公开(公告)号：CZ286945B6

公开(公告)日：2000-08-16

申请号：CZ132397

申请日：1995-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SIPIDO VICTOR KAREL ,  GADEA FRANCISCO JAVIER FERNAND ,  ANDR S-GIL JOS IGNACIO ,  MEERT THEO FRANS ,  GIL LOPETEGUI PILAR

IPC: A61K31/535 ,  A61K31/55 ,  A61P9/00 ,  A61P25/00 ,  A61P25/18 ,  A61P25/24 ,  A61P25/26 ,  C07D223/20 ,  C07D223/30 ,  C07D261/00 ,  C07D498/04

Abstract: In the present invention there are disclosed tetracyclic azepine derivatives of the general formula I, in which Re1 and Re2 represent hydrogen, alkyl, alkylcarbonyl, trihalomethylcarbonyl, alkyl being substituted with hydroxyl, alkoxyl, carbonyl, alkylcarbonyloxy group containing 1 to 6 carbon atoms in the alkyl moiety, alkoxycarbonyl or aryl or Re1 and Re2 together with a nitrogen atom to which they are attached can form a morpholine radical, Re3, Re4, Re5, Re6, Re9, Re10, Re11 and Re12 represent independently on each other hydrogen, halogen, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, carboxy, nitro, amino, mono- or diamino, alkylcarbonylamino, aminosulfonyl, mono- or diaminosulfonyl, alkyl, alkoxy, alkylcarbonyl, or alkoxycarbonyl, Re7 and Re8 represent independently on each other hydrogen, OH, alkyl or alkoxy containing 1 to 6 carbon atoms or Re7 and Re8 together can form methylidene, mono or di(cyano)methylene, the group -(CHi2)i2-, -(CHi2)i3-, -(CHi2)i4-, -(CHi2)i5-, -O-(CHi2)i2-O-, or O-(CHi2)i3-O or together with a carbon atom to which they are attached they can represent carbonyl, Re13 represents hydrogen, alkyl or trifluoromethyl, Re14 represents alkyl, cyano or trifluoromethyl, a is 0 to 6, aryl can be optionally a substituted phenyl, as well as their pharmaceutically acceptable addition salts with acids or bases, their stereochemically isomeric forms and A-oxides. In the present invention there are also claimed process and intermediates for their preparation as well as pharmaceutical preparations based thereon. The compounds are mCPP-antagonists and they can be therefore used for treating or prevention of central nervous system diseases, cardiovascular diseases or gastrointestinal disorders.

公开(公告)号：CZ20001136A3

公开(公告)日：2000-08-16

申请号：CZ20001136

申请日：1998-10-06

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： ANDR S-GIL JOS IGNACIO ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  GIL-LOPETEGUI PILAR ,  DIAZ-MARTINEZ ADOLFO

IPC: A61K31/34 ,  A61K31/343 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4525 ,  A61K31/495 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  A61K31/55 ,  A61P25/00 ,  A61P25/06 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  C07D307/93 ,  C07D401/06 ,  C07D405/06 ,  C07D493/04

Abstract: This invention concerns the compounds of formula (I),the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X is CH2 or O; R and R each independently are hydrogen, C1-6alkyl, C1-6alkylcarbonyl, halomethylcarbonyl or C1-6alkyl substituted with hydroxy, C1-6alkyloxy, carboxyl, C1-6alkylcarbonyloxy, C1-6alkyloxycarbonyl or aryl; or R and R taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; R and R are both halogen; or R is halogen and R is hydrogen; or R is hydrogen and R is halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents selected from halo, hydroxy, C1-6alkyl and halomethyl. The compounds of formula (I) may be used as therapeutic agents.

公开(公告)号：CZ286645B6

公开(公告)日：2000-05-17

申请号：CZ37396

申请日：1994-08-12

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： VAN LOMMEN GUY ROSALIA EUGENE ,  FERNANDEZ-GADEA FRANCISCO JAVI ,  ANDR S-GIL JOS IGNACIO ,  MATESANZ-BALLESTEROS MARIA E E

IPC: A61K31/35 ,  A61K31/436 ,  A61K31/44 ,  A61K31/453 ,  A61K31/505 ,  A61P9/02 ,  A61P9/08 ,  A61P25/04 ,  A61P25/06 ,  C07D405/12 ,  C07D491/04 ,  C07D491/052

Abstract: In the present invention there are disclosed substituted dihydropyranopyridines of the general formula I, in which =ai1-ai2=ai3-ai4= represents a bivalent radical =N-CH=CH-CH=, =CH-N=CH-CH=, =CH-CH=N-CH= or =CH-CH=CH-N=, whereby in those bivalent radicals can be optionally one or two hydrogen atoms substituted with a halogen, hydroxy, alkyl containing 1 to 6 carbon atoms or alkoxyl containing 1 to 6 carbon atoms Re1, Re2 and Re3 represent each independently on each other hydrogen or alkyl containing 1 to 6 carbon atoms, Alke1 represents alkanediyl containing 1 to 5 carbon atoms, Alke2 represents alkanediyl containing 2 to 15 carbon atoms, Q represents a five- or six-membered heterocyclic radical containing at least one nitrogen atom or the radical aa, wherein Re4 represents hydrogen, cyano, aminocarbonyl or alkyl containing 1 to 6 carbon atoms, Re5 represents hydrogen, alkyl containing 1 to 6 carbon atoms alkenyl containing 3 to 6 carbon atoms or alkynyl containing 3 to 6 carbon atoms, Re6 represents hydrogen or alkyl containing 1 to 6 carbon atoms or Re5 and Re6 together form a bivalent radical of the general formula -(CHi2)i4- or -(CHi2)i5-, and their pharmaceutically acceptable acid addition salts, N-oxides and stereochemically isomeric forms per se and for use in medicine. In the present invention there are also claimed a process for preparing those compounds and pharmaceutical preparations based thereon. The above indicated derivatives are suitable for prevention and/or therapy of disorders characterized by excessive vasodilatation, particularly migraine.