Mallinckrodt, Inc.

Specgx LLC

David W Berberich

Peter Xianqi Wang

Gary Lee Cantrell

Tao Jiang

Bobby N Trawick

Christopher W Grote

Subo Liao

Frank William Moser

Jian Bao

John Brandt

Peter X Wang

Raghavan Rajagopalan

Richard Bradley Dorshow

Robert E Halvachs

Joseph P McClurg

Douglas C Miller

Amolkumar Karwa

Hang Sun

Todd Osiek

Joseph P Mcclurg

The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.

(+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof

The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat a variety of disorders.

The present invention provides an efficient process for the preparation of hexahydroisoquinolines from amides. In particular, the invention provides a good yielding, one-pot process for the synthesis of hexahydroisoquinolines.

One-pot preparation of hexahydroisoquinolines from amides

The invention relates generally to anti-angiogenesis agents and related methods of using to anti-angiogenesis agents for biomedical applications including direct monotherapy and combination therapy for treatment of an angiogenesis related condition. In an embodiment, the invention provides a class of opioid compounds and structurally related opioid derivatives exhibiting anti-VEGF activity for use in therapeutic procedures, including phototherapy. Opioid compounds and structurally related opioid derivatives of the invention may be administered alone or in combination with administration of a phototherapy agent and/or other therapeutic agent.

Compounds and compositions for use in phototherapy and in treatment of ocular neovascular disease and cancers

The present invention provides processes for the preparation of N-alkyl morphinans without the isolation of nor-morphinan intermediates. In particular, the invention provides tandem hydrolysis/alkylation reactions for the synthesis of N-alkyl morphinans.

Tandem process for preparing N-alkyl morphinans

The present invention provides 3-oxy-hydromorphone derivatives, and in particular, 3-ester, 3-carbonate, and 3-sulfonate derivatives of hydromorphone.

3-oxy-hydromorphone derivatives

The present invention provides processes for the demethylation of an N-methyl morphinan comprising a ketone functional group. In particular, the invention provides methods for the protection of the ketone functional group such that impurities are not generated during the demethylation of the N-methyl morphinan.

N-demethylation of 6-keto morphinans

The invention relates to processes for the production of alkaloids without the isolation of intermediates.

Production of alkaloids without the isolation of intermediates

The invention generally provides processes and intermediate compounds useful for the production of sinomenine derivatives. In particular, the process may encompass synthetic routes for the production of (+)-sinomenine derivatives and their intermediates.

Sinomenine derivatives and processes for their synthesis

The present invention provides (+)-morphinanium compounds comprising substituted 6-hydroxy or 6-amine groups. The invention also provides methods for inhibiting microglial activation by administering the compounds of the invention.

(+)-6-hydroxy-morphinan or (+)-6-amino-morphinan derivatives

The present invention provides (+)-morphinanium N-oxide compounds or pharmaceutically acceptable salts thereof. The invention also provides processes for producing (+)-morphinanium N-oxides or pharmaceutically acceptable salts thereof from the corresponding tertiary N-substituted (+)-morphinan compound or pharmaceutically acceptable salt thereof.

(+)-morphinanium N-oxides and processes for their production

The present invention provides processes for the preparation of saturated ketone morphinan compounds from a morphinan comprising an allyl alcohol ring moiety, wherein the final product has a low metal content. In particular, the invention provides processes that utilize isomerization reactions catalyzed by transition metal catalysts and the subsequent removal of the transition metal using metal scavengers.

Preparation of saturated ketone morphinan compounds having low metal content

The present invention provides (+)-morphinanium quaternary salts. The invention also provides processes for producing (+)-morphinanium quaternary salts from tertiary N-substituted (+)-morphinan compounds.

Growing community of inventors

St. Peters, MO, United States of America

David W Berberich