Aspergillus species, cyclic dimeric dipeptide derivative substance P antagonist biosynthetic products thereof, and process for preparation thereof

• US 5,338,845 A
• Filed: 12/02/1992
• Issued: 08/16/1994
• Est. Priority Date: 12/02/1992
• Status: Expired due to Fees

• Current Assignee: Sanofi S.A. (Sanofi-Synthélabo SA)
• Original Assignee: Sterling Winthrop, Inc. (GlaxoSmithKline PLC)
• Inventors: Sedlock, David M., Barrow, Colin J., Houck, David R., Brownell, James E., Popp, Janet L., Hong, Anderson C.
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US07/984,668
• Time in Patent Office: 622 Days
• Field of Search: 544/343
• US Class Current: 544/343
• CPC Class Codes: C07D 487/14 Ortho-condensed systems

Abstract

A novel Aspergillus species, cyclic dimeric dipeptide derivatives which are biosynthetic products thereof and are useful as Substance P antagonists and therefore as analgesic and/or antiinflammatory agents, and a process for preparation of the biosynthetic products are disclosed.

Claims

1. A compound having the structural formula ##STR6## wherein R₁ and R₁ '"'"' are the same or different and are selected from the group consisting of hydrogen, halo, lower-alkyl and lower-alkoxy;

R₂ and R₂ '"'"' are the same or different and are selected from the group consisting of phenyl-lower-alkyl wherein phenyl is unsubstituted or substituted by halo or lower-alkyl, lower-alkyl except methyl, lower-alkylthio-lower-alkyl, trifluoromethyl-lower-alkyl, lower-alkenyl, thienyl-lower-alkyl and lower-cycloalkyl-lower-alkyl; and

R and S represent in each instance the steric configuration of the adjacent carbon atom.

2. A compound according to claim 1 wherein

R₁ and R₁ '"'"' are the same or different and are selected from the group consisting of hydrogen, fluoro, bromo, methyl and methoxy;

R₂ and R₂ '"'"' are the same or different and are selected from the group consisting of benzyl benzyl wherein phenyl thereof is substituted by fluoro, chloro or methyl, propyl, 2-methylethyl, 2-methylpropyl, methylthiomethyl, 2-trifluoromethylpropyl, 1-propenyl, 2-propenyl, 2-thienylmethyl and cyclohexylmethyl.

3. A compound according to claim 2 wherein

R₁ and R₁ '"'"' are the same or different and are selected from the group consisting of hydrogen, 5- or 5'"'"'-fluoro, 6- or 6'"'"'-fluoro, 7- or 7'"'"'-fluoro, 6- or 6'"'"'-bromo, 5- or 5'"'"'-methyl, 6- or 6'"'"'-methyl, 7- or 7'"'"'-methyl, and 6- or 6'"'"'-methoxy;

R₂ and R₂ '"'"' are the same or different and are selected from the group consisting of benzyl benzyl wherein phenyl thereof is substituted by o-, m- or p-fluoro, o- or p-chloro or o- or p-methyl, propyl, 2-methylethyl, 2-methylpropyl, methylthiomethyl, 2-trifluoromethylpropyl, 1-propenyl, 2-propenyl, 2-thienylmethyl and cyclohexylmethyl.

4. The compound according to claim 3 wherein R₁ and R₁ '"'"' are both hydrogen and R₂ and R₂ '"'"' are both benzyl.