JP2015500828A5 - - Google Patents

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Publication number

JP2015500828A5

JP2015500828A5 JP2014545417A JP2014545417A JP2015500828A5 JP 2015500828 A5 JP2015500828 A5 JP 2015500828A5 JP 2014545417 A JP2014545417 A JP 2014545417A JP 2014545417 A JP2014545417 A JP 2014545417A JP 2015500828 A5 JP2015500828 A5 JP 2015500828A5

Authority

JP

Japan

Prior art keywords

seq

inhibitor

group

chain variable

pharmaceutical composition

Prior art date

2012-12-04

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Granted

Links

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• 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 claims description 52
• 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 claims description 52
• 239000003112 inhibitor Substances 0.000 claims description 48
• 239000003814 drug Substances 0.000 claims description 46
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 46
• 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 42
• 239000012634 fragment Substances 0.000 claims description 42
• 229940124597 therapeutic agent Drugs 0.000 claims description 40
• 229960004891 lapatinib Drugs 0.000 claims description 29
• 239000003446 ligand Substances 0.000 claims description 26
• 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 claims description 24
• GTTBEUCJPZQMDZ-UHFFFAOYSA-N erlotinib hydrochloride Chemical compound [H+].[Cl-].C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 GTTBEUCJPZQMDZ-UHFFFAOYSA-N 0.000 claims description 22
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
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• 102000001301 EGF receptor Human genes 0.000 claims description 16
• 101100118549 Homo sapiens EGFR gene Proteins 0.000 claims description 16
• 229940116355 PI3 kinase inhibitor Drugs 0.000 claims description 16
• 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 claims description 16
• 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 claims description 16
• 101100123851 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) HER1 gene Proteins 0.000 claims description 16
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• 229940124302 mTOR inhibitor Drugs 0.000 claims description 16
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• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 15
• 229960001972 panitumumab Drugs 0.000 claims description 15
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• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 9
• STUWGJZDJHPWGZ-LBPRGKRZSA-N (2S)-N1-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)-4-pyridinyl]-2-thiazolyl]pyrrolidine-1,2-dicarboxamide Chemical compound S1C(C=2C=C(N=CC=2)C(C)(C)C(F)(F)F)=C(C)N=C1NC(=O)N1CCC[C@H]1C(N)=O STUWGJZDJHPWGZ-LBPRGKRZSA-N 0.000 claims description 8
• 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 claims description 8
• 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 8
• 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 claims description 8
• 239000000654 additive Substances 0.000 claims description 8
• 230000000996 additive effect Effects 0.000 claims description 8
• 229950010482 alpelisib Drugs 0.000 claims description 8
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• 229950006418 dactolisib Drugs 0.000 claims description 8
• JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 229960001433 erlotinib Drugs 0.000 claims description 8
• 229960005167 everolimus Drugs 0.000 claims description 8
• 229960002584 gefitinib Drugs 0.000 claims description 8
• 238000007917 intracranial administration Methods 0.000 claims description 8
• 238000007918 intramuscular administration Methods 0.000 claims description 8
• 238000007912 intraperitoneal administration Methods 0.000 claims description 8
• 238000007913 intrathecal administration Methods 0.000 claims description 8
• 229950008835 neratinib Drugs 0.000 claims description 8
• ZNHPZUKZSNBOSQ-BQYQJAHWSA-N neratinib Chemical compound C=12C=C(NC\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZNHPZUKZSNBOSQ-BQYQJAHWSA-N 0.000 claims description 8
• 229950010203 nimotuzumab Drugs 0.000 claims description 8
• 229960002087 pertuzumab Drugs 0.000 claims description 8
• LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 claims description 8
• 150000003384 small molecules Chemical class 0.000 claims description 8
• 238000007920 subcutaneous administration Methods 0.000 claims description 8
• 229960000235 temsirolimus Drugs 0.000 claims description 8
• 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 claims description 8
• 229960000575 trastuzumab Drugs 0.000 claims description 8
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 5
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 5
• SYYMNUFXRFAELA-BTQNPOSSSA-N 4-[4-[[(1r)-1-phenylethyl]amino]-7h-pyrrolo[2,3-d]pyrimidin-6-yl]phenol;hydrobromide Chemical compound Br.N([C@H](C)C=1C=CC=CC=1)C(C=1C=2)=NC=NC=1NC=2C1=CC=C(O)C=C1 SYYMNUFXRFAELA-BTQNPOSSSA-N 0.000 claims description 3
• -1 3-chloro-4-fluorophenyl Chemical group 0.000 claims 1
• 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 1
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims 1
• 244000144992 flock Species 0.000 claims 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
• 238000000034 method Methods 0.000 description 53
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 7
• 229960001686 afatinib Drugs 0.000 description 7
• ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 7
• 229940082789 erbitux Drugs 0.000 description 7
• 229940084651 iressa Drugs 0.000 description 7
• 229940120982 tarceva Drugs 0.000 description 7
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• 201000009273 Endometriosis Diseases 0.000 description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 description 4
• 206010017758 gastric cancer Diseases 0.000 description 4
• 201000011549 stomach cancer Diseases 0.000 description 4
• 201000000079 gynecomastia Diseases 0.000 description 3
• 201000010536 head and neck cancer Diseases 0.000 description 3
• 208000014829 head and neck neoplasm Diseases 0.000 description 3
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
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• 201000004101 esophageal cancer Diseases 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• RNAMYOYQYRYFQY-UHFFFAOYSA-N 2-(4,4-difluoropiperidin-1-yl)-6-methoxy-n-(1-propan-2-ylpiperidin-4-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound N1=C(N2CCC(F)(F)CC2)N=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1CCN(C(C)C)CC1 RNAMYOYQYRYFQY-UHFFFAOYSA-N 0.000 description 1
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• 208000028299 esophageal disease Diseases 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 229960001320 lapatinib ditosylate Drugs 0.000 description 1
• AZBFJBJXUQUQLF-UHFFFAOYSA-N n-(1,5-dimethylpyrrolidin-3-yl)pyrrolidine-1-carboxamide Chemical compound C1N(C)C(C)CC1NC(=O)N1CCCC1 AZBFJBJXUQUQLF-UHFFFAOYSA-N 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1