Biochem Pharma Inc.

Bio-mega/boehringer Ingelheim Research Inc.

Biomega, Inc.

National Research Council of Canada

Astra Ab

John DiMaio

Julian Adams

Dilip M Dixit

Raymond Plante

Pierre Louis Beaulieu

Neil Moss

John W Gillard

Annette Marian Doherty

Jeremy John Edmunds

Torsten Steinmetzer

Dominik M Wernic

Benoit Bachand

Sophie Levesque

Feng Ni

M Arshad Siddiqui

Yasuo Konishi

Yves St-Denis

Wuyi Wang

Jorge Jaramillo

Patrice Preville

Micheline Tarazi

Pierre Lavalle/ E

Louis Grenier

Robert De/ Ziel

A thrombin inhibitor comprising a first bulky hydrophobic portion interacting with the catalytic site of thrombin responsible for proteolysis and a second portion at least maintaining the hydrophobic and acidic character of amino acids 55 to 60 of native hirudin at the C-terminal non-catalytic region of N-acetyl-hirudin45-65. Between the first and second portions is a divalent linker moiety having a chain length of at least 10 carbon atoms. Connecting the first bulky hydrophobic portion and the linker is a peptidomimetic bond. Preferably, the bulky hydrophobic portion comprises at least one amino acid of D-configuration. The compounds are useful in the treatment of thrombotic disorders.

Thrombin inhibitors based on the amino acid sequence of hirudin

This invention relates to the discovery of heterocyclic competitive inhibitors of the enzyme thrombin, their preparation, and pharmaceutical compositions thereof. As well, this invention relates to the use of such compounds and compositions in vitro as anticoagulants and in vivo as agents for the treatment and prophylaxis of thrombotic disorders such as venous thrombosis, pulmonary embolism and arterial thrombosis resulting in acute ischemic events such as myocardial infarction or cerebral infarction. Moreover, these compounds and compositions have therapeutic utility for the prevention and treatment of coagulopathies associated with coronary bypass operations as well as restenotic events following transluminal angioplasty.

Low molecular weight bicyclic thrombin inhibitors

Heterocyclic compounds for the treatment of pain and use thereof

Isoquinolines useful as analgesics

Polycyclic alcaloid-derivatives as NMDA-receptor antagonists

Disclosed herein are pentapeptide derivatives of the formula X--NR.sup.1 --CH(R.sup.2)--C(W)--NH--CR.sup.3 (R.sup.4)--C(W.sup.2)--NR.sup.5 --CH CH.sub.2 C(O)--Y!--C(W.sup.3)--NH--CR.sup.6 -- CR.sup.7 (R.sup.8)--COOH!--C(W.sup.4)--NH--CR.sup.9 (R.sup.10)--Z wherein X is a terminal group, for example, alkanoyl or phenylalkanoyl radicals, R.sup.1 is hydrogen, alkyl or phenylalkyl, R.sup.2, R.sup.4 and R.sup.10 are selected from amino acid or derived amino acid residues, R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are hydrogen or alkyl or R.sup.7 and R.sup.8 are joined to form a cycloalkyl, W.sup.1, W.sup.2, W.sup.3 and W.sup.4 are oxo or thioxo, Y is, for example, an alkoxy or a mono or disubstituted amino, and Z is a terminal group, for example, COOH or CH.sub.2 OH. The derivatives are useful for treating herpes infections.

Antiherpes pentapeptide derivatives having a substituted aspartic acid

Disclosed herein are cyclic peptide derivatives of the formula ##STR1## wherein A is absent or the tripeptide radical Thr.rarw.Gly.rarw.Ala, R.sup.1 is benzyl or benzyl monosubstituted at position 4 of the aromatic ring with halo, hydroxy, lower alkyl or lower alkoxy, R.sup.2 and R.sup.4 each independently is hydrogen or lower alkyl, R.sup.3 is lower alkyl or lower alkyl monosubstituted with a hydroxy, R.sup.5 is lower alkyl, Y is oxo or thioxo and Z is hydroxy or NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 each independently is hydrogen or lower alkyl. The derivatives are useful for treating herpes infections.

Cyclic peptides for treating herpes infections

Disclosed herein are derivatives of atrial natriuretic peptides wherein the exocyclic N-terminal peptide segment is deleted and the two cysteinyl residues (at positions 105 and 121) of the natural sequence are replaced with a trivalent unit, --NHCH(CO--)--Q--X--Y--CH.sub.2 CH.sub.2 CO-- wherein Q is methylene, ethylene or CR'R' wherein R' and R' each independently is lower alkyl, X is oxy or thio, and Y is methylene or des-Y. The derivatives may be optionally substituted at various positions including positions 106, 107 and 124. The derivatives possess ANF-like activity and are indicated for treating hypertension and for treating pathological conditions resulting from an imbalance of body fluids and electrolytes.

ANE derivatives with novel bridging

Growing community of inventors

Montreal, Canada

John DiMaio