E. R. Squibb Sons, Inc.

Bristol-myers Squibb Compnay

Other

Harvard College

Bristol Meyers Squibb Company

Scott A Biller

R Michael Lawrence

David R Magnin

Richard B Sulsky

John K Dickson

Michael A Poss

Joseph Anthony Tino

Eric M Gordon

Jeffrey A Robl

Donald S Karanewsky

John Kenneth Dickson, Jr

Richard A Partyka

Michael J Sofia

John E Lawson

Henry M Holava

Rex A Parker

Cornelia Forster

Dinesh Vinoobhai Patel

William A Slusarchyk

Haris Jamil

Bruce L Jacobson

Krishna Kodukula

Michael C Badia

Olga M Fryszman

Raj N Misra

Gokhan S Hotamisligil

Mariano Barbacid

Richard E Gregg

John R Wetterau, Ii

Veeraswamy Manne

Daru Young Sharp

Chester A Meyers

A method is provided for treating diabetes and related diseases, especially Type II diabetes, employing an aP2 inhibitor or a combination of an aP2 inhibitor and another antidiabetic agent such as metformin, glyburide, troglitazone and/or insulin.

Method for treating diabetes employing an aP2 inhibitor and combination

A method is provided for treating atherosclerosis and related diseases, employing an aP2 inhibitor or a combination of an aP2 inhibitor and another antiatherosclerotic agent, for example, an HMG CoA reductase inhibitor such as pravastatin.

Method for treating atherosclerosis employing an aP2 inhibitor and combination

Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method

A method is provided by blocking or preventing the prenylation of CAAX box containing proteins including ras oncogene products thereby preventing and/or treating ras-related tumors which includes the step of administering a therapeutically effective amount of a protein-prenyl transferase inhibitor.

Method for blocking neoplastic transformation of cells induced by ras

Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.7, Q, X and Y are as defined herein.

Inhibitors of microsomal triglyceride transfer protein and method

Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.6, Q, and X are as defined herein.

Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein R.sup.1 to R.sup.6, Q, W and X are as defined herein.

Novel compounds are provided which are inhibitors of MTP and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases, and have the structure ##STR1## including pharmaceutically acceptable salts thereof or prodrug esters thereof, wherein q is 0, 1 or 2; R.sup.x is H, alkyl, aryl or halogen; A is

Conformationally restricted aromatic inhibitors of microsomal

A method is provided for preparing various intermediates and final products including MTP inhibitors employing solid phase syntheses. A new dialkoxyaryl aldehyde linker-resin of the structure ##STR1## which serves as a starting material and method for preparing same, are also provided.

Method for preparing compounds employing solid phase synthesis and novel

.alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

.alpha.-phosphonosulfonate squalene synthetase inhibitors

Compounds are provided which inhibit microsomal triglyceride transfer protein and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases. The compounds have the structure ##STR1## wherein Z, X.sup.1, X.sup.2, x and R.sup.5 are as defined herein.

A method is provided for preventing and/or treating hypertriglyceridemia, and/or atherosclerosis and/or pancreatitis resulting from hypertriglyceridemia, employing a squalene synthetase inhibitor.

Method for preventing or treating hypertriglyceridemia

Growing community of inventors

Ewing, NJ, United States of America

Scott A Biller