1,5-diphenylpyrazoles ii as hsp90 inhibitors

Abstract

Novel 1,5-diphenylpyrazole derivatives of the formula (I) in which R 1 -R 6 have the meanings indicated in claim 1 , are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.

1 . A compound of the formula I 
       
         
           
           
               
               
           
         
         in which 
         R 1  is OH, OCH 3 , OCF 3 , OCHF 2 , benzyloxy, acetyloxy, p-methoxybenzyloxy, SH, S(O) m CH 3 , SO 2 NH 2 , Hal, CF 3 , or CH 3 , 
         R 2  is CONA[(CH 2 ) o Ar], CONA[(CH 2 ) o Het′], SO 2 NA[(CH 2 ) o Ar′], or SO 2 NA[(CH 2 ) o Het′], 
         R 3  is H, Hal, CN, NO 2 , A, Alk, (CH 2 ) n Ar, (CH 2 ) n Het′, COOH, COOA, COOAr, COOHet′, CONH 2 , CONHA, CONAA′, CONHAr, CONAAr, CON(Ar) 2 , CONHHet′, CON(Het′) 2 , NH 2 , NHA, NHAr, NHHet′, NAA′, NHCOA, NACOA′, NHCOAr, NHCOHet′, NHCOOA, NHCOOAr, NHCOOHet′, NHCONHA, NHCONHAr, NHCONHHet′, OH, OA, OAr, OHet′, SH, S(O) m A, S(O) m Ar, S(O) m Het′, SO 2 NH 2 , SO 2 NHA, SO 2 NAA′, SO 2 NHAr, SO 2 NAAr, SO 2 NHHet′, SO 2 NAHet′, SO 2 NA-benzyl, SO 2 N(Ar) 2 , or SO 2 N(Het′) 2 , 
         R 6  is H, Hal, CN, NO 2 , A, Alk, (CH 2 ) n Ar, (CH 2 ) n Het′, COOH, COOA, COOAr, COOHet′, CONH 2 , CONHA, CONAA′, CONHAr, CONAAr, CON(Ar) 2 , CONHHet′, CON(Het′) 2 , NH 2 , NHA, NHAr, NHHet′, NAA′, NHCOA, NHCONH 2 , NACOA′, NHCO(CH 2 ) n Ar, NHCOHet′, NHCOOA, NHCOOAr, NHCOOHet′, NHCONHA, NHCONHAr, NHCONHHet′, OH, OA, O(CH 2 ) o Het, O(CH 2 ) o NH 2 , O(CH 2 ) o CN, OAr, OHet′, SH, S(O) m A, S(O) m Ar, S(O) m Het′, SO 2 NH 2 , SO 2 NHA, SO 2 NAA′, SO 2 NHAr, SO 2 NAAr, SO 2 NHHet′, SO 2 N(Ar) 2 , or SO 2 N(Het′) 2 , 
         R 4  and R 5  together are —OCH 2 O—, —OCH 2 CH 2 O—, —CH═CH—CH═CH—, —NH—CH═CH—, or —CH═CH—NH—, 
         Y is OH or SH, 
         A, A′ are each, independently of one another, unbranched or branched alkyl having 1-10 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, NR 8 , or —CH═CH—, and/or 1-5 H atoms are each optionally replaced by F, Cl, Br, or R 7 , Alk or cyclic alkyl having 3-7 C atoms, 
         A and A′ together may also be an alkylene chain having 2, 3, 4, 5 or 6 C atoms, in which a CH 2  group is optionally replaced by O, S, SO, SO 2 , NH, NR 8 , NCOR 8 , or NCOOR 8 , 
         Alk is alkenyl having 2-6 C atoms, 
         R 7  is COOR 9 , CONR 9 R 10 , NR 9 R 10 , NHCOR 9 , NHCOOR 9 , or OR 9 , 
         R 7  is CN, CONR 9 R 10 , NR 9 R 10 , NHCOR 9 , NHCOOR 9 , or OR 9 , 
         R 8  is denotes cycloalkyl having 3-7 C atoms, cycloalkylalkylene having 4-10 C atoms, Alk, or unbranched or branched alkyl having 1-6 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , or NH, and/or 1-5 H atoms are each optionally replaced by F or Cl, 
         R 9 , R 10  are each, independently of one another, H or alkyl having 1-5 C atoms, in which 1-3 CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, N(methyl), or N(ethyl), and/or 1-5 H atoms are each optionally replaced by F or Cl, 
         R 9  and R 10  together may also be denote an alkylene chain having 2, 3, 4, 5 or 6 C atoms, in which a CH 2  group is optionally replaced by O, S, SO, SO 2 , NH, NR 8 , NCOR 8 , or NCOOR 8 , 
         Ar is phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , Y, CN, phenyl, OA, OXR 7 , S(O) m A, S(O) m XR 7 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , NR 9 COR 10 , NR 9 CONR 9 R 10 , and/or NR 9 SO 2 R 10 , 
         Ar′ is phenyl which is mono-, di- or trisubstituted by XR 7′ , 
         Het is a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , Y, CN, Ar, OA, OXR 7 , S(O) m A, S(O) m XR 7 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , to NR 9 COR 10 , NR 9 CONR 9 R NR 10 , SO 2 R 10 , ═S, ═NR 11 , ═NR 11 R 7 , and/or ═O (carbonyl oxygen), 
         Het′ is a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , XR 4 , Y, CN, Ar, Het, OA, OXR 7 , OXR 4 , S(O) m A, S(O) m XR 7 , S(O) m XR 4 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , NR 9 COR 10 , NR 9 CONR 9 R 10 , NR 9 SO 2 R 10 , ═S, ═NR 11 , ═NR 11 R 7 , and/or ═O (carbonyl oxygen), and/or in which a ring nitrogen is optionally may be substituted by —O − , 
         X is unbranched or branched alkylene having 1-10 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, NR 8 , or and/or by —CH═CH—, and/or 1-5 H atoms are each optionally replaced by F, Cl, Br and/or R 7 , 
         R 11  is H or A, 
         Hal is F, Cl, Br or I, 
         m is 0, 1 or 2, 
         n is 0, 1, 2, 3 or 4, and 
         o is 1, 2 or 3; or 
         a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios. 
       
     
     
         2 . A compound according to  claim 1 , wherein
 R 1  is OH or OCH 3 , or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         3 . A compound according to  claim 1 , wherein
 R 3  is H, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         4 . A compound according to  claim 1 , wherein
 R 2  is CONA[(CH 2 ) o Ar], CONA[(CH 2 ) o Het′], SO 2 NA[(CH 2 ) o Ar′] or SO 2 NA[(CH 2 ) o Het′], and   A is alkyl having 1, 2, 3 or 4 C atoms, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         5 . A compound according to  claim 1 , wherein
 R 2  is CON(CH 3 )CH 2 Ar, CON(CH 3 )CH 2 Het′, SO 2 N(CH 3 )CH 2 Ar′ or SO 2 N(CH 3 )CH 2 Het′, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         6 . A compound according to  claim 1 , wherein
 R 6  is H, Hal, CN, A, O(CH 2 ) o Het′, O(CH 2 ) o CN, (CH 2 ) o NH 2 , (CH 2 ) o NHA or (CH 2 ) o NAA′, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         7 . (canceled) 
     
     
         8 . A compound according to  claim 1 , wherein
 X is alkylene having 1-6 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, or NH, or and/or 1-5 H atoms are each optionally replaced by F or Cl, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         9 . A compound according to  claim 1 , wherein
 X is alkylene having 1, 2, 3 or 4 C atoms, in which a CH 2  group is optionally replaced by O or NH, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         10 . A compound according to  claim 1 , wherein
 Ar is phenyl which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , phenyl, S(O) m A, OA, OXR 7  and/or CONR 9 R 10 , or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         11 . A compound according to  claim 1 , wherein
 Ar′ is phenyl which is monosubstituted by XR 7′ , or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         12 . A compound according to  claim 1 , wherein
 R 7′  is CN, CONR 9 R 10 , NR 9 R 10 , or OR 9 , or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         13 . A compound according to  claim 1 , wherein
 Het′ is a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 3 N, O and/or S atoms, which is may be unsubstituted or mono-, di- or trisubstituted by A, Hal, OH, and/or OA, and/or a ring nitrogen is optionally substituted by —O − , or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         14 . A compound according to  claim 1 , wherein
 Het′ is pyridyl, N-oxypyridyl, furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl, pyrazolyl, thiazolyl, pyrazinyl, pyridazinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, benzodioxanyl, benzodioxolyl, indolyl, quinolinyl, benzimidazolyl, benzothiadiazolyl or indazolyl, each of which is unsubstituted or mono-, di- or trisubstituted by A, Hal, OH, and/or OA, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         15 . A compound according to  claim 1 , wherein
 A is Alk, cyclic alkyl having 3-7 C atoms, or unbranched or branched alkyl having 1-6 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, or —CH═CH—, and/or 1-5 H atoms are each optionally replaced by F, Cl or Br or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         16 . A compound according to  claim 1 , wherein
 R 9 , R 10  are each, independently of one another, H or alkyl having 1-5 C atoms, in which 1-5 H atoms are each optionally replaced by F or Cl, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         17 . A compound according to  claim 1 , wherein
 A is unbranched or branched alkyl having 1-6 C atoms, in which 1-5 H atoms are each optionally replaced by F, Cl and/or Br, or is cyclic alkyl having 3-7 C atoms, or   a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios.   
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . A process for the preparation of compounds according to  claim 1 , said process comprising:
 a) reacting a compound of formula II   
       
         
           
           
               
               
           
         
         wherein X is denotes H or methyl, 
         with a compound of formula III 
       
       
         
           
           
               
               
           
         
         and, if in the resultant compound X is methyl, the resultant compound is optionally subsequently, converted by ether cleavage into another compound according to  claim 1  in which X is H; 
         and/or optionally converting one or more radical(s) R 1 , R 2 , R 3 , R 4  and/or R 5  in a compound according to  claim 1  into one or more radical(s) R 1 , R 2 , R 3 , R 4  and/or R 5  by 
         i) reducing a nitro group to an amino group, 
         ii) hydrolyzing an ester group to a carboxyl group, 
         iii) converting an amino group into an alkylated amine by reductive amination, 
         iv) converting a carboxyl group into a sulfonamidocarbonyl group, or 
         v) converting an acid chloride into an amide; 
         and/or a base or acid compound according to  claim 1  is converted into one of its salts. 
       
     
     
         23 . A pharmaceutical composition comprising at least one compound according to  claim 1  and at least one solid, liquid and/or semi-liquid excipient or adjuvant. 
     
     
         24 . A method for the treatment of a patient suffering from a disease in which the inhibition, regulation and/or modulation of HSP90 plays a role, or for promoting nerve regeneration in a patient, for inhibiting the growth of cancer, tumour cells and tumour metastases in a patient, for the protection of normal cells against toxicity caused by chemotherapy in a patient, or for the treatment of a patient suffering from a disease in which incorrect protein folding or aggregation is a principal causal factor, said method comprising administering to said patient an effective amount of a compound according to  claims 1 . 
     
     
         25 . A method according to  claim 24  wherein said disease is tumour disease, viral disease, immune suppression in transplants, inflammation-induced disease, cystic fibrosis, disease associated with angiogenesis, infectious disease, autoimmune disease, ischaemia, fibrogenetic disease, or said method is for the promotion of nerve regeneration, for inhibiting the growth of cancer, tumour cells and tumour metastases, for the protection of normal cells against toxicity caused by chemotherapy, or said method is for the treatment of a disease in which incorrect protein folding or aggregation is a principal causal factor. 
     
     
         26 . A method according to  claim 25 , where the tumour disease is selected from: fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumour, leiosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, syringocarcinoma, sebaceous cell carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinomas, bone marrow carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma, seminoma, embryonic carcinoma, Wilm's tumour, cervical cancer, testicular tumour, lung carcinoma, small-cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, haemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma, leukaemia, lymphoma, multiple myeloma, Waldenström's macroglobulinaemia, and heavy-chain disease. 
     
     
         27 . A method according to  claim 25 , where the viral pathogen of the viral disease is selected from hepatitis type A, hepatitis type B, hepatitis type C, influenza, varicella, adenovirus, herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), cattle plague, rhinovirus, echovirus, rotavirus, respiratory syncytial virus (RSV), papillomavirus, papovavirus, cytomegalovirus, equinovirus, arbovirus, huntavirus, Coxsackie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus type I (HIV-I), and human immunodeficiency virus type II (HIV-II). 
     
     
         28 . A method according to  claim 25 , where the inflammation-induced disease is selected from: rheumatoid arthritis, asthma, multiple sclerosis, type 1 diabetes, lupus erythematosus, psoriasis, and inflammatory bowel disease. 
     
     
         29 . A method according to  claim 25 , where the disease associated with angiogenesis is selected from diabetic retinopathy, haemangiomas, endometriosis, and tumour angiogenesis. 
     
     
         30 . A method according to  claim 25 , where the fibrogenetic disease is selected from dermatosclerosis, polymyositis, systemic lupus, cirrhosis of the liver, keloid formation, interstitial nephritis, and pulmonary fibrosis. 
     
     
         31 . A method according to  claim 25 , where the disease in which incorrect protein folding or aggregation is a principal causal factor is selected from scrapie, Creutzfeldt-Jakob disease, Huntington's disease, and Alzheimer's disease. 
     
     
         32 . A pharmaceutical composition according to  claim 23 , further comprising at least one further medicament active compound. 
     
     
         33 . A set or kit comprising: separate packs of
 (a) an effective amount of a compound according to  claim 1  and/or a pharmaceutically usable derivative, solvate, or stereoisomer thereof, including mixtures thereof in all ratios,   and   (b) an effective amount of a further medicament active compound.   
     
     
         34 . A compound according to  claim 1 , wherein R 4  and R 5  together are OCH 2 O. 
     
     
         35 . A compound according to  claim 1 , wherein R 4  and R 5  together are —OCH 2 CH 2 O—. 
     
     
         36 . A compound according to  claim 1 , wherein R 4  and R 5  together are —CH═CH—CH═CH—. 
     
     
         37 . A compound according to  claim 1 , wherein R 4  and R 5  together are —NH—CH═CH—. 
     
     
         38 . A compound according to  claim 1 , wherein R 4  and R 5  together are —CH═CH—NH—. 
     
     
         39 . A compound selected from:
 5-{5-[N-(Benzodioxol-5-yl)-N-methylaminocarbonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-[5-(N-Benzyl-N-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-{4-[2-(piperazin-4-yl)-ethoxy]phenyl}-1H-pyrazole;   5-[5-(N-Benzyl-N-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-methylphenyl)-1H-pyrazole;   5-[5-(N-Benzyl-N-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(2-Methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(2-Methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(2-Methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(2-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(2-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(2-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(4-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(4-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(4-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(3-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(3-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(3-Fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(3-Methylbenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(3-Methylbenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(3-Methylbenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(4-Methylbenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(4-Methylbenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(4-Methylbenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(3-Chlorobenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(3-Chlorobenzyl)-N-methylamino sulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(3-Chlorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(2-Chlorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(2-Chlorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(2-Chlorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(2-Chloro-6-fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(2-Chloro-6-fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(2-Chloro-6-fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(3-Chloro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(3-Chloro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(3-Chloro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(3-Fluoro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(3-Fluoro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(3-Fluoro-6-methoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(2,3-Dimethoxybenzyl)-N-methyl aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylphenyl)-1H-pyrazole;   5-{5-[N-(2,3-Dimethoxybenzyl)-N-methyl aminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-chlorophenyl)-1H-pyrazole;   5-{5-[N-(2,3-Dimethoxybenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-fluorophenyl)-1H-pyrazole;   5-{5-[N-(4-fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(2-methylaminomethylphenyl)-1H-pyrazole;   5-{5-[N-(4-fluorobenzyl)-N-methylaminosulfonyl]-2,4-dihydroxyphenyl}-1-(3-aminomethylphenyl)-1H-pyrazole;   5-[5-(N-Benzyl-N-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-cyanophenyl)-1H-pyrazole; and   5-[5-(N-Benzyl-N-methylaminosulfonyl)-2,4-dihydroxyphenyl]-1-(2-ethylphenyl)-1H-pyrazole;   
       and pharmaceutically usable salts and stereoisomers thereof. 
     
     
         40 . A pharmaceutical composition comprising at least one compound according to  claim 39  and at least one solid, liquid and/or semi-liquid excipient or adjuvant. 
     
     
         41 . A method of for the treatment of a patient suffering from a disease in which the inhibition, regulation and/or modulation of HSP90 plays a role, or for promoting nerve regeneration in a patient, for inhibiting the growth of cancer, tumour cells and tumour metastases in a patient, for the protection of normal cells against toxicity caused by chemotherapy in a patient, or for the treatment of a patient suffering from a disease in which incorrect protein folding or aggregation is a principal causal factor, said method comprising administering to said patient an effective amount of a compound according to  claim 39 . 
     
     
         42 . A method according to  claim 41 , wherein said disease is tumour disease, viral disease, immune suppression in transplants, inflammation-induced disease, cystic fibrosis, disease associated with angiogenesis, infectious disease, autoimmune disease, ischaemia, fibrogenetic disease, or said method is for the promotion of nerve regeneration, for inhibiting the growth of cancer, tumour cells and tumour metastases, for the protection of normal cells against toxicity caused by chemotherapy, or for the treatment of a disease in which incorrect protein folding or aggregation is a principal causal factor. 
     
     
         43 . A compound of the formula I 
       
         
           
           
               
               
           
         
         in which 
         R 1  is OH, OCH 3 , OCF 3 , OCHF 2 , benzyloxy, acetyloxy, p-methoxybenzyloxy, SH, S(O) m CH 3 , SO 2 NH 2 , Hal, CF 3 , or CH 3 , 
         R 2  is CONA[(CH 2 ) o Ar], CONA[(CH 2 ) o Het′], SO 2 NA[(CH 2 ) o Ar′], or SO 2 NA[(CH 2 ) o Het′], 
         R 3  is H, Hal, CN, NO 2 , A, Alk, (CH 2 ) n Ar, (CH 2 ) n Het′, COOH, COOA, COOAr, COOHet′, CONH 2 , CONHA, CONAA′, CONHAr, CONAAr, CON(Ar) 2 , CONHHet′, CON(Het′) 2 , NH 2 , NHA, NHAr, NHHet′, NAA′, NHCOA, NACOA′, NHCOAr, NHCOHet′, NHCOOA, NHCOOAr, NHCOOHet′, NHCONHA, NHCONHAr, NHCONHHet′, OH, OA, OAr, Met′, SH, S(O) m A, S(O) m Ar, S(O) m Het′, SO 2 NH 2 , SO 2 NHA, SO 2 NAA′, SO 2 NHAr, SO 2 NAAr, SO 2 NHHet′, SO 2 NAHet′, SO 2 NA-benzyl, SO 2 N(Ar) 2 , or SO 2 N(Het′) 2 , 
         R 6  is each, independently of one another, H, Hal, CN, NO 2 , A, Alk, (CH 2 ) n Ar, (CH 2 ) n Het′, COOH, COOA, COOAr, COOHet′, CONH 2 , CONHA, CONAA′, CONHAr, CONAAr, CON(Ar) 2 , CONHHet′, CON(Het′) 2 , NH 2 , NHA, NHAr, NHHet′, NAA′, NHCOA, NHCONH 2 , NACOA′, NHCO(CH 2 ) n Ar, NHCOHet′, NHCOOA, NHCOOAr, NHCOOHet′, NHCONHA, NHCONHAr, NHCONHHet′, OH, OA, O(CH 2 ) o Het, O(CH 2 ) o NH 2 , O(CH 2 ) o CN, OAr, Met′, SH, S(O) m A, S(O) m Ar, S(O) m Het′, SO 2 NH 2 , SO 2 NHA, SO 2 NAA′, SO 2 NHAr, SO 2 NAAr, SO 2 NHHet′, SO 2 N(Ar) 2 , or SO 2 N(Het′) 2 , 
         R 4  and R 5  together are OCH 2 O, OCH 2 CH 2 O, —CH═CH—CH═CH—, NH—CH═CH, or CH═CH—NH, 
         Y is OH or SH, 
         A, A′ are each, independently of one another, unbranched or branched alkyl having 1-10 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, NR 8 , or —CH═CH—, and/or 1-5 H atoms are each optionally replaced by F, Cl, Br, or R 7 , Alk or cyclic alkyl having 3-7 C atoms, 
         A and A′ together may also be an alkylene chain having 2, 3, 4, 5 or 6 C atoms, in which a CH 2  group is optionally replaced by O, S, SO, SO 2 , NH, NR 8 , NCOR 8 , or NCOOR 8 , 
         Alk is alkenyl having 2-6 C atoms, 
         R 7  is COOR 9 , CONR 9 R 10 , NR 9 R 10 , NHCOR 9 , NHCOOR 9 , or OR 9 , 
         R 7′  is CN, CONR 9 R 10 , NR 9 R 10 , NHCOR 9 , NHCOOR 9 , or OR 9 , 
         R 8  is cycloalkyl having 3-7 C atoms, cycloalkylalkylene having 4-10 C atoms, Alk, or unbranched or branched alkyl having 1-6 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , or NH, and/or 1-5H atoms are each optionally replaced by F or Cl, 
         R 9 , R 10  are each, independently of one another, H or alkyl having 1-5 C atoms, in which 1-3 CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, N(methyl), or N(ethyl), and/or 1-5 H atoms are each optionally replaced by F or Cl, 
         R 9  and R 10  together may also be an alkylene chain having 2, 3, 4, 5 or 6 C atoms, in which a CH 2  group is optionally replaced by O, S, SO, SO 2 , NH, NR 8 , NCOR 8 , or NCOOR 8 , 
         Ar is phenyl, naphthyl or biphenyl, each of which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , Y, CN, phenyl, OA, OXR 7 , S(O) m A, S(O) m XR 7 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , NR 9 COR 10 , NR 9 CONR 9 R 10 , and/or NR 9 SO 2 R 10 , 
         Ar′ is phenyl which is mono-, di- or trisubstituted by XR 7′ , 
         Het is a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , Y, CN, Ar, OA, OXR 7 , S(O) m A, S(O) m XR 7 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , NR 9 COR 10 , NR 9 CONR 9 R 10 , NR 9 SO 2 R 10 , ═S, ═NR 11 , ═NR 11 R 7 , and/or ═O (carbonyl oxygen), 
         Het′ is a mono- or bicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N, O and/or S atoms, which is unsubstituted or mono-, di- or trisubstituted by Hal, A, XR 7 , XR 4 , Y, CN, Ar, Het, OA, OXR 7 , OXR 4 , S(O) m A, S(O) m XR 7 , S(O) m XR 4 , NO 2 , NH 2 , NR 9 R 10 , NR 8 R 9 , CONR 9 R 10 , CONR 8 R 9 , SO 2 NR 9 R 10 , SO 2 NR 8 R 9 , NR 9 COR 10 , NR 9 CONR 9 R 10 , NR 9 SO 2 R 10 , ═S, ═NR 11 , ═NR 11 R 7 , and/or ═O (carbonyl oxygen), and/or a ring nitrogen is optionally substituted by —O − , 
         X is unbranched or branched alkylene having 1-10 C atoms, in which one, two or three CH 2  groups are each optionally replaced by O, S, SO, SO 2 , NH, NR 8 , or and/or by —CH═CH—, and/or 1-5H atoms are each optionally replaced by F, Cl, Br and/or R 7 , 
         R 11  is H or A, 
         Hal is F, Cl, Br or I, 
         m is 0, 1 or 2, 
         n is 0, 1, 2, 3 or 4, and 
         o is 1, 2 or 3; or 
         a pharmaceutically usable derivative, salt, solvate, or stereoisomer thereof, including mixtures thereof in all ratios. 
       
     
     
         44 . A pharmaceutical composition comprising at least one compound according to  claim 43  and at least one solid, liquid and/or semi-liquid excipient or adjuvant. 
     
     
         45 . A method of for the treatment of a patient suffering from a disease in which the inhibition, regulation and/or modulation of HSP90 plays a role, or for promoting nerve regeneration in a patient, for inhibiting the growth of cancer, tumour cells and tumour metastases in a patient, for the protection of normal cells against toxicity caused by chemotherapy in a patient, or for the treatment of a patient suffering from a disease in which incorrect protein folding or aggregation is a principal causal factor, said method comprising administering to said patient an effective amount of a compound according to  claim 43 . 
     
     
         46 . A method according to  claim 45 , wherein said disease is tumour disease, viral disease, immune suppression in transplants, inflammation-induced disease, cystic fibrosis, disease associated with angiogenesis, infectious disease, autoimmune disease, ischaemia, fibrogenetic disease, or said method is for the promotion of nerve regeneration, for inhibiting the growth of cancer, tumour cells and tumour metastases, for the protection of normal cells against toxicity caused by chemotherapy, or for the treatment of a disease in which incorrect protein folding or aggregation is a principal causal factor.