JP2011500702A - チエノピリミジンおよびピラゾロピリミジン化合物ならびにmTORキナーゼおよびPI3キナーゼ阻害剤としてのその使用 - Google Patents
チエノピリミジンおよびピラゾロピリミジン化合物ならびにmTORキナーゼおよびPI3キナーゼ阻害剤としてのその使用 Download PDFInfo
- Publication number
- JP2011500702A JP2011500702A JP2010530074A JP2010530074A JP2011500702A JP 2011500702 A JP2011500702 A JP 2011500702A JP 2010530074 A JP2010530074 A JP 2010530074A JP 2010530074 A JP2010530074 A JP 2010530074A JP 2011500702 A JP2011500702 A JP 2011500702A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- alkyl
- oxa
- azabicyclo
- pyrazolo
- 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.)
- Withdrawn
Links
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 title abstract description 84
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 title description 120
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 title description 14
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 title 1
- -1 pyrazolopyrimidine compound Chemical class 0.000 claims abstract description 688
- 150000001875 compounds Chemical class 0.000 claims abstract description 207
- 150000003839 salts Chemical class 0.000 claims abstract description 95
- 239000000203 mixture Substances 0.000 claims abstract description 89
- 238000000034 method Methods 0.000 claims abstract description 67
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 241
- 125000001424 substituent group Chemical group 0.000 claims description 224
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 205
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 194
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 176
- 125000003118 aryl group Chemical group 0.000 claims description 132
- 125000001072 heteroaryl group Chemical group 0.000 claims description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 126
- 125000005843 halogen group Chemical group 0.000 claims description 125
- 229910052736 halogen Inorganic materials 0.000 claims description 117
- 150000002367 halogens Chemical class 0.000 claims description 116
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 100
- 239000004202 carbamide Substances 0.000 claims description 92
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 87
- 125000002252 acyl group Chemical group 0.000 claims description 86
- 229910052799 carbon Inorganic materials 0.000 claims description 85
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 72
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 71
- 125000004432 carbon atom Chemical group C* 0.000 claims description 71
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 60
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 59
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 37
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 34
- 108091007960 PI3Ks Proteins 0.000 claims description 33
- 102000038030 PI3Ks Human genes 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 31
- 125000005431 alkyl carboxamide group Chemical group 0.000 claims description 30
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 30
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 29
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 22
- 125000002619 bicyclic group Chemical group 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 21
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 21
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 17
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 16
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 16
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- 201000011510 cancer Diseases 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 9
- QLHHRYZMBGPBJG-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-pyrazolo[3,4-d]pyrimidinyl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 QLHHRYZMBGPBJG-UHFFFAOYSA-N 0.000 claims description 8
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 229940120638 avastin Drugs 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229960000397 bevacizumab Drugs 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 6
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- 206010038389 Renal cancer Diseases 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 6
- 201000010982 kidney cancer Diseases 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 229960004679 doxorubicin Drugs 0.000 claims description 5
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 4
- CCJBBQMLLPYZTR-UHFFFAOYSA-N 1-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCF)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 CCJBBQMLLPYZTR-UHFFFAOYSA-N 0.000 claims description 4
- LQBQQAXIISEIGM-UHFFFAOYSA-N 1-[4-[1-(4-hydroxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(O)CC3)C2=N1 LQBQQAXIISEIGM-UHFFFAOYSA-N 0.000 claims description 4
- MDAFZGAXBHQRNG-UHFFFAOYSA-N 1-[4-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC=4C=NC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 MDAFZGAXBHQRNG-UHFFFAOYSA-N 0.000 claims description 4
- HMFRTKWUEKZJKW-UHFFFAOYSA-N 1-[4-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC=4C=CN=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 HMFRTKWUEKZJKW-UHFFFAOYSA-N 0.000 claims description 4
- WRCVEGVPVQBJJW-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-oxocyclohexyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(=O)CC3)C2=N1 WRCVEGVPVQBJJW-UHFFFAOYSA-N 0.000 claims description 4
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 4
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 229960003901 dacarbazine Drugs 0.000 claims description 4
- 206010017758 gastric cancer Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 201000011549 stomach cancer Diseases 0.000 claims description 4
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 4
- 206010046766 uterine cancer Diseases 0.000 claims description 4
- SGRCPPFHVNOJSS-UHFFFAOYSA-N 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CCC3COC4)N=2)C=C1 SGRCPPFHVNOJSS-UHFFFAOYSA-N 0.000 claims description 3
- IZEKUGZAKDZVTI-UHFFFAOYSA-N 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 IZEKUGZAKDZVTI-UHFFFAOYSA-N 0.000 claims description 3
- DBNVNMWEQKXYJD-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]-3-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(N(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCF)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 DBNVNMWEQKXYJD-UHFFFAOYSA-N 0.000 claims description 3
- IJQBGHXJLLTXPZ-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C4CCC5(CC4)OCCO5)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 IJQBGHXJLLTXPZ-UHFFFAOYSA-N 0.000 claims description 3
- SDRFXWMDVIHAMJ-UHFFFAOYSA-N 1-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-morpholin-4-ylphenyl)urea Chemical compound N1=C2N(CCF)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 SDRFXWMDVIHAMJ-UHFFFAOYSA-N 0.000 claims description 3
- LOKZPATYWMCLBT-UHFFFAOYSA-N 1-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(hydroxymethyl)phenyl]urea Chemical compound C1=CC(CO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCF)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 LOKZPATYWMCLBT-UHFFFAOYSA-N 0.000 claims description 3
- MXKMECPPQGOGLO-UHFFFAOYSA-N 1-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCF)C2=N1 MXKMECPPQGOGLO-UHFFFAOYSA-N 0.000 claims description 3
- LDOKUGHHYHVRRK-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CCC3COC4)N=2)C=C1 LDOKUGHHYHVRRK-UHFFFAOYSA-N 0.000 claims description 3
- NQESUZMBIJHCOM-UHFFFAOYSA-N 1-[4-[4-(6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(C)N=CC2=C(N2CC3OCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 NQESUZMBIJHCOM-UHFFFAOYSA-N 0.000 claims description 3
- BRFGDDGSUBMDBH-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1h-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=C(C=2N=C3NN=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CN=C1 BRFGDDGSUBMDBH-UHFFFAOYSA-N 0.000 claims description 3
- RTVWGFBQAKFHOF-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CCN(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 RTVWGFBQAKFHOF-UHFFFAOYSA-N 0.000 claims description 3
- KPSKKPDRNSLZRB-HOTGVXAUSA-N 1-cyclopropyl-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 KPSKKPDRNSLZRB-HOTGVXAUSA-N 0.000 claims description 3
- YKHJGTINLIVMSH-UHFFFAOYSA-N 1-methyl-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2C3CCC2COC3)=C(C=NN2CC(F)(F)F)C2=N1 YKHJGTINLIVMSH-UHFFFAOYSA-N 0.000 claims description 3
- GLKBJTKFTXGDAJ-UHFFFAOYSA-N 4-[[1-(1-benzylpiperidin-4-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]amino]phenol Chemical compound C1=CC(O)=CC=C1NC1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC=4C=CC=CC=4)CC3)C2=N1 GLKBJTKFTXGDAJ-UHFFFAOYSA-N 0.000 claims description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
- 208000020084 Bone disease Diseases 0.000 claims description 3
- RIWKUMGHZXCSPC-BZKVGYQJSA-N C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 RIWKUMGHZXCSPC-BZKVGYQJSA-N 0.000 claims description 3
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 108010005716 Interferon beta-1a Proteins 0.000 claims description 3
- 108010005714 Interferon beta-1b Proteins 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 3
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 3
- 230000033115 angiogenesis Effects 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 3
- 229960004562 carboplatin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 229960003668 docetaxel Drugs 0.000 claims description 3
- 229960005420 etoposide Drugs 0.000 claims description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
- 229960003776 glatiramer acetate Drugs 0.000 claims description 3
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 claims description 3
- 229960000930 hydroxyzine Drugs 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 229960004461 interferon beta-1a Drugs 0.000 claims description 3
- 229960003161 interferon beta-1b Drugs 0.000 claims description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 3
- 229960001156 mitoxantrone Drugs 0.000 claims description 3
- 229960005027 natalizumab Drugs 0.000 claims description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 208000037803 restenosis Diseases 0.000 claims description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 3
- VUCWMAJEUOWLEY-UHFFFAOYSA-N 1-$l^{1}-azanylpiperidine Chemical compound [N]N1CCCCC1 VUCWMAJEUOWLEY-UHFFFAOYSA-N 0.000 claims description 2
- VNRJYXRJFNRQRD-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCF)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 VNRJYXRJFNRQRD-UHFFFAOYSA-N 0.000 claims description 2
- RRNFUKFNHGBQEF-UHFFFAOYSA-N 1-(2-fluoroethyl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCF)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 RRNFUKFNHGBQEF-UHFFFAOYSA-N 0.000 claims description 2
- XBLBSXOUHOVQPA-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCO)C2=N1 XBLBSXOUHOVQPA-UHFFFAOYSA-N 0.000 claims description 2
- VTZPAZFULIFFPW-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 VTZPAZFULIFFPW-UHFFFAOYSA-N 0.000 claims description 2
- FGCPYNHZGVJJLS-UHFFFAOYSA-N 1-(4-morpholin-4-ylphenyl)-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 FGCPYNHZGVJJLS-UHFFFAOYSA-N 0.000 claims description 2
- BYGOEBYVFYSDGF-UHFFFAOYSA-N 1-(4-morpholin-4-ylphenyl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 BYGOEBYVFYSDGF-UHFFFAOYSA-N 0.000 claims description 2
- LERUIIPTVXHCLN-GOTSBHOMSA-N 1-(4-morpholin-4-ylphenyl)-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 LERUIIPTVXHCLN-GOTSBHOMSA-N 0.000 claims description 2
- QKQRJVLKJZATTP-UHFFFAOYSA-N 1-(6-aminopyridin-3-yl)-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(N)N=C1 QKQRJVLKJZATTP-UHFFFAOYSA-N 0.000 claims description 2
- XAZGVAFGYQYKTL-UHFFFAOYSA-N 1-(6-morpholin-4-ylpyridin-3-yl)-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 XAZGVAFGYQYKTL-UHFFFAOYSA-N 0.000 claims description 2
- MONILLGMGZKJNK-UHFFFAOYSA-N 1-(6-morpholin-4-ylpyridin-3-yl)-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 MONILLGMGZKJNK-UHFFFAOYSA-N 0.000 claims description 2
- SNOHNXMOFHUTHI-SFTDATJTSA-N 1-(6-morpholin-4-ylpyridin-3-yl)-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 SNOHNXMOFHUTHI-SFTDATJTSA-N 0.000 claims description 2
- UCGFKGIOOUVIOP-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NCCN(C)C)C=C1 UCGFKGIOOUVIOP-UHFFFAOYSA-N 0.000 claims description 2
- OQALSGXMCNMPKF-UHFFFAOYSA-N 1-[2-(dimethylamino)ethyl]-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCN(C)C)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C)C2=N1 OQALSGXMCNMPKF-UHFFFAOYSA-N 0.000 claims description 2
- LYHVJYYVAHOIOZ-UHFFFAOYSA-N 1-[2-fluoro-4-[4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound FC1=CC(C=2N=C3N(C4CCN(CC=5C=NC=CC=5)CC4)N=CC3=C(N3CCOCC3)N=2)=CC=C1NC(=O)NC1=CC=CN=C1 LYHVJYYVAHOIOZ-UHFFFAOYSA-N 0.000 claims description 2
- WOGPOVFUVILBEW-UHFFFAOYSA-N 1-[3-(dimethylamino)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)=C1 WOGPOVFUVILBEW-UHFFFAOYSA-N 0.000 claims description 2
- ZTLYDMQLSAICDR-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCCCN(C)C)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C)C2=N1 ZTLYDMQLSAICDR-UHFFFAOYSA-N 0.000 claims description 2
- WAOKYKONZRCFJW-UHFFFAOYSA-N 1-[3-(hydroxymethyl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound OCC1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)=C1 WAOKYKONZRCFJW-UHFFFAOYSA-N 0.000 claims description 2
- UHVGWFGAZNCSFU-UHFFFAOYSA-N 1-[4-(2-hydroxyethoxy)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(OCCO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 UHVGWFGAZNCSFU-UHFFFAOYSA-N 0.000 claims description 2
- SAXVGQAUJGTTDG-UHFFFAOYSA-N 1-[4-(2-hydroxyethyl)phenyl]-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CCO)C=C1 SAXVGQAUJGTTDG-UHFFFAOYSA-N 0.000 claims description 2
- CKICPWIYCQZPMV-UHFFFAOYSA-N 1-[4-(2-hydroxyethyl)phenyl]-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(CCO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CCC3COC4)N=2)C=C1 CKICPWIYCQZPMV-UHFFFAOYSA-N 0.000 claims description 2
- MURNNMKLHXSXQC-UHFFFAOYSA-N 1-[4-(2-hydroxyethyl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(CCO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 MURNNMKLHXSXQC-UHFFFAOYSA-N 0.000 claims description 2
- ZYENMTFOLXJCOD-SFTDATJTSA-N 1-[4-(2-hydroxyethyl)phenyl]-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CCO)C=C1 ZYENMTFOLXJCOD-SFTDATJTSA-N 0.000 claims description 2
- RBVTXOAIFJHNSX-UHFFFAOYSA-N 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-oxocyclohexyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C4CCC(=O)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 RBVTXOAIFJHNSX-UHFFFAOYSA-N 0.000 claims description 2
- JCDUVMKYALYSCA-UHFFFAOYSA-N 1-[4-(4-methylpiperazin-1-yl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-propoxycyclohexyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CC(OCCC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 JCDUVMKYALYSCA-UHFFFAOYSA-N 0.000 claims description 2
- OGQRLNMAEQPGJF-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CN)C=C1 OGQRLNMAEQPGJF-UHFFFAOYSA-N 0.000 claims description 2
- ODSKIIXTBSXLGG-UHFFFAOYSA-N 1-[4-(aminomethyl)phenyl]-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CN)C=C1 ODSKIIXTBSXLGG-UHFFFAOYSA-N 0.000 claims description 2
- QDQFNJOBXNDVPS-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(N(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 QDQFNJOBXNDVPS-UHFFFAOYSA-N 0.000 claims description 2
- QRPPJJFFSLQATD-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(CO)=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 QRPPJJFFSLQATD-UHFFFAOYSA-N 0.000 claims description 2
- WXBFFWOJWOEYEC-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CO)C=C1 WXBFFWOJWOEYEC-UHFFFAOYSA-N 0.000 claims description 2
- BQEVGAXHNFPCTP-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-[4-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(CO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CCC3COC4)N=2)C=C1 BQEVGAXHNFPCTP-UHFFFAOYSA-N 0.000 claims description 2
- UKWDHIDULSJIRO-UHFFFAOYSA-N 1-[4-(hydroxymethyl)phenyl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(CO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 UKWDHIDULSJIRO-UHFFFAOYSA-N 0.000 claims description 2
- TZFINOAGXDAXAO-PMACEKPBSA-N 1-[4-(hydroxymethyl)phenyl]-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CO)C=C1 TZFINOAGXDAXAO-PMACEKPBSA-N 0.000 claims description 2
- MVWGPMLPVKVJOK-UHFFFAOYSA-N 1-[4-[(dimethylamino)methyl]phenyl]-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CN(C)C)C=C1 MVWGPMLPVKVJOK-UHFFFAOYSA-N 0.000 claims description 2
- XHNJXQFICQUYRG-UHFFFAOYSA-N 1-[4-[(dimethylamino)methyl]phenyl]-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CN(C)C)C=C1 XHNJXQFICQUYRG-UHFFFAOYSA-N 0.000 claims description 2
- HXNLDHXVQFPKQT-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-piperazin-1-ylphenyl)urea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCNCC1 HXNLDHXVQFPKQT-UHFFFAOYSA-N 0.000 claims description 2
- PDSIPAZDJRNBMR-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCN(C)CC1 PDSIPAZDJRNBMR-UHFFFAOYSA-N 0.000 claims description 2
- DZTUYZSGISMBPY-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(dimethylaminocarbamoyl)phenyl]urea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C(=O)NN(C)C)C=C1 DZTUYZSGISMBPY-UHFFFAOYSA-N 0.000 claims description 2
- LQYGYODYVJISNS-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C(COC)COC)C2=N1 LQYGYODYVJISNS-UHFFFAOYSA-N 0.000 claims description 2
- NCUVYNDKUYLZDH-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C(COC)COC)C2=N1 NCUVYNDKUYLZDH-UHFFFAOYSA-N 0.000 claims description 2
- AYTHJCRLZQMVOO-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 AYTHJCRLZQMVOO-UHFFFAOYSA-N 0.000 claims description 2
- OAIVJKNKEIZODY-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 OAIVJKNKEIZODY-UHFFFAOYSA-N 0.000 claims description 2
- WNVWRJZTELCKHK-UHFFFAOYSA-N 1-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 WNVWRJZTELCKHK-UHFFFAOYSA-N 0.000 claims description 2
- LRLKPJBRGFJMKN-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound C1=CC(NC(=O)NCCF)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 LRLKPJBRGFJMKN-UHFFFAOYSA-N 0.000 claims description 2
- RSYAVMKTTXMNDN-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound C1=CC(NC(=O)NCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 RSYAVMKTTXMNDN-UHFFFAOYSA-N 0.000 claims description 2
- UQCOTILHWVGDGS-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound C1CN(C)CCN1CCNC(=O)NC1=CC=C(C=2N=C3N(C4CCC5(CC4)OCCO5)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 UQCOTILHWVGDGS-UHFFFAOYSA-N 0.000 claims description 2
- YCAGJYZYGLPLRL-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 YCAGJYZYGLPLRL-UHFFFAOYSA-N 0.000 claims description 2
- VBYNNESGSHUXND-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound C=1C=C(C=2N=C3N(C4CCC5(CC4)OCCO5)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CC=C1 VBYNNESGSHUXND-UHFFFAOYSA-N 0.000 claims description 2
- QYCBARGBDSITAT-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=CN=CC=1NC(=O)NC(C=C1)=CC=C1C(N=C12)=NC(N3CC4CCC(O4)C3)=C1C=NN2C(CC1)CCC21OCCO2 QYCBARGBDSITAT-UHFFFAOYSA-N 0.000 claims description 2
- HGTXRLXWYACZEB-UHFFFAOYSA-N 1-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C=1C=C(C=2N=C3N(C4CCC5(CC4)OCCO5)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=NC=C1 HGTXRLXWYACZEB-UHFFFAOYSA-N 0.000 claims description 2
- QEZCXGHWXXLBFJ-UHFFFAOYSA-N 1-[4-[1-(1,5-dioxaspiro[5.5]undecan-9-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCCO4)C2=N1 QEZCXGHWXXLBFJ-UHFFFAOYSA-N 0.000 claims description 2
- GYOUBQRXSAHJQZ-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-morpholin-4-ylphenyl)urea Chemical compound C=1C=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 GYOUBQRXSAHJQZ-UHFFFAOYSA-N 0.000 claims description 2
- VLWYJTAQQPZAJL-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(6-morpholin-4-ylpyridin-3-yl)urea Chemical compound C=1C=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 VLWYJTAQQPZAJL-UHFFFAOYSA-N 0.000 claims description 2
- PYMQNCNMPKYHRR-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-hydroxyethyl)phenyl]urea Chemical compound C1=CC(CCO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 PYMQNCNMPKYHRR-UHFFFAOYSA-N 0.000 claims description 2
- ZLEWXVNORLUUGZ-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 ZLEWXVNORLUUGZ-UHFFFAOYSA-N 0.000 claims description 2
- XONAXDSGGBMHNG-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(hydroxymethyl)phenyl]urea Chemical compound C1=CC(CO)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 XONAXDSGGBMHNG-UHFFFAOYSA-N 0.000 claims description 2
- UMLKHSOFLLPNQK-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-[2-(dimethylamino)ethoxy]phenyl]urea Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 UMLKHSOFLLPNQK-UHFFFAOYSA-N 0.000 claims description 2
- NFFZXYXQSLXDSU-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 NFFZXYXQSLXDSU-UHFFFAOYSA-N 0.000 claims description 2
- YXYABVGBCDZUIA-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-cyclopropylurea Chemical compound C=1C=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1CC1 YXYABVGBCDZUIA-UHFFFAOYSA-N 0.000 claims description 2
- HJLBILJRSZZKJL-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCC#N)C2=N1 HJLBILJRSZZKJL-UHFFFAOYSA-N 0.000 claims description 2
- YFADXJFERUTOIB-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CN=C1 YFADXJFERUTOIB-UHFFFAOYSA-N 0.000 claims description 2
- RMJJDRYOMQIVJI-UHFFFAOYSA-N 1-[4-[1-(2-cyanoethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C=1C=C(C=2N=C3N(CCC#N)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=NC=C1 RMJJDRYOMQIVJI-UHFFFAOYSA-N 0.000 claims description 2
- IUCRTPCEYKAVPS-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-morpholin-4-ylphenyl)urea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 IUCRTPCEYKAVPS-UHFFFAOYSA-N 0.000 claims description 2
- ZSUJALVCGZXBPH-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(6-morpholin-4-ylpyridin-3-yl)urea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 ZSUJALVCGZXBPH-UHFFFAOYSA-N 0.000 claims description 2
- SIDHSIRXTZBQCO-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCO)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 SIDHSIRXTZBQCO-UHFFFAOYSA-N 0.000 claims description 2
- YYSOROXNNPPLPX-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(hydroxymethyl)phenyl]urea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CO)C=C1 YYSOROXNNPPLPX-UHFFFAOYSA-N 0.000 claims description 2
- ZGURBBLDZYAUKZ-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CCO)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 ZGURBBLDZYAUKZ-UHFFFAOYSA-N 0.000 claims description 2
- JLRPIYJFNRMCDO-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCO)C2=N1 JLRPIYJFNRMCDO-UHFFFAOYSA-N 0.000 claims description 2
- CKZGHSVVDWPYPE-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 CKZGHSVVDWPYPE-UHFFFAOYSA-N 0.000 claims description 2
- VQSNOIJAOVHRGF-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 VQSNOIJAOVHRGF-UHFFFAOYSA-N 0.000 claims description 2
- CAJRWBWOMGUTOF-UHFFFAOYSA-N 1-[4-[1-(2-hydroxyethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(CCO)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 CAJRWBWOMGUTOF-UHFFFAOYSA-N 0.000 claims description 2
- RZERWDKPRCXFKM-UHFFFAOYSA-N 1-[4-[1-(4,4-dimethoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)(OC)OC)C2=N1 RZERWDKPRCXFKM-UHFFFAOYSA-N 0.000 claims description 2
- ZTEKLKSMMFAWQB-UHFFFAOYSA-N 1-[4-[1-(4-ethoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CC(OCC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 ZTEKLKSMMFAWQB-UHFFFAOYSA-N 0.000 claims description 2
- KJWBIIIGQKNAHW-UHFFFAOYSA-N 1-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-piperazin-1-ylphenyl)urea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCNCC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 KJWBIIIGQKNAHW-UHFFFAOYSA-N 0.000 claims description 2
- SYKXTQULDCRVJS-UHFFFAOYSA-N 1-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 SYKXTQULDCRVJS-UHFFFAOYSA-N 0.000 claims description 2
- VATMREWLTYGLRS-UHFFFAOYSA-N 1-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=NC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 VATMREWLTYGLRS-UHFFFAOYSA-N 0.000 claims description 2
- JSXSGODQMDFQIZ-UHFFFAOYSA-N 1-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=NC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 JSXSGODQMDFQIZ-UHFFFAOYSA-N 0.000 claims description 2
- WYJZUOPYCRSROU-UHFFFAOYSA-N 1-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CN=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 WYJZUOPYCRSROU-UHFFFAOYSA-N 0.000 claims description 2
- ZZISZBHZKQPWHE-UHFFFAOYSA-N 1-[4-[1-[1-(2-methoxybenzoyl)piperidin-4-yl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC3)C(=O)C=3C(=CC=CC=3)OC)C2=N1 ZZISZBHZKQPWHE-UHFFFAOYSA-N 0.000 claims description 2
- JOYQWGOVTXHHHZ-UHFFFAOYSA-N 1-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound C1CN(C(=O)C(C)C)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 JOYQWGOVTXHHHZ-UHFFFAOYSA-N 0.000 claims description 2
- AWUHGWHQDJVGFK-UHFFFAOYSA-N 1-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C1CN(C(=O)C(C)C)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=NC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 AWUHGWHQDJVGFK-UHFFFAOYSA-N 0.000 claims description 2
- UPGZHLYKVZADRQ-UHFFFAOYSA-N 1-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C1CN(C(=O)C(C)C)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CN=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 UPGZHLYKVZADRQ-UHFFFAOYSA-N 0.000 claims description 2
- DCBCEXPXWXJOKW-UHFFFAOYSA-N 1-[4-[1-[1-(3-acetylbenzoyl)piperidin-4-yl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC3)C(=O)C=3C=C(C=CC=3)C(C)=O)C2=N1 DCBCEXPXWXJOKW-UHFFFAOYSA-N 0.000 claims description 2
- ALHMYQNCSUHAKI-UHFFFAOYSA-N 1-[4-[1-[1-[(6-bromopyridin-3-yl)methyl]piperidin-4-yl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC=4C=NC(Br)=CC=4)CC3)C2=N1 ALHMYQNCSUHAKI-UHFFFAOYSA-N 0.000 claims description 2
- AZZAJNGNFJIPRH-UHFFFAOYSA-N 1-[4-[1-[4-(2,2-dimethylhydrazinyl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)NN(C)C)C2=N1 AZZAJNGNFJIPRH-UHFFFAOYSA-N 0.000 claims description 2
- GTWCTQSVXFCJEK-UHFFFAOYSA-N 1-[4-[1-[4-(2-hydroxyethylamino)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)NCCO)C2=N1 GTWCTQSVXFCJEK-UHFFFAOYSA-N 0.000 claims description 2
- GMSMKYNFVQSVJU-UHFFFAOYSA-N 1-[4-[1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound C1CN(C)CCN1C1CCC(N2C3=NC(=NC(=C3C=N2)N2CC3CCC(O3)C2)C=2C=CC(NC(=O)NC=3C=CC=CC=3)=CC=2)CC1 GMSMKYNFVQSVJU-UHFFFAOYSA-N 0.000 claims description 2
- WYTADYJFVUAVOT-UHFFFAOYSA-N 1-[4-[1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C1CN(C)CCN1C1CCC(N2C3=NC(=NC(=C3C=N2)N2CC3CCC(O3)C2)C=2C=CC(NC(=O)NC=3C=NC=CC=3)=CC=2)CC1 WYTADYJFVUAVOT-UHFFFAOYSA-N 0.000 claims description 2
- UPBUHFORXUZSRN-UHFFFAOYSA-N 1-[4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-ethylurea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC=3C=CC=CC=3)C2=N1 UPBUHFORXUZSRN-UHFFFAOYSA-N 0.000 claims description 2
- NCKXTAXYVPUKBK-UHFFFAOYSA-N 1-[4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC=3C=CC=CC=3)C2=N1 NCKXTAXYVPUKBK-UHFFFAOYSA-N 0.000 claims description 2
- NIHOWXYNRHYKFX-UHFFFAOYSA-N 1-[4-[1-benzyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C=1C=C(C=2N=C3N(CC=4C=CC=CC=4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=NC=C1 NIHOWXYNRHYKFX-UHFFFAOYSA-N 0.000 claims description 2
- JQEACQXIVNPOGS-UHFFFAOYSA-N 1-[4-[1-ethyl-3-(4-methylpiperazin-1-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C12=C(N3CC4CCC(O4)C3)N=C(C=3C=CC(NC(=O)NC)=CC=3)N=C2N(CC)N=C1N1CCN(C)CC1 JQEACQXIVNPOGS-UHFFFAOYSA-N 0.000 claims description 2
- RCHWHILZANOZHZ-UHFFFAOYSA-N 1-[4-[1-ethyl-3-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C12=C(N3CC4CCC(O4)C3)N=C(C=3C=CC(NC(=O)NC)=CC=3)N=C2N(CC)N=C1CN1CCN(C)CC1 RCHWHILZANOZHZ-UHFFFAOYSA-N 0.000 claims description 2
- RSKRPMNJXANSOH-UHFFFAOYSA-N 1-[4-[1-ethyl-3-formyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=C(C=O)C2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NC)C=C1 RSKRPMNJXANSOH-UHFFFAOYSA-N 0.000 claims description 2
- ZKHQUVNCZZHVBY-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-pyrrolidin-1-ylethoxy)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1OCCN1CCCC1 ZKHQUVNCZZHVBY-UHFFFAOYSA-N 0.000 claims description 2
- REAZWRUWNZTALY-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCN(C)CC1 REAZWRUWNZTALY-UHFFFAOYSA-N 0.000 claims description 2
- UFTUVGIEUVBLOO-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1CN1CCN(C)CC1 UFTUVGIEUVBLOO-UHFFFAOYSA-N 0.000 claims description 2
- VZPAKKAWVXZJOO-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCN(C)CC1 VZPAKKAWVXZJOO-UHFFFAOYSA-N 0.000 claims description 2
- MKVPTYVBNXITMH-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C1=CC=C(NC(=O)NC)C=C1 MKVPTYVBNXITMH-UHFFFAOYSA-N 0.000 claims description 2
- ISKUMKPOLBEELU-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 ISKUMKPOLBEELU-UHFFFAOYSA-N 0.000 claims description 2
- XRIMHGBOUOLHBI-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 XRIMHGBOUOLHBI-UHFFFAOYSA-N 0.000 claims description 2
- AWTBEQWBRRKGKB-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 AWTBEQWBRRKGKB-UHFFFAOYSA-N 0.000 claims description 2
- FFSFJYJABLLMKY-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(1-methylpiperidin-4-yl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CCN(C)CC1 FFSFJYJABLLMKY-UHFFFAOYSA-N 0.000 claims description 2
- PTVAHFLJYTVLPN-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(2-fluoroethyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NCCF)C=C1 PTVAHFLJYTVLPN-UHFFFAOYSA-N 0.000 claims description 2
- SBGTVFMGDAHBNE-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(2-hydroxyethyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NCCO)C=C1 SBGTVFMGDAHBNE-UHFFFAOYSA-N 0.000 claims description 2
- UBTJIBVOHICGEY-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(2-morpholin-4-ylethyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NCCN1CCOCC1 UBTJIBVOHICGEY-UHFFFAOYSA-N 0.000 claims description 2
- DDPCJPFCPSGJOG-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-methoxyphenyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(OC)C=C1 DDPCJPFCPSGJOG-UHFFFAOYSA-N 0.000 claims description 2
- YFUIEEMMAVGYTI-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-methylphenyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C)C=C1 YFUIEEMMAVGYTI-UHFFFAOYSA-N 0.000 claims description 2
- MHEFFNLOVMOWPU-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-morpholin-4-ylphenyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 MHEFFNLOVMOWPU-UHFFFAOYSA-N 0.000 claims description 2
- OIZVMINJTWHORX-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-piperazin-1-ylphenyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCNCC1 OIZVMINJTWHORX-UHFFFAOYSA-N 0.000 claims description 2
- WLTGGZJCDZMNBZ-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-pyrrolidin-1-ylphenyl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCCC1 WLTGGZJCDZMNBZ-UHFFFAOYSA-N 0.000 claims description 2
- RCWCYHYCUNPFSO-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(6-morpholin-4-ylpyridin-3-yl)urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 RCWCYHYCUNPFSO-UHFFFAOYSA-N 0.000 claims description 2
- WTXTUPLZVSNWLB-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[(1-methylpiperidin-4-yl)methyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NCC1CCN(C)CC1 WTXTUPLZVSNWLB-UHFFFAOYSA-N 0.000 claims description 2
- XGIZKKOTRRCGLQ-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NCC(=O)N1CCN(C)CC1 XGIZKKOTRRCGLQ-UHFFFAOYSA-N 0.000 claims description 2
- CXNZGMDFFGLRLY-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[2-(4-methylpiperazin-1-yl)ethyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NCCN1CCN(C)CC1 CXNZGMDFFGLRLY-UHFFFAOYSA-N 0.000 claims description 2
- KJAJGXINFQAKHZ-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[2-(methylamino)ethyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NCCNC)C=C1 KJAJGXINFQAKHZ-UHFFFAOYSA-N 0.000 claims description 2
- UTMQDJIIJVAEMU-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[3-(4-methylpiperazin-1-yl)-3-oxopropyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NCCC(=O)N1CCN(C)CC1 UTMQDJIIJVAEMU-UHFFFAOYSA-N 0.000 claims description 2
- NEMWIAVOKJWJCS-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[3-(methylamino)propyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NCCCNC)C=C1 NEMWIAVOKJWJCS-UHFFFAOYSA-N 0.000 claims description 2
- JQGIMHVWTOXCTP-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-hydroxyethoxy)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(OCCO)C=C1 JQGIMHVWTOXCTP-UHFFFAOYSA-N 0.000 claims description 2
- ATLHTKSZGMIXLX-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-hydroxyethyl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CCO)C=C1 ATLHTKSZGMIXLX-UHFFFAOYSA-N 0.000 claims description 2
- KYUFDBIYWRJMMF-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCN(C)CC1 KYUFDBIYWRJMMF-UHFFFAOYSA-N 0.000 claims description 2
- HNNBGLRKAYUYCE-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(hydroxymethyl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(CO)C=C1 HNNBGLRKAYUYCE-UHFFFAOYSA-N 0.000 claims description 2
- JGCLMPLLEOAPAC-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(pyrrolidin-1-ylmethyl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1CN1CCCC1 JGCLMPLLEOAPAC-UHFFFAOYSA-N 0.000 claims description 2
- FTRSKAKWKUDZKU-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1CN1CCN(C)CC1 FTRSKAKWKUDZKU-UHFFFAOYSA-N 0.000 claims description 2
- YDFWAAMONNHYQX-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(2-hydroxyethoxy)pyridin-3-yl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(OCCO)N=C1 YDFWAAMONNHYQX-UHFFFAOYSA-N 0.000 claims description 2
- LSPYTXAQSKEIJE-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(2-morpholin-4-ylethoxy)pyridin-3-yl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1OCCN1CCOCC1 LSPYTXAQSKEIJE-UHFFFAOYSA-N 0.000 claims description 2
- VKSCSFHLPAAEGS-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCN(C)CC1 VKSCSFHLPAAEGS-UHFFFAOYSA-N 0.000 claims description 2
- ARKRGLDVMPXTLI-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(methylamino)pyridin-3-yl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(NC)N=C1 ARKRGLDVMPXTLI-UHFFFAOYSA-N 0.000 claims description 2
- DPFONBIFXAOZIL-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NC)C=C1 DPFONBIFXAOZIL-UHFFFAOYSA-N 0.000 claims description 2
- ADCADUHNSKXDGZ-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 ADCADUHNSKXDGZ-UHFFFAOYSA-N 0.000 claims description 2
- AUXKCHHCFDLRBV-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 AUXKCHHCFDLRBV-UHFFFAOYSA-N 0.000 claims description 2
- OIUUQUNTDMZTRN-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 OIUUQUNTDMZTRN-UHFFFAOYSA-N 0.000 claims description 2
- UGUVKBXJXFNVFA-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-methylsulfonylphenyl)urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(S(C)(=O)=O)C=C1 UGUVKBXJXFNVFA-UHFFFAOYSA-N 0.000 claims description 2
- HOYKWWOQTAMPCR-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-morpholin-4-ylphenyl)urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCOCC1 HOYKWWOQTAMPCR-UHFFFAOYSA-N 0.000 claims description 2
- UFQYFACWJGZKBQ-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(6-morpholin-4-ylpyridin-3-yl)urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=N1)=CC=C1N1CCOCC1 UFQYFACWJGZKBQ-UHFFFAOYSA-N 0.000 claims description 2
- IEWKJELUKQVDKG-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(2-piperidin-1-ylethylsulfonyl)phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1S(=O)(=O)CCN1CCCCC1 IEWKJELUKQVDKG-UHFFFAOYSA-N 0.000 claims description 2
- YQGJXFKRKDSFOO-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(4-methylpiperazin-1-yl)phenyl]urea Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 YQGJXFKRKDSFOO-UHFFFAOYSA-N 0.000 claims description 2
- POANRMCBZWELLZ-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]urea Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 POANRMCBZWELLZ-UHFFFAOYSA-N 0.000 claims description 2
- GIQRDHHCACLCDO-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 GIQRDHHCACLCDO-UHFFFAOYSA-N 0.000 claims description 2
- MAMRCWLIONFVJH-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 MAMRCWLIONFVJH-UHFFFAOYSA-N 0.000 claims description 2
- GHDIKFLCCIGIID-UHFFFAOYSA-N 1-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 GHDIKFLCCIGIID-UHFFFAOYSA-N 0.000 claims description 2
- SUAHTQMBINZOHP-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(OCCN(C)C)C=C1 SUAHTQMBINZOHP-UHFFFAOYSA-N 0.000 claims description 2
- PZMZFBMKDSXMES-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(OCCN(C)C)C=C1 PZMZFBMKDSXMES-UHFFFAOYSA-N 0.000 claims description 2
- OSGQEEGQMFEXAB-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-[4-[4-(3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4COCC3COC4)N=2)C=C1 OSGQEEGQMFEXAB-UHFFFAOYSA-N 0.000 claims description 2
- OCKKJHVJQPASQW-UHFFFAOYSA-N 1-[4-[2-(dimethylamino)ethoxy]phenyl]-3-[4-[4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4CNCC3COC4)N=2)C=C1 OCKKJHVJQPASQW-UHFFFAOYSA-N 0.000 claims description 2
- FBZDNEIODKLVDN-UHFFFAOYSA-N 1-[4-[3-(1,2-dihydroxyethyl)-1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=C(C(O)CO)C2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NC)C=C1 FBZDNEIODKLVDN-UHFFFAOYSA-N 0.000 claims description 2
- GWQJCRNIPKKUFO-UHFFFAOYSA-N 1-[4-[3-bromo-1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=C(Br)C2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NC)C=C1 GWQJCRNIPKKUFO-UHFFFAOYSA-N 0.000 claims description 2
- JEJCRWFEOZVUSQ-UHFFFAOYSA-N 1-[4-[3-ethenyl-1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound N1=C2N(CC)N=C(C=C)C2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)NC)C=C1 JEJCRWFEOZVUSQ-UHFFFAOYSA-N 0.000 claims description 2
- IDJREHHFYLMPLX-UHFFFAOYSA-N 1-[4-[4-(3,7-dioxa-9-azabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2C3COCC2COC3)=C(C=NN2CC(F)(F)F)C2=N1 IDJREHHFYLMPLX-UHFFFAOYSA-N 0.000 claims description 2
- XFXAJYFCPLMACD-UHFFFAOYSA-N 1-[4-[4-(3-acetyl-9-oxa-3,7-diazabicyclo[3.3.1]nonan-7-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C1C(O2)CN(C(=O)C)CC2CN1C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 XFXAJYFCPLMACD-UHFFFAOYSA-N 0.000 claims description 2
- PRMNLVQQVAFCRJ-UHFFFAOYSA-N 1-[4-[4-(6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3OCC(O3)C2)=C(C=NN2C)C2=N1 PRMNLVQQVAFCRJ-UHFFFAOYSA-N 0.000 claims description 2
- ZWBNLUMFYUXGMK-UHFFFAOYSA-N 1-[4-[4-(6-hydroxy-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-methylurea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2C3C(O)CC2COC3)=C(C=NN2CC(F)(F)F)C2=N1 ZWBNLUMFYUXGMK-UHFFFAOYSA-N 0.000 claims description 2
- LVOMIMOWTKHHCX-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-pyrrolidin-1-ylcyclohexyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=CN=CC=1NC(=O)NC(C=C1)=CC=C1C(N=C12)=NC(N3CC4CCC(O4)C3)=C1C=NN2C(CC1)CCC1N1CCCC1 LVOMIMOWTKHHCX-UHFFFAOYSA-N 0.000 claims description 2
- YXLIUTQVEMJFQR-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound C=1C=C(C=2N=C3N(C4CCN(CC=5C=NC=CC=5)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CC=C1 YXLIUTQVEMJFQR-UHFFFAOYSA-N 0.000 claims description 2
- LCHYMODHMGJDEG-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=CN=CC=1NC(=O)NC(C=C1)=CC=C1C(N=C12)=NC(N3CC4CCC(O4)C3)=C1C=NN2C(CC1)CCN1CC1=CC=CN=C1 LCHYMODHMGJDEG-UHFFFAOYSA-N 0.000 claims description 2
- YHOJJHQLBNYACI-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C=1C=C(C=2N=C3N(C4CCN(CC=5C=NC=CC=5)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=NC=C1 YHOJJHQLBNYACI-UHFFFAOYSA-N 0.000 claims description 2
- IEUHFTUDDSBTPZ-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound C=1C=C(C=2N=C3N(C4CCNCC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CC=C1 IEUHFTUDDSBTPZ-UHFFFAOYSA-N 0.000 claims description 2
- JXMJEHGYAODUJF-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-phenylurea Chemical compound N1=C2N(C(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CC=C1 JXMJEHGYAODUJF-UHFFFAOYSA-N 0.000 claims description 2
- QGMKUMYDPUQICJ-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound N1=C2N(C(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 QGMKUMYDPUQICJ-UHFFFAOYSA-N 0.000 claims description 2
- IYEVLTXSGWCTAD-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(C(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 IYEVLTXSGWCTAD-UHFFFAOYSA-N 0.000 claims description 2
- VROHDVQPMGULKN-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-phenylurea Chemical compound C=1C=C(C=2N=C3C=CSC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CC=C1 VROHDVQPMGULKN-UHFFFAOYSA-N 0.000 claims description 2
- IKYYAFMKEGKZGC-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C=1C=C(C=2N=C3C=CSC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=CN=C1 IKYYAFMKEGKZGC-UHFFFAOYSA-N 0.000 claims description 2
- BOCKHNDSVLBIHB-UHFFFAOYSA-N 1-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C=1C=C(C=2N=C3C=CSC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1=CC=NC=C1 BOCKHNDSVLBIHB-UHFFFAOYSA-N 0.000 claims description 2
- YCEUUXAHOHKAHA-UHFFFAOYSA-N 1-[4-[4-(9-oxa-3,7-diazabicyclo[3.3.1]nonan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2CC3CNCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 YCEUUXAHOHKAHA-UHFFFAOYSA-N 0.000 claims description 2
- RJGLKNSJUHURHU-QZTJIDSGSA-N 1-[4-[4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C([C@@]1(OC[C@@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 RJGLKNSJUHURHU-QZTJIDSGSA-N 0.000 claims description 2
- KCNLNGDCXVYHOV-GOTSBHOMSA-N 1-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-(4-piperazin-1-ylphenyl)urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1N1CCNCC1 KCNLNGDCXVYHOV-GOTSBHOMSA-N 0.000 claims description 2
- RJGLKNSJUHURHU-ROUUACIJSA-N 1-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=CN=C1 RJGLKNSJUHURHU-ROUUACIJSA-N 0.000 claims description 2
- IHBUIHVFHMETRB-UHFFFAOYSA-N 1-[4-[6-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-3-ylurea Chemical compound C1CN(C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC=4C=NC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 IHBUIHVFHMETRB-UHFFFAOYSA-N 0.000 claims description 2
- HCDQTNKVRADZCI-UHFFFAOYSA-N 1-[4-[6-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-pyridin-4-ylurea Chemical compound C1CN(C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC=4C=CN=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 HCDQTNKVRADZCI-UHFFFAOYSA-N 0.000 claims description 2
- MUHQNYNRDBOJBC-UHFFFAOYSA-N 1-[4-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]-3-phenylurea Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC=4C=CC=CC=4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 MUHQNYNRDBOJBC-UHFFFAOYSA-N 0.000 claims description 2
- MTIARLQVNAAYGF-UHFFFAOYSA-N 1-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C)CCN1C(N=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 MTIARLQVNAAYGF-UHFFFAOYSA-N 0.000 claims description 2
- ZRLCNRCZZGRZFX-UHFFFAOYSA-N 1-[6-(dimethylamino)pyridin-3-yl]-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=C(N(C)C)N=C1 ZRLCNRCZZGRZFX-UHFFFAOYSA-N 0.000 claims description 2
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 claims description 2
- MFTYVNINGHVIAZ-UHFFFAOYSA-N 1-cyclobutyl-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1CCC1 MFTYVNINGHVIAZ-UHFFFAOYSA-N 0.000 claims description 2
- MMBMMCNNHSRFHN-UHFFFAOYSA-N 1-cyclobutyl-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CCC1 MMBMMCNNHSRFHN-UHFFFAOYSA-N 0.000 claims description 2
- YZGNQXOACOIHPE-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CCCCC1 YZGNQXOACOIHPE-UHFFFAOYSA-N 0.000 claims description 2
- FZMBSBWLFYCGKO-UHFFFAOYSA-N 1-cyclopentyl-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1CCCC1 FZMBSBWLFYCGKO-UHFFFAOYSA-N 0.000 claims description 2
- QYDXAFZEYDCSCJ-UHFFFAOYSA-N 1-cyclopentyl-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CCCC1 QYDXAFZEYDCSCJ-UHFFFAOYSA-N 0.000 claims description 2
- WNUHYBGWXNXCSK-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 WNUHYBGWXNXCSK-UHFFFAOYSA-N 0.000 claims description 2
- ZTNUCBXTEODPOV-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C(=O)C(C)C)CCC1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 ZTNUCBXTEODPOV-UHFFFAOYSA-N 0.000 claims description 2
- XYMCMQNRZAYJFU-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1CCC(N2C3=NC(=NC(=C3C=N2)N2CC3CCC(O3)C2)C=2C=CC(NC(=O)NC3CC3)=CC=2)CC1 XYMCMQNRZAYJFU-UHFFFAOYSA-N 0.000 claims description 2
- MNULAUCQBUJRSU-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 MNULAUCQBUJRSU-UHFFFAOYSA-N 0.000 claims description 2
- KCCHNABARLWHHJ-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 KCCHNABARLWHHJ-UHFFFAOYSA-N 0.000 claims description 2
- XCQIYNDFAUQWDO-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 XCQIYNDFAUQWDO-UHFFFAOYSA-N 0.000 claims description 2
- QXXPDHWWQICWNI-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(CC(F)(F)F)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 QXXPDHWWQICWNI-UHFFFAOYSA-N 0.000 claims description 2
- ZHQTWCWSCZLANL-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound N1=C2N(C(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1CC1 ZHQTWCWSCZLANL-UHFFFAOYSA-N 0.000 claims description 2
- HBZPGFLLAMADHT-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C=1C=C(C=2N=C3C=CSC3=C(N3CC4CCC(O4)C3)N=2)C=CC=1NC(=O)NC1CC1 HBZPGFLLAMADHT-UHFFFAOYSA-N 0.000 claims description 2
- KPSKKPDRNSLZRB-HZPDHXFCSA-N 1-cyclopropyl-3-[4-[4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@@]1(OC[C@@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1CC1 KPSKKPDRNSLZRB-HZPDHXFCSA-N 0.000 claims description 2
- ASHVJCPRWLMYPH-UHFFFAOYSA-N 1-cyclopropyl-3-[4-[6-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1CN(C)CCN1CC1=CC2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2S1 ASHVJCPRWLMYPH-UHFFFAOYSA-N 0.000 claims description 2
- FDLVQFRXPKVPPN-UHFFFAOYSA-N 1-ethyl-3-[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)OC)C2=N1 FDLVQFRXPKVPPN-UHFFFAOYSA-N 0.000 claims description 2
- CUNNEAHMWONEIJ-UHFFFAOYSA-N 1-ethyl-3-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC3)C(=O)C(C)C)C2=N1 CUNNEAHMWONEIJ-UHFFFAOYSA-N 0.000 claims description 2
- ZXXBGPFLOBZGTR-UHFFFAOYSA-N 1-ethyl-3-[4-[1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)N3CCN(C)CC3)C2=N1 ZXXBGPFLOBZGTR-UHFFFAOYSA-N 0.000 claims description 2
- FZZHKLCKAGUQLD-UHFFFAOYSA-N 1-ethyl-3-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2C3CCC2COC3)=C(C=NN2CC)C2=N1 FZZHKLCKAGUQLD-UHFFFAOYSA-N 0.000 claims description 2
- DZCKHQBHPTXSEC-UHFFFAOYSA-N 1-ethyl-3-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC)C2=N1 DZCKHQBHPTXSEC-UHFFFAOYSA-N 0.000 claims description 2
- KQLINRHJAKDXAU-UHFFFAOYSA-N 1-ethyl-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C)C2=N1 KQLINRHJAKDXAU-UHFFFAOYSA-N 0.000 claims description 2
- VBYFBAFSCCDPJJ-UHFFFAOYSA-N 1-ethyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 VBYFBAFSCCDPJJ-UHFFFAOYSA-N 0.000 claims description 2
- BMNJFVMKTJUWFA-UHFFFAOYSA-N 1-ethyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC=4C=NC=CC=4)CC3)C2=N1 BMNJFVMKTJUWFA-UHFFFAOYSA-N 0.000 claims description 2
- PBSYYSWMQXZEEP-UHFFFAOYSA-N 1-ethyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C(C)C)C2=N1 PBSYYSWMQXZEEP-UHFFFAOYSA-N 0.000 claims description 2
- XQXVCGDWWAHZSJ-UHFFFAOYSA-N 1-ethyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 XQXVCGDWWAHZSJ-UHFFFAOYSA-N 0.000 claims description 2
- NVKWDJVYEJIVAC-UHFFFAOYSA-N 1-ethyl-3-[4-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC(CN2CCN(CC2)S(C)(=O)=O)=C2)C2=N1 NVKWDJVYEJIVAC-UHFFFAOYSA-N 0.000 claims description 2
- IFCDUAOURDQOHG-UHFFFAOYSA-N 1-methyl-3-[4-[1-[1-(2-methylpropanoyl)piperidin-4-yl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC3)C(=O)C(C)C)C2=N1 IFCDUAOURDQOHG-UHFFFAOYSA-N 0.000 claims description 2
- IWBFIWBQNCLJEG-UHFFFAOYSA-N 1-methyl-3-[4-[1-[1-(2-methylpyridine-3-carbonyl)piperidin-4-yl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC3)C(=O)C=3C(=NC=CC=3)C)C2=N1 IWBFIWBQNCLJEG-UHFFFAOYSA-N 0.000 claims description 2
- QFUOOPGLNQIHSJ-UHFFFAOYSA-N 1-methyl-3-[4-[1-[1-(4-methylpyridine-3-carbonyl)piperidin-4-yl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC3)C(=O)C=3C(=CC=NC=3)C)C2=N1 QFUOOPGLNQIHSJ-UHFFFAOYSA-N 0.000 claims description 2
- OCEMYPICVNLEAL-UHFFFAOYSA-N 1-methyl-3-[4-[1-[4-(4-methylpiperazin-1-yl)cyclohexyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)N3CCN(C)CC3)C2=N1 OCEMYPICVNLEAL-UHFFFAOYSA-N 0.000 claims description 2
- APYPCVRCUBVUDW-UHFFFAOYSA-N 1-methyl-3-[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C)C2=N1 APYPCVRCUBVUDW-UHFFFAOYSA-N 0.000 claims description 2
- PTCNGQVRIOAUFG-UHFFFAOYSA-N 1-methyl-3-[4-[4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2C3CNCC2COC3)=C(C=NN2CC(F)(F)F)C2=N1 PTCNGQVRIOAUFG-UHFFFAOYSA-N 0.000 claims description 2
- LHKWYVSHKLEEJS-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 LHKWYVSHKLEEJS-UHFFFAOYSA-N 0.000 claims description 2
- QUMQCWMSCSDDMX-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(4-pyrrolidin-1-ylcyclohexyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC(CC3)N3CCCC3)C2=N1 QUMQCWMSCSDDMX-UHFFFAOYSA-N 0.000 claims description 2
- DLOCQUMLEMAOPE-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC(F)(F)F)CC3)C2=N1 DLOCQUMLEMAOPE-UHFFFAOYSA-N 0.000 claims description 2
- WOZYVVSCKUPLTE-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC=4C=NC=CC=4)CC3)C2=N1 WOZYVVSCKUPLTE-UHFFFAOYSA-N 0.000 claims description 2
- QAQUVBOSSUCOMU-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C(C)C)C2=N1 QAQUVBOSSUCOMU-UHFFFAOYSA-N 0.000 claims description 2
- ITYGQBOCBCGBAV-UHFFFAOYSA-N 1-methyl-3-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 ITYGQBOCBCGBAV-UHFFFAOYSA-N 0.000 claims description 2
- GBTSKWANNRXPIL-ZIAGYGMSSA-N 1-methyl-3-[4-[4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@@]1(OC[C@@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C1=CC=C(NC(=O)NC)C=C1 GBTSKWANNRXPIL-ZIAGYGMSSA-N 0.000 claims description 2
- GBTSKWANNRXPIL-KBPBESRZSA-N 1-methyl-3-[4-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C1=CC=C(NC(=O)NC)C=C1 GBTSKWANNRXPIL-KBPBESRZSA-N 0.000 claims description 2
- RYTSQRBTBIDDPO-UHFFFAOYSA-N 1-methyl-3-[4-[4-morpholin-4-yl-1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC=4N=CC=CC=4)CC3)C2=N1 RYTSQRBTBIDDPO-UHFFFAOYSA-N 0.000 claims description 2
- YWWSGKYAMVMIMB-UHFFFAOYSA-N 1-methyl-3-[4-[4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC=4C=NC=CC=4)CC3)C2=N1 YWWSGKYAMVMIMB-UHFFFAOYSA-N 0.000 claims description 2
- QYBNTJVELFYLOM-UHFFFAOYSA-N 1-methyl-3-[4-[6-[(4-methylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC(CN2CCN(C)CC2)=C2)C2=N1 QYBNTJVELFYLOM-UHFFFAOYSA-N 0.000 claims description 2
- XUYPPKAYBHIWJO-UHFFFAOYSA-N 1-methyl-3-[4-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC(CN2CCN(CC2)S(C)(=O)=O)=C2)C2=N1 XUYPPKAYBHIWJO-UHFFFAOYSA-N 0.000 claims description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 2
- UNBCXQQDKMJLJR-UHFFFAOYSA-N 2-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]anilino]ethanol Chemical compound C1=CC(NCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 UNBCXQQDKMJLJR-UHFFFAOYSA-N 0.000 claims description 2
- NAUAFJAQVSIKKQ-UHFFFAOYSA-N 2-[6-(4-aminophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]ethanol Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCO)C2=N1 NAUAFJAQVSIKKQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
- FGMZJCUDMPVZPL-UHFFFAOYSA-N 2-fluoroethyl n-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OCCF)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 FGMZJCUDMPVZPL-UHFFFAOYSA-N 0.000 claims description 2
- DLAORXOIJUEBDN-GJZGRUSLSA-N 2-hydroxyethyl N-[4-[4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound [C@@H]12OC[C@@H](N(C1)C1=C3C(=NC(=N1)C1=CC=C(C=C1)NC(OCCO)=O)N(N=C3)CC(F)(F)F)C2 DLAORXOIJUEBDN-GJZGRUSLSA-N 0.000 claims description 2
- JVQGMMPEGNLKNE-UHFFFAOYSA-N 2-hydroxyethyl n-[4-[1-(1,3-dimethoxypropan-2-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound N1=C2N(C(COC)COC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)OCCO)C=C1 JVQGMMPEGNLKNE-UHFFFAOYSA-N 0.000 claims description 2
- DLAORXOIJUEBDN-HUUCEWRRSA-N 2-hydroxyethyl n-[4-[4-[(1r,4r)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OCCO)=CC=C1C1=NC(N2[C@@H]3C[C@@H](OC3)C2)=C(C=NN2CC(F)(F)F)C2=N1 DLAORXOIJUEBDN-HUUCEWRRSA-N 0.000 claims description 2
- JMQPGBQRHYWIGC-UHFFFAOYSA-N 3-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenol Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=CC(O)=C1 JMQPGBQRHYWIGC-UHFFFAOYSA-N 0.000 claims description 2
- GVUAZTSFHDKFPH-UHFFFAOYSA-N 3-[1-ethyl-6-(1h-indol-5-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C(O2)CCC2CN1C1=C2C=NN(CC)C2=NC(C=2C=C3C=CNC3=CC=2)=N1 GVUAZTSFHDKFPH-UHFFFAOYSA-N 0.000 claims description 2
- CMNWKFRKWPPELQ-UHFFFAOYSA-N 3-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenol Chemical compound N1=C2N(C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=CC(O)=C1 CMNWKFRKWPPELQ-UHFFFAOYSA-N 0.000 claims description 2
- XGYOLCHTMBWRGA-UHFFFAOYSA-N 3-[2-(1h-indol-5-yl)thieno[3,2-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1=C2NC=CC2=CC(C=2N=C(C=3SC=CC=3N=2)N2CC3CCC(C2)O3)=C1 XGYOLCHTMBWRGA-UHFFFAOYSA-N 0.000 claims description 2
- IESRDZAZMXANTH-UHFFFAOYSA-N 3-[4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]phenol Chemical compound OC1=CC=CC(C=2N=C3N(C=4C=CC=CC=4)N=CC3=C(N3C4CCC3COC4)N=2)=C1 IESRDZAZMXANTH-UHFFFAOYSA-N 0.000 claims description 2
- XHIBKBRCVQLOJC-UHFFFAOYSA-N 3-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]phenol Chemical compound OC1=CC=CC(C=2N=C3N(C=4C=CC=CC=4)N=CC3=C(N3CC4CCC(O4)C3)N=2)=C1 XHIBKBRCVQLOJC-UHFFFAOYSA-N 0.000 claims description 2
- DCQVJAZICZPUFT-UHFFFAOYSA-N 3-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenol Chemical compound OC1=CC=CC(C=2N=C3C=CSC3=C(N3CC4CCC(O4)C3)N=2)=C1 DCQVJAZICZPUFT-UHFFFAOYSA-N 0.000 claims description 2
- RXVOHEFEHZLXAX-WMZOPIPTSA-N 3-[4-[(1s,4s)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl]-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]phenol Chemical compound C([C@]1(OC[C@]2([H])C1)[H])N2C(C=1C=N2)=NC(C=3C=C(O)C=CC=3)=NC=1N2C1=CC=CC=C1 RXVOHEFEHZLXAX-WMZOPIPTSA-N 0.000 claims description 2
- LWPJUOKZTSXFGN-UHFFFAOYSA-N 3-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=C(C=2N=C3N(C4CCC5(CC4)OCCO5)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 LWPJUOKZTSXFGN-UHFFFAOYSA-N 0.000 claims description 2
- JWHDDZUUGOBHNV-UHFFFAOYSA-N 3-[6-(1h-indol-5-yl)-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1CC(N2C3=NC(=NC(=C3C=N2)N2CC3CCC(O3)C2)C=2C=C3C=CNC3=CC=2)CCN1CC1=CC=CN=C1 JWHDDZUUGOBHNV-UHFFFAOYSA-N 0.000 claims description 2
- IVPDYDHTKYINMP-UHFFFAOYSA-N 4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 IVPDYDHTKYINMP-UHFFFAOYSA-N 0.000 claims description 2
- YTUFNDUAVVBLJJ-UHFFFAOYSA-N 4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 YTUFNDUAVVBLJJ-UHFFFAOYSA-N 0.000 claims description 2
- UDLFOGHOIIYABT-UHFFFAOYSA-N 4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 UDLFOGHOIIYABT-UHFFFAOYSA-N 0.000 claims description 2
- CPEJHBIMMNNRFZ-UHFFFAOYSA-N 4-[[4-[1-(4-methoxycyclohexyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamoylamino]-n-pyrrolidin-1-ylbenzamide Chemical compound C1CC(OC)CCC1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)C(=O)NN4CCCC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 CPEJHBIMMNNRFZ-UHFFFAOYSA-N 0.000 claims description 2
- QWUNRYMMAGVRMS-UHFFFAOYSA-N 4-[[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamoylamino]-n-pyrrolidin-1-ylbenzamide Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1C(=O)NN1CCCC1 QWUNRYMMAGVRMS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- YTNADJDHKAORBK-UHFFFAOYSA-N 5-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 YTNADJDHKAORBK-UHFFFAOYSA-N 0.000 claims description 2
- RQUSSQSOEJOAEP-UHFFFAOYSA-N 5-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]pyrimidin-2-amine Chemical compound C1=NC(N)=NC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 RQUSSQSOEJOAEP-UHFFFAOYSA-N 0.000 claims description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 2
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 2
- 108010024976 Asparaginase Proteins 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- GLPFIJPUIPBENR-RQDRIDHYSA-N C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N([C@@H]4CC[C@@H](O)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N([C@@H]4CC[C@@H](O)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 GLPFIJPUIPBENR-RQDRIDHYSA-N 0.000 claims description 2
- QRFAFGCAVNGXKY-IJDVVPKISA-N C1C[C@@H](O)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](O)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 QRFAFGCAVNGXKY-IJDVVPKISA-N 0.000 claims description 2
- QRFAFGCAVNGXKY-FDRBHKFBSA-N C1C[C@@H](O)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](O)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 QRFAFGCAVNGXKY-FDRBHKFBSA-N 0.000 claims description 2
- SYKXTQULDCRVJS-DPJKZYHESA-N C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 SYKXTQULDCRVJS-DPJKZYHESA-N 0.000 claims description 2
- RIWKUMGHZXCSPC-OIRDZHBESA-N C1C[C@@H](OC)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](OC)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC4CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 RIWKUMGHZXCSPC-OIRDZHBESA-N 0.000 claims description 2
- SYKXTQULDCRVJS-DTVRLADWSA-N C1C[C@@H](OC)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 Chemical compound C1C[C@@H](OC)CC[C@H]1N1C2=NC(C=3C=CC(NC(=O)NC=4C=CC(=CC=4)N4CCN(C)CC4)=CC=3)=NC(N3CC4CCC(O4)C3)=C2C=N1 SYKXTQULDCRVJS-DTVRLADWSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims description 2
- 241000790917 Dioxys <bee> Species 0.000 claims description 2
- MCAHMSDENAOJFZ-UHFFFAOYSA-N Herbimycin A Natural products N1C(=O)C(C)=CC=CC(OC)C(OC(N)=O)C(C)=CC(C)C(OC)C(OC)CC(C)C(OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-UHFFFAOYSA-N 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 claims description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 2
- 229930192392 Mitomycin Natural products 0.000 claims description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 2
- FAUNBOBDFJICCL-XVJQKTIWSA-N N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)N[C@@H]1CC[C@H](N)CC1 Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)N[C@@H]1CC[C@H](N)CC1 FAUNBOBDFJICCL-XVJQKTIWSA-N 0.000 claims description 2
- FAUNBOBDFJICCL-SNXBXODESA-N N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)N[C@H]1CC[C@H](N)CC1 Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)N[C@H]1CC[C@H](N)CC1 FAUNBOBDFJICCL-SNXBXODESA-N 0.000 claims description 2
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 2
- 229960000473 altretamine Drugs 0.000 claims description 2
- 125000005001 aminoaryl group Chemical group 0.000 claims description 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
- 229960004117 capecitabine Drugs 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229960005243 carmustine Drugs 0.000 claims description 2
- QVNZNYAMDUBKRR-UHFFFAOYSA-N chembl595288 Chemical compound C1=CC(O)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 QVNZNYAMDUBKRR-UHFFFAOYSA-N 0.000 claims description 2
- ZDYYEIJLRMPBFE-WHSGIHJSSA-N chembl601445 Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2[C@H]3CC[C@H](CC3)OC)C2=N1 ZDYYEIJLRMPBFE-WHSGIHJSSA-N 0.000 claims description 2
- ZDYYEIJLRMPBFE-GOHCJOFJSA-N chembl602276 Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2[C@@H]3CC[C@H](CC3)OC)C2=N1 ZDYYEIJLRMPBFE-GOHCJOFJSA-N 0.000 claims description 2
- LQBQQAXIISEIGM-VCWRXUFXSA-N chembl606621 Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2[C@H]3CC[C@@H](O)CC3)C2=N1 LQBQQAXIISEIGM-VCWRXUFXSA-N 0.000 claims description 2
- LQBQQAXIISEIGM-RTWGARKQSA-N chembl610630 Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2[C@@H]3CC[C@@H](O)CC3)C2=N1 LQBQQAXIISEIGM-RTWGARKQSA-N 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 229960000684 cytarabine Drugs 0.000 claims description 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 claims description 2
- 229960001842 estramustine Drugs 0.000 claims description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 2
- 235000008191 folinic acid Nutrition 0.000 claims description 2
- 239000011672 folinic acid Substances 0.000 claims description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- 229940045109 genistein Drugs 0.000 claims description 2
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 claims description 2
- 235000006539 genistein Nutrition 0.000 claims description 2
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 claims description 2
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 claims description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 2
- 229960001101 ifosfamide Drugs 0.000 claims description 2
- 229960003685 imatinib mesylate Drugs 0.000 claims description 2
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 claims description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 2
- 229960004768 irinotecan Drugs 0.000 claims description 2
- 229960001691 leucovorin Drugs 0.000 claims description 2
- 229960001614 levamisole Drugs 0.000 claims description 2
- 229960002247 lomustine Drugs 0.000 claims description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 2
- 229960004961 mechlorethamine Drugs 0.000 claims description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 2
- 229960001428 mercaptopurine Drugs 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- FCHXJPIEIHNGJM-UHFFFAOYSA-N methyl n-[4-[1-(1,4-dioxaspiro[4.5]decan-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCC4(CC3)OCCO4)C2=N1 FCHXJPIEIHNGJM-UHFFFAOYSA-N 0.000 claims description 2
- FTFGELDMGOAGIK-UHFFFAOYSA-N methyl n-[4-[1-ethyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound N1=C2N(CC)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(NC(=O)OC)C=C1 FTFGELDMGOAGIK-UHFFFAOYSA-N 0.000 claims description 2
- SQJNNLMDYFXTSS-UHFFFAOYSA-N methyl n-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C(C)C)C2=N1 SQJNNLMDYFXTSS-UHFFFAOYSA-N 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- MMVNGBAMDGGFQY-UHFFFAOYSA-N n-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 MMVNGBAMDGGFQY-UHFFFAOYSA-N 0.000 claims description 2
- LEFZXBFLARQTIC-UHFFFAOYSA-N n-[4-[[4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamoylamino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(C)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 LEFZXBFLARQTIC-UHFFFAOYSA-N 0.000 claims description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
- 239000006186 oral dosage form Substances 0.000 claims description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 2
- 229960001756 oxaliplatin Drugs 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 2
- 229960000624 procarbazine Drugs 0.000 claims description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229940063683 taxotere Drugs 0.000 claims description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
- 229960001278 teniposide Drugs 0.000 claims description 2
- CEPZLSYRIXXARR-UHFFFAOYSA-N tert-butyl 4-[6-[4-(methylcarbamoylamino)phenyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3CCN(CC3)C(=O)OC(C)(C)C)C2=N1 CEPZLSYRIXXARR-UHFFFAOYSA-N 0.000 claims description 2
- QXDYWHWVGFMFNY-UHFFFAOYSA-N tert-butyl 7-[6-[4-(pyridin-4-ylcarbamoylamino)phenyl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(O2)CN(C(=O)OC(C)(C)C)CC2CN1C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 QXDYWHWVGFMFNY-UHFFFAOYSA-N 0.000 claims description 2
- XCNFVVCWUVWYEG-UHFFFAOYSA-N tert-butyl 9-[6-[4-(2-hydroxyethoxycarbonylamino)phenyl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2COCC1N2C(C=1C=NN(CC(F)(F)F)C=1N=1)=NC=1C1=CC=C(NC(=O)OCCO)C=C1 XCNFVVCWUVWYEG-UHFFFAOYSA-N 0.000 claims description 2
- UBCOHNDNSCGERK-UHFFFAOYSA-N tert-butyl 9-[6-[4-(methylcarbamoylamino)phenyl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1=CC(NC(=O)NC)=CC=C1C1=NC(N2C3COCC2CN(C3)C(=O)OC(C)(C)C)=C(C=NN2CC(F)(F)F)C2=N1 UBCOHNDNSCGERK-UHFFFAOYSA-N 0.000 claims description 2
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960003087 tioguanine Drugs 0.000 claims description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 2
- 229960000303 topotecan Drugs 0.000 claims description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 2
- 229960003048 vinblastine Drugs 0.000 claims description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
- 229960004528 vincristine Drugs 0.000 claims description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 claims description 2
- 229960002066 vinorelbine Drugs 0.000 claims description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 8
- ULTTYPMRMMDONC-UHFFFAOYSA-N 5-[(2,5-dihydroxyphenyl)methyl-[(2-hydroxyphenyl)methyl]amino]-2-hydroxybenzoic acid Chemical compound C1=C(O)C(C(=O)O)=CC(N(CC=2C(=CC=CC=2)O)CC=2C(=CC=C(O)C=2)O)=C1 ULTTYPMRMMDONC-UHFFFAOYSA-N 0.000 claims 4
- 206010005003 Bladder cancer Diseases 0.000 claims 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 3
- 201000000849 skin cancer Diseases 0.000 claims 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims 3
- LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 claims 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims 2
- 208000017169 kidney disease Diseases 0.000 claims 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
- 108010092160 Dactinomycin Proteins 0.000 claims 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims 1
- 150000001649 bromium compounds Chemical group 0.000 claims 1
- 229960000640 dactinomycin Drugs 0.000 claims 1
- 229960000975 daunorubicin Drugs 0.000 claims 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 1
- 229960000908 idarubicin Drugs 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- 239000000470 constituent Substances 0.000 abstract description 3
- 235000002639 sodium chloride Nutrition 0.000 description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 94
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
- 239000000243 solution Substances 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 235000013877 carbamide Nutrition 0.000 description 49
- 239000007787 solid Substances 0.000 description 49
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 150000001721 carbon Chemical group 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 27
- 239000003814 drug Substances 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000463 material Substances 0.000 description 21
- 229960005419 nitrogen Drugs 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 229940124597 therapeutic agent Drugs 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000546 pharmaceutical excipient Substances 0.000 description 15
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 14
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 238000013270 controlled release Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 229940124302 mTOR inhibitor Drugs 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000013268 sustained release Methods 0.000 description 12
- 239000012730 sustained-release form Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000002002 slurry Substances 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 239000002775 capsule Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 9
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 8
- ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000012141 concentrate Substances 0.000 description 8
- 235000008504 concentrate Nutrition 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000012948 isocyanate Substances 0.000 description 8
- 150000002513 isocyanates Chemical class 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- 239000000829 suppository Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- KVJIRFGNHAAUNQ-UHFFFAOYSA-N 2,4,6-trichloropyrimidine-5-carbaldehyde Chemical compound ClC1=NC(Cl)=C(C=O)C(Cl)=N1 KVJIRFGNHAAUNQ-UHFFFAOYSA-N 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 239000012038 nucleophile Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 125000006413 ring segment Chemical group 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VCRZEBCHQMOGQZ-UHFFFAOYSA-N 3-(6-chloro-1h-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C(O2)CCC2CN1C1=C(C=NN2)C2=NC(Cl)=N1 VCRZEBCHQMOGQZ-UHFFFAOYSA-N 0.000 description 5
- FYTFCKSXUKINKK-UHFFFAOYSA-N 6,8-dioxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2COC1O2 FYTFCKSXUKINKK-UHFFFAOYSA-N 0.000 description 5
- XADOTNAXKKFKDY-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane;hydrochloride Chemical compound Cl.C1NCC2CCC1O2 XADOTNAXKKFKDY-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- 239000002207 metabolite Substances 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 229940002612 prodrug Drugs 0.000 description 5
- 239000000651 prodrug Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 238000010626 work up procedure Methods 0.000 description 5
- UBUBIMQAMCKQCX-UHFFFAOYSA-N 2,5-dioxa-8-azabicyclo[2.2.2]octane Chemical compound C1OC2CNC1OC2 UBUBIMQAMCKQCX-UHFFFAOYSA-N 0.000 description 4
- KCDXWVLANOYMJG-UHFFFAOYSA-N 2,6-dioxa-8-azabicyclo[2.2.2]octane Chemical compound C1OC2CNC1CO2 KCDXWVLANOYMJG-UHFFFAOYSA-N 0.000 description 4
- YVHBSYTYLQYTOU-UHFFFAOYSA-N 3,6-diazabicyclo[3.1.1]heptane Chemical compound C1NCC2CC1N2 YVHBSYTYLQYTOU-UHFFFAOYSA-N 0.000 description 4
- AYNOATFQHAEZHR-UHFFFAOYSA-N 3,6-dioxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2COC1N2 AYNOATFQHAEZHR-UHFFFAOYSA-N 0.000 description 4
- BXMGZQQTBBJSPP-UHFFFAOYSA-N 3-oxa-6-azabicyclo[3.1.1]heptane Chemical compound C1OCC2CC1N2 BXMGZQQTBBJSPP-UHFFFAOYSA-N 0.000 description 4
- HYJHBSPJETTWEH-UHFFFAOYSA-N 6-oxa-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2COC1N2 HYJHBSPJETTWEH-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 4
- 239000003607 modifier Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 229960002930 sirolimus Drugs 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- DJWDAKFSDBOQJK-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.2]octane Chemical compound C1NC2CCC1NC2 DJWDAKFSDBOQJK-UHFFFAOYSA-N 0.000 description 3
- FZSZWXZCXGPTKY-UHFFFAOYSA-N 2-hydroxyethyl n-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OCCO)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 FZSZWXZCXGPTKY-UHFFFAOYSA-N 0.000 description 3
- JNYWVERKQKRXSL-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.2]octane Chemical compound C1NC2CCC1OC2 JNYWVERKQKRXSL-UHFFFAOYSA-N 0.000 description 3
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 3
- LKDJYZBKCVSODK-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2 LKDJYZBKCVSODK-UHFFFAOYSA-N 0.000 description 3
- VYMZKBNBRXLBDU-UHFFFAOYSA-N 3-[6-chloro-1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C12=NC(Cl)=NC(N3CC4CCC(O4)C3)=C2C=NN1C1CCCCO1 VYMZKBNBRXLBDU-UHFFFAOYSA-N 0.000 description 3
- NBPHZZVDIJRLQC-UHFFFAOYSA-N 4,6-dichloro-1-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[3,4-d]pyrimidine Chemical compound C12=NC(Cl)=NC(Cl)=C2C=NN1C(CC1)CCC21OCCO2 NBPHZZVDIJRLQC-UHFFFAOYSA-N 0.000 description 3
- FMCLKHXUTROOEV-UHFFFAOYSA-N 5-oxa-2,8-diazabicyclo[2.2.2]octane Chemical compound C1NC2CNC1OC2 FMCLKHXUTROOEV-UHFFFAOYSA-N 0.000 description 3
- WDJAQSJMDRFZIX-UHFFFAOYSA-N 6-oxa-3-azabicyclo[3.1.1]heptane Chemical compound C1NCC2CC1O2 WDJAQSJMDRFZIX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000012828 PI3K inhibitor Substances 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 description 3
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 3
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- QCAWEPFNJXQPAN-UHFFFAOYSA-N methoxyfenozide Chemical compound COC1=CC=CC(C(=O)NN(C(=O)C=2C=C(C)C=C(C)C=2)C(C)(C)C)=C1C QCAWEPFNJXQPAN-UHFFFAOYSA-N 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- RZHCQZWEGZHOHP-UHFFFAOYSA-N tert-butyl n-(1,4-dioxaspiro[4.5]decan-8-ylamino)carbamate Chemical compound C1CC(NNC(=O)OC(C)(C)C)CCC21OCCO2 RZHCQZWEGZHOHP-UHFFFAOYSA-N 0.000 description 3
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 229960003986 tuaminoheptane Drugs 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- AXKGIPZJYUNAIW-UHFFFAOYSA-N (4-aminophenyl)methanol Chemical compound NC1=CC=C(CO)C=C1 AXKGIPZJYUNAIW-UHFFFAOYSA-N 0.000 description 2
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 2
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 2
- PRBHEGAFLDMLAL-UHFFFAOYSA-N 1,5-Hexadiene Natural products CC=CCC=C PRBHEGAFLDMLAL-UHFFFAOYSA-N 0.000 description 2
- YSVBDTHDOXANQI-UHFFFAOYSA-N 1-(1-benzylpiperidin-4-yl)-4,6-dichloropyrazolo[3,4-d]pyrimidine Chemical compound C12=NC(Cl)=NC(Cl)=C2C=NN1C(CC1)CCN1CC1=CC=CC=C1 YSVBDTHDOXANQI-UHFFFAOYSA-N 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical compound CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- AFFLGGQVNFXPEV-UHFFFAOYSA-N 1-decene Chemical compound CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 2
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N 1-nonene Chemical compound CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical compound CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 2
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 2
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 2
- RYPKRALMXUUNKS-UHFFFAOYSA-N 2-Hexene Natural products CCCC=CC RYPKRALMXUUNKS-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- XNMQEEKYCVKGBD-UHFFFAOYSA-N 2-butyne Chemical compound CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 2
- DIQOUXNTSMWQSA-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.1]heptane Chemical compound C1OC2CNC1C2 DIQOUXNTSMWQSA-UHFFFAOYSA-N 0.000 description 2
- NKTDTMONXHODTI-UHFFFAOYSA-N 2-pentyne Chemical compound CCC#CC NKTDTMONXHODTI-UHFFFAOYSA-N 0.000 description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 2
- LDCONZAKYQXURF-UHFFFAOYSA-N 3-[1-(1-benzylpiperidin-4-yl)-6-chloropyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C12=NC(Cl)=NC(N3CC4CCC(O4)C3)=C2C=NN1C(CC1)CCN1CC1=CC=CC=C1 LDCONZAKYQXURF-UHFFFAOYSA-N 0.000 description 2
- OVPZJXFVWBCNFZ-UHFFFAOYSA-N 3-[6-(4-nitrophenyl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CC(F)(F)F)C2=N1 OVPZJXFVWBCNFZ-UHFFFAOYSA-N 0.000 description 2
- NBCYBRMEUCHHLV-UHFFFAOYSA-N 3-[6-chloro-1-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C12=NC(Cl)=NC(N3CC4CCC(O4)C3)=C2C=NN1C(CC1)CCC21OCCO2 NBCYBRMEUCHHLV-UHFFFAOYSA-N 0.000 description 2
- PWVHZVWNAGLZFH-UHFFFAOYSA-N 3-azabicyclo[3.1.1]heptane Chemical compound C1C2CC1CNC2 PWVHZVWNAGLZFH-UHFFFAOYSA-N 0.000 description 2
- TYMWHTJGWKSXRY-UHFFFAOYSA-N 4,6-dichloro-1-methylpyrazolo[3,4-d]pyrimidine Chemical compound N1=C(Cl)N=C2N(C)N=CC2=C1Cl TYMWHTJGWKSXRY-UHFFFAOYSA-N 0.000 description 2
- MOZNZNKHRXRLLF-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1 MOZNZNKHRXRLLF-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 2
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
- DUQSGAAQWQIPCL-UHFFFAOYSA-N 4-chloro-6-(4-nitrophenyl)-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidine Chemical compound C1=CC([N+](=O)[O-])=CC=C1C1=NC(Cl)=C(C=NN2CC(F)(F)F)C2=N1 DUQSGAAQWQIPCL-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- PFJVGXGLFJMGRE-UHFFFAOYSA-N 6-(4-nitrophenyl)-1-(2,2,2-trifluoroethyl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound N=1C=2N(CC(F)(F)F)N=CC=2C(O)=NC=1C1=CC=C([N+]([O-])=O)C=C1 PFJVGXGLFJMGRE-UHFFFAOYSA-N 0.000 description 2
- DENNCEQUAZKJGC-UHFFFAOYSA-N 6-azabicyclo[3.1.1]heptane Chemical compound C1CCC2CC1N2 DENNCEQUAZKJGC-UHFFFAOYSA-N 0.000 description 2
- SNZSSCZJMVIOCR-UHFFFAOYSA-N 7-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1N2 SNZSSCZJMVIOCR-UHFFFAOYSA-N 0.000 description 2
- POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 description 2
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 241000792859 Enema Species 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000872931 Myoporum sandwicense Species 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- UTKNUPLTWVCBHU-UHFFFAOYSA-N OBO.CC(C)(O)C(C)(C)O Chemical class OBO.CC(C)(O)C(C)(C)O UTKNUPLTWVCBHU-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 2
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000007605 air drying Methods 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000004069 aziridinyl group Chemical group 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- KDKYADYSIPSCCQ-UHFFFAOYSA-N but-1-yne Chemical compound CCC#C KDKYADYSIPSCCQ-UHFFFAOYSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000007920 enema Substances 0.000 description 2
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 2
- 229960005167 everolimus Drugs 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229960004979 fampridine Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 2
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- PYGSKMBEVAICCR-UHFFFAOYSA-N hexa-1,5-diene Chemical compound C=CCCC=C PYGSKMBEVAICCR-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 2
- 238000007914 intraventricular administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 210000001853 liver microsome Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 description 2
- QMMOXUPEWRXHJS-UHFFFAOYSA-N pentene-2 Natural products CCC=CC QMMOXUPEWRXHJS-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 108700042226 ras Genes Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229960000235 temsirolimus Drugs 0.000 description 2
- UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 2
- IHFLPXWCXWFHFJ-UHFFFAOYSA-N tert-butyl n-(1,4-dioxaspiro[4.5]decan-8-ylideneamino)carbamate Chemical compound C1CC(=NNC(=O)OC(C)(C)C)CCC21OCCO2 IHFLPXWCXWFHFJ-UHFFFAOYSA-N 0.000 description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- 238000001665 trituration Methods 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- VYEWTHXZHHATTA-UHFFFAOYSA-N (4-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=C(B(O)O)C=C1 VYEWTHXZHHATTA-UHFFFAOYSA-N 0.000 description 1
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 description 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- YCTDZYMMFQCTEO-FNORWQNLSA-N (E)-3-octene Chemical compound CCCC\C=C\CC YCTDZYMMFQCTEO-FNORWQNLSA-N 0.000 description 1
- GVRWIAHBVAYKIZ-FNORWQNLSA-N (e)-dec-3-ene Chemical compound CCCCCC\C=C\CC GVRWIAHBVAYKIZ-FNORWQNLSA-N 0.000 description 1
- SOVOPSCRHKEUNJ-VQHVLOKHSA-N (e)-dec-4-ene Chemical compound CCCCC\C=C\CCC SOVOPSCRHKEUNJ-VQHVLOKHSA-N 0.000 description 1
- IICQZTQZQSBHBY-HWKANZROSA-N (e)-non-2-ene Chemical compound CCCCCC\C=C\C IICQZTQZQSBHBY-HWKANZROSA-N 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- QEPOUWFTAJMFDQ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-ylhydrazine Chemical compound C1CC(NN)CCC21OCCO2 QEPOUWFTAJMFDQ-UHFFFAOYSA-N 0.000 description 1
- JDEYBJHOTWGYFE-UHFFFAOYSA-N 1-(4-aminophenyl)ethanol Chemical compound CC(O)C1=CC=C(N)C=C1 JDEYBJHOTWGYFE-UHFFFAOYSA-N 0.000 description 1
- WPNZFLVLMWYSPE-UHFFFAOYSA-N 1-[4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-pyridin-4-ylurea Chemical compound N1=C2N(CCF)N=CC2=C(N2CC3CCC(O3)C2)N=C1C(C=C1)=CC=C1NC(=O)NC1=CC=NC=C1 WPNZFLVLMWYSPE-UHFFFAOYSA-N 0.000 description 1
- IYRBVBTWGPIKNS-UHFFFAOYSA-N 1-[4-[1-ethyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-3-[4-(pyrrolidin-1-ylmethyl)phenyl]urea Chemical compound N1=C2N(CC)N=CC2=C(N2C3CCC2COC3)N=C1C(C=C1)=CC=C1NC(=O)NC(C=C1)=CC=C1CN1CCCC1 IYRBVBTWGPIKNS-UHFFFAOYSA-N 0.000 description 1
- DAYNOULNDBHQFD-UHFFFAOYSA-N 1-benzyl-1-piperidin-4-ylhydrazine;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1N(N)CC1=CC=CC=C1 DAYNOULNDBHQFD-UHFFFAOYSA-N 0.000 description 1
- SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
- CGHIBGNXEGJPQZ-UHFFFAOYSA-N 1-hexyne Chemical compound CCCCC#C CGHIBGNXEGJPQZ-UHFFFAOYSA-N 0.000 description 1
- IBXNCJKFFQIKKY-UHFFFAOYSA-N 1-pentyne Chemical compound CCCC#C IBXNCJKFFQIKKY-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- QDKGOMZIPXGDDJ-UHFFFAOYSA-N 2,3-dihydro-1h-indazole Chemical compound C1=CC=C2CNNC2=C1 QDKGOMZIPXGDDJ-UHFFFAOYSA-N 0.000 description 1
- UKHJNJFJCGBKSF-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.1]heptane Chemical compound C1NC2CNC1C2 UKHJNJFJCGBKSF-UHFFFAOYSA-N 0.000 description 1
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 1
- OTTZHAVKAVGASB-HYXAFXHYSA-N 2-Heptene Chemical compound CCCC\C=C/C OTTZHAVKAVGASB-HYXAFXHYSA-N 0.000 description 1
- GGDYAKVUZMZKRV-UHFFFAOYSA-N 2-fluoroethanol Chemical compound OCCF GGDYAKVUZMZKRV-UHFFFAOYSA-N 0.000 description 1
- OTTZHAVKAVGASB-UHFFFAOYSA-N 2-heptene Natural products CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 description 1
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical group CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 1
- ILPBINAXDRFYPL-UHFFFAOYSA-N 2-octene Chemical compound CCCCCC=CC ILPBINAXDRFYPL-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- IICQZTQZQSBHBY-UHFFFAOYSA-N 2t-nonene Natural products CCCCCCC=CC IICQZTQZQSBHBY-UHFFFAOYSA-N 0.000 description 1
- OWHVATIGFHITHY-UHFFFAOYSA-N 3-(6-chloro-1-ethylpyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C(O2)CCC2CN1C1=C2C=NN(CC)C2=NC(Cl)=N1 OWHVATIGFHITHY-UHFFFAOYSA-N 0.000 description 1
- WWNBSHZOGSBGRJ-UHFFFAOYSA-N 3-(6-chloro-1-phenylpyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C12=NC(Cl)=NC(N3CC4CCC(O4)C3)=C2C=NN1C1=CC=CC=C1 WWNBSHZOGSBGRJ-UHFFFAOYSA-N 0.000 description 1
- WNUSEYDVAHQHQW-UHFFFAOYSA-N 3-(6-chloro-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C12=NC(Cl)=NC(N3CC4CCC(O4)C3)=C2C=NN1C1CCNCC1 WNUSEYDVAHQHQW-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- DQGQKSCDTHITNB-UHFFFAOYSA-N 3-[6-chloro-1-(2-fluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C(O2)CCC2CN1C1=C2C=NN(CCF)C2=NC(Cl)=N1 DQGQKSCDTHITNB-UHFFFAOYSA-N 0.000 description 1
- HGWUUOXXAIISDB-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2CC21 HGWUUOXXAIISDB-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- ZQDPJFUHLCOCRG-UHFFFAOYSA-N 3-hexene Chemical compound CCC=CCC ZQDPJFUHLCOCRG-UHFFFAOYSA-N 0.000 description 1
- DQQNMIPXXNPGCV-UHFFFAOYSA-N 3-hexyne Chemical compound CCC#CCC DQQNMIPXXNPGCV-UHFFFAOYSA-N 0.000 description 1
- YHQXBTXEYZIYOV-UHFFFAOYSA-N 3-methylbut-1-ene Chemical compound CC(C)C=C YHQXBTXEYZIYOV-UHFFFAOYSA-N 0.000 description 1
- LQVCUGATZFCLAS-UHFFFAOYSA-N 3-oxa-7,9-diazabicyclo[3.3.1]nonane Chemical compound C1OCC2CNCC1N2 LQVCUGATZFCLAS-UHFFFAOYSA-N 0.000 description 1
- MNILDQSRDHCFJG-UHFFFAOYSA-N 3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2CCC1N2 MNILDQSRDHCFJG-UHFFFAOYSA-N 0.000 description 1
- DVVZRIIREIUXSR-UHFFFAOYSA-N 3-oxa-9-azabicyclo[3.3.1]nonane Chemical compound C1OCC2CCCC1N2 DVVZRIIREIUXSR-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- VMIPTJUFAWNUEU-UHFFFAOYSA-N 4,6-dichloro-1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidine Chemical compound C12=NC(Cl)=NC(Cl)=C2C=NN1C1CCCCO1 VMIPTJUFAWNUEU-UHFFFAOYSA-N 0.000 description 1
- CTYPROOLWJDUTA-UHFFFAOYSA-N 4,6-dichloro-1h-pyrazolo[3,4-d]pyrimidine Chemical compound ClC1=NC(Cl)=C2C=NNC2=N1 CTYPROOLWJDUTA-UHFFFAOYSA-N 0.000 description 1
- HWVGNHHLGUIAOC-UHFFFAOYSA-N 4-[1-(2-fluoroethyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2CCF)C2=N1 HWVGNHHLGUIAOC-UHFFFAOYSA-N 0.000 description 1
- ZTLHBFNGWZLWQJ-UHFFFAOYSA-N 4-[1-[2-(dimethylamino)ethyl]-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)pyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound N1=C2N(CCN(C)C)N=CC2=C(N2CC3CCC(O3)C2)N=C1C1=CC=C(N)C=C1 ZTLHBFNGWZLWQJ-UHFFFAOYSA-N 0.000 description 1
- CKNHHTRURFNJKG-UHFFFAOYSA-N 4-[2-(dimethylamino)ethoxy]-n,n-dimethylaniline Chemical compound CN(C)CCOC1=CC=C(N(C)C)C=C1 CKNHHTRURFNJKG-UHFFFAOYSA-N 0.000 description 1
- PRFSDPYYQFWJBN-UHFFFAOYSA-N 4-[4-(6,8-dioxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methylpyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound N1=C2N(C)N=CC2=C(N2CC3OCC(O3)C2)N=C1C1=CC=C(N)C=C1 PRFSDPYYQFWJBN-UHFFFAOYSA-N 0.000 description 1
- UDUWDPCDMMAWHJ-UHFFFAOYSA-N 4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(oxan-2-yl)pyrazolo[3,4-d]pyrimidin-6-yl]aniline Chemical compound C1=CC(N)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2C3OCCCC3)C2=N1 UDUWDPCDMMAWHJ-UHFFFAOYSA-N 0.000 description 1
- IRLOZVLSUVCEIJ-UHFFFAOYSA-N 4-[[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)thieno[3,2-d]pyrimidin-2-yl]amino]phenol Chemical compound C1=CC(O)=CC=C1NC1=NC(N2CC3CCC(O3)C2)=C(SC=C2)C2=N1 IRLOZVLSUVCEIJ-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- WSSSPWUEQFSQQG-UHFFFAOYSA-N 4-methyl-1-pentene Chemical compound CC(C)CC=C WSSSPWUEQFSQQG-UHFFFAOYSA-N 0.000 description 1
- OXRWICUICBZVAE-UHFFFAOYSA-N 4-methylpent-1-yne Chemical compound CC(C)CC#C OXRWICUICBZVAE-UHFFFAOYSA-N 0.000 description 1
- PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- RCPFKNIWFCVDLQ-UHFFFAOYSA-N 4-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C2CCC1ONC2 RCPFKNIWFCVDLQ-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- VERUFXOALATMPS-UHFFFAOYSA-N 5,5-diamino-2-(2-phenylethenyl)cyclohex-3-ene-1,1-disulfonic acid Chemical compound C1=CC(N)(N)CC(S(O)(=O)=O)(S(O)(=O)=O)C1C=CC1=CC=CC=C1 VERUFXOALATMPS-UHFFFAOYSA-N 0.000 description 1
- FATPQDPUKVVCLT-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-indole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(NC=C2)C2=C1 FATPQDPUKVVCLT-UHFFFAOYSA-N 0.000 description 1
- WYVFAIDIZFAWMI-UHFFFAOYSA-N 5-azabicyclo[2.1.1]hexane Chemical compound C1CC2CC1N2 WYVFAIDIZFAWMI-UHFFFAOYSA-N 0.000 description 1
- KIWWEIOFOPULSX-UHFFFAOYSA-N 6-oxa-3-azabicyclo[3.1.0]hexane Chemical compound C1NCC2OC12 KIWWEIOFOPULSX-UHFFFAOYSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- GLPFIJPUIPBENR-WNUBJLNHSA-N C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N([C@H]4CC[C@@H](O)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N([C@H]4CC[C@@H](O)CC4)N=CC3=C(N3CC4CCC(O4)C3)N=2)C=C1 GLPFIJPUIPBENR-WNUBJLNHSA-N 0.000 description 1
- 102000002110 C2 domains Human genes 0.000 description 1
- 108050009459 C2 domains Proteins 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108091007958 Class I PI3Ks Proteins 0.000 description 1
- 108091007959 Class II PI3Ks Proteins 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241001480079 Corymbia calophylla Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 240000001238 Gaultheria procumbens Species 0.000 description 1
- 235000007297 Gaultheria procumbens Nutrition 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 108010076876 Keratins Proteins 0.000 description 1
- 102000011782 Keratins Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 235000006552 Liquidambar styraciflua Nutrition 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- OSFPHMZQBQZLAY-UHFFFAOYSA-N OBO.NC1=CC=CC=C1 Chemical compound OBO.NC1=CC=CC=C1 OSFPHMZQBQZLAY-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 101150073900 PTEN gene Proteins 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 description 1
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102000014400 SH2 domains Human genes 0.000 description 1
- 108050003452 SH2 domains Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 244000177154 Solanum pseudocapsicum Species 0.000 description 1
- 235000000340 Solanum pseudocapsicum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000862969 Stella Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 102000014384 Type C Phospholipases Human genes 0.000 description 1
- 108010079194 Type C Phospholipases Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- 235000001978 Withania somnifera Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- BOGSOFADOWIECK-UHFFFAOYSA-N [N].C=1C=NNC=1 Chemical group [N].C=1C=NNC=1 BOGSOFADOWIECK-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 125000004062 acenaphthenyl group Chemical group C1(CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000005377 adsorption chromatography Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 229950003153 amsonate Drugs 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
- 125000005340 bisphosphate group Chemical group 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 206010006007 bone sarcoma Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229940078456 calcium stearate Drugs 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical compound CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- ILLHQJIJCRNRCJ-UHFFFAOYSA-N dec-1-yne Chemical compound CCCCCCCCC#C ILLHQJIJCRNRCJ-UHFFFAOYSA-N 0.000 description 1
- YKNMBTZOEVIJCM-UHFFFAOYSA-N dec-2-ene Chemical compound CCCCCCCC=CC YKNMBTZOEVIJCM-UHFFFAOYSA-N 0.000 description 1
- RWDDSTHSVISBEA-UHFFFAOYSA-N dec-2-yne Chemical compound CCCCCCCC#CC RWDDSTHSVISBEA-UHFFFAOYSA-N 0.000 description 1
- JUWXVJKQNKKRLD-UHFFFAOYSA-N dec-3-yne Chemical compound CCCCCCC#CCC JUWXVJKQNKKRLD-UHFFFAOYSA-N 0.000 description 1
- KVUNBQMRRNMQIZ-UHFFFAOYSA-N dec-4-yne Chemical compound CCCCCC#CCCC KVUNBQMRRNMQIZ-UHFFFAOYSA-N 0.000 description 1
- UURSXESKOOOTOV-UHFFFAOYSA-N dec-5-ene Chemical compound CCCCC=CCCCC UURSXESKOOOTOV-UHFFFAOYSA-N 0.000 description 1
- JWBQJUFCNOLNNC-UHFFFAOYSA-N dec-5-yne Chemical compound CCCCC#CCCCC JWBQJUFCNOLNNC-UHFFFAOYSA-N 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- WZHKDGJSXCTSCK-UHFFFAOYSA-N hept-3-ene Chemical compound CCCC=CCC WZHKDGJSXCTSCK-UHFFFAOYSA-N 0.000 description 1
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 description 1
- MELUCTCJOARQQG-UHFFFAOYSA-N hex-2-yne Chemical compound CCCC#CC MELUCTCJOARQQG-UHFFFAOYSA-N 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- SXQCTESRRZBPHJ-UHFFFAOYSA-M lissamine rhodamine Chemical group [Na+].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S([O-])(=O)=O)C=C1S([O-])(=O)=O SXQCTESRRZBPHJ-UHFFFAOYSA-M 0.000 description 1
- XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000003580 lung surfactant Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- GIFKOQWKTYICIC-UHFFFAOYSA-N n-[4-[4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1h-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=NC(N2CC3CCC(O3)C2)=C(C=NN2)C2=N1 GIFKOQWKTYICIC-UHFFFAOYSA-N 0.000 description 1
- FIVWHKCUOPIMEF-UHFFFAOYSA-N n-[4-cyano-2-(2,2,2-trifluoroethyl)pyrazol-3-yl]-4-nitrobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)NC1=C(C#N)C=NN1CC(F)(F)F FIVWHKCUOPIMEF-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- YCBSHDKATAPNIA-UHFFFAOYSA-N non-3-ene Chemical compound CCCCCC=CCC YCBSHDKATAPNIA-UHFFFAOYSA-N 0.000 description 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- UMIPWJGWASORKV-UHFFFAOYSA-N oct-1-yne Chemical compound CCCCCCC#C UMIPWJGWASORKV-UHFFFAOYSA-N 0.000 description 1
- QCQALVMFTWRCFI-UHFFFAOYSA-N oct-2-yne Chemical compound CCCCCC#CC QCQALVMFTWRCFI-UHFFFAOYSA-N 0.000 description 1
- UDEISTCPVNLKRJ-UHFFFAOYSA-N oct-3-yne Chemical compound CCCCC#CCC UDEISTCPVNLKRJ-UHFFFAOYSA-N 0.000 description 1
- IRUCBBFNLDIMIK-UHFFFAOYSA-N oct-4-ene Chemical compound CCCC=CCCC IRUCBBFNLDIMIK-UHFFFAOYSA-N 0.000 description 1
- GZTNBKQTTZSQNS-UHFFFAOYSA-N oct-4-yne Chemical compound CCCC#CCCC GZTNBKQTTZSQNS-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000009521 phase II clinical trial Methods 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 102000034285 signal transducing proteins Human genes 0.000 description 1
- 108091006024 signal transducing proteins Proteins 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- CKCPUOWKNWAVAW-UHFFFAOYSA-N tert-butyl 9-[6-[4-[[4-[2-(dimethylamino)ethoxy]phenyl]carbamoylamino]phenyl]-1-(2,2,2-trifluoroethyl)pyrazolo[3,4-d]pyrimidin-4-yl]-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1=CC(OCCN(C)C)=CC=C1NC(=O)NC1=CC=C(C=2N=C3N(CC(F)(F)F)N=CC3=C(N3C4COCC3CN(C4)C(=O)OC(C)(C)C)N=2)C=C1 CKCPUOWKNWAVAW-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US98033207P | 2007-10-16 | 2007-10-16 | |
| US2759508P | 2008-02-11 | 2008-02-11 | |
| PCT/US2008/079940 WO2009052145A1 (en) | 2007-10-16 | 2008-10-15 | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mtor kinase and pi3 kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011500702A true JP2011500702A (ja) | 2011-01-06 |
| JP2011500702A5 JP2011500702A5 (OSRAM) | 2011-11-24 |
Family
ID=40345078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010530074A Withdrawn JP2011500702A (ja) | 2007-10-16 | 2008-10-15 | チエノピリミジンおよびピラゾロピリミジン化合物ならびにmTORキナーゼおよびPI3キナーゼ阻害剤としてのその使用 |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US8129371B2 (OSRAM) |
| EP (1) | EP2212333A1 (OSRAM) |
| JP (1) | JP2011500702A (OSRAM) |
| KR (1) | KR20100083170A (OSRAM) |
| CN (1) | CN101883774A (OSRAM) |
| AP (1) | AP2010005234A0 (OSRAM) |
| AR (1) | AR068898A1 (OSRAM) |
| AU (1) | AU2008312631A1 (OSRAM) |
| BR (1) | BRPI0817681A2 (OSRAM) |
| CA (1) | CA2702838A1 (OSRAM) |
| CL (1) | CL2008003061A1 (OSRAM) |
| CO (1) | CO6321257A2 (OSRAM) |
| CR (1) | CR11373A (OSRAM) |
| DO (1) | DOP2010000118A (OSRAM) |
| EA (1) | EA201000484A1 (OSRAM) |
| EC (1) | ECSP10010112A (OSRAM) |
| IL (1) | IL205109A0 (OSRAM) |
| MA (1) | MA31884B1 (OSRAM) |
| MX (1) | MX2010004260A (OSRAM) |
| NI (1) | NI201000060A (OSRAM) |
| PA (1) | PA8799101A1 (OSRAM) |
| PE (1) | PE20091384A1 (OSRAM) |
| TN (1) | TN2010000171A1 (OSRAM) |
| TW (1) | TW200922593A (OSRAM) |
| WO (1) | WO2009052145A1 (OSRAM) |
| ZA (1) | ZA201003430B (OSRAM) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015503546A (ja) * | 2011-12-28 | 2015-02-02 | サノフイ | Fgf受容体(fgfr)アゴニスト二量体化合物、その製造方法及びその治療上の使用 |
| JP2015512920A (ja) * | 2012-04-10 | 2015-04-30 | シャンハイ インリ ファーマシューティカル カンパニー リミティド | 縮合ピリミジン化合物、その調製法、中間体、組成物、及び使用 |
| JP2015518010A (ja) * | 2012-05-31 | 2015-06-25 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズShanghai Institute Of Materia Medica, Chinese Academy Of Sciences | ピロロ[2,1−f][1,2,4]トリアジン系化合物、その製造方法および用途 |
| JP2022519317A (ja) * | 2019-02-06 | 2022-03-22 | ベンセラ,インコーポレイティド | 局所ホスホイノシチド3-キナーゼ阻害剤 |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998010381A1 (en) * | 1996-09-04 | 1998-03-12 | Intertrust Technologies Corp. | Trusted infrastructure support systems, methods and techniques for secure electronic commerce, electronic transactions, commerce process control and automation, distributed computing, and rights management |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| SG10201403526YA (en) | 2005-07-25 | 2014-10-30 | Emergent Product Dev Seattle | B-cell reduction using cd37-specific and cd20-specific binding molecules |
| AU2007257692B2 (en) | 2006-06-12 | 2013-11-14 | Aptevo Research And Development Llc | Single-chain multivalent binding proteins with effector function |
| CA2710194C (en) | 2007-12-19 | 2014-04-22 | Amgen Inc. | Inhibitors of p13 kinase |
| ES2368700T3 (es) | 2008-04-11 | 2011-11-21 | Emergent Product Development Seattle, Llc | Agente inmunoterapéutico para cd37 y combinación con un agente quimioterapéutico bifuncional del mismo. |
| TW201004963A (en) * | 2008-07-03 | 2010-02-01 | Targacept Inc | Derivatives of oxabispidine as neuronal nicotinic acetylcholine receptor ligands |
| KR20110046514A (ko) * | 2008-07-31 | 2011-05-04 | 제넨테크, 인크. | 피리미딘 화합물, 조성물 및 사용 방법 |
| US8450322B2 (en) | 2008-09-22 | 2013-05-28 | Array Biopharma Inc. | Substituted imidazo[1,2b]pyridazine compounds as Trk kinase inhibitors |
| TWI378933B (en) | 2008-10-14 | 2012-12-11 | Daiichi Sankyo Co Ltd | Morpholinopurine derivatives |
| TR201807039T4 (tr) | 2008-10-22 | 2018-06-21 | Array Biopharma Inc | Trk kinaz inhibitörleri olarak sübstitüe edilmiş pirazolo[1,5-]pirimidin bileşikleri. |
| CA2749228C (en) | 2009-01-08 | 2016-05-17 | Curis, Inc. | Phosphoinositide 3-kinase inhibitors with a zinc binding moiety |
| JP5649643B2 (ja) * | 2009-04-17 | 2015-01-07 | ワイス・エルエルシー | ピリミジン化合物、mTORキナーゼおよびPI3キナーゼ阻害剤としてのそれらの使用、ならびにそれらの合成 |
| BRPI1009022A2 (pt) * | 2009-05-27 | 2016-03-08 | Hoffmann La Roche | "composto, composição farmacêutica, processo para produzir uma composição farmacêutica, uso de um composto, método para tratamento de uma doença ou transtorno e kit" |
| SG176959A1 (en) * | 2009-06-24 | 2012-01-30 | Genentech Inc | Oxo-heterocycle fused pyrimidine compounds, compositions and methods of use |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| US20110021515A1 (en) * | 2009-07-24 | 2011-01-27 | Takeda Pharmaceutical Company Limited | Dihyrofuropyrmindine compounds |
| KR101147550B1 (ko) | 2009-10-22 | 2012-05-17 | 한국과학기술연구원 | 단백질 키나아제 저해활성을 가지는 2,7-치환된 티에노[3,2-d]피리미딘 화합물 |
| US8288381B2 (en) * | 2009-11-12 | 2012-10-16 | Genentech, Inc. | N-9 substituted purine compounds, compositions and methods of use |
| ES2567168T3 (es) | 2009-11-12 | 2016-04-20 | F. Hoffmann-La Roche Ag | Compuestos purina y pirazolopirimidina N7-sustituidos, composiciones y métodos de utilización |
| WO2011078795A1 (en) * | 2009-12-21 | 2011-06-30 | S*Bio Pte Ltd | Bridged morpholino substituted purines |
| WO2011090935A1 (en) * | 2010-01-19 | 2011-07-28 | Merck Sharp & Dohme Corp. | PYRAZOLO[1,5-a]PYRIMIDINE COMPOUNDS AS mTOR INHIBITORS |
| ES2670659T3 (es) | 2010-02-03 | 2018-05-31 | Signal Pharmaceuticals, Llc | Identificación de mutación en LKB1 como un biomarcador predictivo para la sensibilidad a inhibidores de la quinasa TOR |
| JP2013523807A (ja) | 2010-04-05 | 2013-06-17 | ワイス・エルエルシー | Pi3kにより誘発される癌のためのバイオマーカー |
| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| EP2580320B1 (en) | 2010-06-14 | 2018-08-01 | The Scripps Research Institute | Reprogramming of cells to a new fate |
| JP2013544829A (ja) * | 2010-11-24 | 2013-12-19 | エクセリクシス, インク. | PI3K/mTORの阻害剤としてのベンゾオキサゼピンおよびその使用と製造方法 |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| WO2012099581A1 (en) | 2011-01-19 | 2012-07-26 | Takeda Pharmaceutical Company Limited | Dihydrofuropyrimidine compounds |
| WO2013019927A1 (en) | 2011-08-03 | 2013-02-07 | Signal Pharmaceuticals, Llc | Identification of gene expression profile as a predictive biomarker for lkb1 status |
| US9458162B2 (en) * | 2012-01-31 | 2016-10-04 | Nanjing Allgen Pharma Co. Ltd. | Cyclic molecules as bruton's tyrosine kinase inhibitors |
| CN103374021B (zh) * | 2012-04-21 | 2015-10-28 | 通化济达医药有限公司 | 含有锌结合基的吡啶并嘧啶类HDAC和mTOR抑制剂 |
| BR112014028881A2 (pt) | 2012-05-23 | 2017-06-27 | Hoffmann La Roche | populações de células, banco de células, métodos de obtenção de uma população de células, métodos de identificação de um fator, métodos de seleção, métodos de fornecimento de terapia, populações de hepatócitos e método de obtenção de células |
| SI2861595T1 (sl) | 2012-06-13 | 2017-04-26 | Incyte Holdings Corporation | Substituirane triciklične spojine kot inhibitorji fgfr |
| US9388185B2 (en) | 2012-08-10 | 2016-07-12 | Incyte Holdings Corporation | Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors |
| AU2013203714B2 (en) | 2012-10-18 | 2015-12-03 | Signal Pharmaceuticals, Llc | Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| US9358232B2 (en) | 2013-04-17 | 2016-06-07 | Signal Pharmaceuticals, Llc | Methods for treating cancer using TOR kinase inhibitor combination therapy |
| NZ631082A (en) | 2013-04-17 | 2017-06-30 | Signal Pharm Llc | Methods for treating cancer using tor kinase inhibitor combination therapy |
| PH12021552945B1 (en) | 2013-04-17 | 2024-02-28 | Signal Pharm Llc | Treatment of cancer with dihydropyrazino-pyrazines |
| UA115805C2 (uk) | 2013-04-17 | 2017-12-26 | Сігнал Фармасьютікалз, Елелсі | Комбінована терапія, яка включає сполуку дигідропіразинопіразину й антагоніст рецептора андрогену, для лікування раку простати |
| WO2014172436A1 (en) | 2013-04-17 | 2014-10-23 | Signal Pharmaceuticals, Llc | Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer |
| EA037683B1 (ru) | 2013-04-17 | 2021-04-29 | СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Фармацевтические составы, способы, твердые формы и способы применения, относящиеся к 1-этил-7-(2-метил-6-(1h-1,2,4-триазол-3-ил)пиридин-3-ил)-3,4-дигидропиразино[2,3-b] пиразин-2(1h)-ону |
| KR102221029B1 (ko) | 2013-04-17 | 2021-02-26 | 시그날 파마소티칼 엘엘씨 | 디하이드로피라지노-피라진을 사용한 암의 치료 |
| LT2986610T (lt) | 2013-04-19 | 2018-04-10 | Incyte Holdings Corporation | Bicikliniai heterociklai, kaip fgfr inhibitoriai |
| CN105407892B (zh) | 2013-05-29 | 2019-05-07 | 西格诺药品有限公司 | 一种化合物的药物组合物、其固体形式及它们的使用方法 |
| AU2014293013A1 (en) | 2013-07-26 | 2016-03-17 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene |
| CN104513254B (zh) * | 2013-09-30 | 2019-07-26 | 上海璎黎药业有限公司 | 稠合嘧啶类化合物、中间体、其制备方法、组合物和应用 |
| FR3015483B1 (fr) * | 2013-12-23 | 2016-01-01 | Servier Lab | Nouveaux derives de thienopyrimidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US9763992B2 (en) | 2014-02-13 | 2017-09-19 | Father Flanagan's Boys' Home | Treatment of noise induced hearing loss |
| NZ714742A (en) | 2014-04-16 | 2017-04-28 | Signal Pharm Llc | Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use |
| WO2015160880A1 (en) | 2014-04-16 | 2015-10-22 | Signal Pharmaceuticals, Llc | SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF |
| PE20161475A1 (es) | 2014-05-14 | 2017-01-08 | Pfizer | Pirazolopiridinas y pirazolopirimidinas |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| PT3699181T (pt) | 2014-11-16 | 2023-04-05 | Array Biopharma Inc | Forma cristalina de hidrogenossulfato de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| WO2016134294A1 (en) | 2015-02-20 | 2016-08-25 | Incyte Corporation | Bicyclic heterocycles as fgfr4 inhibitors |
| SG10201913036RA (en) | 2015-02-20 | 2020-02-27 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| WO2017053469A2 (en) | 2015-09-21 | 2017-03-30 | Aptevo Research And Development Llc | Cd3 binding polypeptides |
| TN2018000138A1 (en) | 2015-10-26 | 2019-10-04 | Array Biopharma Inc | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| FR3046792B1 (fr) * | 2016-01-19 | 2018-02-02 | Les Laboratoires Servier | Nouveaux derives d'ammonium, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| CN109414442B (zh) | 2016-04-04 | 2024-03-29 | 洛克索肿瘤学股份有限公司 | 一种化合物的液体制剂 |
| DK3800189T3 (da) | 2016-05-18 | 2023-07-31 | Loxo Oncology Inc | Fremstilling af (s)-n-(5-((r)-2-(2,5-difluorphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidin-1-carboxamid |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| IL271491B2 (en) | 2017-06-22 | 2023-09-01 | Celgene Corp | Treatment of carcinoma of the liver characterized by hepatitis b virus infection |
| CN111683976B (zh) | 2018-02-05 | 2022-11-18 | 生物辐射实验室股份有限公司 | 具有阴离子交换-疏水混合模式配体的色谱树脂 |
| CN108358949A (zh) * | 2018-03-01 | 2018-08-03 | 南京法恩化学有限公司 | 一种2,4-二氯噻吩并[3,2-d]嘧啶的制备方法 |
| KR20210018264A (ko) | 2018-05-04 | 2021-02-17 | 인사이트 코포레이션 | Fgfr 억제제의 염 |
| PL3788047T3 (pl) | 2018-05-04 | 2025-04-14 | Incyte Corporation | Stałe postacie inhibitora fgfr i sposoby ich otrzymywania |
| CN110850012B (zh) * | 2018-08-21 | 2022-07-08 | 四川弘远药业有限公司 | 一种1-(2,3-二氯苯基)哌嗪盐酸盐及其有关物质的检测方法 |
| CN111646995B (zh) * | 2019-03-04 | 2023-03-21 | 四川大学 | 4-氨基-嘧啶并氮杂环-苯基脲类衍生物及其制备方法和用途 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| CN109824701B (zh) * | 2019-03-26 | 2021-08-13 | 武汉工程大学 | 一种吡啶并噻唑类化合物及其制备方法和应用 |
| US11591329B2 (en) | 2019-07-09 | 2023-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| EP3800188A1 (en) | 2019-10-02 | 2021-04-07 | Bayer AG | Substituted pyrazolopyrimidines as irak4 inhibitors |
| CR20220169A (es) | 2019-10-14 | 2022-10-27 | Incyte Corp | Heterociclos bicíclicos como inhibidores de fgfr |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| JP7720840B2 (ja) | 2019-12-04 | 2025-08-08 | インサイト・コーポレイション | Fgfr阻害剤としての三環式複素環 |
| WO2021146424A1 (en) | 2020-01-15 | 2021-07-22 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| TW202304459A (zh) | 2021-04-12 | 2023-02-01 | 美商英塞特公司 | 包含fgfr抑制劑及nectin-4靶向劑之組合療法 |
| CN113278015B (zh) * | 2021-05-31 | 2022-05-13 | 云南大学 | 一种荧光探针及其制备方法和应用 |
| US11939331B2 (en) | 2021-06-09 | 2024-03-26 | Incyte Corporation | Tricyclic heterocycles as FGFR inhibitors |
| EP4352060A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| CN120718043A (zh) * | 2024-03-28 | 2025-09-30 | 励缔(杭州)医药科技有限公司 | 具有mTOR抑制活性的有机化合物及其用途 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100774855B1 (ko) | 2000-04-27 | 2007-11-08 | 아스텔라스세이야쿠 가부시키가이샤 | 축합 헤테로아릴 유도체 |
-
2008
- 2008-10-15 MX MX2010004260A patent/MX2010004260A/es not_active Application Discontinuation
- 2008-10-15 EP EP08839537A patent/EP2212333A1/en not_active Withdrawn
- 2008-10-15 AP AP2010005234A patent/AP2010005234A0/xx unknown
- 2008-10-15 AU AU2008312631A patent/AU2008312631A1/en not_active Abandoned
- 2008-10-15 JP JP2010530074A patent/JP2011500702A/ja not_active Withdrawn
- 2008-10-15 KR KR1020107010683A patent/KR20100083170A/ko not_active Ceased
- 2008-10-15 WO PCT/US2008/079940 patent/WO2009052145A1/en not_active Ceased
- 2008-10-15 US US12/251,712 patent/US8129371B2/en not_active Expired - Fee Related
- 2008-10-15 CA CA2702838A patent/CA2702838A1/en not_active Abandoned
- 2008-10-15 CN CN2008801190434A patent/CN101883774A/zh active Pending
- 2008-10-15 BR BRPI0817681 patent/BRPI0817681A2/pt not_active Application Discontinuation
- 2008-10-15 EA EA201000484A patent/EA201000484A1/ru unknown
- 2008-10-16 CL CL2008003061A patent/CL2008003061A1/es unknown
- 2008-10-16 TW TW097139718A patent/TW200922593A/zh unknown
- 2008-10-16 AR ARP080104520A patent/AR068898A1/es unknown
- 2008-10-16 PA PA20088799101A patent/PA8799101A1/es unknown
- 2008-10-16 PE PE2008001780A patent/PE20091384A1/es not_active Application Discontinuation
-
2010
- 2010-04-15 IL IL205109A patent/IL205109A0/en unknown
- 2010-04-15 NI NI201000060A patent/NI201000060A/es unknown
- 2010-04-15 CR CR11373A patent/CR11373A/es not_active Application Discontinuation
- 2010-04-16 DO DO2010000118A patent/DOP2010000118A/es unknown
- 2010-04-16 TN TN2010000171A patent/TN2010000171A1/fr unknown
- 2010-04-16 MA MA32778A patent/MA31884B1/fr unknown
- 2010-04-16 EC EC2010010112A patent/ECSP10010112A/es unknown
- 2010-04-20 CO CO10046199A patent/CO6321257A2/es not_active Application Discontinuation
- 2010-05-14 ZA ZA2010/03430A patent/ZA201003430B/en unknown
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015503546A (ja) * | 2011-12-28 | 2015-02-02 | サノフイ | Fgf受容体(fgfr)アゴニスト二量体化合物、その製造方法及びその治療上の使用 |
| JP2015512920A (ja) * | 2012-04-10 | 2015-04-30 | シャンハイ インリ ファーマシューティカル カンパニー リミティド | 縮合ピリミジン化合物、その調製法、中間体、組成物、及び使用 |
| US9499561B2 (en) | 2012-04-10 | 2016-11-22 | Shanghai Yingli Pharmaceutical Co., Ltd. | Fused pyrimidine compound, and preparation method, intermediate, composition, and uses thereof |
| JP2015518010A (ja) * | 2012-05-31 | 2015-06-25 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズShanghai Institute Of Materia Medica, Chinese Academy Of Sciences | ピロロ[2,1−f][1,2,4]トリアジン系化合物、その製造方法および用途 |
| JP2022519317A (ja) * | 2019-02-06 | 2022-03-22 | ベンセラ,インコーポレイティド | 局所ホスホイノシチド3-キナーゼ阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| CL2008003061A1 (es) | 2009-01-09 |
| PA8799101A1 (es) | 2009-05-15 |
| MA31884B1 (fr) | 2010-12-01 |
| NI201000060A (es) | 2010-10-04 |
| CR11373A (es) | 2010-05-03 |
| DOP2010000118A (es) | 2010-06-30 |
| WO2009052145A1 (en) | 2009-04-23 |
| BRPI0817681A2 (pt) | 2015-04-14 |
| PE20091384A1 (es) | 2009-09-09 |
| CO6321257A2 (es) | 2011-09-20 |
| AU2008312631A1 (en) | 2009-04-23 |
| TN2010000171A1 (fr) | 2011-11-11 |
| EA201000484A1 (ru) | 2010-12-30 |
| KR20100083170A (ko) | 2010-07-21 |
| AR068898A1 (es) | 2009-12-16 |
| ZA201003430B (en) | 2011-02-23 |
| IL205109A0 (en) | 2010-11-30 |
| ECSP10010112A (es) | 2010-08-31 |
| CA2702838A1 (en) | 2009-04-23 |
| EP2212333A1 (en) | 2010-08-04 |
| US8129371B2 (en) | 2012-03-06 |
| TW200922593A (en) | 2009-06-01 |
| US20090098086A1 (en) | 2009-04-16 |
| MX2010004260A (es) | 2010-04-30 |
| AP2010005234A0 (en) | 2010-04-30 |
| CN101883774A (zh) | 2010-11-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8129371B2 (en) | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors | |
| JP7734586B2 (ja) | Shp2アンタゴニストとしてのカルボキサミド-ピリミジン誘導体 | |
| US10752624B2 (en) | Kinase inhibitors | |
| KR101331341B1 (ko) | Pi3 키나제 및 mtor 억제제로서의 트리아진 화합물 | |
| US20090181963A1 (en) | 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES | |
| US20080234262A1 (en) | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors | |
| KR102757425B1 (ko) | 염증 질환의 치료를 위한 신규 화합물 및 그의 약학 조성물 | |
| JP2021518395A (ja) | Shp2阻害剤およびその使用 | |
| US20090192176A1 (en) | 1H-PYRAZOLO[3,4-D]PYRIMIDINE, PURINE, 7H-PURIN-8(9H)-ONE, 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE, AND THIENO[3,2-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES | |
| US20090298820A1 (en) | 3-substituted-1h-pyrrolo[2,3-b]pyridine and 3-substituted-1h-pyrrolo[3,2-b]pyridine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses | |
| WO2010120994A2 (en) | Ureidoaryl-and carbamoylaryl-morpholino- pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their synthesis | |
| AU2007251283A1 (en) | Triazolopyrazine derivatives useful as anti-cancer agents | |
| US20100015141A1 (en) | 4-phenoxy-6-aryl-1h-pyrazolo[3,4-d]pyrimidine and n-aryl-6-aryl-1h-pyrazolo[3,4-d]pyrimidin-4-amine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses | |
| WO2010002954A1 (en) | (2-aryl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses | |
| JP5649643B2 (ja) | ピリミジン化合物、mTORキナーゼおよびPI3キナーゼ阻害剤としてのそれらの使用、ならびにそれらの合成 | |
| US20200055847A1 (en) | Modulators of hedgehog (hh) signalling pathway | |
| RU2785126C2 (ru) | Новые соединения и их фармацевтические композиции для лечения воспалительных заболеваний | |
| CN121079299A (zh) | 作为激酶抑制剂的双环脲 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111006 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20111006 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20130307 |