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 |
| AU2009242279B2 (en) | 2008-04-29 | 2012-08-30 | Novartis Ag | Spiro-indole derivatives for the treatment of parasitic diseases |
| WO2010091306A1 (en) | 2009-02-05 | 2010-08-12 | Tokai Pharmaceuticals | Novel prodrugs of steroidal cyp17 inhibitors/antiandrogens |
| 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 |
| DK2841075T3 (da) | 2012-04-26 | 2020-06-22 | Massachusetts Gen Hospital | Midler og fremgangsmåder til behandling og forebyggelse af seboroisk keratose |
| KR20150127720A (ko) | 2013-03-14 | 2015-11-17 | 유니버시티 오브 매릴랜드, 발티모어 | 안드로겐 수용체 하향 조절제 및 그의 용도 |
| WO2014186663A2 (en) * | 2013-05-17 | 2014-11-20 | The General Hospital Corporation | Methods for detecting and treating variants of seborrheic keratoses |
| CA2920317A1 (en) | 2013-08-12 | 2015-02-19 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
| WO2016126726A1 (en) | 2015-02-02 | 2016-08-11 | Forma Therapeutics, Inc. | Bicyclic [4,6,0] hydroxamic acids as hdac6 inhibitors |
| SG11201708622UA (en) | 2015-02-02 | 2017-11-29 | Forma Therapeutics Inc | 3-aryl-4-amido-bicyclic [4,5,0] hydroxamic acids as hdac inhibitors |
| US9745253B2 (en) | 2015-03-13 | 2017-08-29 | Forma Therapeutics, Inc. | Alpha-cinnamide compounds and compositions as HDAC8 inhibitors |
| EP3472131B1 (en) | 2016-06-17 | 2020-02-19 | Forma Therapeutics, Inc. | 2-spiro-5- and 6-hydroxamic acid indanes as hdac inhibitors |
| EP3703675A4 (en) | 2017-10-30 | 2021-06-16 | Neuropore Therapies, Inc. | SUBSTITUTED PHENYLSULFONYLPHÉNYLTRIAZOLETHIONES AND ASSOCIATED USES |
| 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 |
| CN114981298B (zh) | 2019-12-12 | 2024-08-20 | 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 |
| US12540141B2 (en) | 2020-11-23 | 2026-02-03 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
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| 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 |
| WO2023086352A1 (en) | 2021-11-12 | 2023-05-19 | Enanta Pharmaceuticals, Inc. | Novel spiropyrrolidine derived antiviral agents |
| WO2023086350A1 (en) | 2021-11-12 | 2023-05-19 | Enanta Pharmaceuticals, Inc. | Alkyne-containing antiviral agents |
| US11919910B2 (en) | 2021-11-12 | 2024-03-05 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| US20230159546A1 (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 |
| WO2023196307A1 (en) | 2022-04-05 | 2023-10-12 | Enanta Pharmaceuticals, Inc. | Novel 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 |
| AU2023279857A1 (en) * | 2022-06-03 | 2024-11-14 | Domain Therapeutics | Novel par-2 inhibitors |
| 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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| EP1317450B1 (en) | 2000-09-15 | 2006-11-22 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| CA2546754A1 (en) * | 2003-11-21 | 2005-06-09 | 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 |
| US20090111805A1 (en) * | 2005-02-24 | 2009-04-30 | Pfizer Inc. | Bicyclic heteroaromatic derivatives useful as anticancer agents |
| US7495007B2 (en) * | 2006-03-13 | 2009-02-24 | Hoffmann-La Roche Inc. | Spiroindolinone derivatives |
| EP2049500B1 (en) | 2006-07-06 | 2011-09-07 | 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 |
| TW200904423A (en) * | 2007-06-20 | 2009-02-01 | Glaxo Group Ltd | Spiroindolines as modulators of chemokine receptors |
| CN103396409B (zh) * | 2007-07-05 | 2015-03-11 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
| CN102015708B (zh) | 2008-01-09 | 2014-03-26 | 阵列生物制药公司 | 作为akt蛋白激酶抑制剂的嘧啶基环戊烷 |
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