University of Pennsylvania

Merck + Co., Inc.

Other

Ralph F Hirschmann

Paul A Sprengeler

Amos B Smith, Iii

Daniel F Veber

Ruth F Nutt

Rolando A Spanevello

Ellen Leahy

Frederick W Holly

Terence Keenan

Mark Guzman

John L Wood

Wenqing Yao

Ryan C Holcomb

Hiroyuki Ikumura

Hu Liu

Akihisa Yokoyama

Edward J Cragoe, Jr

Joshua Rokach

Kyriacos Costa Nicolaou

Tsung-Ying Shen

David R Jones

Pierre A Hamel

Paul S Anderson

Arthur F Wagner

Barry S Cooperman

Catherine D Strader

William J Paleveda, Jr

Robert G Strachan

Jonathan A Tobert

Edward H Blaine

Alison L Fisher

David A Favor

Andrew B Benowitz

Sherrie Pietranico-Cole

Bari A Barwis

Alexander Pasternak

Setsuya Sasho

William C Shakespeare

Paul Laub

Tsau-Yen Lin

Shrikumar Nair

P Grant Spoors

John D Milkowski

Burwell F Powell

Paul E Curley

Rachel D Van Rijn

By Elisabeth Nancarrow, Executrix

John F Nancarrow, Deceased

Thomas Nittoli

T R Reisine

Maria A Cichy-Knight

Sherrie Pietranico

John Hynes, Jr

Joseph M Salvino

The invention provides a new process for the preparation of polypyrrolinones (I) of various sizes which have found to be useful peptidomimetics. One aspect of the invention is a new process utilizing &#x3b1;-amino-&#x3b1;-substituted-valerolactones as synthons. A second aspect of the invention is a process for the synthesis of polypyrrolinones using solid-phase techniques. 

Solution and solid phase synthesis of pyrrolinones and polypyrrolinones

The invention provides a new process for the preparation of polypyrrolinones (I) of various sizes which have found to be useful peptidomimetics. One aspect of the invention is a new process utilizing &#x3b1;-amino-&#x3b1;-substituted-valerolactones as synthons. A second aspect of the invention is a process for the synthesis of polypyrrolinones using solid-phase techniques.

Polypyrrolinone based inhibitors of matrix metalloproteases

Compounds are provided which are crossreactive with peptides such as those which bind G-protein-linked receptors, together with preparative and therapeutic methods therefor. The compounds have the general structure:

Non-peptide peptidomimetics

Synthetic methods for pyrrolinone-based compounds are provided. Such compounds mimic or inhibit the biological and/or chemical activity of peptides.

Oxazolidinones and methods for the synthesis and use of same

The invention relates to compositions which are useful for inhibiting ribonucleotide reductase enzymes, including the mammalian ribonucleotide reductase enzyme. The compositions include, but are not limited to, linear peptides, cyclic peptides, peptide analogs, and peptidomimetics. Methods of using the compositions of the invention to treat cancer and viral and bacterial infections are disclosed.

Peptides peptide analogs peptidomimetics and other small molecules

Relatively small cyclic peptides that mimic the biological and/or chemical activity of larger cyclic peptide such as somatostatin, as well as synthetic methods therefor. In certain embodiments, cyclic peptides of the invention have structure: ##STR1## wherein R.sub.NP1 is H, an amine protecting group, or a solid support and R.sub.NP2 is H or an amine protecting group.

Synthetic somatostatin mimics

Somatostatin mimics and synthetic methods therefor

This invention relates to chemical compounds that contain adjacent carbonyl groups, which effectively inhibit the biological, chemical, and/or physical properties of enzymes and other medicinally-significant proteins. In particular, the invention relates to dicarbonyl compounds that are capable of acting as enzyme inhibitors, including irreversible inhibitors of HIV-1 protease.

Dicarbonyl-containing compounds

Compounds are provided which are crossreactive with peptides such as those bound by G-protein-linked receptors, together with preparative and therapeutic methods therefor. The compounds have the general structure: ##STR1## wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 or R.sub.6 comprises a chemical functional group which causes the compounds to be crossreactive with the peptide of interest.

Alicyclic peptidomimetics

Compounds are provided which are crossreactive with peptides such as those which bind G-protein-linked receptors, together with preparative and therapeutic methods therefor.

Non-peptide peptidomimetics and related cyclic hexapeptides

Novel pyrrolinone-based compounds mimic or inhibit the biological and/or chemical activity of peptides, including peptide .beta.-strand conformations. Certain compounds contain functionalized pyrrolinone units in place of one or more amino acids of a target peptide.

Pyrrolinone-based peptidomimetics

2-Hydroxy-3-aminopropylsulfonamides are provided along with methods for synthesizing and using such compounds, and chemical intermediates employed in the synthetic methods.

2-Hydroxy-3-aminopropylsulfonamides

Compounds are provided which are crossreactive with peptides such as those which bind G-protein-linked receptors, together with preparative and therapeutic methods therefor. The compounds have the general structure: ##STR1## wherein at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, or R.sub.5 comprises a functional group which is chemically similar to that found in the peptide of interest.

Non-Peptide peptidomimetics

Growing community of inventors

Blue Bell, PA, United States of America

Ralph F Hirschmann