Abstract: Amidino and benzamidino compounds, including compounds of the formula: ##STR1## wherein R.sup.1 -R.sup.4, R.sup.6 -R.sup.9, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin are described. Also described are methods for preparing the compounds of Formula I.
Type:
Grant
Filed:
March 27, 1997
Date of Patent:
April 6, 1999
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Richard M. Soll, Tianbao Lu, Cynthia L. Fedde, Bruce E. Tomczuk, Carl Illig
Abstract: Compounds of the formula: ##STR1## wherein R.sup.1 --R.sup.4, R.sup.7 --R.sup.8, R.sup.a, R.sup.b, R.sup.c, Y, Z, n and m are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit a number of proteolytic enzymes are described. Also described are methods for preparing the compounds of Formula I.
Type:
Grant
Filed:
August 15, 1996
Date of Patent:
August 11, 1998
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Tianbao Lu, Carl R. Illig, Bruce E. Tomczuk, Richard M. Soll, Nalin L. Subasinghe, Roger F. Bone
Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The factor Xa inhibitors provide compounds of structure: ##STR1## or pharmaceutically acceptable salts thereof; whereinR.sup.1 is alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; R.sup.2 is one of hydrogen, alkyl, cycloalkyl or aryl; R.sup.3 is one of hydrogen, hydroxy or alkoxy; R.sup.4 is one of --NH.sub.2, phenyl or pyridyl, wherein said phenyl and said pyridyl are optionally substituted with one or two of halogen, hydroxy, hydroxyalkyl, alkoxy, amino, monoalkylamino, dialkylamino, aminoalkyl, monoalkylaminoalkyl and/or dialkylaminoalkyl; X is one of --CH.sub.2 -- or --C(O)--; and n is from zero to eleven; provided that when R.sup.4 is --NH.sub.2, then R.sup.3 is hydrogen and n is other than zero; and also provided that when R.sup.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
April 21, 1998
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Carl R. Illig, Richard M. Soll, Joseph M. Salvino, Bruce E. Tomczuk, Tianbao Lu, Nalin L. Subasinghe
Abstract: A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.
Type:
Grant
Filed:
August 15, 1996
Date of Patent:
November 4, 1997
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Dimitris K. Agrafiotis, Roger F. Bone, Francis R. Salemme, Richard M. Soll
Abstract: The present invention is directed to novel compounds that are thrombin inhibitors and are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The compounds have the general Formula I: ##STR1## and pharmaceutically acceptable salts thereof; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, n and m are defined herein.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
March 18, 1997
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Roger F. Bone, Richard M. Soll, Carl L. Illig, Tianbao Lu, Nalin L. Subasinghe
Abstract: The present invention is directed to non-peptidic factor Xa inhibitors which are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases. The factor Xa inhibitors provide compounds of structure: ##STR1## wherein each R.sup.1 is independently one of alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;each R.sup.2 and R.sup.3 is independently one of hydrogen, alkyl, aryl or arylalkyl;Y is a bond, or is one of --(CH.sub.2).sub.p --, cycloalkyl, aryl or C.sub.2-10 heterocycle; andm, n and p are each independently 1 to 10.
Abstract: A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.
Type:
Grant
Filed:
September 28, 1995
Date of Patent:
November 12, 1996
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Dimitris K. Agrafiotis, Roger F. Bone, Francis R. Salemme, Richard M. Soll
Abstract: The present invention is directed to novel compounds that are non-peptidic thrombin inhibitors. The compounds have the structure: ##STR1## and pharmaceutically acceptable salts thereof; wherein R.sup.1 is one of alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl; and n is from zero to five. The compounds of the invention are useful for the treatment of arterial and venous thrombotic occlusive disorders, inflammation, cancer, and neurodegenerative diseases.
Abstract: A computer based, iterative process for generating chemical entities with defined physical, chemical and/or bioactive properties. During each iteration of the process, (1) a directed diversity chemical library is robotically generated in accordance with robotic synthesis instructions; (2) the compounds in the directed diversity chemical library are analyzed to identify compounds with the desired properties; (3) structure-property data are used to select compounds to be synthesized in the next iteration; and (4) new robotic synthesis instructions are automatically generated to control the synthesis of the directed diversity chemical library for the next iteration.
Type:
Grant
Filed:
September 16, 1994
Date of Patent:
October 31, 1995
Assignee:
3-Dimensional Pharmaceuticals, Inc.
Inventors:
Dimitris K. Agrafiotis, Roger F. Bone, Francis R. Salemme, Richard M. Soll