公开(公告)号：CZ9703600A3

公开(公告)日：1998-06-17

申请号：CZ360097

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D233/76 ,  A61K31/415 ,  A61K31/4166 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07K5/02 ,  C07K5/023 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117 ,  C07D207/00 ,  C07D213/00

CPC classification number: C07K5/1024 ,  C07K5/0202

公开(公告)号：CZ9703599A3

公开(公告)日：1998-06-17

申请号：CZ359997

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  BARTNIK ECKART DR ,  HULS CHRISTOPH DR

IPC: C07D233/00 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/4178 ,  A61K31/421 ,  A61K31/426 ,  A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/39 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76 ,  C07D233/86 ,  C07D257/00 ,  C07D403/12 ,  C07D405/12 ,  C07K5/02 ,  C07K5/023 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78 ,  C07D207/00 ,  C07D213/00

CPC classification number: C07K7/06 ,  A61K38/00 ,  C07K5/0202 ,  C07K5/0821 ,  C07K5/1024 ,  Y02A50/411 ,  Y02P20/55

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer (or mixture) forms, or their salts for inhibiting the adhesion and/or migration of leukocytes or inhibiting VLA-4 receptors is new. W = R1-A-CR13 or R1A-CH=C; Y = CO, CS or CH2; Z = O, S or CH2 etc.; A = 1-6C alkylene, 3-7C cycloalkylene, (1-6C) alkylene-phenylene, or the divalent residue of a 5- or 6-membered ring containing 1 or 2 N (optionally substituted); B = 1-6C alkylene (optionally substituted), 2-6C alkenylene, phenylene, phenylene-(1-3C) alkyl or (1-3C) alkylene-phenylene; D = CR2R3, NR3 or CH=CR3; E = tetrazolyl, SO3H etc.; R = H, alkyl, 3-8C cycloalkyl, Ar or Ar-alkyl ; R1 = X-NH-C(=NH)-(CH2)p or X1-NH-(CH2)p; p = 0-3; X = H, 1-6C alkyl, (1-6C) alkylcarbonyl, Ar-(1-6C) alkoxycarbonyl, CN, OH, etc.; X1 = X etc.; R2 = H, alkyl, Ar, Ar-alkyl or 3-8C cycloalkyl; R3 = H, alkyl, Ar, alkenyl, alkynyl, pyridyl etc.; R13 = H, 1-6C alkyl, Ar-alkyl or 3-8C cycloalkyl; b, c, d, f = 0 or 1, but not all 0; e, g, h= 0-6; Ar = optionally substituted 6-14C aryl; unless specified otherwise alkyl moieties have 1-8C, alkenyl or alkynyl moieties 2-8C, cycloalkyl moieties 3-12C and bi- or tri-cycloalkyl moieties 6-12C.

公开(公告)号：MY119617A

公开(公告)日：2005-06-30

申请号：MYPI9705419

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  BARTNIK ECKART DR ,  HULS CHRISTOPH DR

IPC: C07D233/00 ,  A61K31/415 ,  C07K5/023 ,  A61K31/4166 ,  A61K31/4178 ,  A61K31/421 ,  A61K31/426 ,  A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/39 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76 ,  C07D233/86 ,  C07D257/00 ,  C07D403/12 ,  C07D405/12 ,  C07K5/02 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78

Abstract: 5-MEMBERED RING HETEROCYCLES AS INHIBITORS OF LEUCOCYTE ADHESION AND AS VLA-4 ANTAGONISTS COMPOUNDS OF THE FORMULA I(FORMULA 1)IN WHICH B, D, E, R, W, Y, Z, b, c, d, e, f, g AND h HAVE THE MEANINGS INDICATED IN THE CLAIMS, ARE INHIBITORS OF THE ADHESION AND MIGRATION OF LEUCOCYTES AND/OR ANTAGONISTS OF THE ADHESION RECEPTOR VLA-4 WHICH BELONGS TO THE GROUP OF INTEGRINS. THE INVENTION RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I AND OF PHARMACEUTICAL PREPARATIONS WHICH CONTAIN SUCH COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF DISEASES WHICH ARE CAUSED BY AN UNDESIRED EXTENT OF LEUCOCYTE ADHESION AND/OR LEUCOCYTE MIGRATION OR WHICH ARE ASSOCIATED THEREWITH OR IN WHICH CELL-CELL OR CELL-MATRIX INTERACTIONS WHICH ARE BASED ON INTERACTION OF VLA-4 RECEPTORS WITH THEIR LIGANDS PLAY A PART, FOR EXAMPLE OF INFLAMMATORY PROCESSES, OF RHEUMATOID ARTHRITIS OR OF ALLERGIC DISORDERS, AND IT ALSO RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I FOR THE PRODUCTION OF PHARMACEUTICALS FOR USE IN SUCH DISEASES. IT FURTHER RELATES TO NOVEL COMPOUNDS OF THE FORMULA I.

公开(公告)号：CZ360197A3

公开(公告)日：1998-06-17

申请号：CZ360197

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D277/20 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07D277/34 ,  C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117 ,  C07K5/08 ,  C07D207/00 ,  C07D213/00

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer or mixture forms, or their salts as medicaments is new. W = R1-A-CR13 or R1A-CH=C; Y = CO, CS or CH2; Z = O, S or CH2 etc.; A = direct bond, 3-12C cycloalkylene, (1-6C) alkylene-(3-12C) cycloalkylene, phenylene, or the divalent residue of a 5- or 6-membered ring containing 1 or 2 N (optionally mono- or disubstituted) etc.; B = 1-6C alkylene (optionally substituted), 2-6C alkenylene, phenylene, phenylene-(1-3C) alkyl or (1-3C) alkylene-phenylene; D = CR2R3, NR3 or CH=CR3; E = tetrazolyl, SO3H etc.; R = H, alkyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het '-alkyl (where alkyl residues are optionally substituted by one or more F); R1 = SR21, SSR21, SOR22, SO2R22, S-OR21, SO-OR21, SO2-OR21, SCOR21, SCOOR22, SCSSR22, OCOR21, OCSR21, OCOOR22, OSO2R22, OSO-R22, OP(O)(OR21)2, P(O)(OR21)2, P(O)(R22)OR21, CN, halo etc.; R2 = H, alkyl, Ar, Ar-alkyl or 3-8C cycloalkyl; R3 = H, alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl, alkenyl, alkynyl, alkenylcarbonyl, alkynylcarbonyl, pyridyl etc.; R13 = H, 1-6C alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl or (3-8C) cycloalkylalkyl; R21 = H, alkyl, hydroxyalkyl, alkenyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het'-alkyl (where alkyl residues are optionally substituted by one or more F); b, c, d, f = 0 or 1 provided not all are 0; e, g,h = 0-6; Ar = optionally substituted 6-14C aryl; Het' = optionally substituted heteroaryl; unless specified otherwise alkyl moieties have 1-8C, alkenyl or alkynyl moieties 2-8C, cycloalkyl moieties 3-12C and bi- or tri-cycloalkyl moieties 6-12C.

公开(公告)号：CZ9602940A3

公开(公告)日：1997-04-16

申请号：CZ294096

申请日：1996-10-07

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  SCHOLKENS BERNWARD PROF DR ,  KLEMM PETER DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D295/20 ,  A61K31/215 ,  A61K31/33 ,  A61K31/40 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P17/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D207/08 ,  C07D207/16 ,  C07D211/34 ,  C07D211/62 ,  C07D405/00 ,  C07H15/203 ,  C07H15/207 ,  C07H17/00 ,  C07H19/04

CPC classification number: C07H15/207

公开(公告)号：MY118176A

公开(公告)日：2004-09-30

申请号：MYPI9705417

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: A61K38/06 ,  A61K31/415 ,  C07D233/76 ,  A61K31/4166 ,  A61K38/00 ,  A61K38/05 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07K5/02 ,  C07K5/023 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117

Abstract: COMPOUNDS OF THE FORMULA I IN WHICH B, D, E, R, W, Y, Z, B, C, D, E, F, G AND HAVE THE MEANINGS INDICATED IN THE CLAIMS, ARE INHIBITORS OF THE ADHESION AND MIGRATION OF LEUCOCYTES AND/OR ANTAGONISTS OF THE ADHESION RECEPTOR VLA-4 WHICH BELONGS TO THE GROUP OF INTEGRINS. THE INVENTION RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I, AND OF PHARMACEUTICAL PREPARATIONS WHICH CONTAIN SUCH COMPOUNDS, FOR THE TREATMENT AND PROPHYLAXIS OF DISEASES WHICH ARE CAUSED BY AN UN DESIRED EXTENT OF LEUCOCYTE ADHESION AND/OR LEUCOCYTE MIGRATION OR WHICH ARE ASSOCIATED THEREWITH OR IN WHICH CELL-CELL OR CELL-MATRIX INTERACTIONS PLAY A PART WHICH ARE BASED ON INTERACTIONS OF VLA-4 RECEPTORS WITH THEIR LIGANDS, FOR EXAMPLE OF INFLAMMATORY PROCESSES, RHEUMATOID ARTHRITIS OR ALLERGIC DISORDERS, AND IT ALSO RELATES TO THE USE OF COMPOUNDS OF THE FORMULA I FOR THE PRODUCTION OF PHARMACEUTICALS FOR USE IN SUCH DISEASES. IT FURTHER RELATES TO NOVEL COMPOUNDS OF THE FORMULA I.

公开(公告)号：CZ292521B6

公开(公告)日：2003-10-15

申请号：CZ360097

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D233/76 ,  A61K31/415 ,  A61K31/4166 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07K5/02 ,  C07K5/023 ,  C07K5/06 ,  C07K5/08 ,  C07K5/10 ,  C07K5/117

Abstract: In the present invention there are disclosed compounds of the general formula I, in which the symbols B, D, E, R, W, Y, Z, b, c, d, e, f, g, and h have specific meanings, are inhibitors of the adhesion and migration of leucocytes and/or antagonists of the adhesion receptor VLA-4, which belongs to the group of integrins. The invention describes the use of compounds of the general formula I, for the preparation of medicaments intended for the treatment and prophylaxis of diseases, which are caused by an un desired extent of leucocyte adhesion and/or leucocyte migration or which are associated with leucocyte adhesion and/or leucocyte migration or in which cell-cell or cell-matrix interactions play a part which are based on interactions of VLA-4 receptors with their ligands, for example of inflammatory processes, rheumatoid arthritis or allergic disorders. Further described are novel compounds of the formula I per se, and pharmaceutical preparations containing these novel compounds.

公开(公告)号：CZ9703601A3

公开(公告)日：1998-06-17

申请号：CZ360197

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D277/20 ,  A61K38/00 ,  A61K38/05 ,  A61K38/06 ,  A61K38/07 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/54 ,  C07D233/72 ,  C07D277/34 ,  C07K5/06 ,  C07K5/078 ,  C07K5/097 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117 ,  C07K5/08 ,  C07D207/00 ,  C07D213/00

CPC classification number: C07K5/1016 ,  A61K38/00 ,  C07K5/1019 ,  Y02A50/411

Abstract: Use of N-substituted pyrrolidone, imidazolidinone, oxazolidinone or thiazolidinone derivatives of formula (I), in all stereoisomer or mixture forms, or their salts as medicaments is new. W = R1-A-CR13 or R1A-CH=C; Y = CO, CS or CH2; Z = O, S or CH2 etc.; A = direct bond, 3-12C cycloalkylene, (1-6C) alkylene-(3-12C) cycloalkylene, phenylene, or the divalent residue of a 5- or 6-membered ring containing 1 or 2 N (optionally mono- or disubstituted) etc.; B = 1-6C alkylene (optionally substituted), 2-6C alkenylene, phenylene, phenylene-(1-3C) alkyl or (1-3C) alkylene-phenylene; D = CR2R3, NR3 or CH=CR3; E = tetrazolyl, SO3H etc.; R = H, alkyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het '-alkyl (where alkyl residues are optionally substituted by one or more F); R1 = SR21, SSR21, SOR22, SO2R22, S-OR21, SO-OR21, SO2-OR21, SCOR21, SCOOR22, SCSSR22, OCOR21, OCSR21, OCOOR22, OSO2R22, OSO-R22, OP(O)(OR21)2, P(O)(OR21)2, P(O)(R22)OR21, CN, halo etc.; R2 = H, alkyl, Ar, Ar-alkyl or 3-8C cycloalkyl; R3 = H, alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl, alkenyl, alkynyl, alkenylcarbonyl, alkynylcarbonyl, pyridyl etc.; R13 = H, 1-6C alkyl, Ar, Ar-alkyl, 3-8C cycloalkyl or (3-8C) cycloalkylalkyl; R21 = H, alkyl, hydroxyalkyl, alkenyl, cycloalkyl, cycloalkylalkyl, Ar, Ar-alkyl, Het' or Het'-alkyl (where alkyl residues are optionally substituted by one or more F); b, c, d, f = 0 or 1 provided not all are 0; e, g,h = 0-6; Ar = optionally substituted 6-14C aryl; Het' = optionally substituted heteroaryl; unless specified otherwise alkyl moieties have 1-8C, alkenyl or alkynyl moieties 2-8C, cycloalkyl moieties 3-12C and bi- or tri-cycloalkyl moieties 6-12C.

公开(公告)号：CZ294096A3

公开(公告)日：1997-04-16

申请号：CZ294096

申请日：1996-10-07

Applicant: HOECHST AG

Inventor： TOEPFER ALEXANDER DR ,  KRETZSCHMAR GERHARD DR ,  SCHOLKENS BERNWARD PROF DR ,  KLEMM PETER DR ,  HULS CHRISTOPH DR ,  SEIFFGE DIRK DR

IPC: C07D295/20 ,  A61K31/215 ,  A61K31/33 ,  A61K31/40 ,  A61K31/435 ,  A61K31/445 ,  A61K31/495 ,  A61K31/70 ,  A61K31/7028 ,  A61K31/7034 ,  A61P3/08 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P17/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D207/08 ,  C07D207/16 ,  C07D211/34 ,  C07D211/62 ,  C07D405/00 ,  C07H15/203 ,  C07H15/207 ,  C07H17/00 ,  C07H19/04

Abstract: The invention relates to conjugates which consist of mono- or polycarboxylated piperidine or pyrrolidine derivatives and pyranoses, furanoses or polyalcohols linked via a chain or a cyclic system. The carboxyl groups of the piperidine derivatives can either be located directly on the ring or linked to the ring via a short chain. The invention additionally relates to the preparation of these compounds and to their use for the production of pharmaceuticals and diagnostics.

公开(公告)号：CZ293351B6

公开(公告)日：2004-04-14

申请号：CZ359997

申请日：1997-11-13

Applicant: HOECHST AG

Inventor： STILZ HANS ULRICH DR ,  WEHNER VOLKMAR DR ,  KNOLLE JOCHEN DR ,  BARTNIK ECKART DR ,  HULS CHRISTOPH DR

IPC: C07D233/00 ,  A61K31/415 ,  A61K31/4166 ,  A61K31/4178 ,  A61K31/421 ,  A61K31/426 ,  A61K38/00 ,  A61K38/06 ,  A61K38/07 ,  A61K38/39 ,  A61P3/08 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00 ,  A61P19/02 ,  A61P29/00 ,  A61P33/02 ,  A61P35/00 ,  A61P37/00 ,  A61P37/08 ,  A61P43/00 ,  C07D233/32 ,  C07D233/72 ,  C07D233/74 ,  C07D233/76 ,  C07D233/86 ,  C07D257/00 ,  C07D403/12 ,  C07D405/12 ,  C07K5/02 ,  C07K5/023 ,  C07K5/078 ,  C07K5/08 ,  C07K5/097 ,  C07K5/10 ,  C07K5/117 ,  C07K7/06 ,  C07K14/78

Abstract: In the present invention, there are disclosed compounds of the general formula I, in which the symbols B, D, E, R, W, Y, Z, b, c, d, e, f, g and h have specific meanings. These compounds are inhibitors of adhesion and migration of leukocytes and/or antagonists of VLA-4 adhesion receptor, which pertains to the group of integrins. Described is also the use of the compounds of the general formula I for preparing medicaments intended for treating or prophylaxis of diseases caused by undesired extent of leukocyte adhesion and/or migration or in which the cell-cell or cell-matrix interaction play a role, which are based on interaction of VLA-4 receptors with ligands thereof, such as inflammatory processes, rheumatic arthritis or allergic diseases. Further described are novel compounds of the general formula I per se as well as pharmaceutical compositions in which the novel compounds are comprised.