Inflazyme Pharmaceuticals Ltd.

The University of British Columbia

University of Alberta

Biolipox Ab

Other

Yaping Shen

David L Burgoyne

Yuanlin Zhou

Hassan Salari

Ronald W Lauener

Patrick J Rebstein

Edward Piers

Christine Rogers

John M Langlands

Joseph H-l Chau

Jeffery R Raymond

Nicholas D Paschalides

Gueijun Ji

Eugene W Kelleher

Kishore Ramachandran

Samuel D M Abraham

Claudia E Kasserra

Joseph H L Chau

Samuel D Abraham

The present invention is directed to a method for reducing the emetogenic effects of PDE inhibitors, and more particularly is directed to compounds having PDE4 inhibition activity with little or no emetogenic side-effects, and chemical methods including benzylation for preparing such compounds. A benzyl group may be attached to either a carbon or nitrogen atom of a PDE4 inhibitor. Suitable benzylation chemistry is to extract a hydrogen from a PDE4 inhibitor, preferably with a base, and then react the resulting nucleophilic PDE4 inhibitor with a benzylating agent, e.g., benzyl bromide or a derivative thereof.

Benzylated PDE4 inhibitors

A compound of the formula: and pharmaceutically acceptable salts, solvates, stereoisomers and prodrugs thereof, in isolation or in mixture, wherein R groups are as defined by the present specification. The compounds may be formulated into pharmaceutical compositions, and used in the treatment and/or prevention of various conditions, including inflammation, asthma, an allergic disease, chronic obstructive pulmonary disease, atopic dermatitis, solid tumors, AIDS, ischemia, and cardiac arrhythmias.

3-nitrogen-6, 7-dioxygen steroids and uses related thereto

Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6&#x3b1; and 7&#x3b2; oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6&#x3b1; and 7&#x3b2; oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and &#x3b4;-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed.

6,7-Oxygenated steroids and uses related thereto

Steroids containing a cyclohexene moiety are efficiently oxidized to the corresponding &#x3b1;,&#x3b2;-unsaturated ketone using copper iodide and t-butyl hydroperoxide. A steroid compound containing the &#x3b1;,&#x3b2;-unsaturated ketone structure is efficiently converted to the corresponding vicinal diol using a hydroborating reagent followed by oxidative workup, e.g., borane followed by sodium perborate. Benzoyl and substituted benzoyls are superior protecting groups for hydroxyl groups present in the compounds.

Process improvements in steroid chemistry

&ggr;-Phenyl-substituted &Dgr;-lactams are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.

Substituted &ggr;-phenyl-&Dgr;-lactams and uses related thereto

Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6&agr; and 7&bgr; oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6&agr; and 7&bgr; oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and &dgr;-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed.

6, 7-oxygenated steroids and uses related thereto

Steroids containing a cyclohexene moiety are efficiently oxidized to the corresponding &agr;,&bgr;-unsaturated ketone using copper iodide and t-butyl hydroperoxide. A steroid compound containing the &agr;,&bgr;-unsaturated ketone structure is efficiently converted to the corresponding vicinal diol using a hydroborating reagent followed by oxidative workup, e.g., borane followed by sodium perborate. Benzoyl and substituted benzoyls are superior protecting groups for hydroxyl groups present in the compounds.

Process for the production of 6,7-diols of steroidal compounds

3-nitrogen-6,7-dioxygen steroids and uses related thereto

&ggr;-Phenyl-substituted &Dgr;-lactones and analogs thereof, including lactams, are disclosed. They may be formulated into pharmaceutical compositions, and/or used in the treatment or prevention of inflammation or other conditions or disease states.

Substituted &ggr;-phenyl-&Dgr;-lactones and analogs thereof and uses related thereto

Steroid compounds having various oxygen substitution on the steroid nucleus are disclosed. A specific functionality present on many of the steroid compounds is oxygen substitution at both of positions 6 and 7. Thus, certain steroids have oxygen substitution at C6 and C7, and some have specific stereochemistries such as 6.alpha. and 7.beta. oxygen substitution, and an alpha hydrogen at the 5 position in addition to having 6.alpha. and 7.beta. oxygen substitution. Steroids having 3,4-epoxy functionality are also disclosed. In addition, steroids having C17 pyran and .delta.-lactone functionality, with oxygen substitution at C6 and C7, or at C15, of the steroid nucleus, are disclosed.

6,7-oxygenated steroids and uses related thereto

A 'mirror' amide cord factor or 'mirror' thioester cord factor having the following generic formula: ##STR1## is alkyl having 8 to 90 carbons or alkoxy having 8 to 90 carbons, and R.sub.2 is hydrogen, alkyl having 8 to 90 carbons or alkoxy having 8 to 90 carbons; and when T is sulphur, R.sub.1 is alkyl having 8 to 90 carbons or alkoxy having 8 to 90 carbons and R.sub.2 is absent.

Growing community of inventors

Coquitlam, Canada

Yaping Shen