JP2011509307A5 - - Google Patents
Download PDFInfo
- 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
Links
- 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
- GVRMLHVGEWEIDI-MRXNPFEDSA-N 3-[5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-1'-yl]propan-1-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC21CCN(CCCN)CC2 GVRMLHVGEWEIDI-MRXNPFEDSA-N 0.000 claims description 2
- KBKVPYYEWYCXRP-ADRQNKRLSA-N 3-[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 C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(F)C=C11)CC21CCCN(CCCN)C2 KBKVPYYEWYCXRP-ADRQNKRLSA-N 0.000 claims description 2
- YGIXNQNDFMVHCV-HXUWFJFHSA-N 4,4-dimethyl-n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]cyclohexan-1-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC1CCC(C)(C)CC1)CC12CCNCC1 YGIXNQNDFMVHCV-HXUWFJFHSA-N 0.000 claims description 2
- JHNPQSUJGXKJLM-GFCCVEGCSA-N 4,5-difluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=C(F)C=C1)F)CC12CCNCC1 JHNPQSUJGXKJLM-GFCCVEGCSA-N 0.000 claims description 2
- KNGMXBHNPBTTOB-GFCCVEGCSA-N 4-bromo-5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=C(Cl)C=C1)Br)CC12CCNCC1 KNGMXBHNPBTTOB-GFCCVEGCSA-N 0.000 claims description 2
- FNSPOPNMKFZOEZ-GFCCVEGCSA-N 5,6-difluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC(F)=C(F)C=C11)CC21CCNCC2 FNSPOPNMKFZOEZ-GFCCVEGCSA-N 0.000 claims description 2
- RHQIODMIALNFGJ-GOSISDBHSA-N 5-[(3-fluorophenyl)methyl]-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(CC=2C=C(F)C=CC=2)C=C11)CC21CCNCC2 RHQIODMIALNFGJ-GOSISDBHSA-N 0.000 claims description 2
- VWASTLFRTNZCLA-CYBMUJFWSA-N 5-bromo-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Br)C=C11)CC21CCNCC2 VWASTLFRTNZCLA-CYBMUJFWSA-N 0.000 claims description 2
- FHJAZBSOQMUVLO-MRXNPFEDSA-N 5-chloro-1'-(cyclopropylmethyl)-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC1(CC1)CCN1CC1CC1 FHJAZBSOQMUVLO-MRXNPFEDSA-N 0.000 claims description 2
- GJHGVIAOMOJRBJ-GOSISDBHSA-N 5-chloro-1'-[(4-chlorophenyl)methyl]-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC1(CC1)CCN1CC1=CC=C(Cl)C=C1 GJHGVIAOMOJRBJ-GOSISDBHSA-N 0.000 claims description 2
- BSKQROWBULRFDR-CQSZACIVSA-N 5-chloro-1'-methyl-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC21CCN(C)CC2 BSKQROWBULRFDR-CQSZACIVSA-N 0.000 claims description 2
- JQOYJYCPSPKFQG-UHFFFAOYSA-N 5-chloro-1-(6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)spiro[2h-indole-3,4'-piperidine] Chemical compound C12=CC(Cl)=CC=C2N(C=2C=3CCCC=3N=CN=2)CC21CCNCC2 JQOYJYCPSPKFQG-UHFFFAOYSA-N 0.000 claims description 2
- SCKYDDYMNJOVPP-MRXNPFEDSA-N 5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]-1'-propan-2-ylspiro[2h-indole-3,4'-piperidine] Chemical compound C1CN(C(C)C)CCC11C2=CC(Cl)=CC=C2N(C=2C=3[C@H](C)CCC=3N=CN=2)C1 SCKYDDYMNJOVPP-MRXNPFEDSA-N 0.000 claims description 2
- XATMNHOGMFTHIQ-CYBMUJFWSA-N 5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(Cl)C=C11)CC21CCNCC2 XATMNHOGMFTHIQ-CYBMUJFWSA-N 0.000 claims description 2
- UGVRXWVXNMVTHV-CYBMUJFWSA-N 5-chloro-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(=C(Cl)C=C1)C#N)CC12CCNCC1 UGVRXWVXNMVTHV-CYBMUJFWSA-N 0.000 claims description 2
- SNJWNRBAUDHGNS-IUODEOHRSA-N 5-chloro-1-[(5r,7r)-7-fluoro-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C1([C@H](F)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC21CCNCC2 SNJWNRBAUDHGNS-IUODEOHRSA-N 0.000 claims description 2
- SNJWNRBAUDHGNS-DOMZBBRYSA-N 5-chloro-1-[(5r,7s)-7-fluoro-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C1([C@@H](F)C[C@H](C=21)C)=NC=NC=2N(C1=CC=C(Cl)C=C11)CC21CCNCC2 SNJWNRBAUDHGNS-DOMZBBRYSA-N 0.000 claims description 2
- YLJBLMJDJAERNW-GFCCVEGCSA-N 5-chloro-4-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=C(Cl)C=C1)F)CC12CCNCC1 YLJBLMJDJAERNW-GFCCVEGCSA-N 0.000 claims description 2
- JSJLTHVPTPJHOT-GFCCVEGCSA-N 5-chloro-6-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC(F)=C(Cl)C=C11)CC21CCNCC2 JSJLTHVPTPJHOT-GFCCVEGCSA-N 0.000 claims description 2
- JQEZVHMVGVUDFS-GFCCVEGCSA-N 5-chloro-7-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C(F)C=C(Cl)C=C11)CC21CCNCC2 JQEZVHMVGVUDFS-GFCCVEGCSA-N 0.000 claims description 2
- YVGCEMSQTHLNIJ-OAHLLOKOSA-N 5-cyclopropyl-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(C=C11)C2CC2)CC21CCNCC2 YVGCEMSQTHLNIJ-OAHLLOKOSA-N 0.000 claims description 2
- OWOQTIGIMGFTBK-OAHLLOKOSA-N 5-ethoxy-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C12=CC(OCC)=CC=C2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 OWOQTIGIMGFTBK-OAHLLOKOSA-N 0.000 claims description 2
- WCYLDZCGIOKXMD-CYBMUJFWSA-N 5-fluoro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine] Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(F)C=C11)CC21CCNCC2 WCYLDZCGIOKXMD-CYBMUJFWSA-N 0.000 claims description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 2
- 208000003200 Adenoma Diseases 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 206010061424 Anal cancer Diseases 0.000 claims description 2
- 208000007860 Anus Neoplasms Diseases 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000020084 Bone disease Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- VUBATRVFAXLOAU-CQSZACIVSA-N C[C@@H]1CCC=2N=CN=C(C=21)N1CC2(CCNCC2)C2=CC=CC=C12 Chemical compound C[C@@H]1CCC=2N=CN=C(C=21)N1CC2(CCNCC2)C2=CC=CC=C12 VUBATRVFAXLOAU-CQSZACIVSA-N 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims description 2
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims description 2
- 208000006029 Cardiomegaly Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 208000035473 Communicable disease Diseases 0.000 claims description 2
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- PNWSTZBUHRNKGQ-RNNSPPARSA-N F[C@H]1N(CCCC12CN(C1=CC=CC=C12)C=1C2=C(N=CN1)CC[C@H]2C)C Chemical compound F[C@H]1N(CCCC12CN(C1=CC=CC=C12)C=1C2=C(N=CN1)CC[C@H]2C)C PNWSTZBUHRNKGQ-RNNSPPARSA-N 0.000 claims description 2
- 208000004463 Follicular Adenocarcinoma Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 206010021143 Hypoxia Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 2
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 2
- 206010062038 Lip neoplasm Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000018501 Lymphatic disease Diseases 0.000 claims description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 claims description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 208000025966 Neurological disease Diseases 0.000 claims description 2
- 206010029350 Neurotoxicity Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims description 2
- 206010034299 Penile cancer Diseases 0.000 claims description 2
- 206010034811 Pharyngeal cancer Diseases 0.000 claims description 2
- 102000001253 Protein Kinase Human genes 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims description 2
- 206010061934 Salivary gland cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 201000010208 Seminoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 206010042674 Swelling Diseases 0.000 claims description 2
- 230000006044 T cell activation Effects 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 108090000190 Thrombin Proteins 0.000 claims description 2
- 206010062129 Tongue neoplasm Diseases 0.000 claims description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 2
- 206010047741 Vulval cancer Diseases 0.000 claims description 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 2
- RUIYTHOMJGWHKV-UHFFFAOYSA-N [1-(5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl)spiro[2h-indole-3,4'-piperidine]-4-yl]methanamine Chemical compound C=12C(C)CCC2=NC=NC=1N(C1=C2C(=CC=C1)CN)CC12CCNCC1 RUIYTHOMJGWHKV-UHFFFAOYSA-N 0.000 claims description 2
- ZSZSXJPPBRTWMO-CQSZACIVSA-N [1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-yl]methanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(CN)C=C11)CC21CCNCC2 ZSZSXJPPBRTWMO-CQSZACIVSA-N 0.000 claims description 2
- VRIKUWYGQFRSMO-CYBMUJFWSA-N [5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=C(Cl)C=C1)CN)CC12CCNCC1 VRIKUWYGQFRSMO-CYBMUJFWSA-N 0.000 claims description 2
- 208000009956 adenocarcinoma Diseases 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 239000003443 antiviral agent Substances 0.000 claims description 2
- 201000011165 anus cancer Diseases 0.000 claims description 2
- 201000009036 biliary tract cancer Diseases 0.000 claims description 2
- 208000020790 biliary tract neoplasm Diseases 0.000 claims description 2
- 210000004027 cell Anatomy 0.000 claims description 2
- 230000030833 cell death Effects 0.000 claims description 2
- 201000007455 central nervous system cancer Diseases 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 208000010247 contact dermatitis Diseases 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 230000001066 destructive effect Effects 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 125000006437 ethyl cyclopropyl group Chemical group 0.000 claims description 2
- 229930195712 glutamate Natural products 0.000 claims description 2
- 208000014951 hematologic disease Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 230000007954 hypoxia Effects 0.000 claims description 2
- 239000002955 immunomodulating agent Substances 0.000 claims description 2
- 229940121354 immunomodulator Drugs 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
- 230000003780 keratinization Effects 0.000 claims description 2
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 2
- 201000006721 lip cancer Diseases 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 201000005243 lung squamous cell carcinoma Diseases 0.000 claims description 2
- 208000018555 lymphatic system disease Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 2
- 210000000214 mouth Anatomy 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- JZJSPSXLZHEYNN-GOSISDBHSA-N n-[[1'-methyl-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCN(C)CC2 JZJSPSXLZHEYNN-GOSISDBHSA-N 0.000 claims description 2
- TXNVAWFIQWLMLU-GOSISDBHSA-N n-[[1-[(5r)-5-ethyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C([C@H](C=12)CC)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC(C)C)CC12CCNCC1 TXNVAWFIQWLMLU-GOSISDBHSA-N 0.000 claims description 2
- KQSSTMFNPHOIJB-HXUWFJFHSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]-1-phenylmethanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNCC=1C=CC=CC=1)CC12CCNCC1 KQSSTMFNPHOIJB-HXUWFJFHSA-N 0.000 claims description 2
- SKUQYAGICGJLCQ-QNSVNVJESA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]butan-2-amine Chemical compound C1=2C(CNC(C)CC)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 SKUQYAGICGJLCQ-QNSVNVJESA-N 0.000 claims description 2
- LUHXXXGWYMUGQM-GOSISDBHSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]cyclopentanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC1CCCC1)CC12CCNCC1 LUHXXXGWYMUGQM-GOSISDBHSA-N 0.000 claims description 2
- JVXULOOJNMHOHS-MRXNPFEDSA-N 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(CNCC)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 JVXULOOJNMHOHS-MRXNPFEDSA-N 0.000 claims description 2
- TVRMMKZOGXQALD-GOSISDBHSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]oxan-4-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC1CCOCC1)CC12CCNCC1 TVRMMKZOGXQALD-GOSISDBHSA-N 0.000 claims description 2
- UCMQZGBLPJSYEF-GOSISDBHSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]pentan-3-amine Chemical compound C1=2C(CNC(CC)CC)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 UCMQZGBLPJSYEF-GOSISDBHSA-N 0.000 claims description 2
- PBFZZGUGQULGBJ-QGZVFWFLSA-N 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(CNCCC)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 PBFZZGUGQULGBJ-QGZVFWFLSA-N 0.000 claims description 2
- PXHUIAPRRSRXHV-QGZVFWFLSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C)CCC=3N=CN=2)CC21CCNCC2 PXHUIAPRRSRXHV-QGZVFWFLSA-N 0.000 claims description 2
- ZIRDNXVKPVHHHQ-GOSISDBHSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]pyridin-2-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC=1N=CC=CC=1)CC12CCNCC1 ZIRDNXVKPVHHHQ-GOSISDBHSA-N 0.000 claims description 2
- FLLGGKKPIBTGSD-QGZVFWFLSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]pyrimidin-2-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC=1N=CC=CN=1)CC12CCNCC1 FLLGGKKPIBTGSD-QGZVFWFLSA-N 0.000 claims description 2
- IYXVUXJFZUPBDJ-RDTXWAMCSA-N n-[[1-[(5r,7r)-7-hydroxy-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]acetamide Chemical compound C1([C@H](O)C[C@H](C=21)C)=NC=NC=2N(C1=C2C(=CC=C1)CNC(C)=O)CC12CCNCC1 IYXVUXJFZUPBDJ-RDTXWAMCSA-N 0.000 claims description 2
- AVXJSNYYFBUCHQ-AEFFLSMTSA-N n-[[1-[(5r,7s)-7-fluoro-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C)C[C@H](F)C=3N=CN=2)CC21CCNCC2 AVXJSNYYFBUCHQ-AEFFLSMTSA-N 0.000 claims description 2
- XZFMAJHRNHYZEJ-QFIPXVFZSA-N n-[[1-[(5s)-5-cyclopentyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C4CCCC4)CCC=3N=CN=2)CC21CCNCC2 XZFMAJHRNHYZEJ-QFIPXVFZSA-N 0.000 claims description 2
- GENGMIRNOQKVQD-QFIPXVFZSA-N n-[[1-[(5s)-5-propan-2-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]cyclopentanamine Chemical compound C([C@H](C=12)C(C)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CNC1CCCC1)CC12CCNCC1 GENGMIRNOQKVQD-QFIPXVFZSA-N 0.000 claims description 2
- BECBVHZWHYLFJV-FQEVSTJZSA-N n-[[1-[(5s)-5-propan-2-yl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]propan-2-amine Chemical compound C1=2C(CNC(C)C)=CC=CC=2N(C=2C=3[C@H](C(C)C)CCC=3N=CN=2)CC21CCNCC2 BECBVHZWHYLFJV-FQEVSTJZSA-N 0.000 claims description 2
- KWUNASPZIIYLQK-QGZVFWFLSA-N n-[[5-chloro-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]cyclopentanamine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=C(Cl)C=C1)CNC1CCCC1)CC12CCNCC1 KWUNASPZIIYLQK-QGZVFWFLSA-N 0.000 claims description 2
- 230000007135 neurotoxicity Effects 0.000 claims description 2
- 231100000228 neurotoxicity Toxicity 0.000 claims description 2
- 239000003900 neurotrophic factor Substances 0.000 claims description 2
- 201000005443 oral cavity cancer Diseases 0.000 claims description 2
- 210000000056 organ Anatomy 0.000 claims description 2
- 210000004798 organs belonging to the digestive system Anatomy 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000001575 pathological effect Effects 0.000 claims description 2
- 201000002628 peritoneum cancer Diseases 0.000 claims description 2
- 210000003800 pharynx Anatomy 0.000 claims description 2
- 201000008006 pharynx cancer Diseases 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 108060006633 protein kinase Proteins 0.000 claims description 2
- 206010038038 rectal cancer Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 2
- 201000002314 small intestine cancer Diseases 0.000 claims description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 2
- 230000008961 swelling Effects 0.000 claims description 2
- 201000003120 testicular cancer Diseases 0.000 claims description 2
- 229960004072 thrombin Drugs 0.000 claims description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 2
- 201000006134 tongue cancer Diseases 0.000 claims description 2
- 238000002054 transplantation Methods 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 208000027930 type IV hypersensitivity disease Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 201000005102 vulva cancer Diseases 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
- PVBCJJRNVMOSDK-UHFFFAOYSA-N 5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-7-ol Chemical compound C1=NC=C2C(C)CC(O)C2=N1 PVBCJJRNVMOSDK-UHFFFAOYSA-N 0.000 claims 1
- FQMVKWHBGPDGJC-UHFFFAOYSA-N 5H-cyclopenta[d]pyrimidin-7-ol Chemical compound N1=CN=CC2=C1C(=CC2)O FQMVKWHBGPDGJC-UHFFFAOYSA-N 0.000 claims 1
- 208000019838 Blood disease Diseases 0.000 claims 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 claims 1
- 230000007812 deficiency Effects 0.000 claims 1
- 239000003966 growth inhibitor Substances 0.000 claims 1
- 208000018706 hematopoietic system disease Diseases 0.000 claims 1
- 230000036039 immunity Effects 0.000 claims 1
- 230000002584 immunomodulator Effects 0.000 claims 1
- KVEOOZYQDATXON-QGZVFWFLSA-N n-(3-chlorophenyl)-1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-5-amine Chemical class C([C@H](C=12)C)CC2=NC=NC=1N(C1=CC=C(NC=2C=C(Cl)C=CC=2)C=C11)CC21CCNCC2 KVEOOZYQDATXON-QGZVFWFLSA-N 0.000 claims 1
- 125000003003 spiro group Chemical group 0.000 claims 1
- 230000005951 type IV hypersensitivity Effects 0.000 claims 1
- 0 CCN(*)*C(*)(C1)c(cccc2)c2N1c1c(C(*)CC2(*)*)c2ncn1 Chemical compound CCN(*)*C(*)(C1)c(cccc2)c2N1c1c(C(*)CC2(*)*)c2ncn1 0.000 description 22
- 238000000034 method Methods 0.000 description 14
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 description 5
- PWATWSYOIIXYMA-UHFFFAOYSA-N CCCCCc1ccccc1 Chemical compound CCCCCc1ccccc1 PWATWSYOIIXYMA-UHFFFAOYSA-N 0.000 description 2
- YTWNKXOCQCPCMN-ZCFIWIBFSA-N CC[C@H](CCc1ncn2)c1c2I Chemical compound CC[C@H](CCc1ncn2)c1c2I YTWNKXOCQCPCMN-ZCFIWIBFSA-N 0.000 description 2
- GPOFSFLJOIAMSA-UHFFFAOYSA-N CCc(cc1)ccc1Cl Chemical compound CCc(cc1)ccc1Cl GPOFSFLJOIAMSA-UHFFFAOYSA-N 0.000 description 2
- MAKXDSDRVPVCOY-UHFFFAOYSA-N CC1(C)C2C(CNCc3ccccc3)=CC=CC2NC1 Chemical compound CC1(C)C2C(CNCc3ccccc3)=CC=CC2NC1 MAKXDSDRVPVCOY-UHFFFAOYSA-N 0.000 description 1
- UTGWOBHYRMZUCY-UHFFFAOYSA-N CC1(C)c(c(C2NCCC2)ccc2)c2N(C)C1 Chemical compound CC1(C)c(c(C2NCCC2)ccc2)c2N(C)C1 UTGWOBHYRMZUCY-UHFFFAOYSA-N 0.000 description 1
- GCNUZBFYOPFJBU-UHFFFAOYSA-N CC1(C2C(CNc3ncccn3)=CC=CC2NC1)I Chemical compound CC1(C2C(CNc3ncccn3)=CC=CC2NC1)I GCNUZBFYOPFJBU-UHFFFAOYSA-N 0.000 description 1
- TVJDRHDUEYZDIJ-UHFFFAOYSA-N CC1(c(c(CNc2ncccc2)ccc2)c2N(C)C1)I Chemical compound CC1(c(c(CNc2ncccc2)ccc2)c2N(C)C1)I TVJDRHDUEYZDIJ-UHFFFAOYSA-N 0.000 description 1
- JFBCRLJNPGHAQW-UHFFFAOYSA-N CCC(CC)NCc1c(C(C)(C)CN2)c2ccc1 Chemical compound CCC(CC)NCc1c(C(C)(C)CN2)c2ccc1 JFBCRLJNPGHAQW-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000026037 malignant tumor of neck Diseases 0.000 description 1
- GRPJFVXMGAGGIY-JOCHJYFZSA-N n-[[1-[(5r)-5-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-4-yl]spiro[2h-indole-3,4'-piperidine]-4-yl]methyl]-n-pyridin-2-ylpyridin-2-amine Chemical compound C([C@H](C=12)C)CC2=NC=NC=1N(C1=C2C(=CC=C1)CN(C=1N=CC=CC=1)C=1N=CC=CC=1)CC12CCNCC1 GRPJFVXMGAGGIY-JOCHJYFZSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2012508P | 2008-01-09 | 2008-01-09 | |
| US61/020,125 | 2008-01-09 | ||
| PCT/US2009/030603 WO2009089454A1 (en) | 2008-01-09 | 2009-01-09 | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011509307A JP2011509307A (ja) | 2011-03-24 |
| JP2011509307A5 true JP2011509307A5 (https=) | 2013-01-31 |
| JP5512545B2 JP5512545B2 (ja) | 2014-06-04 |
Family
ID=40436385
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010542374A Active JP5512545B2 (ja) | 2008-01-09 | 2009-01-09 | Ａｋｔタンパク質キナーゼ阻害剤としてのピリミジルシクロペンタン類 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US8324221B2 (https=) |
| EP (1) | EP2240483B8 (https=) |
| JP (1) | JP5512545B2 (https=) |
| CN (1) | CN102015708B (https=) |
| AR (1) | AR070136A1 (https=) |
| CA (1) | CA2714888C (https=) |
| CL (1) | CL2009000035A1 (https=) |
| ES (1) | ES2403284T3 (https=) |
| PE (1) | PE20091315A1 (https=) |
| TW (1) | TW200940542A (https=) |
| WO (1) | WO2009089454A1 (https=) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200940542A (en) | 2008-01-09 | 2009-10-01 | Array Biopharma Inc | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| US20100048913A1 (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 |
| CN102015711B (zh) | 2008-04-29 | 2013-05-01 | 诺瓦提斯公司 | 用于治疗寄生虫病的螺-吲哚衍生物 |
| 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 |
| EP2781521A4 (en) | 2011-10-19 | 2015-03-04 | Kowa Co | NEW SPIROINDOLIN COMPOUND AND MEDICAL AGENT THEREFOR |
| HUE051096T2 (hu) | 2012-04-26 | 2021-03-01 | Massachusetts Gen Hospital | Ágensek és módszerek a sebészeti keratózis kezelésére és megelõzésére |
| RU2015137617A (ru) | 2013-03-14 | 2017-04-18 | Юниверсити Оф Мэриленд, Балтимор Офис Оф Текнолоджи Трансфер | Агенты, подавляющие андрогенные рецепторы, и их применение |
| US10508309B2 (en) | 2013-05-17 | 2019-12-17 | The General Hospital Corporation | Methods for detecting and treating variants of seborrheic keratoses |
| CN105636594A (zh) | 2013-08-12 | 2016-06-01 | 托凯药业股份有限公司 | 使用雄激素靶向疗法用于治疗肿瘤性疾病的生物标记物 |
| TW201636329A (zh) | 2015-02-02 | 2016-10-16 | 佛瑪治療公司 | 作為ｈｄａｃ抑制劑之雙環［４，６，０］異羥肟酸 |
| PL3292116T3 (pl) | 2015-02-02 | 2022-02-21 | Valo Health, Inc. | 3-arylo-4-amidobicykliczne kwasy [4,5,0]hydroksamowe jako inhibitory hdac |
| 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 |
| 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 |
| US12540141B2 (en) | 2020-11-23 | 2026-02-03 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| KR20230124583A (ko) | 2020-11-23 | 2023-08-25 | 이난타 파마슈티칼스, 인코포레이티드 | 신규한 스피로피롤리딘 유래 항바이러스제 |
| 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 |
| US11912714B2 (en) | 2021-11-12 | 2024-02-27 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| US11858945B2 (en) | 2021-11-12 | 2024-01-02 | Enanta Pharmaceuticals, Inc. | Alkyne-containing 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 |
| US12145941B2 (en) | 2021-12-08 | 2024-11-19 | Enanta Pharmaceuticals, Inc. | Heterocyclic antiviral agents |
| WO2023107419A1 (en) | 2021-12-08 | 2023-06-15 | Enanta Pharmaceuticals, Inc. | Saturated spirocyclics as 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 |
| 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 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022605A1 (en) * | 2000-09-15 | 2002-03-21 | Vertex Pharmaceuticals Incorporated | Pyrazole compounds useful as protein kinase inhibitors |
| NZ590160A (en) * | 2003-11-21 | 2012-07-27 | 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 |
| US8063050B2 (en) * | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| ATE523499T1 (de) * | 2006-07-06 | 2011-09-15 | Array Biopharma Inc | Cyclopenta [d]-pyrimidine als akt-proteinkinasehemmer |
| 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 |
| CL2008001810A1 (es) * | 2007-06-20 | 2008-12-26 | Glaxo Group Ltd | Compuestos derivados de espiroindolinas, moduladores de receptores de quimiocinas; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar aterosclerosis, dolor inflamatorio, influenza, sindrome metabolico, entre otras enfermedades. |
| WO2009006567A2 (en) * | 2007-07-05 | 2009-01-08 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as akt protein kinase inhibitors |
| TW200940542A (en) | 2008-01-09 | 2009-10-01 | Array Biopharma Inc | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
-
2009
- 2009-01-09 TW TW098100759A patent/TW200940542A/zh unknown
- 2009-01-09 EP EP09700747A patent/EP2240483B8/en active Active
- 2009-01-09 WO PCT/US2009/030603 patent/WO2009089454A1/en not_active Ceased
- 2009-01-09 CN CN200980108322.5A patent/CN102015708B/zh active Active
- 2009-01-09 PE PE2009000021A patent/PE20091315A1/es not_active Application Discontinuation
- 2009-01-09 CL CL2009000035A patent/CL2009000035A1/es unknown
- 2009-01-09 CA CA2714888A patent/CA2714888C/en not_active Expired - Fee Related
- 2009-01-09 ES ES09700747T patent/ES2403284T3/es active Active
- 2009-01-09 JP JP2010542374A patent/JP5512545B2/ja active Active
- 2009-01-09 US US12/812,384 patent/US8324221B2/en active Active
- 2009-01-09 AR ARP090100067A patent/AR070136A1/es not_active Application Discontinuation
-
2012
- 2012-11-14 US US13/676,963 patent/US9346805B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2011509307A5 (https=) | ||
| US11136326B2 (en) | Pyrrolopyrimidine derivatives as TAM inhibitors | |
| US8637537B2 (en) | Serine/threonine kinase inhibitors | |
| US11084786B2 (en) | Compounds and pharmaceutical composition associated with ubiquitination-proteasome system | |
| WO2020094018A1 (zh) | 一种螺芳环化合物及其应用 | |
| US20240246915A1 (en) | Aminonaphthoquinone compounds and pharmaceutical composition for blocking ubiquitination-proteasome system in diseases | |
| US9708333B2 (en) | Fused bicyclic 1,2,4-triazine compounds as TAM inhibitors | |
| RU2019120986A (ru) | Фармацевтическая комбинация, содержащая ингибитор alk и ингибитор shp2 | |
| JP7301390B2 (ja) | ヘテロ環式化合物、ヘテロ環式化合物を含む組成物、及びその使用方法 | |
| PT2758401T (pt) | Imidazopiridazinas amino-substituídas | |
| CN104755478A (zh) | 丝氨酸/苏氨酸激酶抑制剂 | |
| US8815877B2 (en) | Serine/threonine kinase inhibitors | |
| US20190016743A1 (en) | Compounds for inhibiting cancer and virus | |
| HK40034342A (zh) | 杂环化合物及其组合物和使用方法 | |
| HK40097521A (zh) | 三环类化合物及其用途 | |
| TW201348240A (zh) | 噻吩并嘧啶 |