The Medicines Company (Leipzig) Gmbh

The Medicines Company

Friedrich-Alexander Ludwig

Claudia Reichelt

Alexander Schulze

Andrea Schweinitz

Mohammed Daghish

Jochen Heinicke

Peter Herold

Torsten Steinmetzer

Stjepan Jelakovic

Joerg Stuerzebecher

Anett Soeffing

Silke Nicklisch

Andreas Van De Locht

Adel Rafai Far

Jörg Stürzebecher

Peter Steinmetzer

Ting Kang

Joseph DeAngelo

Mohammed Daghisch

Konrad Herrmann

Maj Schuster

Sven Letschert

Kenneth Mugridge

Anett Söffing

The invention provides compounds that are effective as inhibitors of human plasmin and plasma kallikrein, and that are useful for the prevention of blood loss and as components of fibrin adhesives. The invention further provides methods of making and using the compounds.

Trypsin-like serine protease inhibitors, and their preparation and use

The invention relates to compounds of general formula 1 to processes for the production thereof, to pharmaceutical preparations containing said compounds and/or physiologically compatible salts and/or solvates which can be produced therefrom as well as to the pharmaceutical use of said compounds, the salts or solvates thereof as inductors of apoptosis in the case of non-solid malignant tumors of the hematopoietic system, in particular in the case of leukemias and lymphomas, more particularly in the case of leukemic B lymphocytes.

Substituted 5H-pyrimido[5,4-B]indoles, method for the production thereof and use thereof for treating non-solid malignant tumors of the blood-producing system

The invention relates to inhibitors of trypsin-like serine proteases, including those of the general formula (IV) which, as well as plasmin, also inhibit plasma kallikrien, and to their use as medicaments, preferably for treatment of blood loss, especially in the case of hyperfibrinolytic states, in organ transplants or heart surgery interventions, in particular with a cardiopulmonary bypass, or as a constituent of a fibrin adhesive.

The invention provides methods of making and using compounds of the formula: or a pharmaceutically acceptable salt thereof; wherein n is an integer between 1 and 2 inclusively; m is an integer between 0 and 2 inclusively; X is selected from the group consisting of CH or N; Ris selected from the group consisting of &#x2014;CHNH, and Ris selected from the group consisting of &#x2014;H, &#x2014;OH, &#x2014;NHand acetyl; Ris selected from the group consisting of &#x2014;H, benzyloxycarbonyl and benzylsulfonyl; and Ris selected from the group consisting of &#x2014;OH, wherein p is an integer between 0 and 2 inclusively, Y is selected from the group consisting of &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014;, &#x2014;SO&#x2014;, methylene, &#x2014;CH(OH)&#x2014;, &#x2014;CH(NH)&#x2014;, &#x2014;CH(CH&#x2014;OH)&#x2014;, &#x2014;CH(CH&#x2014;NH)&#x2014; or &#x2014;N(R)&#x2014;, Ris selected from the group consisting of &#x2014;H or a simple (C-C) alkyl and Ris selected from the group consisting of &#x2014;H, a simple (C-C) alkyl or a simple (C-C) acyl. These compounds are useful as anticoagulant agents as a result of their selective dual inhibition of thrombin and prothrombinase.

Trypsin-like serine protease inhibitors, their preparation and use as selective inhibitors of the clotting factors IIa and Xa

The invention relates to inhibitors of trypsin-like serine proteases of the general formula (I) which, as well as plasmin, also inhibit plasma kallikrein, and to their preparation and use as medicaments, preferably for treatment of blood loss, especially in the case of hyperfibrinolytic states, in organ transplants or heart surgery interventions, in particular with a cardiopulmonary bypass, or as a constituent of a fibrin adhesive.

The invention relates to inhibitors of trypsin-like serine proteases of the general formula (I) which, as well as plasmin, also inhibit plasma kallikrien, and to their preparation and use as medicaments, preferably for treatment of blood loss, especially in the case of hyperfibrinolytic states, in organ transplants or heart surgery interventions, in particular with a cardiopulmonary bypass, or as a constituent of a fibrin adhesive.

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Leipzig, Germany

Friedrich-Alexander Ludwig