JP2013511526A5 - - Google Patents
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- JP2013511526A5 JP2013511526A5 JP2012539987A JP2012539987A JP2013511526A5 JP 2013511526 A5 JP2013511526 A5 JP 2013511526A5 JP 2012539987 A JP2012539987 A JP 2012539987A JP 2012539987 A JP2012539987 A JP 2012539987A JP 2013511526 A5 JP2013511526 A5 JP 2013511526A5
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- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 13
- 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 10
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 10
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 10
- 208000000172 Medulloblastoma Diseases 0.000 claims description 8
- 229960005167 everolimus Drugs 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 5
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 4
- 229940124302 mTOR inhibitor Drugs 0.000 claims description 4
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims description 4
- 241000289669 Erinaceus europaeus Species 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000037361 pathway Effects 0.000 claims description 3
- VZZJRYRQSPEMTK-CALCHBBNSA-N sonidegib Chemical group C1[C@@H](C)O[C@@H](C)CN1C(N=C1)=CC=C1NC(=O)C1=CC=CC(C=2C=CC(OC(F)(F)F)=CC=2)=C1C VZZJRYRQSPEMTK-CALCHBBNSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 description 72
- 125000003545 alkoxy group Chemical group 0.000 description 38
- 229910052736 halogen Inorganic materials 0.000 description 30
- 150000002367 halogens Chemical class 0.000 description 30
- 229910052739 hydrogen Inorganic materials 0.000 description 16
- 239000001257 hydrogen Substances 0.000 description 14
- 150000002431 hydrogen Chemical class 0.000 description 12
- 125000005915 C6-C14 aryl group Chemical group 0.000 description 10
- 125000003118 aryl group Chemical group 0.000 description 10
- 125000000753 cycloalkyl group Chemical group 0.000 description 10
- 229940125904 compound 1 Drugs 0.000 description 9
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 125000001072 heteroaryl group Chemical group 0.000 description 8
- 229940126062 Compound A Drugs 0.000 description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 6
- -1 6-benzyl-4,5-dimethyl-pyridazi N-3-yl Chemical group 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000008410 smoothened signaling pathway Effects 0.000 description 5
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
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- 201000000050 myeloid neoplasm Diseases 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 2
- 125000006652 (C3-C12) cycloalkyl group Chemical group 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
- KVLFRAWTRWDEDF-IRXDYDNUSA-N AZD-8055 Chemical compound C1=C(CO)C(OC)=CC=C1C1=CC=C(C(=NC(=N2)N3[C@H](COCC3)C)N3[C@H](COCC3)C)C2=N1 KVLFRAWTRWDEDF-IRXDYDNUSA-N 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- RFSMUFRPPYDYRD-CALCHBBNSA-N Ku-0063794 Chemical compound C1=C(CO)C(OC)=CC=C1C1=CC=C(C(=NC(=N2)N3C[C@@H](C)O[C@@H](C)C3)N3CCOCC3)C2=N1 RFSMUFRPPYDYRD-CALCHBBNSA-N 0.000 description 2
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 2
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 2
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 2
- 206010039491 Sarcoma Diseases 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
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 230000000735 allogeneic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 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 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 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 description 2
- 229960000235 temsirolimus Drugs 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 206010003571 Astrocytoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000027355 Ferocactus setispinus Species 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 206010023347 Keratoacanthoma Diseases 0.000 description 1
- 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 1
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940125528 allosteric inhibitor Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 201000005787 hematologic cancer Diseases 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
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- 210000002307 prostate Anatomy 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 210000004116 schwann cell Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 208000001608 teratocarcinoma Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26234209P | 2009-11-18 | 2009-11-18 | |
| US61/262,342 | 2009-11-18 | ||
| US29203210P | 2010-01-04 | 2010-01-04 | |
| US61/292,032 | 2010-01-04 | ||
| PCT/US2010/056942 WO2011062939A1 (en) | 2009-11-18 | 2010-11-17 | Methods and compositions for treating solid tumors and other malignancies |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013511526A JP2013511526A (ja) | 2013-04-04 |
| JP2013511526A5 true JP2013511526A5 (US07794700-20100914-C00152.png) | 2015-06-11 |
Family
ID=43384585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012539987A Ceased JP2013511526A (ja) | 2009-11-18 | 2010-11-17 | 固形腫瘍及びその他の悪性腫瘍を治療するための方法及び組成物 |
Country Status (17)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2012005827A (es) | 2009-11-18 | 2012-06-19 | Plexxikon Inc | Compuestos y metodos para la modulacion de cinasas, e indicaciones para ello. |
| KR20140026537A (ko) * | 2011-06-02 | 2014-03-05 | 노파르티스 아게 | 헤지호그 억제제 요법을 위한 바이오마커 |
| US9655909B2 (en) | 2012-01-12 | 2017-05-23 | Board Of Regents, The University Of Texas System | Personalized medicine for the prediction of therapy targeting the hedgehog pathway |
| CA2890002A1 (en) * | 2012-11-05 | 2014-05-08 | Nant Holdings Ip, Llc | Cyclic sulfonamide containing derivatives as inhibitors of hedgehog signaling pathway |
| CN103524535B (zh) * | 2013-10-16 | 2016-07-13 | 苏州云轩医药科技有限公司 | 具有刺猬通路拮抗剂活性的胺基噻唑-吡啶杂环化合物 |
| HRP20230502T1 (hr) | 2017-10-27 | 2023-09-15 | Boehringer Ingelheim International Gmbh | Inhibitori trpc6 |
| WO2020010073A1 (en) | 2018-07-02 | 2020-01-09 | Palvella Therapeutics, Inc. | ANHYDROUS COMPOSITIONS OF mTOR INHIBITORS AND METHODS OF USE |
| WO2020061584A1 (en) * | 2018-09-21 | 2020-03-26 | Msb Holdings, Inc. | Taste-masked dosage forms |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| AU2006318948B2 (en) | 2005-11-22 | 2011-02-24 | Kudos Pharmaceuticals Limited | Pyrido-,pyrazo- and pyrimido-pyrimidine derivatives as mTOR inhibitors |
| UA93548C2 (uk) * | 2006-05-05 | 2011-02-25 | Айерем Елелсі | Сполуки та композиції як модулятори хеджхогівського сигнального шляху |
| KR101438245B1 (ko) | 2006-08-23 | 2014-09-04 | 쿠도스 파마슈티칼스 리미티드 | Ｍｔｏｒ 억제제로서의 2-메틸모르폴린 피리도-, 피라조- 및 피리미도-피리미딘 유도체 |
| SG182205A1 (en) * | 2007-03-15 | 2012-07-30 | Novartis Ag | Organic compounds and their uses |
| WO2008154259A1 (en) * | 2007-06-07 | 2008-12-18 | Irm Llc | Biphenylcarboxamide derivatives as hedgehog pathway modulators |
| US8153633B2 (en) * | 2007-06-25 | 2012-04-10 | Amgen Inc. | Phthalazine compounds, compositions and methods of use |
| WO2009112266A1 (en) * | 2008-03-12 | 2009-09-17 | Ludwig-Maximilians-Universität | Active substance combination with gemcitabine for the treatment of epithelial cancer |
| EA201071248A1 (ru) * | 2008-04-29 | 2011-06-30 | Эли Лилли Энд Компани | Дизамещенные фталазиновые антагонисты пути hedgehog |
| US20100041663A1 (en) * | 2008-07-18 | 2010-02-18 | Novartis Ag | Organic Compounds as Smo Inhibitors |
-
2010
- 2010-11-17 CA CA2781210A patent/CA2781210A1/en not_active Abandoned
- 2010-11-17 CN CN2010800517592A patent/CN102665700A/zh active Pending
- 2010-11-17 MX MX2012005695A patent/MX2012005695A/es not_active Application Discontinuation
- 2010-11-17 RU RU2012125152/15A patent/RU2012125152A/ru unknown
- 2010-11-17 EP EP10782767A patent/EP2501370A1/en not_active Withdrawn
- 2010-11-17 AU AU2010322114A patent/AU2010322114B2/en not_active Ceased
- 2010-11-17 CN CN201410410334.6A patent/CN104224791A/zh active Pending
- 2010-11-17 WO PCT/US2010/056942 patent/WO2011062939A1/en active Application Filing
- 2010-11-17 NZ NZ599964A patent/NZ599964A/en not_active IP Right Cessation
- 2010-11-17 KR KR1020127015545A patent/KR20120107962A/ko not_active Application Discontinuation
- 2010-11-17 BR BR112012011823A patent/BR112012011823A2/pt not_active IP Right Cessation
- 2010-11-17 US US13/509,857 patent/US20120232087A1/en not_active Abandoned
- 2010-11-17 JP JP2012539987A patent/JP2013511526A/ja not_active Ceased
-
2012
- 2012-05-07 IL IL219636A patent/IL219636A0/en unknown
- 2012-05-07 TN TNP2012000205A patent/TN2012000205A1/en unknown
- 2012-05-07 ZA ZA2012/03325A patent/ZA201203325B/en unknown
- 2012-05-11 MA MA34856A patent/MA33739B1/fr unknown
- 2012-05-16 CL CL2012001271A patent/CL2012001271A1/es unknown
-
2014
- 2014-10-09 US US14/510,713 patent/US20150025074A1/en not_active Abandoned
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