公开(公告)号：JP2002012594A

公开(公告)日：2002-01-15

申请号：JP2001167003

申请日：2001-06-01

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

Abstract: PROBLEM TO BE SOLVED: To provide a fused imidazole derivative having multidrug resistance modulating properties capable of inhibiting or reversing multiple drug resistance of a carcinoma cell or a pathogen. SOLUTION: This compound is expressed by formula (I). [In the formula a dotted line is a bond existing according to circumstances; n is 1 or 2; R1 is H, a halo, formyl group, a l-4C (substituted)alkyl group, -X-CO-OR5,-X-CO-NR6 R7 or -X-CO-R10; R2 is H, a halo, a 1-4C alkyl group, a 1-4C hydroxyalkyl group, a 1-4C alkyloxycarbonyl group, a carboxyl group, formyl group or a phenyl group; R3 is H, a 1-4C alkyl group, or a 1-4C alkyloxy group; R4 is H, a halo, a 1-4C alkyl group, or a 1-4C alkyloxy group or a 1-4C haloalkyl group; Z is -CH2-, -CH2-CH2-, -CH=CH-, -CHOH-CH2-, -O-CH2, -C(=O)-CH2- or -C(= NOH)-CH2-; -A-B- is a divalent group; -A1- is a direct bond, a 1-6C substituted alkanediyl, a 1-6C alkanediyl-oxy-1-6C alkanediyl, a carbonyl, a 1-6C alkanediylcarbonyl, 1-6C (substituted) alkanediyloxy; A2 is a direct bond or a 1-6C alkanediyl; Q is an aryl group].

公开(公告)号：CA2237594C

公开(公告)日：2006-05-30

申请号：CA2237594

申请日：1997-03-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: C07D487/04 ,  A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

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 the dotted line is an optional bond; n is 1 or 2; R1 is hydrogen; halo; formyl; C1-4alkyl optionally substituted with hydroxy, C1-4alkyloxy, C1-4alkylcarbonyloxy, imidazolyl, thiazolyl or oxazolyl; or a radical of formula -X-COOR5, -X-CONR6R7 or -X-COR10 wherein -X- is a direct bond, C1-4alkanediyl or C2-6alkenediyl; R5 is hydrogen, C1-12alkyl, Ar, Het, C1-6alkyl substituted with C1-4alkyloxy, aryl or heteroaryl; R6 and R7 each independently are hydrogen or C1-4alkyl; R2 is hydrogen, halo, C1-4alky l, hydroxyC1-4alkyl, C1-4alkyloxycarbonyl, carboxyl, formyl or phenyl; R3 is hydrogen, C1-4alkyl or C1-4alkyloxy; R4 is hydrogen, halo, C1- 4alkyl, C1-4alkyloxy or haloC1-4alkyl; Z is -CH2-, -CH2-CH2-, CH=CH-, -CHOH-CH2-, -O-CH2-, -C(=O)-CH2- or -C(=NOH)-CH2-; -A-B- is a bivale nt radical; A1 is a direct bond, optionally substituted C1-6alkanediyl, 1-6alkanediyl-oxy-C1-6alkanediyl, carbonyl, C1- 6alkanediylcarbonyl, optionally substituted C1-6alkanediyloxy; A2 is a direc t bond or C1-6alkanediyl; and Q is aryl. Processes for preparing said products , formulations comprising said products and their use as a medicine are disclosed, in particular for inhibiting or reversing the effect s of multidrug resistance.

公开(公告)号：SK284434B6

公开(公告)日：2005-04-01

申请号：SK66298

申请日：1997-03-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

Abstract: The compounds of formula (I) are disclosed, the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein the dotted line is an optional bond; n is 1 or 2. Processes for preparing said products, formulations comprising said products and their use in medicine are disclosed, in particular for inhibiting or reversing the effects of resistance to drug therapy.

公开(公告)号：PT869955E

公开(公告)日：2002-04-29

申请号：PT96944686

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： SURLERAUX DOMINIQUE LOUIS NEST ,  JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  LEENAERTS JOSEPH ELISABETH

IPC: A61K31/00 ,  A61K31/415 ,  A61K31/435 ,  A61K31/4418 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/55 ,  A61P1/00 ,  A61P9/00 ,  A61P11/00 ,  A61P17/00 ,  A61P25/00 ,  A61P25/04 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

Abstract: N-heterocyclic compounds of formula (I), and their N-oxides, salts and isomers, are new. n = 0, 1 or 2; m = 1 or 2, provided that when m is 2, then n is 1; X = a bond, O, S or NR3; Q = O or NR3; R1 = Ar1, Ar1(1-6C alkyl) or di(Ar1)(1-6C alkyl), where the 1-6C alkyl groups are optionally substituted by OH, TO, oxo or a ketalised oxo substituent of formula OCH2CH2O or OCH2CH2CH2O; R2 = Ar2, Ar2(1-6C alkyl), Het or Het(1-6C alkyl); L = a group of formula (i) or (ii); p = 0, 1 or 2; Y, depending on whether the optional second bond is present or not, is (i) a bivalent radical of formula CH2, CH(OH), C(O), O, S, SO, SO2, NR3, CH2NR3 or CONR3, or (ii) a trivalent radical of formula CH; A=B is a bivalent radical of formula CH=CH, N=CH or CH=N; R3 = H or R; R4 = H, R, 3-7C cycloalkyl, Alk-R7 or Alk-Z-R8; Alk = 1-6C alkanediyl; Z = O, S or NR3; R7 = Ph (optionally substituted by 1-2 halo, R or RO); furanyl (optionally substituted by 1-2 R or hydroxy(1-6C alkyl)); thienyl (optionally substituted by 1-2 halo or R); oxazolyl, thiazolyl or pyridinyl (all optionally substituted by 1-2 R); R8 = R (optionally substituted by OH, COOH or COOR); R5 = H, halo, OH or RO; R6 = H, R or Ar1(1-6 alkyl); Ar1 = Ph (optionally substituted by 1-3 halo, T, T', CN, CONH2, TO or T'O); Ar2 = naphthalenyl, or Ph (optionally substituted by 1-3 OH, halo, CN, NO2, NH2, NHT, N(T)2, T, T', TO, T'O, COOH, COOT, CONH2, CONHT or CON(T)2); Het = pyrrolyl, pyrazolyl, imidazolyl, furanyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, quinoxalinyl, indolyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl, benzofuranyl or benzothienyl (all optionally substituted on carbon by 1-2 halo, T or mono-, di- or tri(halo)methyl); T, T', R, = 1-4C alkyl, halo(1-4C alkyl), 1-6C alkyl respectively.

公开(公告)号：NO310659B1

公开(公告)日：2001-08-06

申请号：NO982124

申请日：1998-05-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

Abstract: This invention concerns the compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein the dotted line is an optional bond; n is 1 or 2; R1 is hydrogen; halo; formyl; C1-4alkyl optionally substituted with hydroxy, C1-4alkyloxy, C1-4alkylcarbonyloxy, imidazolyl, thiazolyl or oxazolyl; or a radical of formula -X-COOR5, -X-CONR6R7 or -X-COR10 wherein -X- is a direct bond, C1-4alkanediyl or C2-6alkenediyl; R5 is hydrogen, C1-12alkyl, Ar, Het, C1-6alkyl substituted with C1-4alkyloxy, aryl or heteroaryl; R6 and R7 each independently are hydrogen or C1-4alkyl; R2 is hydrogen, halo, C1-4alkyl, hydroxyC1-4alkyl, C1-4alkyloxycarbonyl, carboxyl, formyl or phenyl; R3 is hydrogen, C1-4alkyl or C1-4alkyloxy; R4 is hydrogen, halo, C1-4alkyl, C1-4alkyloxy or haloC1-4alkyl; Z is -CH2-, -CH2-CH2-, -CH=CH-, -CHOH-CH2-, -O-CH2-, -C(=O)-CH2- or -C(=NOH)-CH2-; -A-B- is a bivalent radical; A1 is a direct bond, optionally substituted C1-6alkanediyl, C1-6alkanediyl-oxy-C1-6alkanediyl, carbonyl, C1-6alkanediylcarbonyl, optionally substituted C1-6alkanediyloxy; A2 is a direct bond or C1-6alkanediyl; and Q is aryl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for inhibiting or reversing the effects of multidrug resistance.

公开(公告)号：AU707037B2

公开(公告)日：1999-07-01

申请号：AU1308497

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST ,  ROOSBROECK YVES EMIEL MARIA VA

IPC: A61K31/00 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/505 ,  A61K31/506 ,  A61P43/00 ,  C07D211/44 ,  C07D211/46 ,  C07D211/52 ,  C07D211/58 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/10 ,  C07D491/10 ,  C07D491/113

Abstract: The present invention concerns compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; =Q is =O or =NR3; X is a covalent bond or a bivalent radical of formula -O-, -S-, -NR3-; R1 is Ar1; Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2-O- or -O-CH2-CH2-CH2-O-; R2 is Ar2; Ar2C1-6alkyl; Het or HetC1-6alkyl; R3 is hydrogen or C1-6alkyl; R4 is hydrogen; C1-4alkyl; C1-4aklyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4aklyloxycarbonyl or Ar3; R5 is hydrogen; hydroxy; Ar3; Ar3C1-6alkyloxy; di(Ar3)C1-6alkyloxy; Ar3C1-6alkylthio; di(Ar3)C1-6alkylthio; Ar3C1-6alkylsulfoxy; di(Ar3)C1-6alkylsulfoxy; Ar3C1-6alkylsulfonyl; di(Ar3)C1-6alkylsulfonyl; -NR7R8; C1-6alkyl substituted with -NR7R8; or a radical of formula (a-1) or (a-2); R4 and R5 may also be taken together; R6 is hydrogen; hydroxy; C1-6alkyloxy; C1-6alkyl or Ar3C1-6alkyl; Ar1, Ar2 and Ar3 are phenyl or

公开(公告)号：CZ9801529A3

公开(公告)日：1999-02-17

申请号：CZ152998

申请日：1997-03-11

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  LEENAERTS JOSEPH ELISABETH ,  SOMMEN FRANEOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: A61K31/00 ,  A61K31/445 ,  A61K31/47 ,  A61K31/4738 ,  A61K31/4745 ,  A61K31/5365 ,  A61K31/55 ,  A61K31/553 ,  A61K45/00 ,  A61P31/00 ,  A61P31/06 ,  A61P33/00 ,  A61P33/02 ,  A61P33/04 ,  A61P33/06 ,  A61P35/00 ,  A61P35/02 ,  A61P43/00 ,  C07D471/04 ,  C07D487/04 ,  C07D487/14 ,  C07D491/147 ,  C07D495/14 ,  C07D498/04 ,  C07D498/14

CPC classification number: C07D487/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/14

公开(公告)号：CZ186498A3

公开(公告)日：1998-12-16

申请号：CZ186498

申请日：1996-12-20

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST ,  VAN ROOSBROECK YVES EMIEL MARI

IPC: A61K31/00 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/505 ,  A61K31/506 ,  A61P43/00 ,  C07D211/44 ,  C07D211/46 ,  C07D211/52 ,  C07D211/58 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/10 ,  C07D491/10 ,  C07D491/113

Abstract: The present invention concerns compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; =Q is =O or =NR3; X is a covalent bond or a bivalent radical of formula -O-, -S-, -NR3-; R1 is Ar1; Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2-O- or -O-CH2-CH2-CH2-O-; R2 is Ar2; Ar2C1-6alkyl; Het or HetC1-6alkyl; R3 is hydrogen or C1-6alkyl; R4 is hydrogen; C1-4alkyl; C1-4aklyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4aklyloxycarbonyl or Ar3; R5 is hydrogen; hydroxy; Ar3; Ar3C1-6alkyloxy; di(Ar3)C1-6alkyloxy; Ar3C1-6alkylthio; di(Ar3)C1-6alkylthio; Ar3C1-6alkylsulfoxy; di(Ar3)C1-6alkylsulfoxy; Ar3C1-6alkylsulfonyl; di(Ar3)C1-6alkylsulfonyl; -NR7R8; C1-6alkyl substituted with -NR7R8; or a radical of formula (a-1) or (a-2); R4 and R5 may also be taken together; R6 is hydrogen; hydroxy; C1-6alkyloxy; C1-6alkyl or Ar3C1-6alkyl; Ar1, Ar2 and Ar3 are phenyl or

公开(公告)号：EA199800404A1

公开(公告)日：1998-10-29

申请号：EA199800404

申请日：1996-10-25

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  ROOSBROECK YVES EMIEL MARIA V ,  SOMMEN FRANCOIS MARIA ,  LEENAERTS JOSEPH ELISABETH ,  SURLERAUX DOMINIQUE LOUIS NEST

IPC: C07D401/04 ,  A61K31/00 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61P1/08 ,  A61P23/00 ,  A61P29/00 ,  A61P37/02 ,  A61P37/08 ,  A61P43/00 ,  C07D211/58 ,  C07D401/12 ,  C07D401/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/14

Abstract: Настоящееизобретениеотноситсяк соединениямформулы (I)их N-оксиднымформам, фармацевтическиприемлемымаддитивнымсолями стереоизомернымформам, где n равно 0, 1 или 2; m равно 1 или 2, приусловии, чтоесли m равно 2, то n равно 1; p равно 1 или 2; =Q представляет =O или =NR; X представляетковалентнуюсвязьилидвухвалентныйрадикалформулы -O-, -S-, -NR-; Rпредставляет Ar, ArCалкилилиди(Ar)Cалкил, гдекаждая Cалкильнаягруппанеобязательнозамещенагидрокси, Cалкилокси, оксоиликетализированнымоксозаместителем, Rпредставляет Ar, ArCалкил, Hetили HetCалкил; Rпредставляетводородили Cалкил; L представляетводород; Ar; Cалкил; Cалкил, замещенный 1 или 2 заместителями, выбраннымиизгидрокси, Cалкилокси, Ar, ArCалкилоксии Het; Cалкенил; ArCалкенил; ди(Ar)Cалкенилилирадикалформулы (а-1), (а-2), (а-3), (а-4) или (а-5); каждыйиз Ar, Arи Arпредставляетфенилилизамещенныйфенил; каждыйиз Hetи Hetпредставляетмоноциклическийилибициклическийгетероцикл; вкачествеантагонистоввещества P; ихполучению, композициям, содержащимих, иихиспользованиюв качествелекарственногосредства.Международнаязаявкабылаопубликованавместес отчетомо международномпоиске.

公开(公告)号：NO982404L

公开(公告)日：1998-08-19

申请号：NO982404

申请日：1998-05-27

Applicant: JANSSEN PHARMACEUTICA NV

Inventor： JANSSENS FRANS EDUARD ,  SOMMEN FRANCOIS MARIA ,  SURLERAUX DOMINIQUE LOUIS NEST ,  ROOSBROECK YVES EMIEL MARIA VA

IPC: A61K31/00 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/445 ,  A61K31/4465 ,  A61K31/4523 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/498 ,  A61K31/505 ,  A61K31/506 ,  A61P43/00 ,  C07D211/44 ,  C07D211/46 ,  C07D211/52 ,  C07D211/58 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/10 ,  C07D491/10 ,  C07D491/113

Abstract: The present invention concerns compounds of formulathe N-oxide forms, the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is 0, 1 or 2; m is 1 or 2, provided that if m is 2, then n is 1; p is 0, 1 or 2; =Q is =O or =NR3; X is a covalent bond or a bivalent radical of formula -O-, -S-, -NR3-; R1 is Ar1; Ar1C1-6alkyl or di(Ar1)C1-6alkyl, wherein each C1-6alkyl group is optionally substituted with hydroxy, C1-4alkyloxy, oxo or a ketalized oxo substituent of formula -O-CH2-CH2-O- or -O-CH2-CH2-CH2-O-; R2 is Ar2; Ar2C1-6alkyl; Het or HetC1-6alkyl; R3 is hydrogen or C1-6alkyl; R4 is hydrogen; C1-4alkyl; C1-4aklyloxyC1-4alkyl; hydroxyC1-4alkyl; carboxyl; C1-4aklyloxycarbonyl or Ar3; R5 is hydrogen; hydroxy; Ar3; Ar3C1-6alkyloxy; di(Ar3)C1-6alkyloxy; Ar3C1-6alkylthio; di(Ar3)C1-6alkylthio; Ar3C1-6alkylsulfoxy; di(Ar3)C1-6alkylsulfoxy; Ar3C1-6alkylsulfonyl; di(Ar3)C1-6alkylsulfonyl; -NR7R8; C1-6alkyl substituted with -NR7R8; or a radical of formula (a-1) or (a-2); R4 and R5 may also be taken together; R6 is hydrogen; hydroxy; C1-6alkyloxy; C1-6alkyl or Ar3C1-6alkyl; Ar1, Ar2 and Ar3 are phenyl or