Eli Lilly and Company

Lawrence E Stramm

Michael R Jirousek

Douglas Kirk Ways

William F Heath, Jr

Louis Vignati

William Terry Johnson

Fatima Emitsel Yakubu-Madus

Colin W Smith

Jai P Singh

Samantha J Ambler

Richard Dennis DiMarchi

Mark Louis Heiman

Vignati Louis

Carol Lynn Broderick

Thiazolidinedione (TZD) and its pharmacologically active derivatives can be used in combination with agonists of glucagon-like peptide-1 (GLP-1), to treat non-insulin dependent diabetes mellitus, optionally with other therapies, by improving glycemic control while minimizing side effects, such as heart hypertrophy and elevated fed-state plasma glucose, which are associated with both TZD and GLP-1 monotherapies. Thus, the co-administration of TZD and GLP-1 helps regulate glucose homeostasis in Type II diabetic patients.

Method for treating non-insulin dependent diabetes using thiazolidinediones with glucagonlike peptide-1 and agonists thereof

Thiazolidinedione (TZD) and its pharmacologically active derivatives can be used, in combination with agonists of glucagon-like peptide-1 (GLP-1), to treat non-insulin dependent diabetes mellitus, optionally with other therapies, by improving glycemic control while minimizing side effects, such as heart hypertrophy and elevated fed-state plasma glucose, which are associate with both TZD and GLP-1 monotherapies. Thus, the co-administration of TZD and GLP-1 helps regulate glucose homeostasis in Type II diabetic patients.

Synergistic use of thiazolidinediones with glucagon-like peptide-1 and agonists thereof to treat metabolic instability associated with non-insulin dependent diabetes

Method for treating non-insulin dependent diabetes using thiazolidinediones with glucagon-like peptide-1 and agonists thereof

A method for treating neoplasms is disclosed, particularly using the &bgr;-isozyme selective PKC inhibitor, (S)-3,4-&lsqb;N, N&prime;-1,1&prime;-((2&Prime;-ethoxy)-3&prime;&Prime;(O)-4&prime;&Prime;-(N,N-dimethylamino)-butane)-bis-(3,3&prime;-indolyl)&rsqb;-1(H)-pyrrole-2,5-dione or one of its salts, such PKC inhibitors enhance the clinical efficacy of oncolytic agents and radiation therapy.

Use of protein kinase C inhibitors to enhance the clinical efficacy of oncolytic agents and radiation therapy

A method for treating neoplasms is disclosed, particularly using the &bgr;-isozyme selective PKC inhibitor, (S)-3,4-&lsqb;N,N&prime;-1,1&prime;-((2&Prime;-ethoxy)-3&prime;&Prime;(O)-4&prime;&Prime;-(N,N -dimethylamino)butane)-bis-(3,3&prime;-indolyl)&rsqb;-1(H)-pyrrole-2,5-dione or one of its salts, such PKC inhibitors enhance the clinical efficacy of oncolytic agents and radiation therapy.

Use of protein kinase C inhibitors to enhance the clinical efficacy of radiation therapy

A method for treating neoplasms is disclosed, particularly using the &bgr;-isozyme selective PKC inhibitor, (S)-3,4-&lsqb;N, N&prime;-1,1&prime;-((2&Prime;-ethoxy)-3&prime;&Prime;-(O)-4&prime;&Prime;-(N,N-dimethylamino)-butane)-bis-(3,3&prime;-indolyl)&rsqb;-,(H)-pyrrole-2,5-dione or one of its salts, such PKC inhibitors enhance the clinical efficacy of oncolytic agents and radiation therapy.

A method for treating HIV infection is disclosed, particularly using the isozyme selective PKC inhibitor, (S)-3,4-[N, N'-1,1'-((2'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bis-(3,3'-indo lyl)]-1(H)-pyrrole-2,5-dione or its acid salt.

Therapeutic treatment for HIV infection

A method for treating sexual dysfunctions is disclosed, particularly using the isozyme selective PKC inhibitor, (S)-3,4-[N,N'-1,1'-((2'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bis -(3,3'-indoly1)]-1(H)-pyrrole-2,5-dione, particularly its hydrochloride, or mesylate salt.

Therapeutic treatment for sexual dysfunctions

A method for reducing or inhibiting vascular permeability especially the increased vascular permeability associated with VPF/VEGF, and dermal edema exhibited with bullous phemigoid, erythema multiforme, dermatitis herpetiformis, contact dermatitis/delayed hypersensitivity is disclosed, particularly using the .beta.-isozyme selective PKC inhibitor, (S)-3,4-[N,N'-1,1'-((2'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bis -(3,3'-indolyl)]-1(H)-pyrrole-2,5-dione and its pharmaceutically acceptable salts.

Therapeutic treatment for skin disorders

A method for treating human T cell lymphotrophic virus type 1 infection using an isozyme selective PKC inhibitor, particularly using the isozyme selective PKC inhibitor, (S)-3,4-�N,N'-1,1'-((2'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bis -(3,3'-indolyl)!-1(H)-pyrrole-2,5-dione hydrochloride salt.

Therapetutic treatment for human T cell lymphotrophic virus type 1

The present invention is in the field of human medicine, particularly in the treatment of Non-insulin Dependent Diabetes Mellitus (NIDDM) and other insulin resistant states such as those associated with obesity and aging. The invention provides a method of treating insulin resistant mammals, which comprises administering to a mammal in need thereof a growth hormone releasing agent.

Method of treating insulin resistance

A method for treating endothelial cell dysfunction, such as associated with cardiovascular disease are disclosed, particularly using the isozyme selective PKC inhibitor, (S)-3,4-�N,N'-1,1'-((27'-ethoxy)-3''(O)-4''-(N,N-dimethylamino)-butane)-bi s-(3,3'-indolyl)!-1(H)-pyrrole-2,5-dione hydrochloride salt.

Therapeutic treatment for cardiovascular diseases

This invention provides novel compounds and pharmaceutical methods comprising the administration of a compound of the Formula I: ##STR1## wherein n, m, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are variables.

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Indianapolis, IN, United States of America

Lawrence E Stramm