HRP20140516T1 - Farmaceutski spojevi - Google Patents
Farmaceutski spojevi Download PDFInfo
- Publication number
- HRP20140516T1 HRP20140516T1 HRP20140516AT HRP20140516T HRP20140516T1 HR P20140516 T1 HRP20140516 T1 HR P20140516T1 HR P20140516A T HRP20140516A T HR P20140516AT HR P20140516 T HRP20140516 T HR P20140516T HR P20140516 T1 HRP20140516 T1 HR P20140516T1
- Authority
- HR
- Croatia
- Prior art keywords
- isopropyl
- methyl
- piperazin
- ylmethyl
- group
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims 19
- 229910052739 hydrogen Inorganic materials 0.000 claims 14
- 239000001257 hydrogen Substances 0.000 claims 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 13
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 125000000623 heterocyclic group Chemical group 0.000 claims 9
- 229910052757 nitrogen Inorganic materials 0.000 claims 8
- 229910052717 sulfur Inorganic materials 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 238000011282 treatment Methods 0.000 claims 7
- 201000001441 melanoma Diseases 0.000 claims 6
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 4
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 4
- 150000001204 N-oxides Chemical class 0.000 claims 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims 4
- 208000019691 hematopoietic and lymphoid cell neoplasm Diseases 0.000 claims 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 4
- 125000004043 oxo group Chemical group O=* 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 4
- 239000012453 solvate Substances 0.000 claims 4
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 4
- 206010016935 Follicular thyroid cancer Diseases 0.000 claims 3
- 206010027480 Metastatic malignant melanoma Diseases 0.000 claims 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 208000029824 high grade glioma Diseases 0.000 claims 3
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- 201000011614 malignant glioma Diseases 0.000 claims 3
- 208000021039 metastatic melanoma Diseases 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 3
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims 2
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 2
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims 2
- 206010003571 Astrocytoma Diseases 0.000 claims 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims 2
- 206010048832 Colon adenoma Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims 2
- 208000032612 Glial tumor Diseases 0.000 claims 2
- 206010018338 Glioma Diseases 0.000 claims 2
- 208000017604 Hodgkin disease Diseases 0.000 claims 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 2
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 2
- 208000014767 Myeloproliferative disease Diseases 0.000 claims 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- SZQAMLOTJYQITA-UHFFFAOYSA-N [5-hydroxy-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] n,n-dimethylcarbamate Chemical compound C1=C(OC(=O)N(C)C)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCN(C)CC4)=CC=C3C2)=C1O SZQAMLOTJYQITA-UHFFFAOYSA-N 0.000 claims 2
- 208000009956 adenocarcinoma Diseases 0.000 claims 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims 2
- 229960001467 bortezomib Drugs 0.000 claims 2
- 210000000481 breast Anatomy 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- -1 carboxylic acid tert-butyl ester 5-dimethylcarbamoyloxy-4-isopropyl-2-[5-(4-methyl-piperazin-1-ylmethyl)-1,3-dihydro-isoindole-2-carbonyl]-phenyl ester Chemical class 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 210000003169 central nervous system Anatomy 0.000 claims 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 2
- 210000001072 colon Anatomy 0.000 claims 2
- 201000010897 colon adenocarcinoma Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 210000002615 epidermis Anatomy 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 claims 2
- 208000010749 gastric carcinoma Diseases 0.000 claims 2
- 210000005095 gastrointestinal system Anatomy 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 210000003734 kidney Anatomy 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 210000004185 liver Anatomy 0.000 claims 2
- 210000004072 lung Anatomy 0.000 claims 2
- 230000003211 malignant effect Effects 0.000 claims 2
- 230000001394 metastastic effect Effects 0.000 claims 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims 2
- 208000025113 myeloid leukemia Diseases 0.000 claims 2
- 201000008968 osteosarcoma Diseases 0.000 claims 2
- 210000001672 ovary Anatomy 0.000 claims 2
- 210000000496 pancreas Anatomy 0.000 claims 2
- 210000001428 peripheral nervous system Anatomy 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 210000002307 prostate Anatomy 0.000 claims 2
- 206010038038 rectal cancer Diseases 0.000 claims 2
- 201000001275 rectum cancer Diseases 0.000 claims 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 201000000849 skin cancer Diseases 0.000 claims 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 210000001685 thyroid gland Anatomy 0.000 claims 2
- 210000003932 urinary bladder Anatomy 0.000 claims 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 206010055113 Breast cancer metastatic Diseases 0.000 claims 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims 1
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 claims 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims 1
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 1
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 1
- 206010023347 Keratoacanthoma Diseases 0.000 claims 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 1
- 201000010208 Seminoma Diseases 0.000 claims 1
- FMMCBTKUCXDRLO-UHFFFAOYSA-N [2,4-bis(methoxymethoxy)-5-propan-2-ylphenyl]-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(C(C)C)C(OCOC)=CC(OCOC)=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 FMMCBTKUCXDRLO-UHFFFAOYSA-N 0.000 claims 1
- WJAFKWCVPKKBGZ-UHFFFAOYSA-N [2-hydroxy-4-(methoxymethoxy)-5-propan-2-ylphenyl]-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone Chemical compound C1=C(C(C)C)C(OCOC)=CC(O)=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 WJAFKWCVPKKBGZ-UHFFFAOYSA-N 0.000 claims 1
- DIKNBPCALKQCPW-UHFFFAOYSA-N [4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-yl-5-(pyrrolidine-1-carbonyloxy)phenyl] pyrrolidine-1-carboxylate Chemical compound C1CCCN1C(=O)OC=1C=C(OC(=O)N2CCCC2)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 DIKNBPCALKQCPW-UHFFFAOYSA-N 0.000 claims 1
- ZPZYLJFCZPEYKY-UHFFFAOYSA-N [4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-5-(2-methylpropanoyloxy)-2-propan-2-ylphenyl] 2-methylpropanoate Chemical compound C1=C(C(C)C)C(OC(=O)C(C)C)=CC(OC(=O)C(C)C)=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 ZPZYLJFCZPEYKY-UHFFFAOYSA-N 0.000 claims 1
- DPGWTHWBSQXWLN-UHFFFAOYSA-N [4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-5-(morpholine-4-carbonyloxy)-2-propan-2-ylphenyl] morpholine-4-carboxylate Chemical compound C1COCCN1C(=O)OC=1C=C(OC(=O)N2CCOCC2)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 DPGWTHWBSQXWLN-UHFFFAOYSA-N 0.000 claims 1
- AZTYLHKKDGSPJJ-UHFFFAOYSA-N [4-hydroxy-2-(methoxymethoxy)-5-propan-2-ylphenyl]-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindol-2-yl]methanone Chemical compound COCOC1=CC(O)=C(C(C)C)C=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 AZTYLHKKDGSPJJ-UHFFFAOYSA-N 0.000 claims 1
- LHQYQZUUURBMLU-UHFFFAOYSA-N [5-(2,2-dimethylpropanoyloxy)-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] 2,2-dimethylpropanoate Chemical compound C1=C(OC(=O)C(C)(C)C)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCN(C)CC4)=CC=C3C2)=C1OC(=O)C(C)(C)C LHQYQZUUURBMLU-UHFFFAOYSA-N 0.000 claims 1
- LFNVHOYUFYCRFV-UHFFFAOYSA-N [5-(diethylcarbamoyloxy)-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] n,n-diethylcarbamate Chemical compound C1=C(C(C)C)C(OC(=O)N(CC)CC)=CC(OC(=O)N(CC)CC)=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 LFNVHOYUFYCRFV-UHFFFAOYSA-N 0.000 claims 1
- FRCZIBDEGYRAOE-UHFFFAOYSA-N [5-(dimethylcarbamoyloxy)-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] n,n-dimethylcarbamate Chemical compound C1=C(OC(=O)N(C)C)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCN(C)CC4)=CC=C3C2)=C1OC(=O)N(C)C FRCZIBDEGYRAOE-UHFFFAOYSA-N 0.000 claims 1
- QTRMNIWSMPZZFQ-UHFFFAOYSA-N [5-hydroxy-2-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-4-propan-2-ylphenyl] morpholine-4-carboxylate Chemical compound C1COCCN1C(=O)OC=1C=C(O)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 QTRMNIWSMPZZFQ-UHFFFAOYSA-N 0.000 claims 1
- RGIUMTFGGDIKBF-UHFFFAOYSA-N [5-hydroxy-2-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-4-propan-2-ylphenyl] n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)OC1=CC(O)=C(C(C)C)C=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 RGIUMTFGGDIKBF-UHFFFAOYSA-N 0.000 claims 1
- JORQZLDRJSPOIC-UHFFFAOYSA-N [5-hydroxy-2-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-4-propan-2-ylphenyl] n,n-dimethylcarbamate Chemical compound C1=C(O)C(C(C)C)=CC(C(=O)N2CC3=CC(CN4CCN(C)CC4)=CC=C3C2)=C1OC(=O)N(C)C JORQZLDRJSPOIC-UHFFFAOYSA-N 0.000 claims 1
- WBWBTTYOQVXARG-UHFFFAOYSA-N [5-hydroxy-2-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-4-propan-2-ylphenyl] pyrrolidine-1-carboxylate Chemical compound C1CCCN1C(=O)OC=1C=C(O)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 WBWBTTYOQVXARG-UHFFFAOYSA-N 0.000 claims 1
- MRVIBWKULAOJDC-UHFFFAOYSA-N [5-hydroxy-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] morpholine-4-carboxylate Chemical compound OC=1C=C(OC(=O)N2CCOCC2)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 MRVIBWKULAOJDC-UHFFFAOYSA-N 0.000 claims 1
- XUEUKRNPYQWRER-UHFFFAOYSA-N [5-hydroxy-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] n,n-diethylcarbamate Chemical compound C1=C(C(C)C)C(OC(=O)N(CC)CC)=CC(O)=C1C(=O)N1CC2=CC(CN3CCN(C)CC3)=CC=C2C1 XUEUKRNPYQWRER-UHFFFAOYSA-N 0.000 claims 1
- FTJHBVVSBFSORP-UHFFFAOYSA-N [5-hydroxy-4-[5-[(4-methylpiperazin-1-yl)methyl]-1,3-dihydroisoindole-2-carbonyl]-2-propan-2-ylphenyl] pyrrolidine-1-carboxylate Chemical compound OC=1C=C(OC(=O)N2CCCC2)C(C(C)C)=CC=1C(=O)N(CC1=C2)CC1=CC=C2CN1CCN(C)CC1 FTJHBVVSBFSORP-UHFFFAOYSA-N 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 230000010261 cell growth Effects 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 210000000232 gallbladder Anatomy 0.000 claims 1
- 201000007487 gallbladder carcinoma Diseases 0.000 claims 1
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 claims 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims 1
- 229960002411 imatinib Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 208000007538 neurilemmoma Diseases 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 201000005825 prostate adenocarcinoma Diseases 0.000 claims 1
- 206010039667 schwannoma Diseases 0.000 claims 1
- 208000001608 teratocarcinoma Diseases 0.000 claims 1
- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/155—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (15)
1. Spoj čija je formula (1a):
[image]
ili neka sol, solvat, N-oksid ili tautomer tog spoja;
naznačen time da je ili R1 je R1a a R2 je R2a; ili da R1 je R1b a R2 je R2b; s time da je u svakom slučaju barem jedan od R1 i R2 nešto drugo a ne vodik;
R1a i R2a su isti ili različiti a svaki se bira iz skupine koju čine vodik, C1-4 alkil, C2-4 alkenil i C2-4 alkinil, pri čemu je C1-4 alkil supstituiran sa C1-2 alkoksi;
R1b i R2b su isti ili različiti a biraju se a biraju se iz skupine koju čine vodik, C(O)NR4R5, C(O)R6 i C(O)OR6, gdje je R6 je C1-4 alkil, a R4 i R5 su C1-4 alkil, ili NR4R5 tvori jedan 4-člani do 7-člani zasićeni heterociklički prsten koji opcionalno sadrži jednog drugog člana heteroatomskog prstena odabranog iz skupine koju čine O, N ili S i oksidirani oblici N i S, pri čemu se taj heterociklički prsten opcionalno supstituira s jednom ili dvije skupine C1-4 alkil ili jednom ili dvije okso skupine; a R3 je skupina D:
[image]
pri čemu asterisk označava točku spajanja na izoindolinski prsten, ali isključujući spoj 5-acetoksi-4-izopropil-2-[5-(4-metil-piperazin-1-ilmetill)-1,3-dihidro-izonidol-2-carbonil]-fenil ester octene kiseline.
2. Spoj prema zahtjevu 1 čija je formula (1 b):
[image]
ili neka sol, solvat, N-oksid ili tautomer tog spoja;
naznačen time da je ili R1 je R1a a R2 je R2a; ili da je R1 je R1b a R2 je R2b; s time da je u svakom slučaju barem jedan od R1 i R2 nešto drugo a ne vodik;
R1a i R2a su isti ili različiti a svaki se bira iz skupine koju čine vodik, C1-2 alkil, C2-3 alkenil i C2-3alkinil pri čemu je C1-2 alkil supstituiran s metoksi;
R1b i R2b su isti ili različiti a biraju se iz skupine koju čine vodik, C(O)NR4R5, pri čemu su i R4 i R5 C1-4 alkil; ili NR4R5 tvori jedan 4-člani do 7-člani zasićeni heterociklički prsten koji opcionalno sadrži jednog drugog člana heteroatomskog prstena odabranog iz skupine koju čine O, N ili S i oksidirani oblici N i S, pri čemu se taj heterociklički prsten opcionalno supstituira s jednom ili dvije skupine C1-4 alkil i/ili s jednom ili dvije okso skupine;
ili su R1b i R2b isti ili različiti a biraju se iz skupine koju čine vodik i C(O)R6a, s time da R6a je C2-4 alkil; ili su
R1b i R2b isti ili različiti a biraju se iz skupine koju čine vodik, C(O)R6 pri čemu se R6 bira iz skupine koju čine metil, etil, propil, izopropil, butil, 1-metilpropil, 2-metilpropil i tert-butil; ili je jedan od R1b i R2b C(O)NR4aR5a pri čemu su i R4a i R5a C1-4 alkil, a drugi od R1b i R2b je odabran iz C(O)R6 i C(O)OR6;
a R3 je skupina D:
[image]
pri čemu asterisk označava točku spajanja na izoindolinski prsten.
3. Spoj prema zahtjevu 2 čija je formula (1c):
[image]
ili neka sol, solvat, N-oksid ili tautomer tog spoja;
naznačen time da R1 je R1b a R2 je R2b; s time da je barem jedan od R1 i R2 nešto drugo a ne vodik;
R1b i R2b su isti ili različiti a biraju se iz skupine koju čine vodik i C(O)NR4R5, pri čemu su i R4 i R5 C1-4 alkil; ili NR4R5 tvori jedan 4-člani do 7-člani zasićeni heterociklički prsten koji opcionalno sadrži jednog drugog člana heteroatomskog prstena odabranog iz skupine koju čine O, N ili S i oksidirani oblici N i S, pri čemu se taj heterociklički prsten opcionalno supstituira s jednom ili dvije skupine C1-4 alkil i/ili jednom ili dvije okso skupine; a
R3 je skupina D:
[image]
pri čemu asterisk označava točku spajanja na izoindolinski prsten.
4. Spoj prema zahtjevu 1 naznačen time da R1 je R1a a R2 je R2a te da su i R1a i R2a odabrani iz skupine koju čine vodik, metil, metoksimetil i alil.
5. Spoj prema zahtjevu 1 ili zahtjevu 2 naznačen time da R1 je R1b a R2 je R2b a R1b i R2b su isti ili različiti a odabiru se iz skupine koju čine vodik, C(O)NR4R5, C(O)R6 i C(O)OR6 pri čemu R6 jeC1-4 alkil, dok su i R4 i R5 C1-4 alkil.
6. Spoj prema zahtjevu 1 naznačen time da se R6 odabire iz skupine koju čine metil, etil, propil, izopropil, butil, 1-metilpropil, 2-metilpropil i tert-butil.
7. Spoj prema zahtjevu 6 naznačen time da je R6 C2-4 alkil.
8. Spoj prema zahtjevu 5 naznačen time:
- da su R1b i R2b isti ili različiti a biraju se iz skupine koju čine vodik i C(O)OR6; a
- R6 je tert-butil ili izopropil.
9. Spoj prema zahtjevu 3 ili zahtjevu 5 naznačen time da su R1b i R2b isti ili različiti a svaki je vodik ili skupina C(O)NR4R5, pri čemu NR4R5 tvori jedan 4-člani do 7-člani zasićeni heterociklički prsten koji opcionalno sadrži jednog drugog člana heteroatomskog prstena odabranog iz skupine koju čine O, N ili S i oksidirani oblici N i S, pri čemu se taj heterociklički prsten opcionalno supstituira s jednom ili dvije skupine C1-4 alkil i/ili jednom ili dvije okso skupine.
10. Spoj prema zahtjevu 8 naznačen time da je taj zasićeni heterociklički prsten odabran iz skupine koju čine pirolidin, piperidin, piperazin, 4-metilpiperazin i morfolin.
11. Spoj prema zahtjevu 1 koji se odabire iz skupine koju čine:
(2-aliloksi-4-hidroksi-5-izopropil-fenil)-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
(4-aliloksi-2-hidroksi-5-izopropil-fenil)-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
(2,4-bis-aliloksi-5-izopropil-fenil)-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
[4-hidroksi-5-izopropil-2-(metoksimetiloksi)-fenil]-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
[2-hidroksi-5-izopropil-4-(metoksimetiloksi)-fenil]-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
[5-izopropil-2,4-bis-(metoksimetiloksi)-fenil]-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-il]-metanon;
5-dietilkarbamoiloksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dietil-karbamske kiseline;
5-dimetilkarbamoiloksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihydroisoindole-2-karbonil]-fenil ester dimetil-karbamske kiseline;
2-[2,4-bis-(pirolidin-1-ilkarboniloksi)-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol;
2-[2,4-bis-(morfolin-4-ilkarboniloksi)-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidroizoindol;
5-hidroksi-4-izopropil-2-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dietil-karbamske kiseline;
5-hidroksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dietil-karbamske kiseline;
5-hidroksi-4-izopropil-2-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dimetil-karbamske kiseline;
5-hidroksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dimetil-karbamske kiseline;
2-[2-(pirolidin-1-ilkarboniloksi)-4-hidroksi-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol;
2-[4-(pirolidin-1-ilkarboniloksi)-2-hidroksi-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol;
2-[2-(morfolin-4-ilkarboniloksi)-4-hidroksi-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol;
2-[4-(morfolin-4-ilkarboniloksi)-2-hidroksi-5-izopropil-benzoil]-5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol;
tert-butil ester karbonske kiseline 5-dimetilkarbamoiloksi-4-izopropil-2-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester;
5-tert-butoksikarboniloksi-4-izopropil-2-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester tert-butil ester karbonske kiseline;
2,2-dimetil-propionska kiselina 5-(2,2-dimetil-propioniloksi)-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester;
5-isobutiriloksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester izobutrične kiseline;
te njihove soli, solvati, tautomeri i N-oksidi.
12. 5-hidroksi-2-izopropil-4-[5-(4-metil-piperazin-1-ilmetil)-1,3-dihidro-izoindol-2-karbonil]-fenil ester dimetil-karbamske kiseline.
13. Farmaceutski pripravak koji sadrži neki spoj prema bilo kojem od zahtjeva od 1 do 12 i neki farmaceutski prihvatljiv nosač.
14. Spoj prema bilo kojem od zahtjeva od 1 do 10 ili farmaceutski pripravak u skladu sa zahtjevom 13, za primjenu:
(i) kao inhibitor Hsp90; ili
(ii) u profilaksi ili liječenju nekog bolesnog stanja ili stanja posredovanog od strane Hsp90; ili
(iii) u liječenju neke bolesti ili stanja koje uključuje ili proizlazi iz abnormalnog rasta stanica kod nekog sisavca; ili
(iv) u liječenju karcinoma; ili
(v) u liječenju karcinoma mjehura, dojke, debelog crijeva (npr. kolorektalnih karcinoma kao što su adenokarcinom debelog crijeva i adenom debelog crijeva), bubrega, epiderme, jetre, pluća, na primjer adenokarcinoma, sitnostaničnog karcinoma pluća i ne-sitnostaničnog karcinoma pluća, karcinoma jednjaka, žučne kesice, jajnika, gušterače, npr. egzokrinog karcinoma gušterače, karcinoma želuca, vrata maternice, štitnjače, prostate, gastrointestinalnog sustava, npr. gastrointestinalnih stromalnih tumora, ili karcinoma kože, na primjer karcinoma skvamoznih stanica; hematopoeznog tumora limfoidne loze, na primjer leukemije, akutne limfocitne leukemije, kronične limfocitne leukemije, lilmfoma B-stanica (kao što je difuzni limfom velikih B-stanica), limfoma T-stanica, Hodgkinovog limfoma, ne-Hodgkinovog limfoma, limfoma dlakavih stanica ili Burkittovog limfoma, hematopoeznog tumora mijeolidne loze, uključujući akutnu mijeloidnu leukemiju, kronične mijeolidne leukemije, mijelogene leukemije, mijelodisplastični sindrom, Bortezomib senzitivni i refraktorni multipli mijelom, mijeloproliferativna oboljenja ili promijelocitnu leukemiju; folikularni karcinom štitnjače; tumore mezenhimalnog podrijetla, na primjer fibrosarkom ili rabadomiosarkom; tumora središnjeg ili perifernog živčanog sustava, na primjer astrocitoma, neuroblastoma, glioma (glioma visokog stupnja) ili švanoma; melanoma (npr. zloćudnog ili metastatičnog melanoma); seminoma; teratokarcinoma; osteosarkoma; keratoakantoma; folikularnog karcinoma štitnjače; ili Kaposijevog sarkoma.
Daljnji primjer tumora mezenhimalnog podrijetla je Ewingov sarkom; ili
(vi) u liječenju karcinoma mjehura, dojke, debelog crijeva (npr. kolorektalnih karcinoma kao što su adenokarcinom debelog crijeva i adenom debelog crijeva), bubrega, epiderme, jetre, pluća, na primjer adenokarcinoma, sitnostaničnog karcinoma pluća i ne-sitnostaničnog karcinoma pluća, karcinoma žučne kesice, jajnika, gušterače, npr. egzokrinog karcinoma gušterače, karcinoma želuca, štitnjače, prostate, gastrointestinalnog sustava, npr. gastrointestinalnih stromalnih tumora, ili karcinoma kože, na primjer karcinoma skvamoznih stanica; hematopoeznog tumora limfoidne loze, na primjer leukemije, akutne limfocitne leukemije, kronične limfocitne leukemije, lilmfoma B-stanica (kao što je difuzni limfom velikih B-stanica), limfoma T-stanica, Hodgkinovog limfoma., ne-Hodgkinovog limfoma, limfoma dlakavih stanica ili Burkittovog limfoma; hematopoeznog tumora mijeolidne loze, uključujući mijeloidne leukemije, kronične mijeolidne leukemije, mijelogene leukemije, i Imatinib senzitivne i refraktorne kronične mijelogene leukemije, mijelodisplastični sindrom, Bortezomib senzitivni i refraktorni multipli mijelom, mijeloproliferativna oboljenja ili promijelocitnu leukemiju; folikularni karcinom štitnjače; tumore mezenhimalnog podrijetla, na primjer fibrosarkom ili rabadomiosarkom; tumora središnjeg ili perifernog živčanog sustava, na primjer astrocitoma, glioma (glioma visokog stupnja), melanoma (npr. zloćudnog ili metastatičnog melanoma), osteosarkoma, folikularnog karcinoma štitnjače; Daljnji primjer tumora mezenhimalnog podrijetla je Ewingov sarkom; ili
(vii) u liječenju karcinoma iz skupine metastatičkih karcinoma dojke pozitivnih na HER2; adenokarcinoma prostate; metastatičkog melanoma, ne-sitnostaničnog karcinoma pluća (NSCLC); sitnostaničnog karcinoma pluća (SCLC); glioma visokog stupnja; gastrointestinalnih stromalnih tumora (GIST); kolorektalnog karcinoma; glioblastoma; melanoma, metastatičnog karcinoma štitnjače; karcinoma prostate; i karcinoma rektuma; ili
(viii) u liječenju karcinoma odabranih iz skupine kolorektalnog karcinoma; glioblastoma; melanoma; metastatičnog karcinoma štitnjače, karcinoma prostate i karcinoma rektuma; ili
(ix) u medicini.
15. Primjena spoja definiranog u bilo kojem od zahtjeva od 1 do 12 ili farmaceutskog pripravka prema zahtjevu 13 za proizvodnju medikamenta za bilo koju ili više primjena definiranih u zahtjevu 14.
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-
2008
- 2008-04-11 GB GBGB0806527.8A patent/GB0806527D0/en not_active Ceased
-
2009
- 2009-04-09 SI SI200930943T patent/SI2271618T1/sl unknown
- 2009-04-09 ES ES09731468.6T patent/ES2469797T3/es active Active
- 2009-04-09 PT PT97314686T patent/PT2271618E/pt unknown
- 2009-04-09 PL PL09731468T patent/PL2271618T3/pl unknown
- 2009-04-09 JP JP2011503505A patent/JP5653903B2/ja not_active Expired - Fee Related
- 2009-04-09 EP EP09731468.6A patent/EP2271618B1/en active Active
- 2009-04-09 RS RS20140346A patent/RS53389B/en unknown
- 2009-04-09 WO PCT/GB2009/050358 patent/WO2009125230A1/en active Application Filing
- 2009-04-09 DK DK09731468.6T patent/DK2271618T3/da active
- 2009-04-10 TW TW098112063A patent/TWI453201B/zh not_active IP Right Cessation
-
2010
- 2010-10-12 US US12/902,658 patent/US8383619B2/en not_active Expired - Fee Related
-
2013
- 2013-01-30 US US13/753,904 patent/US8664218B2/en not_active Expired - Fee Related
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2014
- 2014-06-04 HR HRP20140516AT patent/HRP20140516T1/hr unknown
- 2014-07-07 CY CY20141100506T patent/CY1115256T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
PT2271618E (pt) | 2014-07-28 |
ES2469797T3 (es) | 2014-06-20 |
US20110098290A1 (en) | 2011-04-28 |
JP5653903B2 (ja) | 2015-01-14 |
GB0806527D0 (en) | 2008-05-14 |
US8383619B2 (en) | 2013-02-26 |
EP2271618A1 (en) | 2011-01-12 |
WO2009125230A1 (en) | 2009-10-15 |
CY1115256T1 (el) | 2017-01-04 |
TW201002688A (en) | 2010-01-16 |
US8664218B2 (en) | 2014-03-04 |
US20130210820A1 (en) | 2013-08-15 |
EP2271618B1 (en) | 2014-05-21 |
DK2271618T3 (da) | 2014-06-16 |
JP2011516536A (ja) | 2011-05-26 |
RS53389B (en) | 2014-10-31 |
TWI453201B (zh) | 2014-09-21 |
PL2271618T3 (pl) | 2014-09-30 |
SI2271618T1 (sl) | 2014-07-31 |
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