JP2011515415A5 - - Google Patents

Info

Publication number

JP2011515415A5

JP2011515415A5 JP2011500985A JP2011500985A JP2011515415A5 JP 2011515415 A5 JP2011515415 A5 JP 2011515415A5 JP 2011500985 A JP2011500985 A JP 2011500985A JP 2011500985 A JP2011500985 A JP 2011500985A JP 2011515415 A5 JP2011515415 A5 JP 2011515415A5

Authority

JP

Japan

Prior art keywords

opioid receptor

receptor antagonist

combination agent

mtor inhibitor

cells

Prior art date

2009-03-20

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

• Espacenet
• Global Dossier
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• 239000003795 chemical substances by application Substances 0.000 claims 19
• 239000002623 mu opiate receptor antagonist Substances 0.000 claims 18
• 229940124302 mTOR inhibitor Drugs 0.000 claims 10
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims 10
• 210000004027 cell Anatomy 0.000 claims 8
• 229940079593 drug Drugs 0.000 claims 8
• 239000003814 drug Substances 0.000 claims 8
• 239000000203 mixture Substances 0.000 claims 6
• 206010028980 Neoplasm Diseases 0.000 claims 5
• 201000011510 cancer Diseases 0.000 claims 5
• -1 TAFA93 Chemical compound 0.000 claims 4
• 238000013508 migration Methods 0.000 claims 4
• 230000005012 migration Effects 0.000 claims 4
• 230000035755 proliferation Effects 0.000 claims 4
• 150000003839 salts Chemical class 0.000 claims 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 3
• 230000037396 body weight Effects 0.000 claims 3
• 238000000034 method Methods 0.000 claims 3
• 229940002612 prodrug Drugs 0.000 claims 3
• 239000000651 prodrug Substances 0.000 claims 3
• 230000011664 signaling Effects 0.000 claims 3
• 239000012453 solvate Substances 0.000 claims 3
• JVLBPIPGETUEET-WIXLDOGYSA-O (3r,4r,4as,7ar,12bs)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7-one Chemical group C([N@+]1(C)[C@@H]2CC=3C4=C(C(=CC=3)O)O[C@@H]3[C@]4([C@@]2(O)CCC3=O)CC1)C1CC1 JVLBPIPGETUEET-WIXLDOGYSA-O 0.000 claims 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 claims 2
• 208000023275 Autoimmune disease Diseases 0.000 claims 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 2
• 101710088998 Response regulator inhibitor for tor operon Proteins 0.000 claims 2
• 210000002889 endothelial cell Anatomy 0.000 claims 2
• 239000003102 growth factor Substances 0.000 claims 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 2
• 230000002401 inhibitory effect Effects 0.000 claims 2
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims 2
• 229960002921 methylnaltrexone Drugs 0.000 claims 2
• 230000002093 peripheral effect Effects 0.000 claims 2
• 229960001302 ridaforolimus Drugs 0.000 claims 2
• PCSQOABIHJXZMR-MGQKVWQSSA-O (4r,4as,7ar,12bs)-4a,9-dihydroxy-3-methyl-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7-one Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CC[N+](C)(CC=C)[C@@H]3CC5=CC=C4O PCSQOABIHJXZMR-MGQKVWQSSA-O 0.000 claims 1
• HJDWPCLBBHHTIG-NNJWZEOZSA-O (4r,7s,7ar,12bs)-3-methyl-3-prop-2-enyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7,9-diol Chemical compound O([C@H]1[C@H](C=CC23)O)C4=C5[C@@]12CC[N+](C)(CC=C)[C@@H]3CC5=CC=C4O HJDWPCLBBHHTIG-NNJWZEOZSA-O 0.000 claims 1
• 102100032187 Androgen receptor Human genes 0.000 claims 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 claims 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
• 102100038595 Estrogen receptor Human genes 0.000 claims 1
• 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 1
• 208000009386 Experimental Arthritis Diseases 0.000 claims 1
• 208000003807 Graves Disease Diseases 0.000 claims 1
• 208000015023 Graves' disease Diseases 0.000 claims 1
• 229940123257 Opioid receptor antagonist Drugs 0.000 claims 1
• 102100025803 Progesterone receptor Human genes 0.000 claims 1
• 208000017442 Retinal disease Diseases 0.000 claims 1
• 206010038923 Retinopathy Diseases 0.000 claims 1
• 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims 1
• 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims 1
• 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 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 1
• 206010052428 Wound Diseases 0.000 claims 1
• 208000027418 Wounds and injury Diseases 0.000 claims 1
• 230000002411 adverse Effects 0.000 claims 1
• 125000003342 alkenyl group Chemical group 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 claims 1
• 125000000304 alkynyl group Chemical group 0.000 claims 1
• 229960004516 alvimopan Drugs 0.000 claims 1
• UPNUIXSCZBYVBB-JVFUWBCBSA-N alvimopan Chemical group C([C@@H](CN1C[C@@H]([C@](CC1)(C)C=1C=C(O)C=CC=1)C)C(=O)NCC(O)=O)C1=CC=CC=C1 UPNUIXSCZBYVBB-JVFUWBCBSA-N 0.000 claims 1
• 108010080146 androgen receptors Proteins 0.000 claims 1
• 230000033115 angiogenesis Effects 0.000 claims 1
• 125000003118 aryl group Chemical group 0.000 claims 1
• 239000008280 blood Substances 0.000 claims 1
• 210000004369 blood Anatomy 0.000 claims 1
• 210000001185 bone marrow Anatomy 0.000 claims 1
• 201000006491 bone marrow cancer Diseases 0.000 claims 1
• 210000004556 brain Anatomy 0.000 claims 1
• 210000000481 breast Anatomy 0.000 claims 1
• JROFGZPOBKIAEW-HAQNSBGRSA-N chembl3120215 Chemical compound N1C=2C(OC)=CC=CC=2C=C1C(=C1C(N)=NC=NN11)N=C1[C@H]1CC[C@H](C(O)=O)CC1 JROFGZPOBKIAEW-HAQNSBGRSA-N 0.000 claims 1
• 238000011260 co-administration Methods 0.000 claims 1
• 150000001875 compounds Chemical class 0.000 claims 1
• 201000001981 dermatomyositis Diseases 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
• 208000035475 disorder Diseases 0.000 claims 1
• 230000000694 effects Effects 0.000 claims 1
• 210000004696 endometrium Anatomy 0.000 claims 1
• 201000004101 esophageal cancer Diseases 0.000 claims 1
• 210000003238 esophagus Anatomy 0.000 claims 1
• 108010038795 estrogen receptors Proteins 0.000 claims 1
• 229960005167 everolimus Drugs 0.000 claims 1
• 210000003128 head Anatomy 0.000 claims 1
• 208000014829 head and neck neoplasm Diseases 0.000 claims 1
• 201000005787 hematologic cancer Diseases 0.000 claims 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
• 108091008039 hormone receptors Proteins 0.000 claims 1
• 238000007918 intramuscular administration Methods 0.000 claims 1
• 238000001990 intravenous administration Methods 0.000 claims 1
• 210000004185 liver Anatomy 0.000 claims 1
• 210000004072 lung Anatomy 0.000 claims 1
• 206010025135 lupus erythematosus Diseases 0.000 claims 1
• 208000026037 malignant tumor of neck Diseases 0.000 claims 1
• 210000004962 mammalian cell Anatomy 0.000 claims 1
• 230000011987 methylation Effects 0.000 claims 1
• 238000007069 methylation reaction Methods 0.000 claims 1
• JVLBPIPGETUEET-GAAHOAFPSA-O methylnaltrexone Chemical compound C[N+]1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@@H]3[C@]4([C@@]2(O)CCC3=O)CC1)CC1CC1 JVLBPIPGETUEET-GAAHOAFPSA-O 0.000 claims 1
• INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical group C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims 1
• 102000051367 mu Opioid Receptors Human genes 0.000 claims 1
• 201000006417 multiple sclerosis Diseases 0.000 claims 1
• DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 claims 1
• 229960003086 naltrexone Drugs 0.000 claims 1
• 210000003739 neck Anatomy 0.000 claims 1
• 229940051807 opiod analgesics morphinan derivative Drugs 0.000 claims 1
• 210000001672 ovary Anatomy 0.000 claims 1
• 108090000468 progesterone receptors Proteins 0.000 claims 1
• 210000002307 prostate Anatomy 0.000 claims 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 claims 1
• 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
• 208000007056 sickle cell anemia Diseases 0.000 claims 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical group 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 claims 1
• 229960002930 sirolimus Drugs 0.000 claims 1
• 210000003491 skin Anatomy 0.000 claims 1
• 210000004927 skin cell Anatomy 0.000 claims 1
• 210000002784 stomach Anatomy 0.000 claims 1
• 238000007920 subcutaneous administration Methods 0.000 claims 1
• 125000003107 substituted aryl group Chemical group 0.000 claims 1
• 229960000235 temsirolimus Drugs 0.000 claims 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 claims 1
• 210000001550 testis Anatomy 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 claims 1
• 230000000699 topical effect Effects 0.000 claims 1
• 230000004614 tumor growth Effects 0.000 claims 1
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
• 230000002792 vascular Effects 0.000 claims 1
• 210000003556 vascular endothelial cell Anatomy 0.000 claims 1
• 108020001612 μ-opioid receptors Proteins 0.000 claims 1