IL235146A - Converted heterocyclic compounds, preparations and their medical applications - Google Patents
Converted heterocyclic compounds, preparations and their medical applicationsInfo
- Publication number
- IL235146A IL235146A IL235146A IL23514614A IL235146A IL 235146 A IL235146 A IL 235146A IL 235146 A IL235146 A IL 235146A IL 23514614 A IL23514614 A IL 23514614A IL 235146 A IL235146 A IL 235146A
- Authority
- IL
- Israel
- Prior art keywords
- phenyl
- pyrrolo
- dihydro
- methyl
- cyclopropyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 39
- 125000002618 bicyclic heterocycle group Chemical group 0.000 title 1
- -1 heterocyclylene Chemical group 0.000 claims description 148
- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 103
- 125000005842 heteroatom Chemical group 0.000 claims description 87
- 238000000034 method Methods 0.000 claims description 83
- 125000001188 haloalkyl group Chemical group 0.000 claims description 82
- 125000001424 substituent group Chemical group 0.000 claims description 75
- 125000000623 heterocyclic group Chemical group 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 69
- 229910052736 halogen Inorganic materials 0.000 claims description 61
- 150000002367 halogens Chemical group 0.000 claims description 61
- 125000002947 alkylene group Chemical group 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000003342 alkenyl group Chemical group 0.000 claims description 40
- 125000000304 alkynyl group Chemical group 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
- 229920006395 saturated elastomer Polymers 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 26
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 125000002950 monocyclic group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000004419 alkynylene group Chemical group 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 229910052705 radium Inorganic materials 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 229910052701 rubidium Inorganic materials 0.000 claims description 15
- 125000004450 alkenylene group Chemical group 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
- 230000001404 mediated effect Effects 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 10
- 125000000468 ketone group Chemical group 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 229940124291 BTK inhibitor Drugs 0.000 claims description 9
- 125000000732 arylene group Chemical group 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000001506 immunosuppresive effect Effects 0.000 claims description 5
- 101000864342 Homo sapiens Tyrosine-protein kinase BTK Proteins 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 3
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 3
- 230000000779 depleting effect Effects 0.000 claims description 3
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 3
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 229940122739 Calcineurin inhibitor Drugs 0.000 claims description 2
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 claims description 2
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 claims description 2
- 229930105110 Cyclosporin A Natural products 0.000 claims description 2
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 2
- 108010036949 Cyclosporine Proteins 0.000 claims description 2
- 102000042838 JAK family Human genes 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 102100038183 Tyrosine-protein kinase SYK Human genes 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- ZDQSOHOQTUFQEM-PKUCKEGBSA-N ascomycin Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C\C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](O)[C@H](OC)C1 ZDQSOHOQTUFQEM-PKUCKEGBSA-N 0.000 claims description 2
- ZDQSOHOQTUFQEM-XCXYXIJFSA-N ascomycin Natural products CC[C@H]1C=C(C)C[C@@H](C)C[C@@H](OC)[C@H]2O[C@@](O)([C@@H](C)C[C@H]2OC)C(=O)C(=O)N3CCCC[C@@H]3C(=O)O[C@H]([C@H](C)[C@@H](O)CC1=O)C(=C[C@@H]4CC[C@@H](O)[C@H](C4)OC)C ZDQSOHOQTUFQEM-XCXYXIJFSA-N 0.000 claims description 2
- 229960001265 ciclosporin Drugs 0.000 claims description 2
- 239000003246 corticosteroid Substances 0.000 claims description 2
- 229960001334 corticosteroids Drugs 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229940043355 kinase inhibitor Drugs 0.000 claims description 2
- 229960000951 mycophenolic acid Drugs 0.000 claims description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 235
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 95
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 74
- 125000004093 cyano group Chemical group *C#N 0.000 claims 46
- 150000002431 hydrogen Chemical group 0.000 claims 28
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims 23
- 125000004966 cyanoalkyl group Chemical group 0.000 claims 22
- 125000002252 acyl group Chemical group 0.000 claims 19
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 19
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 17
- 229910052717 sulfur Inorganic materials 0.000 claims 17
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims 14
- 229910006069 SO3H Inorganic materials 0.000 claims 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 12
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims 11
- 125000004043 oxo group Chemical group O=* 0.000 claims 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 10
- 229930194542 Keto Natural products 0.000 claims 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 9
- 125000004442 acylamino group Chemical group 0.000 claims 8
- 125000004423 acyloxy group Chemical group 0.000 claims 8
- 125000005157 alkyl carboxy group Chemical group 0.000 claims 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 8
- 125000005549 heteroarylene group Chemical group 0.000 claims 8
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 8
- 125000004414 alkyl thio group Chemical group 0.000 claims 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 7
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 5
- 125000004976 cyclobutylene group Chemical group 0.000 claims 5
- 125000004980 cyclopropylene group Chemical group 0.000 claims 5
- 125000000033 alkoxyamino group Chemical group 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 4
- 125000005724 cycloalkenylene group Chemical group 0.000 claims 4
- ZGNXATVKGIJQGC-UHFFFAOYSA-N piperidine-3-carbonitrile Chemical compound N#CC1CCCNC1 ZGNXATVKGIJQGC-UHFFFAOYSA-N 0.000 claims 4
- UNTNRNUQVKDIPV-UHFFFAOYSA-N 3h-dithiazole Chemical compound N1SSC=C1 UNTNRNUQVKDIPV-UHFFFAOYSA-N 0.000 claims 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims 3
- 125000002393 azetidinyl group Chemical group 0.000 claims 3
- 239000013078 crystal Substances 0.000 claims 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 3
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims 3
- 125000002541 furyl group Chemical group 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 3
- 125000002757 morpholinyl group Chemical group 0.000 claims 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 3
- 125000002971 oxazolyl group Chemical group 0.000 claims 3
- 125000005564 oxazolylene group Chemical group 0.000 claims 3
- 125000003566 oxetanyl group Chemical group 0.000 claims 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims 3
- FSDNTQSJGHSJBG-UHFFFAOYSA-N piperidine-4-carbonitrile Chemical compound N#CC1CCNCC1 FSDNTQSJGHSJBG-UHFFFAOYSA-N 0.000 claims 3
- 125000003386 piperidinyl group Chemical group 0.000 claims 3
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 3
- 125000005550 pyrazinylene group Chemical group 0.000 claims 3
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 3
- 125000005551 pyridylene group Chemical group 0.000 claims 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 239000012453 solvate Substances 0.000 claims 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 3
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims 3
- 125000000335 thiazolyl group Chemical group 0.000 claims 3
- 125000005557 thiazolylene group Chemical group 0.000 claims 3
- 125000005556 thienylene group Chemical group 0.000 claims 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims 3
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 claims 3
- 150000003852 triazoles Chemical class 0.000 claims 3
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims 2
- RPDYTAUMOYXWQZ-UHFFFAOYSA-N 6-cyclopropyl-2-[2-methyl-3-[6-[4-[(3-oxopiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]phenyl]-3,4-dihydroisoquinolin-1-one Chemical compound CC1=C(N2C(C3=CC=C(C=C3CC2)C2CC2)=O)C=CC=C1C(C=1C=2)=NC=NC=1NC=2C(C=C1)=CC=C1CN1CCNC(=O)C1 RPDYTAUMOYXWQZ-UHFFFAOYSA-N 0.000 claims 2
- GYNGMWFFLDXWPR-UHFFFAOYSA-N 6-cyclopropyl-2-[3-[6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-2-methylphenyl]-3,4-dihydroisoquinolin-1-one Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(=C3C=2)C=2C(=C(N3C(C4=CC=C(C=C4CC3)C3CC3)=O)C=CC=2)C)C=C1 GYNGMWFFLDXWPR-UHFFFAOYSA-N 0.000 claims 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 2
- 229930012538 Paclitaxel Natural products 0.000 claims 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 2
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims 2
- 229960001592 paclitaxel Drugs 0.000 claims 2
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 claims 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 2
- ASUGUQWIHMTFJL-QGZVFWFLSA-N (2r)-2-methyl-2-[[2-(1h-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]-n-(2,2,2-trifluoroethyl)butanamide Chemical compound FC(F)(F)CNC(=O)[C@@](C)(CC)NC1=CC=NC(C=2C3=CC=CN=C3NC=2)=N1 ASUGUQWIHMTFJL-QGZVFWFLSA-N 0.000 claims 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims 1
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims 1
- MPWRITRYGLHZBT-VAWYXSNFSA-N (e)-n-benzyl-3-phenylprop-2-enamide Chemical compound C=1C=CC=CC=1/C=C/C(=O)NCC1=CC=CC=C1 MPWRITRYGLHZBT-VAWYXSNFSA-N 0.000 claims 1
- KTGWVDVOBBVFEC-UHFFFAOYSA-N 1-[[4-[4-[3-(6-cyclopropyl-1-oxo-3,4-dihydroisoquinolin-2-yl)-2-methylphenyl]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]phenyl]methyl]piperidine-4-carbonitrile Chemical compound C1(CC1)C=1C=C2CCN(C(C2=CC1)=O)C=1C(=C(C=CC1)C=1C2=C(N=CN1)NC(=C2)C2=CC=C(C=C2)CN2CCC(CC2)C#N)C KTGWVDVOBBVFEC-UHFFFAOYSA-N 0.000 claims 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 claims 1
- YVCXQRVVNQMZEI-UHFFFAOYSA-N 2,6-dibromo-4-[(6,7-dimethoxy-4-quinazolinyl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC(Br)=C(O)C(Br)=C1 YVCXQRVVNQMZEI-UHFFFAOYSA-N 0.000 claims 1
- PPSDFDFYVHJNDI-UHFFFAOYSA-N 2-[3-[2-amino-6-(1-methylpyrazol-4-yl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-2-methylphenyl]-6-cyclopropylisoquinolin-1-one Chemical compound CC1=C(C=2C=3C=C(NC=3N=C(N)N=2)C2=CN(C)N=C2)C=CC=C1N(C(C1=CC=2)=O)C=CC1=CC=2C1CC1 PPSDFDFYVHJNDI-UHFFFAOYSA-N 0.000 claims 1
- RAJIXYLIGUBDRN-UHFFFAOYSA-N 2-[3-[2-amino-6-(4-morpholin-4-ylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]-2-methylphenyl]-6-cyclopropylphthalazin-1-one Chemical compound CC1=C(C=2C=3C=C(NC=3N=C(N)N=2)C=2C=CC(=CC=2)N2CCOCC2)C=CC=C1N(C(C1=CC=2)=O)N=CC1=CC=2C1CC1 RAJIXYLIGUBDRN-UHFFFAOYSA-N 0.000 claims 1
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| EP2571361A4 (en) | 2010-05-19 | 2013-11-13 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| KR102063098B1 (ko) | 2011-10-03 | 2020-01-08 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | 암 치료를 위한 피롤로피리미딘 화합물 |
| WO2013177168A1 (en) | 2012-05-22 | 2013-11-28 | The University Of North Carolina At Chapel Hill | Pyrimidine compounds for the treatment of cancer |
| WO2014025976A1 (en) | 2012-08-10 | 2014-02-13 | Boehringer Ingelheim International Gmbh | Heteroaromatic compounds as bruton's tyrosine kinase (btk) inhibitors |
| EP2909211A4 (en) | 2012-10-17 | 2016-06-22 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| EP2925752A4 (en) | 2012-11-27 | 2016-06-01 | Univ North Carolina | PYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| BR112015023187A2 (pt) * | 2013-03-14 | 2017-07-18 | Abbvie Inc | inibidores de pirrolo[2,3 - b] piridina cdk9 kinase |
| CN104211703B (zh) * | 2013-05-30 | 2018-04-03 | 南京勇山生物科技有限公司 | 一类作为布鲁顿激酶抑制剂的稠杂环化合物 |
| US9512084B2 (en) | 2013-11-29 | 2016-12-06 | Novartis Ag | Amino pyrimidine derivatives |
| AU2015244171A1 (en) * | 2014-04-11 | 2016-11-03 | The University Of North Carolina At Chapel Hill | MerTK-specific pyrimidine compounds |
| CN105294571B (zh) * | 2014-07-03 | 2019-04-23 | 浙江九洲药业股份有限公司 | 一种依鲁替尼中间体及其制备方法和用途 |
| RS63190B1 (sr) | 2014-08-04 | 2022-06-30 | Nuevolution As | Opciono fuzionisani derivati pirimidina zamenjeni heterociklilom korisni za lečenje zapaljenskih, metaboličkih, onkoloških i autoimunskih bolesti |
| CA2960401C (en) | 2014-10-06 | 2022-07-26 | Merck Patent Gmbh | Heteroaryl compounds as btk inhibitors and uses thereof |
| US10272070B2 (en) | 2014-10-14 | 2019-04-30 | The Board of Trustees of the Leland Stanford Junio r University | Method for treating neurodegenerative diseases |
| LT3461821T (lt) * | 2014-10-24 | 2020-08-10 | Bristol-Myers Squibb Company | Indolo karboksamido junginiai, naudotini kaip kinazės inhibitoriai |
| EP3042903B1 (en) * | 2015-01-06 | 2019-08-14 | Impetis Biosciences Ltd. | Substituted hetero-bicyclic compounds, compositions and medicinal applications thereof |
| ES2821049T3 (es) | 2015-06-18 | 2021-04-23 | 89Bio Ltd | Derivados de piperidina 1,4 sustituidos |
| US10919875B2 (en) | 2015-06-18 | 2021-02-16 | 89Bio Ltd | Substituted 4-benzyl and 4-benzoyl piperidine derivatives |
| GB201517217D0 (en) * | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| GB201517216D0 (en) * | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| CN108884053B (zh) | 2015-12-15 | 2022-01-04 | 斯坦福大学托管董事会 | 预防和/或治疗与衰老有关的认知障碍和神经炎症的方法 |
| WO2017123695A1 (en) * | 2016-01-13 | 2017-07-20 | Boehringer Ingelheim International Gmbh | Isoquinolones as btk inhibitors |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| JP7017521B2 (ja) | 2016-04-15 | 2022-02-08 | ブループリント メディシンズ コーポレイション | アクチビン受容体様キナーゼの阻害剤 |
| CA2969295A1 (en) | 2016-06-06 | 2017-12-06 | Pfizer Inc. | Substituted carbonucleoside derivatives, and use thereof as a prmt5 inhibitor |
| US10266528B2 (en) * | 2016-08-16 | 2019-04-23 | Merck Patent Gmbh | 2-oxo-imidazopyridines as reversible BTK inhibitors and uses thereof |
| US10793575B2 (en) | 2016-11-25 | 2020-10-06 | Carna Biosciences, Inc. | Oxoisoquinoline derivatives |
| CN106883235B (zh) * | 2016-12-29 | 2019-04-30 | 天津国际生物医药联合研究院 | 恶二唑类化合物的制备和应用 |
| JP7164203B2 (ja) * | 2017-02-08 | 2022-11-01 | 中国医▲薬▼研究▲開▼▲発▼中心有限公司 | ピロロ芳香族複素環化合物及びその製造方法並びに医薬用途 |
| CN108794480A (zh) * | 2017-04-28 | 2018-11-13 | 天津药物研究院有限公司 | 吡咯并嘧啶类化合物、其制备方法和用途 |
| CN111566102B (zh) | 2017-10-18 | 2023-09-08 | 缆图药品公司 | 作为激活素受体样激酶抑制剂的取代的吡咯并吡啶 |
| IL274936B2 (en) * | 2017-12-13 | 2023-09-01 | Lupin Ltd | Transmuted heterocyclic bicyclic compounds as prmt5 inhibitors |
| CN109293638B (zh) * | 2018-03-27 | 2020-08-14 | 大连理工大学 | 一种增强型的靶向识别受体酪氨酸激酶的荧光传感器及细胞膜荧光成像的应用 |
| CN108707154A (zh) * | 2018-07-10 | 2018-10-26 | 刘凤娟 | 一种治疗癌症的药物溶剂合物及其制备方法 |
| KR20210068399A (ko) * | 2018-08-06 | 2021-06-09 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 주니어 유니버시티 | 신경퇴행성 질병의 치료를 위한 피피에이알지씨1알파 활성제로서 2-아릴벤즈이미다졸 |
| CN112654618A (zh) * | 2018-09-06 | 2021-04-13 | 豪夫迈·罗氏有限公司 | 用于治疗自身免疫性疾病的新型环脒化合物 |
| CN109180643A (zh) * | 2018-10-04 | 2019-01-11 | 南京先进生物材料与过程装备研究院有限公司 | 酞嗪酮类化合物晶型a及其制备方法 |
| CN109336863A (zh) * | 2018-10-04 | 2019-02-15 | 南京先进生物材料与过程装备研究院有限公司 | 一种新型酞嗪酮类btk抑制剂、制备及其应用 |
| CN109180644A (zh) * | 2018-10-04 | 2019-01-11 | 南京先进生物材料与过程装备研究院有限公司 | 一种新型btk激酶抑制剂的甲磺酸盐及其制备方法与用途 |
| CN109369619A (zh) * | 2018-10-04 | 2019-02-22 | 南京先进生物材料与过程装备研究院有限公司 | 酞嗪酮类化合物晶型b及其制备方法 |
| CN109336864A (zh) * | 2018-10-04 | 2019-02-15 | 南京先进生物材料与过程装备研究院有限公司 | 酞嗪酮类化合物晶型n及其制备方法 |
| CN109293635A (zh) * | 2018-10-04 | 2019-02-01 | 南京先进生物材料与过程装备研究院有限公司 | 一种新型btk激酶抑制剂的p晶型及其制备方法 |
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| CA2869954C (en) | 2023-01-03 |
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