JP2017531624A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2017531624A5 JP2017531624A5 JP2017513748A JP2017513748A JP2017531624A5 JP 2017531624 A5 JP2017531624 A5 JP 2017531624A5 JP 2017513748 A JP2017513748 A JP 2017513748A JP 2017513748 A JP2017513748 A JP 2017513748A JP 2017531624 A5 JP2017531624 A5 JP 2017531624A5
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- nhc
- nhnh
- heteroaryl
- 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.)
- Granted
Links
- 125000001072 heteroaryl group Chemical group 0.000 claims 55
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 52
- 125000000217 alkyl group Chemical group 0.000 claims 48
- 125000003118 aryl group Chemical group 0.000 claims 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims 48
- 125000004404 heteroalkyl group Chemical group 0.000 claims 48
- 229910052736 halogen Inorganic materials 0.000 claims 43
- 150000002367 halogens Chemical class 0.000 claims 43
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 38
- 150000001875 compounds Chemical class 0.000 claims 35
- 125000004474 heteroalkylene group Chemical group 0.000 claims 27
- -1 —OH Inorganic materials 0.000 claims 18
- 125000005549 heteroarylene group Chemical group 0.000 claims 16
- 229910052739 hydrogen Inorganic materials 0.000 claims 16
- 239000001257 hydrogen Substances 0.000 claims 16
- 150000002431 hydrogen Chemical class 0.000 claims 14
- 239000008194 pharmaceutical composition Substances 0.000 claims 14
- 125000002947 alkylene group Chemical group 0.000 claims 12
- 125000000732 arylene group Chemical group 0.000 claims 12
- 125000002993 cycloalkylene group Chemical group 0.000 claims 12
- 125000006588 heterocycloalkylene group Chemical group 0.000 claims 12
- 229910052757 nitrogen Inorganic materials 0.000 claims 10
- 150000003839 salts Chemical class 0.000 claims 9
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims 8
- 101150065749 Churc1 gene Proteins 0.000 claims 8
- 102100038239 Protein Churchill Human genes 0.000 claims 8
- 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 claims 8
- 201000010099 disease Diseases 0.000 claims 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 7
- 125000005647 linker group Chemical group 0.000 claims 6
- GYLDXIAOMVERTK-UHFFFAOYSA-N 5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine Chemical compound C12=C(N)N=CN=C2N(C(C)C)N=C1C1=CC=C(OC(N)=N2)C2=C1 GYLDXIAOMVERTK-UHFFFAOYSA-N 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 4
- 125000004043 oxo group Chemical group O=* 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims 4
- 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 4
- 229950009216 sapanisertib Drugs 0.000 claims 4
- 229960002930 sirolimus Drugs 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 claims 3
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 claims 3
- 230000000694 effects Effects 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000000335 thiazolyl group Chemical group 0.000 claims 3
- SVNJBEMPMKWDCO-KCHLEUMXSA-N (2s)-2-[[(2s)-3-carboxy-2-[[2-[[(2s)-5-(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl)morpholin-4-ium-4-yl]methoxy]butanoyl]amino]pentanoyl]amino]acetyl]amino]propanoyl]amino]-3-hydroxypropanoate Chemical compound C=1C(=O)C2=CC=CC(C=3C=CC=CC=3)=C2OC=1[N+]1(COC(=O)CCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C([O-])=O)CCOCC1 SVNJBEMPMKWDCO-KCHLEUMXSA-N 0.000 claims 2
- 125000006587 (C5-C10) heteroarylene group Chemical group 0.000 claims 2
- DWZAEMINVBZMHQ-UHFFFAOYSA-N 1-[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea Chemical compound C1CC(N(C)C)CCN1C(=O)C(C=C1)=CC=C1NC(=O)NC1=CC=C(C=2N=C(N=C(N=2)N2CCOCC2)N2CCOCC2)C=C1 DWZAEMINVBZMHQ-UHFFFAOYSA-N 0.000 claims 2
- RGJOJUGRHPQXGF-INIZCTEOSA-N 1-ethyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-7-(oxetan-3-yl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C1=CC(NC(=O)NCC)=CC=C1C(N=C1N2[C@H](COCC2)C)=NC2=C1CCN(C1COC1)C2 RGJOJUGRHPQXGF-INIZCTEOSA-N 0.000 claims 2
- XDLYKKIQACFMJG-UHFFFAOYSA-N 2-amino-8-[4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=NC(OC)=CC=C1C(C1=O)=CC2=C(C)N=C(N)N=C2N1C1CCC(OCCO)CC1 XDLYKKIQACFMJG-UHFFFAOYSA-N 0.000 claims 2
- JUSFANSTBFGBAF-IRXDYDNUSA-N 3-[2,4-bis[(3s)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(C=2N=C3N=C(N=C(C3=CC=2)N2[C@H](COCC2)C)N2[C@H](COCC2)C)=C1 JUSFANSTBFGBAF-IRXDYDNUSA-N 0.000 claims 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 claims 2
- YUXMAKUNSXIEKN-BTJKTKAUSA-N BGT226 Chemical compound OC(=O)\C=C/C(O)=O.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 YUXMAKUNSXIEKN-BTJKTKAUSA-N 0.000 claims 2
- UFKLYTOEMRFKAD-SHTZXODSSA-N C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=NC(=CC=3)C(C)(C)O)=CN=C2NCC1=O Chemical compound C1C[C@@H](OC)CC[C@@H]1N1C2=NC(C=3C=NC(=CC=3)C(C)(C)O)=CN=C2NCC1=O UFKLYTOEMRFKAD-SHTZXODSSA-N 0.000 claims 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 2
- TUVCWJQQGGETHL-UHFFFAOYSA-N PI-103 Chemical compound OC1=CC=CC(C=2N=C3C4=CC=CN=C4OC3=C(N3CCOCC3)N=2)=C1 TUVCWJQQGGETHL-UHFFFAOYSA-N 0.000 claims 2
- NVRXTLZYXZNATH-UHFFFAOYSA-N PP121 Chemical compound N1=C(C=2C=C3C=CNC3=NC=2)C=2C(N)=NC=NC=2N1C1CCCC1 NVRXTLZYXZNATH-UHFFFAOYSA-N 0.000 claims 2
- 208000031481 Pathologic Constriction Diseases 0.000 claims 2
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000005874 benzothiadiazolyl group Chemical group 0.000 claims 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 235000010290 biphenyl Nutrition 0.000 claims 2
- 239000004305 biphenyl Substances 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 229950006418 dactolisib Drugs 0.000 claims 2
- 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 2
- 125000002720 diazolyl group Chemical group 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 229940124302 mTOR inhibitor Drugs 0.000 claims 2
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims 2
- VDOCQQKGPJENHJ-UHFFFAOYSA-N methyl n-[4-[4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC)=CC=C1C1=NC(N2CCOCC2)=C(C=NN2C3CCN(CC=4C=NC=CC=4)CC3)C2=N1 VDOCQQKGPJENHJ-UHFFFAOYSA-N 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 125000005493 quinolyl group Chemical group 0.000 claims 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 2
- 208000037804 stenosis Diseases 0.000 claims 2
- 230000036262 stenosis Effects 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- AKCRNFFTGXBONI-UHFFFAOYSA-N torin 1 Chemical compound C1CN(C(=O)CC)CCN1C1=CC=C(N2C(C=CC3=C2C2=CC(=CC=C2N=C3)C=2C=C3C=CC=CC3=NC=2)=O)C=C1C(F)(F)F AKCRNFFTGXBONI-UHFFFAOYSA-N 0.000 claims 2
- GUXXEUUYCAYESJ-UHFFFAOYSA-N torin 2 Chemical compound C1=NC(N)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C=CC=4)C(F)(F)F)C(=O)C=C2)C3=C1 GUXXEUUYCAYESJ-UHFFFAOYSA-N 0.000 claims 2
- MFAQYJIYDMLAIM-UHFFFAOYSA-N torkinib Chemical compound C12=C(N)N=CN=C2N(C(C)C)N=C1C1=CC2=CC(O)=CC=C2N1 MFAQYJIYDMLAIM-UHFFFAOYSA-N 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 208000026372 Congenital cystic kidney disease Diseases 0.000 claims 1
- 208000026292 Cystic Kidney disease Diseases 0.000 claims 1
- 206010017533 Fungal infection Diseases 0.000 claims 1
- 208000031888 Mycoses Diseases 0.000 claims 1
- 206010052779 Transplant rejections Diseases 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
- 230000005784 autoimmunity Effects 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 230000004770 neurodegeneration Effects 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 125000005559 triazolylene group Chemical group 0.000 claims 1
- VMXMBPPFDJEVAB-UHFFFAOYSA-P CC(CC(CCC1OCCOCC(N=N)=C[NH2+]CCOCCOCCOCCOCCOCCOCCOCCOCCC(NCCCC[NH2+]c2ncnc(N)c2C(c2ccc3[o]c(N)nc3c2)=N)=O)CC1OC)C(CC(C(C)C=C(C)C(C(C(C(C)CC(C)C=CC=CC=C(C)C(CC(CCC1C)OC1(C(C(N1C2CCCC1)=O)=O)O)OC)=O)OC)O)=O)OC2=O Chemical compound CC(CC(CCC1OCCOCC(N=N)=C[NH2+]CCOCCOCCOCCOCCOCCOCCOCCOCCC(NCCCC[NH2+]c2ncnc(N)c2C(c2ccc3[o]c(N)nc3c2)=N)=O)CC1OC)C(CC(C(C)C=C(C)C(C(C(C(C)CC(C)C=CC=CC=C(C)C(CC(CCC1C)OC1(C(C(N1C2CCCC1)=O)=O)O)OC)=O)OC)O)=O)OC2=O VMXMBPPFDJEVAB-UHFFFAOYSA-P 0.000 description 1
- 0 C[C@](C[C@](CC[C@@]1O)(C[C@]1OC)I#C)[C@](CC([C@](C)C=C(C)[C@@](*)[C@](C([C@](C)C[C@](C)C=CC=CC=C(C)[C@](C[C@@](CC[C@]1C)(C#C)OC1(C(C(*(CCCC1)[C@@]11C=C)=O)=O)OC)OC)=O)OC)=O)OC1=O Chemical compound C[C@](C[C@](CC[C@@]1O)(C[C@]1OC)I#C)[C@](CC([C@](C)C=C(C)[C@@](*)[C@](C([C@](C)C[C@](C)C=CC=CC=C(C)[C@](C[C@@](CC[C@]1C)(C#C)OC1(C(C(*(CCCC1)[C@@]11C=C)=O)=O)OC)OC)=O)OC)=O)OC1=O 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462049186P | 2014-09-11 | 2014-09-11 | |
| US62/049,186 | 2014-09-11 | ||
| PCT/US2015/049693 WO2016040806A1 (en) | 2014-09-11 | 2015-09-11 | mTORC1 INHIBITORS |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020072118A Division JP7057798B2 (ja) | 2014-09-11 | 2020-04-14 | ｍＴＯＲＣ１阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017531624A JP2017531624A (ja) | 2017-10-26 |
| JP2017531624A5 true JP2017531624A5 (enExample) | 2019-03-28 |
| JP6692798B2 JP6692798B2 (ja) | 2020-05-13 |
Family
ID=55459613
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017513748A Active JP6692798B2 (ja) | 2014-09-11 | 2015-09-11 | ｍＴＯＲＣ１阻害剤 |
| JP2020072118A Active JP7057798B2 (ja) | 2014-09-11 | 2020-04-14 | ｍＴＯＲＣ１阻害剤 |
| JP2022064349A Pending JP2022091995A (ja) | 2014-09-11 | 2022-04-08 | ｍＴＯＲＣ１阻害剤 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020072118A Active JP7057798B2 (ja) | 2014-09-11 | 2020-04-14 | ｍＴＯＲＣ１阻害剤 |
| JP2022064349A Pending JP2022091995A (ja) | 2014-09-11 | 2022-04-08 | ｍＴＯＲＣ１阻害剤 |
Country Status (7)
| Country | Link |
|---|---|
| US (5) | US10117945B2 (enExample) |
| EP (1) | EP3193902A4 (enExample) |
| JP (3) | JP6692798B2 (enExample) |
| CN (2) | CN107073066B (enExample) |
| CA (1) | CA2960992C (enExample) |
| MX (2) | MX2017001981A (enExample) |
| WO (1) | WO2016040806A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107073066B (zh) * | 2014-09-11 | 2021-09-17 | 加利福尼亚大学董事会 | mTORC1抑制剂 |
| US20180141897A1 (en) | 2014-12-08 | 2018-05-24 | The Research Foundation For The State University Of New York | Anti-fungals targeting the synthesis of fungal shingolipids |
| WO2017044720A1 (en) * | 2015-09-11 | 2017-03-16 | Navitor Pharmaceuticals, Inc. | Rapamycin analogs and uses thereof |
| JP7348071B2 (ja) * | 2017-05-02 | 2023-09-20 | レヴォリューション・メディスンズ，インコーポレイテッド | ｍＴＯＲ阻害剤としてのラパマイシン類似体 |
| EP3638649A4 (en) | 2017-06-16 | 2021-03-17 | The Research Foundation for The State University of New York | Anti-fungals compounds targeting the synthesis of fungal sphingolipids |
| US10947542B2 (en) * | 2017-07-20 | 2021-03-16 | Curigin Co., Ltd. | Nucleic acid simultaneously inhibiting expression of AR gene and mTOR gene |
| WO2019178536A1 (en) * | 2018-03-16 | 2019-09-19 | The Regents Of The University Of California | Mtor inhibitors and uses thereof |
| TW202014208A (zh) | 2018-05-01 | 2020-04-16 | 美商銳新醫藥公司 | 作為ｍＴＯＲ抑制劑之Ｃ４０-、Ｃ２８-及Ｃ-３２連接之雷帕黴素類似物 |
| CA3098698A1 (en) | 2018-05-01 | 2019-11-07 | Revolution Medicines, Inc. | C26-linked rapamycin analogs as mtor inhibitors |
| CN108676882B (zh) * | 2018-05-30 | 2022-02-22 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | NOP14基因及其蛋白作为肿瘤对mTOR抑制剂敏感性的标志物的应用 |
| CN117843659A (zh) | 2018-06-15 | 2024-04-09 | 詹森药业有限公司 | 雷帕霉素类似物和其用途 |
| CA3236782A1 (en) * | 2019-01-22 | 2020-07-30 | Aeovian Pharmaceuticals, Inc. | Mtorc modulators and uses thereof |
| US20230063768A1 (en) * | 2019-02-07 | 2023-03-02 | The Regents Of The University Of California | Immunophilin binding agents and uses thereof |
| US20220193242A1 (en) * | 2019-02-07 | 2022-06-23 | The Regents Of The University Of California | Immunophilin-dependent inhibitors and uses thereof |
| CN110152004B (zh) * | 2019-07-08 | 2021-09-03 | 天津医科大学 | 甘氨酸在制备药物递送增强剂及细胞移植试剂方面的用途 |
| KR20220128345A (ko) | 2019-12-05 | 2022-09-20 | 아나쿠리아 테라퓨틱스, 인코포레이티드 | 라파마이신 유사체 및 이의 용도 |
| CA3173722A1 (en) | 2020-03-27 | 2021-09-30 | John Kincaid | Mtorc1 modulators and uses thereof |
| MX2022016355A (es) | 2020-06-18 | 2023-04-03 | Revolution Medicines Inc | Metodos para retardar, prevenir, y tratar la resistencia adquirida a inhibidores de ras. |
| WO2022020522A2 (en) * | 2020-07-21 | 2022-01-27 | Aeovian Pharmaceuticals, Inc. | Mtorc1 modulators and uses thereof |
| CN114507236A (zh) * | 2022-02-28 | 2022-05-17 | 山东中医药大学 | mTOR蛋白降解靶向嵌合体及其制备方法和应用 |
| EP4531859A1 (en) | 2022-05-25 | 2025-04-09 | Revolution Medicines, Inc. | Methods of treating cancer with an mtor inhibitor |
| CN119462690A (zh) * | 2024-11-08 | 2025-02-18 | 西安交通大学 | 一类基于自噬-溶酶体途径的选择性mTORC1降解剂及其制备方法和应用 |
Family Cites Families (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA737247B (en) | 1972-09-29 | 1975-04-30 | Ayerst Mckenna & Harrison | Rapamycin and process of preparation |
| US4316885A (en) | 1980-08-25 | 1982-02-23 | Ayerst, Mckenna And Harrison, Inc. | Acyl derivatives of rapamycin |
| US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
| FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
| US4650803A (en) | 1985-12-06 | 1987-03-17 | University Of Kansas | Prodrugs of rapamycin |
| US5023264A (en) | 1990-07-16 | 1991-06-11 | American Home Products Corporation | Rapamycin oximes |
| US5023263A (en) | 1990-08-09 | 1991-06-11 | American Home Products Corporation | 42-oxorapamycin |
| US5130307A (en) | 1990-09-28 | 1992-07-14 | American Home Products Corporation | Aminoesters of rapamycin |
| US5221670A (en) | 1990-09-19 | 1993-06-22 | American Home Products Corporation | Rapamycin esters |
| PT98990A (pt) | 1990-09-19 | 1992-08-31 | American Home Prod | Processo para a preparacao de esteres de acidos carboxilicos de rapamicina |
| US5233036A (en) | 1990-10-16 | 1993-08-03 | American Home Products Corporation | Rapamycin alkoxyesters |
| DK0495421T3 (da) | 1991-01-15 | 1996-12-09 | Alcon Lab Inc | Anvendelse af carragenaner i topiske ophthalmiske sammensætninger |
| GB9103430D0 (en) | 1991-02-19 | 1991-04-03 | Smithkline Beecham Plc | Novel compound |
| US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
| US5120842A (en) | 1991-04-01 | 1992-06-09 | American Home Products Corporation | Silyl ethers of rapamycin |
| US5100883A (en) | 1991-04-08 | 1992-03-31 | American Home Products Corporation | Fluorinated esters of rapamycin |
| US5118678A (en) | 1991-04-17 | 1992-06-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5118677A (en) | 1991-05-20 | 1992-06-02 | American Home Products Corporation | Amide esters of rapamycin |
| US5162333A (en) | 1991-09-11 | 1992-11-10 | American Home Products Corporation | Aminodiesters of rapamycin |
| US5151413A (en) | 1991-11-06 | 1992-09-29 | American Home Products Corporation | Rapamycin acetals as immunosuppressant and antifungal agents |
| GB9125660D0 (en) | 1991-12-03 | 1992-01-29 | Smithkline Beecham Plc | Novel compound |
| US5177203A (en) | 1992-03-05 | 1993-01-05 | American Home Products Corporation | Rapamycin 42-sulfonates and 42-(N-carboalkoxy) sulfamates useful as immunosuppressive agents |
| ZA935112B (en) | 1992-07-17 | 1994-02-08 | Smithkline Beecham Corp | Rapamycin derivatives |
| ZA935111B (en) | 1992-07-17 | 1994-02-04 | Smithkline Beecham Corp | Rapamycin derivatives |
| US5256790A (en) | 1992-08-13 | 1993-10-26 | American Home Products Corporation | 27-hydroxyrapamycin and derivatives thereof |
| GB9221220D0 (en) | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| US5480989A (en) | 1992-10-13 | 1996-01-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5411967A (en) | 1992-10-13 | 1995-05-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5302584A (en) | 1992-10-13 | 1994-04-12 | American Home Products Corporation | Carbamates of rapamycin |
| US5480988A (en) | 1992-10-13 | 1996-01-02 | American Home Products Corporation | Carbamates of rapamycin |
| US5489680A (en) | 1992-10-13 | 1996-02-06 | American Home Products Corporation | Carbamates of rapamycin |
| US5262423A (en) | 1992-10-29 | 1993-11-16 | American Home Products Corporation | Rapamycin arylcarbonyl and alkoxycarbonyl carbamates as immunosuppressive and antifungal agents |
| US5258389A (en) | 1992-11-09 | 1993-11-02 | Merck & Co., Inc. | O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives |
| US5260300A (en) | 1992-11-19 | 1993-11-09 | American Home Products Corporation | Rapamycin carbonate esters as immuno-suppressant agents |
| US5252579A (en) | 1993-02-16 | 1993-10-12 | American Home Products Corporation | Macrocyclic immunomodulators |
| US5504091A (en) | 1993-04-23 | 1996-04-02 | American Home Products Corporation | Biotin esters of rapamycin |
| US5378836A (en) | 1993-10-08 | 1995-01-03 | American Home Products Corporation | Rapamycin oximes and hydrazones |
| US5373014A (en) | 1993-10-08 | 1994-12-13 | American Home Products Corporation | Rapamycin oximes |
| US5391730A (en) | 1993-10-08 | 1995-02-21 | American Home Products Corporation | Phosphorylcarbamates of rapamycin and oxime derivatives thereof |
| CA2175215C (en) | 1993-11-19 | 2008-06-03 | Yat Sun Or | Semisynthetic analogs of rapamycin (macrolides) being immunomodulators |
| US5385908A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Hindered esters of rapamycin |
| US5385909A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Heterocyclic esters of rapamycin |
| US5385910A (en) | 1993-11-22 | 1995-01-31 | American Home Products Corporation | Gem-distributed esters of rapamycin |
| HUT74686A (en) | 1993-12-17 | 1997-01-28 | Sandoz Ag | Rapamycin derivatives, their pharmaceutical use, process for producing them and pharmaceutical composition containing them as active agents |
| US5389639A (en) | 1993-12-29 | 1995-02-14 | American Home Products Company | Amino alkanoic esters of rapamycin |
| US5362718A (en) | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| US5463048A (en) | 1994-06-14 | 1995-10-31 | American Home Products Corporation | Rapamycin amidino carbamates |
| US5491231A (en) | 1994-11-28 | 1996-02-13 | American Home Products Corporation | Hindered N-oxide esters of rapamycin |
| US5563145A (en) | 1994-12-07 | 1996-10-08 | American Home Products Corporation | Rapamycin 42-oximes and hydroxylamines |
| US6323201B1 (en) | 1994-12-29 | 2001-11-27 | The Regents Of The University Of California | Compounds for inhibition of ceramide-mediated signal transduction |
| PT833828E (pt) | 1995-06-09 | 2003-02-28 | Novartis Ag | Derivados de rapamicina |
| US5780462A (en) | 1995-12-27 | 1998-07-14 | American Home Products Corporation | Water soluble rapamycin esters |
| IL127559A0 (en) | 1996-06-20 | 1999-10-28 | Univ Texas | Compounds and methods for providing pharmacologically active preparations and uses thereof |
| CN1293081C (zh) | 1999-08-24 | 2007-01-03 | 阿里亚德基因治疗公司 | 28－表雷帕霉素类似物,其制备方法，药物组合物和用途 |
| US6277983B1 (en) | 2000-09-27 | 2001-08-21 | American Home Products Corporation | Regioselective synthesis of rapamycin derivatives |
| JP2004161716A (ja) | 2002-11-15 | 2004-06-10 | Takeda Chem Ind Ltd | Ｊｎｋ阻害剤 |
| US7429596B2 (en) | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| US7220755B2 (en) | 2003-11-12 | 2007-05-22 | Biosensors International Group, Ltd. | 42-O-alkoxyalkyl rapamycin derivatives and compositions comprising same |
| ATE418559T1 (de) | 2004-03-01 | 2009-01-15 | Terumo Corp | Verfahren zur herstellung von o-alkylierten rapamycinderivaten |
| ZA200609259B (en) | 2004-04-30 | 2008-07-30 | Takeda Pharmaceutical | Heterocyclic amide compound and use thereof as an mmp-13 inhibitor |
| CN100516195C (zh) | 2004-07-19 | 2009-07-22 | 汕头市双骏生物科技有限公司 | 一种新的菌株及应用该菌株生产紫杉醇的方法 |
| EP1831225A2 (en) | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| GB0504994D0 (en) | 2005-03-11 | 2005-04-20 | Biotica Tech Ltd | Novel compounds |
| US7642059B2 (en) * | 2005-09-07 | 2010-01-05 | Roche Diagnostics Operations, Inc. | Single receptor assays for immunosuppressive drugs |
| JP2009532507A (ja) | 2006-04-04 | 2009-09-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｐｉ３キナーゼアンタゴニスト |
| US20090274739A1 (en) | 2006-04-13 | 2009-11-05 | The Trustees Of Columbia University In The City Of New York | Methods and compositions for treating neointimal hyperplasia |
| WO2007121453A2 (en) | 2006-04-17 | 2007-10-25 | The Regents Of The University Of California | 2-hydroxy-1-oxo 1,2 dihydro isoquinoline chelating agents |
| US20090287133A1 (en) | 2006-06-06 | 2009-11-19 | Lagreca Sr Alfred J | Disposable or Reclosable Wound or Skin Condition Dressing and Treatment System |
| EP2298772A1 (en) | 2006-10-18 | 2011-03-23 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compounds |
| CN101522691B (zh) | 2006-11-27 | 2012-08-22 | 泰尔茂株式会社 | O-烷基化雷帕霉素衍生物的制备方法及o-烷基化雷帕霉素衍生物 |
| US20080249123A1 (en) | 2007-04-05 | 2008-10-09 | Wyeth | Wortmannin-rapamycin conjugate and uses thereof |
| US20090074831A1 (en) * | 2007-09-18 | 2009-03-19 | Robert Falotico | LOCAL VASCULAR DELIVERY OF mTOR INHIBITORS IN COMBINATION WITH PEROXISOME PROLIFERATORS-ACTIVATED RECEPTOR STIMULATORS |
| WO2009046436A1 (en) * | 2007-10-04 | 2009-04-09 | Memorial Sloan-Kettering Cancer Center | Methods for inhibiting senescence of epithelial cells |
| KR101660050B1 (ko) | 2008-01-04 | 2016-09-26 | 인텔리카인, 엘엘씨 | 특정 화학 물질, 조성물 및 방법 |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
| US20110098241A1 (en) | 2008-04-14 | 2011-04-28 | Poniard Pharmaceuticals, Inc. | Rapamycin analogs as anti-cancer agents |
| TW200948361A (en) | 2008-05-26 | 2009-12-01 | Chunghwa Chemical Synthesis & Biotech Co Ltd | Method for synthesizing Biolimus A9 and the like and method for improving stability of the same |
| MX2011000216A (es) | 2008-07-08 | 2011-03-29 | Intellikine Inc | Inhibidores de cinasa y metodos para su uso. |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| US20100055145A1 (en) | 2008-08-29 | 2010-03-04 | Biosensors International Group | Stent coatings for reducing late stent thrombosis |
| US8703778B2 (en) | 2008-09-26 | 2014-04-22 | Intellikine Llc | Heterocyclic kinase inhibitors |
| DK2358720T3 (en) | 2008-10-16 | 2016-06-06 | Univ California | Heteroarylkinaseinhibitorer fused-ring |
| US8110578B2 (en) * | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| US8476282B2 (en) | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| US20110269779A1 (en) | 2008-11-18 | 2011-11-03 | Intellikine, Inc. | Methods and compositions for treatment of ophthalmic conditions |
| EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| ES2709108T3 (es) | 2009-08-17 | 2019-04-15 | Intellikine Llc | Compuestos heterocíclicos y usos de los mismos |
| TWI428336B (zh) * | 2009-10-12 | 2014-03-01 | Hoffmann La Roche | Ｐｉ３ｋ抑制劑及ｍｅｋ抑制劑之組合 |
| US8980899B2 (en) | 2009-10-16 | 2015-03-17 | The Regents Of The University Of California | Methods of inhibiting Ire1 |
| AU2011255218B2 (en) | 2010-05-21 | 2015-03-12 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| WO2012024558A2 (en) * | 2010-08-20 | 2012-02-23 | The University Of North Carolina At Chapel Hill | Light mediated regulation of protein dimerization |
| WO2012066502A1 (en) | 2010-11-19 | 2012-05-24 | Biocon Limited | Processes for preparation of everolimus and intermediates thereof |
| EP2670756B1 (en) | 2011-02-04 | 2017-06-21 | Synthon BV | Process for making everolimus |
| CA2828483A1 (en) | 2011-02-23 | 2012-11-01 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
| JP6491879B2 (ja) * | 2011-04-29 | 2019-03-27 | セレクタ バイオサイエンシーズ インコーポレーテッドＳｅｌｅｃｔａ Ｂｉｏｓｃｉｅｎｃｅｓ，Ｉｎｃ． | 制御性ｂ細胞を誘導するための寛容原性合成ナノキャリア |
| EP2705181B1 (en) * | 2011-05-04 | 2016-12-21 | Intellikine, LLC | Combination pharmaceutical compositions and uses thereof |
| CA2835197A1 (en) | 2011-05-06 | 2012-11-15 | Intellikine Llc | Treatment of polycystic disease |
| CA2846496C (en) | 2011-09-02 | 2020-07-14 | The Regents Of The University Of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
| CN107073066B (zh) | 2014-09-11 | 2021-09-17 | 加利福尼亚大学董事会 | mTORC1抑制剂 |
| JP7348071B2 (ja) * | 2017-05-02 | 2023-09-20 | レヴォリューション・メディスンズ，インコーポレイテッド | ｍＴＯＲ阻害剤としてのラパマイシン類似体 |
-
2015
- 2015-09-11 CN CN201580057417.4A patent/CN107073066B/zh active Active
- 2015-09-11 JP JP2017513748A patent/JP6692798B2/ja active Active
- 2015-09-11 WO PCT/US2015/049693 patent/WO2016040806A1/en not_active Ceased
- 2015-09-11 CA CA2960992A patent/CA2960992C/en active Active
- 2015-09-11 CN CN202111002275.5A patent/CN113620978A/zh active Pending
- 2015-09-11 MX MX2017001981A patent/MX2017001981A/es unknown
- 2015-09-11 EP EP15840163.8A patent/EP3193902A4/en active Pending
-
2017
- 2017-02-13 MX MX2022013114A patent/MX2022013114A/es unknown
- 2017-03-10 US US15/455,727 patent/US10117945B2/en active Active
-
2018
- 2018-09-10 US US16/126,210 patent/US10646577B2/en active Active
-
2020
- 2020-03-24 US US16/828,774 patent/US11452780B2/en active Active
- 2020-04-14 JP JP2020072118A patent/JP7057798B2/ja active Active
-
2022
- 2022-04-08 JP JP2022064349A patent/JP2022091995A/ja active Pending
-
2023
- 2023-02-28 US US18/176,335 patent/US12097262B2/en active Active
-
2024
- 2024-08-12 US US18/801,301 patent/US20250099597A1/en active Pending