemical formula (I) and its pharmaceutically acceptable salt: ##STR1## wherein Y is C.sub.2 -C.sub.4 alkylene; Z is a valence bond or C.sub.1 -C.sub.6 alkylene; R.sup.1 is substituted or unsubstituted aryl (e.g., phenyl and naphthyl) or heteroaryl (e.g., thienyl and furyl); R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl; R.sup.3 is hydrogen, hydroxy or the like; R.sup.4 is substituted or unsubstituted benzyl or the like. Typical examples are (2S*,3S*,4R*,5R*)-4-Carboxy-3-[N-(5-Isopropyl-2-methoxy-benzyl)amino]-5-me thyl-2-phenylpyrrolidine and (2S*,3S*,5S*)-5-Carboxy-3-[N-(2-methoxy-5-trifluoromethoxybenzyl)amino]-2- phenylpiperidine. The novel substituted azaheterocyclecarboxylic acids in this invention have excellent substance P antagonistic activity and are thus useful for the treatment of gastrointestinal disorders, central nervous system disorders, allergy, inflammatory diseases, asthma, pain, emesis or migraine in mammals, especially humans.

Substituted azaheterocyclecarboxylic acid

Substituted benzylamino nitrogen containing non-aromatic heterocycles

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Kobe, Japan

Masaya Ikunaka