JP2012526772A5 - - Google Patents
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- Publication number
- JP2012526772A5 JP2012526772A5 JP2012510289A JP2012510289A JP2012526772A5 JP 2012526772 A5 JP2012526772 A5 JP 2012526772A5 JP 2012510289 A JP2012510289 A JP 2012510289A JP 2012510289 A JP2012510289 A JP 2012510289A JP 2012526772 A5 JP2012526772 A5 JP 2012526772A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- cancer
- methyl
- pharmaceutically acceptable
- 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.)
- Pending
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 150000001875 compounds Chemical class 0.000 claims description 20
- 230000002062 proliferating effect Effects 0.000 claims description 20
- 201000010099 disease Diseases 0.000 claims description 18
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 claims description 13
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 13
- 239000003623 enhancer Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 208000020816 lung neoplasm Diseases 0.000 claims description 8
- 102000038030 PI3Ks Human genes 0.000 claims description 6
- 108091007960 PI3Ks Proteins 0.000 claims description 6
- 239000008280 blood Substances 0.000 claims description 6
- 210000004369 blood Anatomy 0.000 claims description 6
- 230000005764 inhibitory process Effects 0.000 claims description 6
- 230000037361 pathway Effects 0.000 claims description 6
- BMMXYEBLEBULND-UHFFFAOYSA-N BGT226 free base Chemical compound C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 BMMXYEBLEBULND-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- -1 cyano, imidazolyl Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000008103 glucose Substances 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical class CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 5
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 claims description 4
- 108010011376 AMP-Activated Protein Kinases Proteins 0.000 claims description 4
- 102000014156 AMP-Activated Protein Kinases Human genes 0.000 claims description 4
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 4
- 229940123208 Biguanide Drugs 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
- 206010014733 Endometrial cancer Diseases 0.000 claims description 4
- 206010014759 Endometrial neoplasm 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
- 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 claims description 4
- 101710181599 Serine/threonine-protein kinase STK11 Proteins 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 230000004777 loss-of-function mutation Effects 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000037841 lung tumor Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- JTSLALYXYSRPGW-UHFFFAOYSA-N n-[5-(4-cyanophenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=C(C#N)C=C1 JTSLALYXYSRPGW-UHFFFAOYSA-N 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 238000006029 Jeger synthesis reaction Methods 0.000 claims description 3
- 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 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- 239000012190 activator Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 11
- 229910052736 halogen Inorganic materials 0.000 claims 10
- 150000002367 halogens Chemical class 0.000 claims 10
- 229910052739 hydrogen Inorganic materials 0.000 claims 10
- 239000001257 hydrogen Substances 0.000 claims 10
- 125000003545 alkoxy group Chemical group 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 4
- 125000000623 heterocyclic group Chemical group 0.000 claims 4
- CWHUFRVAEUJCEF-UHFFFAOYSA-N BKM120 Chemical compound C1=NC(N)=CC(C(F)(F)F)=C1C1=CC(N2CCOCC2)=NC(N2CCOCC2)=N1 CWHUFRVAEUJCEF-UHFFFAOYSA-N 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000000304 alkynyl group Chemical group 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 102000004877 Insulin Human genes 0.000 claims 1
- 108090001061 Insulin Proteins 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 229940125396 insulin Drugs 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 125000001624 naphthyl group Chemical group 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
- 238000000034 method Methods 0.000 description 7
- RWGBXAQMUBGGKQ-UHFFFAOYSA-N 4-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC(C(F)(F)F)=CC=N1 RWGBXAQMUBGGKQ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09160440 | 2009-05-15 | ||
| EP09160440.5 | 2009-05-15 | ||
| PCT/EP2010/056538 WO2010130779A2 (en) | 2009-05-15 | 2010-05-12 | COMBINATION OF A PBOSPBOINOSITKLE 3-KSπASE INHIBITOR AND AN ANTIDIABETIC COMPOUND |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012526772A JP2012526772A (ja) | 2012-11-01 |
| JP2012526772A5 true JP2012526772A5 (https=) | 2013-06-27 |
Family
ID=40983590
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012510289A Pending JP2012526772A (ja) | 2009-05-15 | 2010-05-12 | ホスホイノシチド３−キナーゼ阻害剤および抗糖尿病性化合物の組合せ剤 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20120059005A1 (https=) |
| EP (1) | EP2429516A2 (https=) |
| JP (1) | JP2012526772A (https=) |
| KR (1) | KR20120096869A (https=) |
| CN (1) | CN102958518A (https=) |
| AU (1) | AU2010247397B2 (https=) |
| BR (1) | BRPI1010979A2 (https=) |
| CA (1) | CA2760179A1 (https=) |
| MX (1) | MX2011012201A (https=) |
| RU (1) | RU2011150619A (https=) |
| WO (1) | WO2010130779A2 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR081060A1 (es) | 2010-04-15 | 2012-06-06 | Bayer Schering Pharma Ag | Procedimiento para preparar 4-{4-[({[4-cloro-3-(trifluorometil)fenil]amino}carbonil)amino]-3-fluorofenoxi}-n-metilpiridin-2-carboxamida |
| SG188439A1 (en) | 2010-10-01 | 2013-05-31 | Novartis Ag | Manufacturing process for pyrimidine derivatives |
| CN112022853A (zh) | 2013-04-12 | 2020-12-04 | 内德生物系统有限公司 | 癌症的治疗 |
| JP7187035B2 (ja) * | 2016-08-03 | 2022-12-12 | アールイーエムディー バイオセラピューティクス，インコーポレイテッド | 癌を治療するためのグルカゴン受容体アンタゴニストとｐｉ３ｋ経路阻害剤との組み合わせ |
| CA3102279A1 (en) * | 2018-06-01 | 2019-12-05 | Cornell University | Combination therapy for pi3k-associated disease or disorder |
| TW202011966A (zh) * | 2018-07-23 | 2020-04-01 | 瑞士商赫孚孟拉羅股份公司 | 用pi3k抑制劑gdc-0077治療癌症之方法 |
| EP3863618A1 (en) * | 2018-10-08 | 2021-08-18 | F. Hoffmann-La Roche AG | Methods of treating cancer with pi3k alpha inhibitors and metformin |
| JP2023507797A (ja) * | 2019-12-20 | 2023-02-27 | リキュリウム アイピー ホールディングス リミテッド ライアビリティー カンパニー | 組み合わせ |
| CN120361228B (zh) * | 2025-04-08 | 2025-11-21 | 复旦大学附属妇产科医院 | 一种葡萄糖激酶激活剂与pi3k抑制剂的组合物 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040176425A1 (en) * | 2003-01-24 | 2004-09-09 | Washburn William N. | Cycloalkyl containing anilide ligands for the thyroid receptor |
| JP5371426B2 (ja) * | 2004-07-09 | 2013-12-18 | プロルックス ファーマシューティカルズ コープ． | ワートマニン類似体及び化学療法薬と組み合わせた同一物を使用する方法 |
| WO2006069186A2 (en) * | 2004-12-22 | 2006-06-29 | The Ohio State Research Foundation | Small molecule bcl-xl/bcl-2 binding inhibitors |
| GB0510390D0 (en) * | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| JO2660B1 (en) * | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| US20080044390A1 (en) * | 2006-08-11 | 2008-02-21 | Xiaowei Jin | Methods and compositions for the treatment of neurodegenerative disorders |
| EP2120909A2 (en) * | 2006-12-15 | 2009-11-25 | Ordway Research Institute | Treatments of therapy-resistant diseases comprising drug combinations |
| EP2231147A2 (en) * | 2007-12-13 | 2010-09-29 | Novartis AG | Combinations of therapeutic agents for treating cancer |
| WO2009155659A1 (en) * | 2008-06-27 | 2009-12-30 | The University Of Queensland | Combination therapy |
| US20110105521A1 (en) * | 2008-07-11 | 2011-05-05 | Novartis Ag | Combination of (a) a phosphoinositide 3-kinase inhibitor and (b) a modulator of ras/raf/mek pathway |
-
2010
- 2010-05-12 AU AU2010247397A patent/AU2010247397B2/en not_active Ceased
- 2010-05-12 RU RU2011150619/02A patent/RU2011150619A/ru not_active Application Discontinuation
- 2010-05-12 WO PCT/EP2010/056538 patent/WO2010130779A2/en not_active Ceased
- 2010-05-12 KR KR1020117027030A patent/KR20120096869A/ko not_active Withdrawn
- 2010-05-12 CA CA2760179A patent/CA2760179A1/en not_active Abandoned
- 2010-05-12 JP JP2012510289A patent/JP2012526772A/ja active Pending
- 2010-05-12 US US13/319,536 patent/US20120059005A1/en not_active Abandoned
- 2010-05-12 BR BRPI1010979A patent/BRPI1010979A2/pt not_active IP Right Cessation
- 2010-05-12 MX MX2011012201A patent/MX2011012201A/es not_active Application Discontinuation
- 2010-05-12 CN CN2010800199053A patent/CN102958518A/zh active Pending
- 2010-05-12 EP EP10718226A patent/EP2429516A2/en not_active Withdrawn
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