公开(公告)号：WO9940067A2

公开(公告)日：1999-08-12

申请号：PCT/EP9900852

申请日：1999-02-05

Applicant: DUPHAR INT RES ,  HARTOG JACOBUS A J ,  VISSER GERBEN M ,  STEEN BARTHOLOMEUS J VAN ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G ,  LANGE JOSEPHUS H M

Inventor： DEN HARTOG JACOBUS A J ,  VISSER GERBEN M ,  VAN STEEN BARTHOLOMEUS J ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G ,  LANGE JOSEPHUS H M

IPC: A61K31/445 ,  A61K31/454 ,  A61K31/55 ,  A61P25/00 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D413/14 ,  C07D

CPC classification number: C07D413/14

Abstract: The present invention relates to a group of novel benzisoxazole derivatives which are potent and selective antagonists of the dopamine D4-receptor. The compounds have general formula (I) wherein (R1)n represents 0, 1, or 2 substituents, which can be the same or different, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino mono- or dialkyl (C1-2)-amino, sulfonyl-(C1-3)alkyl or -alkoxy, sulfonyl trifluoromethyl, sulfonyl amino, and sulfonyl mono- or dialkyl (C1-2)-amino, X is O, S, NH or NCH3, Y represents CH2 or (CH2)2, (R2)m represents 0, 1, or 2 substituents, which can be the same or different, from the group methyl and ethyl, or (R2)m is a methylene bridge or ethylene bridge, A is a group -CH2-(CRH)p- wherein R is hydrogen or methyl and p is 0 or 1, and B represents 2- or 3-indolyl or 2-benzimidazolyl, which groups may be substituted at carbon with 1 or 2 substituents from the group C-1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, mono- or dialkyl (C1-2)amino, sulfonyl-(C1-3)alkyl or -alkoxy, sulfonyl trifluoromethyl, sulfonyl amino, and sulfonyl mono- or dialkyl (C1-2)-amino.

Abstract translation: 本发明涉及一组新颖的苯并异恶唑衍生物，它们是多巴胺D4-受体的有效和选择性拮抗剂。 所述化合物具有通式（I）：其中（R 1）n表示0,1或2个取代基，所述取代基可以相同或不同，选自C 1-3烷基或烷氧基，卤素，三氟甲基，硝基， （C1-2） - 氨基，磺酰基 - （C1-3）烷基或 - 烷氧基，磺酰基三氟甲基，磺酰基氨基和磺酰基单或二烷基（C1-2） - 氨基，X是O，S，NH或 NCH 3，Y代表CH 2或（CH 2）2，（R 2）m代表0,1或2个可与甲基和乙基相同或不同的取代基，或（R 2）m是亚甲基桥或亚乙基 桥基，A是基团-CH 2 - （CRH）p - ，其中R是氢或甲基，p是0或1，B代表2-或3-吲哚基或2-苯并咪唑基，这些基团可以在碳上被1 或C1-C3-烷基或烷氧基，卤素，三氟甲基，硝基，氨基，单或二烷基（C1-2）氨基，磺酰基 - （C1-3）烷基或 - 烷氧基，磺酰基三氟甲基， 磺酰基氨基和磺酰基单或二烷基（C1-2） - 氨基。

公开(公告)号：WO9940068A2

公开(公告)日：1999-08-12

申请号：PCT/EP9900855

申请日：1999-02-05

Applicant: DUPHAR INT RES ,  HARTOG JACOBUS A J ,  VISSER GERBEN M ,  STEEN BARTHOLOMEUS J VAN ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G

Inventor： DEN HARTOG JACOBUS A J ,  VISSER GERBEN M ,  VAN STEEN BARTHOLOMEUS J ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G

IPC: A61K31/4709 ,  A61K31/496 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D201/00 ,  C07D215/38 ,  C07D401/12 ,  C07D405/12 ,  C07D

CPC classification number: C07D215/38 ,  C07D401/12 ,  C07D405/12

Abstract: The present invention relates to a group of novel 2-aminoquinoline derivatives which are potent and selective agonists of the dopamine D4-receptor. The compounds have general formula (I) wherein (R1)n represents 1 or 2 substituents, which can be the same or different, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)-amino, or two groups R1 at adjacent carbon atoms together with the benzene ring may form the benzdioxane group or benzofuran group, X represents nitrogen or carbon, and the dotted line may represent a double bond, (R2)p represents 0, 1 or 2 substituents, which can be the same or different, from the group methyl and ethyl, or (R2)p is a methylene bridge or ethylene bridge, R3 is hydrogen or methyl, and (R)m represents 0, 1, or 2 substituents, which can be the same or different and can be located at all available positions of the quinolyl group, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)-amino, on the understanding that R1 cannot represent o-OCH3 when X is nitrogen, (R2)p and R3 are hydrogen, m is 0 and n is 1.

Abstract translation: 本发明涉及一组新的2-氨基喹啉衍生物，其是多巴胺D4-受体的有效和选择性激动剂。 化合物具有通式（I），其中（R1）n表示1或2个可以相同或不同的取代基，可以是C1-3 - 烷基或烷氧基，卤素，三氟甲基，硝基，氨基和单 - 或 二烷基（C1-2） - 氨基或两个相邻碳原子的R1与苯环一起形成苯并二恶烷基或苯并呋喃基，X表示氮或碳，虚线表示双键，（R2） p表示0,1或2个与甲基和乙基基团相同或不同的取代基，或（R2）p是亚甲基桥或乙烯桥，R3是氢或甲基，（R）m表示0 ，1或2个取代基，其可以相同或不同，并且可以位于喹啉基的所有可用位置，C 1-3 - 烷基或烷氧基，卤素，三氟甲基，硝基，氨基和单 - 或 二烷基（C 1-2） - 氨基，但应理解，当X为氮时，R 1不能表示o-OCH 3，（R 2）p和R 3为氢，m为0，n为 是1。

公开(公告)号：JPH11147871A

公开(公告)日：1999-06-02

申请号：JP25910598

申请日：1998-08-31

Applicant: DUPHAR INT RES

Inventor： FEENSTRA ROELOF W ,  VISSER GERBEN M ,  KRUSE CORNELIS G ,  TULP MARTINUS T M ,  LONG STEPHEN K

IPC: C07D215/06 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61P25/18 ,  A61P43/00 ,  C07D209/08 ,  C07D209/34 ,  C07D215/14 ,  C07D215/38 ,  C07D223/16 ,  C07D263/58 ,  C07D265/36 ,  C07D279/16 ,  C07D401/04 ,  C07D401/12 ,  C07D409/12

Abstract: PROBLEM TO BE SOLVED: To obtain a new piperazine compound exhibiting high affinity for both dopamine D2 and serotonin 5-HT A receptors and useful for treating schizophrenia and other psychopathy. SOLUTION: The compound of formula I R1 is H or fluoro; R' is H or a 1-4C alkyl; R2 is H, a 1-4C alkyl or oxo; or R1 and R2 together form a bond; R" is H or a 1-4C alkyl; the dotted line is a single or double bond; (p) is 0-2; Y is C, O, N or S; Y is N or C; R3 and R4 are each H or a 1-4C alkyl; (n) is 1 or 2; Q is CH2 -C(R5 ,R6 )-Z-R7 [R5 and R6 are each H or the like; Z is C(R8 ,R9 )-0 (R8 and R9 are H or the like) or the like; R7 is a cyclic group or the like]}, for example, a compound of formula II, is obtained from a compound of formula III as a starting raw material by a known method.

公开(公告)号：JPH11302279A

公开(公告)日：1999-11-02

申请号：JP28357898

申请日：1998-09-21

Applicant: DUPHAR INT RES

Inventor： TULP MARTINUS T M ,  LONG STEPHEN K ,  DEN HARTOG JACOBUS A J ,  FEENSTRA ROELOF W ,  KRUSE CORNELIS G

IPC: C07D411/12 ,  A61K31/00 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P25/04 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D411/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14

Abstract: PROBLEM TO BE SOLVED: To provide the subject compounds having an affinity for dopamine D2 and D4 receptors, without showing a noted preference for one over the other, also having an affinity for serotonin 5-HT1a , and useful for treatment of mental diseases, e.g. schizophrenia. SOLUTION: The compounds are shown by formula I [A is a 5- to 7-membered heterocyclic group having 1 to 3 hetero atoms selected from the group consisting of O, N and S; R1 is H or fluoro; R2 is a 1-4C alkyl, oxo or the like; (p) is 0 to 2; Z is C or N; broken line is a single bond when Z is N and single or double bond when Z is C; R3 and R4 are each H or a 1-4C alkyl; (n) is 1 or 2; R5 is a 2-, 3- or 4-pyridyl substituted with Y at the meta site for methylene cross-linking; and Y is phenyl or furanyl] and salts thereof, e.g. a compound shown by formula II. The compound shown by formula I is obtained by reacting a compound shown by formula III with a compound shown by the formula; R5 -CH2 -X (X is an eliminable group).

公开(公告)号：CA2320116C

公开(公告)日：2011-02-01

申请号：CA2320116

申请日：1999-02-05

Applicant: DUPHAR INT RES

Inventor： DEN HARTOG JACOBUS A J ,  VISSER GERBEN M ,  VAN STEEN BARTHOLOMEUS J ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G

IPC: C07D215/38 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D201/00 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14

Abstract: The present invention relates to a group of novel 2-aminoquinoline derivatives which are potent and selective agonists of the dopamine D4-receptor. The compounds have general formula (I) wherein (R1)n represents 1 or 2 substituents, which can be the same or different, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)-amino, or two groups R1 at adjacent carbon atoms together with the benzene ring may form the benzdioxane group or benzofuran group, X represents nitrogen or carbon, and the dotted line may represent a double bond, (R2)p represents 0, 1 or 2 substituents, which can be the same or different, from the group methyl and ethyl, or (R2)p is a methylene bridge or ethylene bridge, R3 is hydrogen or methyl, and (R)m represents 0, 1, or 2 substituents, which can be the same or different and can be located at all available positions of the quinolyl group, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)-amino, on the understanding that R1 cannot represent o-OCH3 when X is nitrogen, (R2)p and R3 are hydrogen, m is 0 and n is 1.

公开(公告)号：ES2196785T3

公开(公告)日：2003-12-16

申请号：ES99910210

申请日：1999-02-05

Applicant: DUPHAR INT RES

Inventor： DEN HARTOG JACOBUS A J ,  VISSER GERBEN M ,  VAN STEEN BARTHOLOMEUS J ,  TULP MARTINUS T M ,  RONKEN ERIC ,  KRUSE CORNELIS G

IPC: A61K31/4709 ,  A61K31/496 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P43/00 ,  C07D201/00 ,  C07D215/38 ,  C07D401/12 ,  C07D405/12

Abstract: The present invention relates to a group of novel 2-aminoquinoline derivatives which are potent and selective agonists of the dopamine D4-receptor. The compounds have general formula (I) wherein (R1)n represents 1 or 2 substituents, which can be the same or different, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)amino, or two groups R1 at adjacent carbon atoms together with the benzene ring may form the benzdioxane group or benzofuran group, X represents nitrogen or carbon, and the dotted line may represent a double bond, (R2)p represents 0, 1 or 2 substituents, which can be the same or different, from the group methyl and ethyl, or (R2)p is a methylene bridge or ethylene bridge, R3 is hydrogen or methyl, and (R)m represents 0, 1, or 2 substituents, which can be the same or different and can be located at all available positions of the quinolyl group, from the group C1-3-alkyl or alkoxy, halogen, trifluoromethyl, nitro, amino, and mono- or dialkyl (C1-2)amino, on the understanding that R1 cannot represent o-OCH3 when X is nitrogen, (R2)p and R3 are hydrogen, m is 0 and n is 1

公开(公告)号：AT230741T

公开(公告)日：2003-01-15

申请号：AT99952604

申请日：1999-10-15

Applicant: DUPHAR INT RES

Inventor： TULP MARTINUS T M ,  VAN DER HEIJDEN JOHANNES A M ,  VAN VLIET BERNARD ,  TIPKER JACOBUS ,  VAN HES ROELOF ,  KRUSE CORNELIS G ,  VISSER GERBEN M

IPC: A61K31/435 ,  A61K31/475 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D401/14

Abstract: The invention is related to the following compounds:wherein all variables are as defined in the specification. The compounds are useful for treating psychotic disorders.

公开(公告)号：AU750811B2

公开(公告)日：2002-07-25

申请号：AU6474199

申请日：1999-10-15

Applicant: DUPHAR INT RES

Inventor： TULP MARTINUS T M ,  HEIJDEN JOHANNES A M VAN DER ,  VLIET BERNARD VAN ,  TIPKER JACOBUS ,  HES ROELOF VAN ,  KRUSE CORNELIS G ,  VISSER GERBEN M

IPC: A61K31/435 ,  A61K31/475 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D401/14

Abstract: The invention is related to the following compounds:wherein all variables are as defined in the specification. The compounds are useful for treating psychotic disorders.

公开(公告)号：SK5122001A3

公开(公告)日：2001-10-08

申请号：SK5122001

申请日：1999-10-15

Applicant: DUPHAR INT RES

Inventor： TULP MARTINUS T M ,  VAN DER HEIJDEN JOHANNES A M ,  VAN VLIET BERNARD ,  TIPKER JACOBUS ,  VAN HES ROELOF ,  KRUSE CORNELIS G ,  VISSER GERBEN M

IPC: A61K31/435 ,  A61K31/475 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D401/14

Abstract: The invention is related to the following compounds:wherein all variables are as defined in the specification. The compounds are useful for treating psychotic disorders.

公开(公告)号：BR9803497A

公开(公告)日：2000-05-02

申请号：BR9803497

申请日：1998-09-21

Applicant: DUPHAR INT RES

Inventor： TULP MARTINUS T M ,  LONG STEPHEN K ,  DEN HARTOG JACOBUS A J ,  FEENSTRA ROELOF W ,  KRUSE CORNELIS G

IPC: C07D411/12 ,  A61K31/00 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61P25/04 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D411/14 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D409/10 ,  C07D411/10 ,  C07D413/10

Abstract: The invention relates to a group of new piperazine and piperidine compounds having interesting pharmacological properties. It has been found that compounds of the formula (a) wherein A represents a heterocyclic group of 5-7 ring atoms wherein 1 - 3 heteroatoms from the group O, N and S are present, R1 is hydrogen or fluoro, R2 is C1-4-alkyl, C1-4-alkoxy or an oxo group, and p is 0, 1 or 2, Z represents carbon or nitrogen, and the dotted line is a single bond when Z is nitrogen, and a single or double bond when Zis carbon, R3 and R4 independently are hydrogen or C1-4-alkyl, n has the value 1 or 2, R5 is 2-pyridyl, 3-pyridyl or 4-pyridyl substituted at the meta-position with respect to the methylene bridge with a group Y, and optionally substituted with (R6)q, Y is phenyl, furanyl or thienyl, which groups may be substituted with 1-3 substituents of the group hydroxy, halogen, CF3, C1-4-alkoxy, C1-4-alkyl, cyano, aminocarbonyl, mono- or di-C1-4-alkylaminocarbonyl, R6 is halogen, hydroxy, C1-4-alkoxy or C1-4-alkyl, and q is 0, 1, 2 or 3 and salts thereof, show affinities for both the dopamine D2-, D3-, D4- receptors and the serotonin 5-HT1A receptor.