Protein kinase C inhibitor

• US 6,117,861 A
• Filed: 12/07/1999
• Issued: 09/12/2000
• Est. Priority Date: 11/20/1995
• Status: Expired due to Term

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Winneroski, Leonard Larry Jr., Farid, Nagy Alphonse, Faul, Margaret Mary, Engel, Gary Lowell, Jirousek, Michael Robert, Richardson, Lori Ann
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): TRUONG, TAMTHOM NGO
• Application Number:
  US09/455,697
• Time in Patent Office: 280 Days
• Field of Search: 514/183, 514/185, 514/410, 540/469
• US Class Current: 514/183
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 498/22 in which the condensed system contains four or more hetero rings

Abstract

This invention provides novel bis-indolylmaleimide macrocycle derivatives of the formula: ##STR1## and solvates thereof. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.

Claims

1. A pharmaceutical formulation comprising (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:

16,21-dimetheno-1H,13H-dibenzo[E,K]pyrrolo[3,4-H][1,4,13]-oxadiazacyclohexadecine-1,3(2H)-dione methanesulfonate monohydrate together with one or more pharmaceutically acceptable diluents, excipients, or carriers.

2. A method of treating complications of diabetes mellitus, which comprises administering to a mammal in need thereof, a pharmaceutically effective amount of a pharmaceutical formulation of claim 1.

3. A method of treating microvascular diabetic complications, which comprises administering to a mammal in need thereof, a pharmaceutically effective amount of a pharmaceutical formulation of claim 1.

4. A method of claim 2, wherein the complication of diabetes mellitus is selected from a group consisting of ischemia, inflammation, central nervous system disorders, cardiovascular disease, dermatological disease and cancer.

5. A method of claim 3, wherein the microvascular diabetic complication is selected from a group consisting of diabetic retinopathy, nephropathay, and neuropathy.