Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-06-01
1997-10-07
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540472, 540467, 540480, 514185, A61K 31395, C07D26900, C07D41314
Patent
active
056748620
ABSTRACT:
This invention provides novel bis-indolemaleimide macrocycle derivatives of the formula: ##STR1## The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.
REFERENCES:
patent: 4785085 (1988-11-01), Kaneko et al.
patent: 4808613 (1989-02-01), Kaneko et al.
patent: 4923986 (1990-05-01), Murakata et al.
patent: 5043335 (1991-08-01), Kleinschroth et al.
patent: 5057614 (1991-10-01), Davis et al.
patent: 5292747 (1994-03-01), Davis et al.
patent: 5380746 (1995-01-01), Barth et al.
patent: 5438050 (1995-08-01), Kleinschroth et al.
Derwent Abstract 90-132947/18; 21.10.88-DE-835842, 1988.
Derwent Abstract 92-274042/33;90.11.20 90JP-314628, 1990.
Meier, et al., Tetrahedron Letters, 34:33, 5277-5280 (1993).
Wilkinson, et al., Bichem. J., 294, 335-337 (1993).
Bit, et al., J. Med. Chem., 36, 21-29 (1993).
Martiny-Baron, et al., The Journal of Biological Chemistry, 268:13, 9194-9197 (1993).
Krakowiak, et al, Synlett, 611-620, (Sep. 1993).
Mulqueen, et al., Agents Actions, 37, 85-89 (1992).
Davis, et al., J. Med. Chem., 35, 177-184 (1992).
Davis, et al., J. Med. Chem., 35, 994-1001 (1992).
Toullec, et al., The Journal of Biological Chemistry, 266:24, 15771-15781 (1991).
Nixon, et al., Drugs Exptl. Clin. Res., 17:8, 389-393 (1991).
Davis, et al., Tetrahedron Letters, 31:36, 5201-5204 (1990).
Brenner, et al., Tetrahedron Letters, 44:10, 2887-2892 (1988).
Joyce, et al., The Journal of Organic Chemistry, 52:7, 1177-1186 (1987).
Buchdunger, et al., Proc. Natl. Acad. Sci. USA, 91, 2334-2338 (Mar. 1994).
Kobayashi, et al., The American Physiological Society, H1214-H1220 (1994).
Felsenstein, et al., Neuroscience Letters, 174 173-176 (1994).
Demaerschalck, et al., Biochimica et Biophysica Acta, 1181 214-218 (1993).
Shimohama, et al., Neurology, 43 1407-1413 (1993).
Fieser and Fieser, Reagents for Organic Synthesis, XII, John Wiley & Sons, p. 108 (1986).
Knaack, et al. "Clonal Insulinoma Cell Line That Stably Maintains Correct Glucose Responsiveness", Diabetes, vol. 43, 1413-1417, Dec. 1994.
DeFronzo, R. A., "Diabetic nephropathy: etiologic and therapeutic considerations", Diabetes Reviews, vol. 3, No. 3, 510-564, 1995.
Inoguchi, et al., "Preferential elevation of protein kinase C isoform .beta.II and diacylglycerol levels in the aorta and heart of diabetic rate: Differential reversibility to glycemic control by islet cell transplantation", Proc. Natl. Acad. Sci. USA, vol. 89, 11059-11063, Nov. 1992.
Ishii et al., "Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC .beta. Inhibitor", Science, vol. 272, 728-731, 3 May 1996.
Porte, et al., "Diabetes Complications: Why is Glucose Potentially Toxic?", Science, vol. 272, 699-700, 3 May 1996.
Kowluru, et al., "Diabetes-induced Disorders of Retinal Protein Kinase C and Na, K-ATPase are Inhibited by LY333531", Abstract, American Diabetes Association Meeting Jun. 8-11, 1996.
Ishii, et al. "Treatment with Protein Kinase C .beta. isoform Inhibitor Normalized Urinary Albumin Exeretion and Glomerular Filtration Rate in Diabetic Rats", Abstract, American Diabetes Association Meeting Jun. 8-11, 1996.
Koya, et al. "Normalization of Hyperglycemia-Induced Inhibition of Na.sup.+ -K.sup.+ ATPase Activity by Protein Kinase C (PKC) .beta.-Selective Inhibitor in Giomerular Mesangial Cells", Abstract, American Diabetes Association Meeting Jun. 8-11, 1996.
Chen, et al, "Diacylglycerol-Protein Kinase C Signaling in Skeletal Muscle: A Possible Link to Insulin Resistance", Trans. Assoc. Am. Phys. 104: 206-12 (1991).
Wolf, et al., "Diacylglycerol Accumulation and Microvascular Abnormalities Induced by Elevated Glucose Levels", J. Clin. Invest., 87: 31-38 (1991).
Lee, et al. "Activation of protein kinase C by elevation of glucose concentration: Proposal for a mechanism in the development of diabetic vascular complications", Proc. Natl. Acad. Sci. USA, 86: 5141-5145. 1989.
Keen, H. "Chronic Complications of Diabetes Mellitus", Diabetes Mellitus, 9th Ed., Eli Lilly and Company 1988.
Heath, Jr. William F.
Jirousek Michael R.
McDonald, III John H.
Rito Christopher J.
Boone David E.
Caltrider Steven P.
Eli Lilly and Company
Shah Mukund J.
Sripada Pavanaram K.
LandOfFree
Methods of treating diabetic mellitus and its complications does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods of treating diabetic mellitus and its complications, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of treating diabetic mellitus and its complications will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2357520