公开(公告)号：EP0715628A1

公开(公告)日：1996-06-12

申请号：EP95921777.0

申请日：1995-05-30

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  BRASCA, Gabriella, Maria ,  LONGO, Antonio ,  BALLINARI, Dario

IPC分类号： A61K31 ,  A61K45 ,  A61P35 ,  C07D471 ,  C07F9

CPC分类号： C07D471/04 ,  C07F9/6561

摘要： The present invention relates to compounds useful as tyrosine kinase inhibitors, having general formula (I) wherein one of the groups X?1, X2, X3, X4¿ is N and the others are CH; R is a group of formula (a), (b), (c) or (d) each of R?1 and R3¿ independently is hydrogen, amino, carboxy, cyano, -SO¿3?R?4. -SO¿2NHR5. (1), -COOR6, -CONH(CH¿2?)oPh, -CONHCH2(CHOH)nCH2OH, (2), -N(CH2CH2OH)2, -NHCH2(CHOH)nCH2OH, -NHCONH2, -NHC(NH2)=NH, -NHCO(CHOH)nCH2OH, (3), -NHSO2R?7¿, -OCH¿2?(CHOH)nCH2OH, -OOC(CHOH)nCH2OH, -OPO(OH)2, -OCH2SO2NH2, -CH2NH2, -C(NH2)=NH, -CH2NHC(NH2)=NH, (4), -CH2OH, -CH2OOC(CHOH)nC2OH, -CH2OPO(OH)2, -PO(OH)2; R?2¿ is H, C¿1?-C6 alkyl, C2-C6 alkanoyl, -CH2OH, -CH2CH2CONH2, -SO2Me, -COCH2SO2NH2; R?4¿ is H, -CH¿2?(CHOH)nCH2OH, C1-C6 alkyl; R?5¿ is H, C¿1?-C6 alkyl, -CH2(CHOH)nCH2OH, -(CH2)mNMe2; R?6 is C¿1-C6 alkyl, unsubstituted or substituted by phenyl, -CH2(CHOH)nCH2OH; R7 is Me, -C¿6?H4Me; Z is CH2, O, NH, NCH2CH2OH; n is 0 or 1; m is 2 or 3; o is 0, 1, 2 or 3; p is 1, 2 or 3; provided that when R is (a), (b), or (c) then R?1¿ is not H and when R is (d) then one of R?1 and R3¿ is not H; and the pharmaceutically acceptable salts thereof.

公开(公告)号：EP0700388A1

公开(公告)日：1996-03-13

申请号：EP95910542.0

申请日：1995-03-02

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  CRUGNOLA, Angelo ,  LONGO, Antonio ,  BRASCA, Gabriella, Maria ,  BALLINARI, Dario

IPC分类号： A61K31 ,  A61P35 ,  A61P37 ,  A61P43 ,  C07C255 ,  C07D209 ,  C07D213 ,  C07D215 ,  C07D217 ,  C07D401

CPC分类号： C07D401/12 ,  C07C255/41 ,  C07C2602/10 ,  C07D209/12 ,  C07D209/18 ,  C07D215/12 ,  C07D215/26 ,  C07D217/14 ,  C07D217/16

摘要： The present invention relates to new compounds of formula (I), wherein A is a bicyclic ring chosen from naphthalene, tetrahydronaphthalene, quinoline, isoquinoline and indole; B is an R2 substituted benzene ring or an unsubstituted pyridine or thiphene ring; R is hydrogen, C¿1?-C6 alkyl, halogen, nitro, cyano, carboxy or a group NR?3R4¿, wherein each of R?3 and R4¿ is independently hydrogen or C¿1?-C6 alkyl; R?1¿ is hydrogen, C¿1?-C6 alkyl or C1-C6 alkanoyl; R?2¿ is hydrogen, C¿1?-C6 alkyl, halogen, nitro, cyano, carboxy, hydroxy, C1-C6 alkoxy, C1-C6 alkanoyloxy or a group NR?3R4¿, wherein R?3 and R4¿ are as defined above; n is zero or an integer of 1 to 2; x is zero or an integer of 1 to 5; and the pharmaceutically acceptable salts thereof. The compounds of the invention are useful as tyrosine kinase inhibitors.

摘要翻译： PCT No.PCT / EP95 / 00758 Sec。 371日期：1995年11月21日 102（e）1995年11月21日日期PCT 1995年3月2日PCT公布。 WO95 / 26341 PCT出版物 日期：1995年10月5日本发明涉及新的式（I）化合物，其中A是选自萘，四氢萘，喹啉，异喹啉和吲哚的双环。 B是R2取代的苯环或未取代的吡啶或噻吩环; R是氢，C 1 -C 6烷基，卤素，硝基，氰基，羧基或NR 3 R 4基团，其中R 3和R 4各自独立地是氢或C 1 -C 6烷基; R1是氢，C1-C6烷基或C1-C6烷酰基; R 2是氢，C 1 -C 6烷基，卤素，硝基，氰基，羧基，羟基，C 1 -C 6烷氧基，C 1 -C 6烷酰氧基或NR 3 R 4基团，其中R 3和R 4如上定义; n为0或1〜2的整数; x为0或1〜5的整数; 及其药学上可接受的盐。 本发明的化合物可用作酪氨酸激酶抑制剂。

公开(公告)号：EP0684820A1

公开(公告)日：1995-12-06

申请号：EP94931583.0

申请日：1994-11-08

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  LONGO, Antonio ,  BRASCA, Maria Gabriella ,  ORZI, Fabrizio ,  CRUGNOLA, Angelo ,  BALLINARI, Dario ,  MARIANI, Mariangela

IPC分类号： C07D401 ,  A61K31 ,  A61K38 ,  A61P27 ,  A61P29 ,  A61P35 ,  C07D209

CPC分类号： A61K31/70 ,  A61K31/40 ,  A61K31/47 ,  A61K31/475 ,  A61K31/505 ,  A61K31/675 ,  A61K38/04 ,  Y10S514/825 ,  Y10S514/863 ,  Y10S514/866 ,  Y10S514/886 ,  Y10S514/908 ,  A61K2300/00

摘要： The new use of a compound of formula (I) wherein Y is a bicyclic ring selected from naphthalene, tetralin, quinoline, isoquinoline and indole; n is zero or an integer of 1 to 3; R1 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; R2 is hydrogen, halogen, C1-C6 alkyl, cyano, carboxy, nitro, or NHR, wherein R is hydrogen or C1-C6 alkyl; R3 is hydrogen or C1-C6 alkyl; R4 is hydrogen, hydroxy, C1-C6 alkoxy, C2-C6 alkanoyloxy, carboxy, nitro or NHR, wherein R is as defined above; R5 is hydrogen, C1-C6 alkyl or halogen; or a pharmaceutically acceptable salt thereof; and wherein when Y is naphthalene then n is zero or an integer of 1 to 3, whereas when Y is tetralin, quinoline, isoquinoline or indole then n is zero, 1 or 2; and wherein when the bicyclic ring Y is naphthalene, quinoline, isoquinoline or indole, then each of the substituents OR1, R2 and oxindolylidene may be independently on either of the aryl or heteroaryl moieties of said bicyclic ring, whereas only the benzene moiety is substituted when Y is tetralin; and wherein when Y is naphthalene, tetralin, quinoline or isoquinoline, then R2 is hydrogen, halogen, cyano or C1-C6 alkyl and R3, R4 and R5 are hydrogen; whereas when Y is indole, then R2 is hydrogen, halogen, C1-C6 alkyl, cyano, carboxy, nitro or -NHR, in which R is as defined above, R3 is hydrogen or C1-C6 alkyl, R4 is hydrogen, hydroxy, C1-C6 alkoxy, C2-C6 alkanoyloxy, carboxy, nitro or -NHR, wherein R is as defined above, and R5 is hydrogen, halogen or C1-C6 alkyl; as anti-angiogenic agent is disclosed.

公开(公告)号：EP0656901A1

公开(公告)日：1995-06-14

申请号：EP94919642.0

申请日：1994-06-06

申请人： Pharmacia S.p.A.

发明人： BUZZETTI, Franco ,  LONGO, Antonio ,  DI SALLE, Enrico

IPC分类号： A61K31 ,  C07J1 ,  C07J71

CPC分类号： C07J71/001 ,  C07J1/0011 ,  C07J1/0022 ,  C07J1/0025

摘要： The present invention relates to compounds of formula (I) wherein A is a ⊃C=O, ⊃CHvvvOH or ⊃CHvvvOR4 group, in which R4 is an acyl group; one or two of R?1, R2 and R3¿ is fluorine and the others are hydrogens; provided that when R2 is fluorine one of R?1 and R3¿ is also fluorine. The compounds of the invention are useful as aromatase inhibitors.

摘要翻译： 本发明涉及式（I）的化合物，其中A是其中A是C = O，-CHVvvOH或CHVvvOR4基团，其中R4是酰基; R 1，R 2和R 3中的一个或两个是氟而另一个是氢; 条件是当R2是氟时，R1和R3中的一个也是氟。 本发明的化合物可用作芳香酶抑制剂。

公开(公告)号：EP0741726A1

公开(公告)日：1996-11-13

申请号：EP95937030.0

申请日：1995-10-30

申请人： Pharmacia S.p.A.

发明人： BUZZETTI, Franco ,  BRASCA, Gabriella, Maria ,  LONGO, Antonio ,  BALLINARI, Dario

IPC分类号： A61K31 ,  A61P9 ,  A61P35 ,  A61P43 ,  C07D471 ,  C07D519

CPC分类号： C07D471/04

摘要： The present invention relates to compound of formula (I) wherein A is benzene, naphthalene, 5,6,7,8,-tetrahydronaphthalene, quinoline, isoquinoline, indole or 7-azaindole; R1 is -H, -CN, -SO3R4, -SO2NHR5, (i), -COOR6, -CONHCH2(CHOH)nCH2OH, (ii), -NR7R8, -N(CH2CH2OH)2, -NHCH2(CHOH)nCH2OH, -NHCONH2, -NH-C(NH2)=NH, -NHCO(CH)OH)nCH2OH, (iii), -NHSO2R9, -OR10, -OCH2(CHOH)nCH2OH, -OOC(CHOH)nCH2OH, -OPO(OH)2, -CH2NH2, -C(NH2)=NH, -CH2NHC(NH2)=NH, (iv), -CH2OH, -CH2OOC(CHOH)nCH2OH, -CH2OPO(OH)2 or -PO(OH)2; R2 is C1-C6 alkyl, halogen, or hydroxy; R3 is -H or C1-C6 alkyl; R4 is -H, C1-C6 alkyl or -CH2(CHOH)nCH2OH; R5 is -H, C1-C6 alkyl, -CH2(CHOH)nCH2OH or -(CH2)mNMe2; R6 is -H, C1-C6 alkyl or -CH2(CHOH)nCH2OH; each of R7 and R8 independently is -H or C1-C6 alkyl; R9 is methyl or tolyl; R10 is -H, C1-C6 alkyl or C2-C6 alkanoyl; Z is ⊃CH2, ⊃0, ⊃NH or ⊃NCH2CH2OH; n is zero or 1; m is 2 or 3; p is 1, 2 or 3; q is zero, 1 or 2; and the pharmaceutically acceptable salt thereof, for use as tyrosine kinase inhibitors.

公开(公告)号：EP0658159A1

公开(公告)日：1995-06-21

申请号：EP94918379.0

申请日：1994-05-26

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  LONGO, Antonio ,  BRASCA, Maria, Gabriella ,  ORZI, Fabrizio ,  CRUGNOLA, Angelo ,  BALLINARI, Dario ,  MARIANI, Mariangela

IPC分类号： A61K31 ,  A61P35 ,  A61P43 ,  C07C255 ,  C07C327 ,  C07D209 ,  C07D215 ,  C07D401

CPC分类号： C07D401/06 ,  C07C255/36 ,  C07C255/37 ,  C07C255/41 ,  C07C327/42 ,  C07C2602/10 ,  C07D209/18 ,  C07D209/34 ,  C07D215/14

摘要： Arylidene and heteroarylidene oxindole derivatives of formula (I) wherein, subject to provisos, Y is a bicyclic ring system chosen from naphthalene, tetralin, quinoline and isoquinoline; R is hydrogen or an oxo (=O) group when Y is tetralin; or R is hydrogen when Y is naphthalene, quinoline or isoquinoline; each of R?1 and R2¿ independently is hydrogen, C¿1?-C6 alkyl or C2-C6 alkanoyl; m is zero, 1 or 2; n is zero, 1, 2 or 3; each of R?3 and R4¿ independently is hydrogen, halogen, cyano, C¿1?-C6 alkyl, carboxy, nitro or -NR?6R7¿ in which each of R?6 and R7¿ independently is hydrogen or C¿1?-C6 alkyl; R?5¿ is hydrogen or C¿1?-C6 alkyl; and their pharmaceutically acceptable salts, which are useful as tyrosine kinase inhibitors.

摘要翻译： 羟吲哚，丙烯酰胺，硫代丙烯酰胺和丙烯腈化合物及其药学上可接受的盐，其可用作酪氨酸激酶抑制剂。

公开(公告)号：EP0608404B1

公开(公告)日：1996-03-27

申请号：EP93917746.5

申请日：1993-08-05

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  LONGO, Antonio ,  DI SALLE, Enrico

IPC分类号： C07J71/00 ,  A61K31/58

CPC分类号： C07J71/0042 ,  C07J7/0085

摘要： This invention provides compounds of formula (I), wherein x, y, z represent single or double bonds; R is hydrogen or C1-C4 alkyl; R1 is hydrogen or an acyl group; R2 is hydrogen; C1-C4 alkyl unsubstituted or substituted by phenyl; phenyl unsubstituted or substituted by C1-C4 alkyl or C1-C4 alkoxy; and A is a >C=O, >CH OH or >CH OR3 group, in which R3 is an acyl group provided that one of z and y is a double bond and the other is a single bond. The compounds are useful as aromatase inhibitors.

公开(公告)号：EP0470221B1

公开(公告)日：1995-12-13

申请号：EP91904125.1

申请日：1991-02-26

申请人： PHARMACIA S.p.A.

发明人： BUZZETTI, Franco ,  LONGO, Antonio ,  COLOMBO, Maristella

IPC分类号： C07C255/40 ,  C07C255/41 ,  C07C255/43 ,  C07C327/44 ,  C07C233/29 ,  C07C59/52 ,  C07C59/54

CPC分类号： C07D215/227 ,  C07C59/52 ,  C07C59/54 ,  C07C235/34 ,  C07C255/36 ,  C07C255/41 ,  C07C327/44 ,  C07C2602/10 ,  C07D209/34 ,  C07D215/14 ,  C07D215/20 ,  C07D215/233 ,  C07D215/26 ,  C07D401/06 ,  C07D403/06

摘要： Aryl- and heteroarylethenylene derivatives of formula (I) wherein Y is a mono- or bicyclic ring system chosen from (A), (B), (C), (D), (E), (F) and (G); R is a group of formula (a), (b), (c), (d), (e), (f), (g), (h), (i) or (j) in which R3 is -OH or -NH2 and Ph means phenyl; R1 is hydrogen, C1-C6 alkyl or C2-C6 alkanoyl; R2 is hydrogen, halogen, cyano or C1-C6 alkyl; n is zero or an integer of 1 to 3; n is zero or an integer of 1 to 3 when Y is a ring system (A); it is zero, 1 or 2 when Y is a ring system (B), (E), (F) or (G); or it is zero or 1 when Y is a ring system (C) or (D); and the pharmaceutically acceptable salts thereof; and wherein each of the substituents R, OR1 and R2 may be independently on either of the aryl or heteroaryl moieties of the bicyclic ring system (A), (E), (F) and (G), whereas only the benzene moiety may be substituted in the bicyclic ring system (B), are useful as tyrosine kinase activity inhibitors.

摘要翻译： 通式（I）的化合物其中Y是选自（B），（A），（E），（F）和（G）的化合物。 ，C 1 -C 6烷基或C 2 -C 6烷酰基; R2是氢，卤素，氰基或C1-C6烷基; 当Y为环状体系（A）时，n为0或1〜3的整数，n为0或1〜3的整数，Y为环状体系（B）时为0或1， E），（F）或（G）; 及其药学上可接受的盐; 并且其中取代基R，OR 2和R 2中的每一个可以独立地在二环系统（A），（E），（F）和（G）的芳基或芳基部分的任一个上，而只有苯部分可以是 在双环（B）中被取代。 本发明的化合物具有特异的酪氨酸激酶抑制活性。 因此，它们可用于治疗癌症和其他病理性增殖病症。