JP2011509307A5 - - Google Patents
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- Publication number
- JP2011509307A5 JP2011509307A5 JP2010542374A JP2010542374A JP2011509307A5 JP 2011509307 A5 JP2011509307 A5 JP 2011509307A5 JP 2010542374 A JP2010542374 A JP 2010542374A JP 2010542374 A JP2010542374 A JP 2010542374A JP 2011509307 A5 JP2011509307 A5 JP 2011509307A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- indoline
- cyclopenta
- dihydro
- pyrimidin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims description 116
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 206010028980 Neoplasm Diseases 0.000 claims description 23
- 201000011510 cancer Diseases 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- -1 cycloal Kill Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
- 238000010276 construction Methods 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 12
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 8
- 108091008611 Protein Kinase B Proteins 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 claims description 4
- 101100162366 Caenorhabditis elegans akt-2 gene Proteins 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims description 4
- 108091000080 Phosphotransferase Proteins 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 208000019423 liver disease Diseases 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 102000020233 phosphotransferase Human genes 0.000 claims description 4
- 230000002062 proliferating effect Effects 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 4
- 239000003981 vehicle Substances 0.000 claims description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 3
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 208000033065 inborn errors of immunity Diseases 0.000 claims description 3
- 239000002207 metabolite Substances 0.000 claims description 3
- 208000028529 primary immunodeficiency disease Diseases 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- CIYQEURPTVHUDC-IUUIHGGBSA-N (2'r,3s)-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-2'-phenylspiro[2h-indole-3,3'-pyrrolidine] Chemical compound C1([C@H]2NCC[C@]22CN(C3=CC=C(Cl)C=C32)C=2N=CN=C3CC[C@H](C=23)C)=CC=CC=C1 CIYQEURPTVHUDC-IUUIHGGBSA-N 0.000 claims description 2
- CIYQEURPTVHUDC-PWBHZWRTSA-N (2's,3s)-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-2'-phenylspiro[2h-indole-3,3'-pyrrolidine] Chemical compound C1([C@@H]2NCC[C@]22CN(C3=CC=C(Cl)C=C32)C=2N=CN=C3CC[C@H](C=23)C)=CC=CC=C1 CIYQEURPTVHUDC-PWBHZWRTSA-N 0.000 claims description 2
- BTFAVOGGBKYWBK-WXTAPIANSA-N (3r)-1'-benzyl-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@]1(CN(C2=CC=C(Cl)C=C21)C=1N=CN=C2CC[C@H](C=12)C)C1)CN1CC1=CC=CC=C1 BTFAVOGGBKYWBK-WXTAPIANSA-N 0.000 claims description 2
- JVOVSFLQQWIRFB-KECVGCMWSA-N (3r)-3-(4-chlorophenyl)-3-[(3r)-5-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-piperidine]-1'-yl]propan-1-amine Chemical compound C1([C@@H](CCN)N2CCC[C@]3(CN(C4=CC=C(F)C=C43)C=3N=CN=C4CC[C@H](C=34)C)C2)=CC=C(Cl)C=C1 JVOVSFLQQWIRFB-KECVGCMWSA-N 0.000 claims description 2
- JGEDZLJLAJGANY-ZUOKHONESA-N (3r)-5-chloro-1'-methyl-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)C[C@@]21CCN(C)C2 JGEDZLJLAJGANY-ZUOKHONESA-N 0.000 claims description 2
- RHCCOTJQMGRAFO-CWTRNNRKSA-N (3r)-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)C[C@@]21CCNC2 RHCCOTJQMGRAFO-CWTRNNRKSA-N 0.000 claims description 2
- KDSDVNYISAQTNU-ZUOKHONESA-N (3r)-5-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(F)C=C11)C[C@@]21CCCNC2 KDSDVNYISAQTNU-ZUOKHONESA-N 0.000 claims description 2
- BTFAVOGGBKYWBK-DWXRJYCRSA-N (3s)-1'-benzyl-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@@]1(CN(C2=CC=C(Cl)C=C21)C=1N=CN=C2CC[C@H](C=12)C)C1)CN1CC1=CC=CC=C1 BTFAVOGGBKYWBK-DWXRJYCRSA-N 0.000 claims description 2
- JVOVSFLQQWIRFB-RXIOXGHVSA-N (3s)-3-(4-chlorophenyl)-3-[(3r)-5-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-piperidine]-1'-yl]propan-1-amine Chemical compound C1([C@H](CCN)N2CCC[C@]3(CN(C4=CC=C(F)C=C43)C=3N=CN=C4CC[C@H](C=34)C)C2)=CC=C(Cl)C=C1 JVOVSFLQQWIRFB-RXIOXGHVSA-N 0.000 claims description 2
- JGEDZLJLAJGANY-XCLFUZPHSA-N (3s)-5-chloro-1'-methyl-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)C[C@]21CCN(C)C2 JGEDZLJLAJGANY-XCLFUZPHSA-N 0.000 claims description 2
- RHCCOTJQMGRAFO-BLVKFPJESA-N (3s)-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)C[C@]21CCNC2 RHCCOTJQMGRAFO-BLVKFPJESA-N 0.000 claims description 2
- KDSDVNYISAQTNU-XCLFUZPHSA-N (3s)-5-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(F)C=C11)C[C@]21CCCNC2 KDSDVNYISAQTNU-XCLFUZPHSA-N 0.000 claims description 2
- CMZQQNKPDGPZPW-BLXRZLIXSA-N (5r,7r)-4-(2'-benzyl-5-chlorospiro[2h-indole-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC1(C1)CCNC1CC1=CC=CC=C1 CMZQQNKPDGPZPW-BLXRZLIXSA-N 0.000 claims description 2
- QQLSXKBZWCKNBE-MDNDKPPQSA-N (5r,7r)-4-(5-chlorospiro[2h-indole-3,3'-pyrrolidine]-1-yl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC21CCNC2 QQLSXKBZWCKNBE-MDNDKPPQSA-N 0.000 claims description 2
- OXHNGOKZNXXJAW-MLGOLLRUSA-N (5r,7r)-4-(5-chlorospiro[2h-indole-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC21CCNCC2 OXHNGOKZNXXJAW-MLGOLLRUSA-N 0.000 claims description 2
- AOSUARAORKVTKK-MLGOLLRUSA-N (5r,7r)-4-[4-(aminomethyl)-5-chlorospiro[2h-indole-3,4'-piperidine]-1-yl]-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=C2C(=C(Cl)C=C1)CN)CC12CCNCC1 AOSUARAORKVTKK-MLGOLLRUSA-N 0.000 claims description 2
- GFAZWQDLFJTDIV-FOIQADDNSA-N (5r,7r)-4-[5-chloro-1'-(cyclopropylmethyl)spiro[2h-indole-3,4'-piperidine]-1-yl]-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC1(CC1)CCN1CC1CC1 GFAZWQDLFJTDIV-FOIQADDNSA-N 0.000 claims description 2
- RSKLVGHFKJHZTP-WZONZLPQSA-N (5r,7r)-5-methyl-4-(5-phenylmethoxyspiro[2h-indole-3,4'-piperidine]-1-yl)-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(OCC=2C=CC=CC=2)C=C11)CC21CCNCC2 RSKLVGHFKJHZTP-WZONZLPQSA-N 0.000 claims description 2
- UGWOANGMUQTAGK-WAWZGNHOSA-N (5r,7r)-5-methyl-4-[(3r)-4-methylspiro[2h-indole-3,3'-pyrrolidine]-1-yl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=C2C(=CC=C1)C)C[C@@]12CCNC1 UGWOANGMUQTAGK-WAWZGNHOSA-N 0.000 claims description 2
- VFKHNGZYFPVEPS-VQIMIIECSA-N (5r,7r)-5-methyl-4-[4-[(propan-2-ylamino)methyl]spiro[2h-indole-3,4'-piperidine]-1-yl]-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C)C[C@@H](O)C=3N=CN=2)CC21CCNCC2 VFKHNGZYFPVEPS-VQIMIIECSA-N 0.000 claims description 2
- OXHNGOKZNXXJAW-WBMJQRKESA-N (5r,7s)-4-(5-chlorospiro[2h-indole-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1([C@@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC21CCNCC2 OXHNGOKZNXXJAW-WBMJQRKESA-N 0.000 claims description 2
- MQTJECMKSKGEPV-SJLPKXTDSA-N 1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-4-[(2r)-pyrrolidin-2-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)[C@@H]1NCCC1)CC12CCNCC1 MQTJECMKSKGEPV-SJLPKXTDSA-N 0.000 claims description 2
- YKHIXJAQBQDQMP-LJQANCHMSA-N 1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-5-phenylmethoxyspiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(OCC=2C=CC=CC=2)C=C11)CC21CCNCC2 YKHIXJAQBQDQMP-LJQANCHMSA-N 0.000 claims description 2
- PXDBDBMRDICFHQ-CQSZACIVSA-N 1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-carbonitrile Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)C#N)CC12CCNCC1 PXDBDBMRDICFHQ-CQSZACIVSA-N 0.000 claims description 2
- NTJVBDOLKOACBN-CQSZACIVSA-N 1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-carbonitrile Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(C=C11)C#N)CC21CCNCC2 NTJVBDOLKOACBN-CQSZACIVSA-N 0.000 claims description 2
- PXJBTOPLGPEHTL-CYBMUJFWSA-N 1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-ol Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(O)C=C11)CC21CCNCC2 PXJBTOPLGPEHTL-CYBMUJFWSA-N 0.000 claims description 2
- IARDDBRJMFTTJL-GICMACPYSA-N 1-[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]ethanol Chemical compound C1=2C(C(O)C)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 IARDDBRJMFTTJL-GICMACPYSA-N 0.000 claims description 2
- MHLOMDLOXYFQHJ-QGZVFWFLSA-N 1-cyclopropyl-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]methanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCC1CC1)CC12CCNCC1 MHLOMDLOXYFQHJ-QGZVFWFLSA-N 0.000 claims description 2
- XDTVZZIBANFIOP-OAHLLOKOSA-N 2,2-difluoro-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]ethanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCC(F)F)CC12CCNCC1 XDTVZZIBANFIOP-OAHLLOKOSA-N 0.000 claims description 2
- SEKSMQYBQXKQQP-OAHLLOKOSA-N 2-[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-yl]ethanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(CCN)C=C11)CC21CCNCC2 SEKSMQYBQXKQQP-OAHLLOKOSA-N 0.000 claims description 2
- FUKCEEQQOQIZRB-OAHLLOKOSA-N 2-[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-yl]ethanol Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(CCO)C=C11)CC21CCNCC2 FUKCEEQQOQIZRB-OAHLLOKOSA-N 0.000 claims description 2
- SGBGODIIJXSBEZ-OEPVSBQMSA-N 2-[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-yl]oxy-2-phenylethanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(OC(CN)C=2C=CC=CC=2)C=C11)CC21CCNCC2 SGBGODIIJXSBEZ-OEPVSBQMSA-N 0.000 claims description 2
- SGZIYIQDZQOFIY-OAHLLOKOSA-N 2-[5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-1'-yl]ethanol Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC21CCN(CCO)CC2 SGZIYIQDZQOFIY-OAHLLOKOSA-N 0.000 claims description 2
- OEWUGMFOQVTQBH-MRXNPFEDSA-N 2-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methylamino]ethanol Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCCO)CC12CCNCC1 OEWUGMFOQVTQBH-MRXNPFEDSA-N 0.000 claims description 2
- MRMAXCFZNDKFSJ-MRXNPFEDSA-N 2-fluoro-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]ethanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCCF)CC12CCNCC1 MRMAXCFZNDKFSJ-MRXNPFEDSA-N 0.000 claims description 2
- XNOVMEKYXLWMOA-QGZVFWFLSA-N 2-methoxy-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]ethanamine Chemical compound C1=2C(CNCCOC)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 XNOVMEKYXLWMOA-QGZVFWFLSA-N 0.000 claims description 2
- NHLOOCMMUHSWRS-GOSISDBHSA-N 2-methyl-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-1-amine Chemical compound C1=2C(CNCC(C)C)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 NHLOOCMMUHSWRS-GOSISDBHSA-N 0.000 claims description 2
- DOFBTDSZDQCFTO-MRXNPFEDSA-N 3,3,3-trifluoro-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-1-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCCC(F)(F)F)CC12CCNCC1 DOFBTDSZDQCFTO-MRXNPFEDSA-N 0.000 claims description 2
- GPRQMCAVOZQKBS-QRQCRPRQSA-N 3-[(3s)-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,3'-pyrrolidine]-1'-yl]propan-1-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)C[C@]21CCN(CCCN)C2 GPRQMCAVOZQKBS-QRQCRPRQSA-N 0.000 claims description 2
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| US20100048524A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
| EA019601B1 (ru) | 2008-04-29 | 2014-04-30 | Новартис Аг | Производные спироиндола, предназначенные для лечения паразитарных заболеваний |
| CN102686600A (zh) | 2009-02-05 | 2012-09-19 | 托凯药业股份有限公司 | 甾体cyp17抑制剂/抗雄激素物质的新型药物前体 |
| TWI466885B (zh) | 2009-07-31 | 2015-01-01 | Japan Tobacco Inc | 含氮螺環化合物及其醫藥用途 |
| US8921576B2 (en) | 2011-10-19 | 2014-12-30 | Kowa Company, Ltd. | Spiroindoline compound, and medicinal agent comprising same |
| AU2013251475B2 (en) | 2012-04-26 | 2018-01-04 | The General Hospital Corporation | Agents and methods for treating and preventing seborrheic keratosis |
| CA2904170A1 (en) | 2013-03-14 | 2014-09-25 | University Of Maryland, Baltimore | Androgen receptor down-regulating agents and uses thereof |
| US10508309B2 (en) | 2013-05-17 | 2019-12-17 | The General Hospital Corporation | Methods for detecting and treating variants of seborrheic keratoses |
| JP2016528252A (ja) | 2013-08-12 | 2016-09-15 | トーカイ ファーマシューティカルズ， インコーポレイテッド | アンドロゲン標的治療を使用する新生物障害の処置のためのバイオマーカー |
| CN107801396B (zh) | 2015-02-02 | 2021-10-22 | 福马治疗股份有限公司 | 作为hdac抑制剂的3-芳基-4-酰氨基-二环[4,5,0]异羟肟酸 |
| WO2016126726A1 (en) | 2015-02-02 | 2016-08-11 | Forma Therapeutics, Inc. | Bicyclic [4,6,0] hydroxamic acids as hdac6 inhibitors |
| EA201792028A1 (ru) | 2015-03-13 | 2018-04-30 | Форма Терапьютикс, Инк. | Альфа-цинамидные соединения и композиции как ингибиторы hdac8 |
| EP3472131B1 (en) | 2016-06-17 | 2020-02-19 | Forma Therapeutics, Inc. | 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors |
| SG11202003879RA (en) | 2017-10-30 | 2020-05-28 | Neuropore Therapies Inc | Substituted phenyl sulfonyl phenyl triazole thiones and uses thereof |
| TWI830733B (zh) * | 2018-05-11 | 2024-02-01 | 中國大陸商迪哲（江蘇）醫藥有限公司 | 環戊烷化合物 |
| CN118767143A (zh) | 2019-12-12 | 2024-10-15 | 听治疗有限责任公司 | 用于预防和治疗听力损失的组合物和方法 |
| WO2022109360A1 (en) | 2020-11-23 | 2022-05-27 | Enanta Pharmaceuticals, Inc. | Novel spiropyrrolidine derived antiviral agents |
| WO2022235605A1 (en) | 2021-05-04 | 2022-11-10 | Enanta Pharmaceuticals, Inc. | Novel macrocyclic antiviral agents |
| US12398147B2 (en) | 2021-05-11 | 2025-08-26 | Enanta Pharmaceuticals, Inc. | Macrocyclic spiropyrrolidine derived antiviral agents |
| US12479854B2 (en) | 2021-07-29 | 2025-11-25 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| US11858945B2 (en) | 2021-11-12 | 2024-01-02 | Enanta Pharmaceuticals, Inc. | Alkyne-containing antiviral agents |
| WO2023086352A1 (en) | 2021-11-12 | 2023-05-19 | Enanta Pharmaceuticals, Inc. | Novel spiropyrrolidine derived antiviral agents |
| US11919910B2 (en) | 2021-11-12 | 2024-03-05 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| WO2023091561A1 (en) * | 2021-11-18 | 2023-05-25 | Enanta Pharmaceuticals, Inc. | Novel spiropyrrolidine derived antiviral agents |
| US11993600B2 (en) | 2021-12-08 | 2024-05-28 | Enanta Pharmaceuticals, Inc. | Saturated spirocyclics as antiviral agents |
| US12145941B2 (en) | 2021-12-08 | 2024-11-19 | Enanta Pharmaceuticals, Inc. | Heterocyclic antiviral agents |
| US12145942B2 (en) | 2022-04-05 | 2024-11-19 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| CN114751852B (zh) * | 2022-05-23 | 2023-09-15 | 山西库邦生物医药科技有限公司 | 一种西咯多辛关键中间体的制备方法 |
| KR20250057699A (ko) * | 2022-06-03 | 2025-04-29 | 도메인 테라퓨틱스 | 신규한 par-2 억제제 |
| CN116903625B (zh) * | 2023-02-16 | 2025-09-23 | 广州安岩仁医药科技有限公司 | 一种egfr抑制剂中间体及其合成方法与应用 |
| CN117700429A (zh) * | 2023-12-21 | 2024-03-15 | 广州白云科技股份有限公司 | 聚氨酯扩链剂、聚氨酯预聚体、力致变色聚氨酯胶及其制备方法 |
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| PH12012501891A1 (en) * | 2003-11-21 | 2013-09-02 | Array Biopharma Inc | Akt protein kinase inhibitors |
| WO2005113762A1 (en) | 2004-05-18 | 2005-12-01 | Pfizer Products Inc. | CRYSTAL STRUCTURE OF PROTEIN KINASE B-α (AKT-1) AND USES THEREOF |
| CA2598956A1 (en) * | 2005-02-24 | 2006-08-31 | Pfizer Products Inc. | Bicyclic heteroaromatic derivatives useful as anticancer agents |
| US7495007B2 (en) * | 2006-03-13 | 2009-02-24 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
| NZ573979A (en) * | 2006-07-06 | 2012-02-24 | Array Biopharma Inc | Cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
| US8063050B2 (en) * | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| UA95641C2 (xx) | 2006-07-06 | 2011-08-25 | Эррей Биофарма Инк. | Гідроксильовані піримідильні циклопентани як інгібітори акт протеїнкінази$гидроксилированные пиримидильные циклопентаны как ингибиторы акт протеинкиназы |
| US20080051419A1 (en) * | 2006-07-26 | 2008-02-28 | Pfizer Inc. | Amine derivatives useful as anticancer agents |
| PE20090829A1 (es) * | 2007-06-20 | 2009-07-25 | Glaxo Group Ltd | Espiroindolinas como moduladores de receptores de quimioquinas |
| ES2551352T3 (es) * | 2007-07-05 | 2015-11-18 | Array Biopharma, Inc. | Pirimido ciclopentanos útiles para el tratamiento de enfermedades inflamatorias o hiperproliferativas |
| EP2240483B8 (en) | 2008-01-09 | 2013-04-03 | Array Biopharma, Inc. | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
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