MX2011007064A - Compuestos de quinazolina substituidos. - Google Patents
Compuestos de quinazolina substituidos.Info
- Publication number
- MX2011007064A MX2011007064A MX2011007064A MX2011007064A MX2011007064A MX 2011007064 A MX2011007064 A MX 2011007064A MX 2011007064 A MX2011007064 A MX 2011007064A MX 2011007064 A MX2011007064 A MX 2011007064A MX 2011007064 A MX2011007064 A MX 2011007064A
- Authority
- MX
- Mexico
- Prior art keywords
- phenyl
- quinazolin
- ylamino
- chloro
- compound
- Prior art date
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- -1 { 2- [4- (2-pyrrolidin-1-yl-ethoxy) -phenylamino] -quinazolin-6-yl} - phenol Chemical compound 0.000 claims description 48
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- MCWXXILNYUKEIR-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CC2=CN=C1NC(C=C1)=CC=C1N(C1=O)CCN1CCN1CCCC1 MCWXXILNYUKEIR-UHFFFAOYSA-N 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- SIACCBGVOWSQAC-AREMUKBSSA-N (2r)-1-[2-[4-[[6-(2,6-dimethylphenyl)quinazolin-2-yl]amino]phenoxy]ethyl]pyrrolidine-2-carboxylic acid Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(OCCN3[C@H](CCC3)C(O)=O)=CC=2)N=C2)C2=C1 SIACCBGVOWSQAC-AREMUKBSSA-N 0.000 claims description 2
- SUSIZIGAKZXBKA-UHFFFAOYSA-N 4-chloro-3-[2-[3-(hydroxymethyl)anilino]-8-methylquinazolin-6-yl]phenol Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CC2=CN=C1NC1=CC=CC(CO)=C1 SUSIZIGAKZXBKA-UHFFFAOYSA-N 0.000 claims description 2
- XMEMWQHGCLIHOM-UHFFFAOYSA-N 6-(2,6-dimethylphenyl)-n-[4-(2-pyrrolidin-1-ylethoxy)phenyl]quinazolin-2-amine Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(OCCN3CCCC3)=CC=2)N=C2)C2=C1 XMEMWQHGCLIHOM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 2
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 claims description 2
- AMMREYAIIGJNRT-UHFFFAOYSA-N 1-[4-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=C2C)C=3C(=CC=C(O)C=3)Cl)C2=N1 AMMREYAIIGJNRT-UHFFFAOYSA-N 0.000 claims 1
- SDNJFGWENJJGAI-AREMUKBSSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]-3-[2-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]ethyl]imidazolidin-2-one Chemical compound C1[C@H](N(C)C)CCN1CCN1C(=O)N(C=2C=CC(NC=3N=C4C(C)=CC(=CC4=CN=3)C=3C(=CC=C(O)C=3)Cl)=CC=2)CC1 SDNJFGWENJJGAI-AREMUKBSSA-N 0.000 claims 1
- UKZPNRGUTKWSFX-UHFFFAOYSA-N [4-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]piperazin-1-yl]-pyridin-3-ylmethanone Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CC2=CN=C1NC(C=C1)=CC=C1N(CC1)CCN1C(=O)C1=CC=CN=C1 UKZPNRGUTKWSFX-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 55
- 208000035475 disorder Diseases 0.000 abstract description 34
- 206010028980 Neoplasm Diseases 0.000 abstract description 18
- 201000010099 disease Diseases 0.000 abstract description 18
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 16
- 201000011510 cancer Diseases 0.000 abstract description 16
- 102000020233 phosphotransferase Human genes 0.000 abstract description 16
- 208000002780 macular degeneration Diseases 0.000 abstract description 10
- 230000001404 mediated effect Effects 0.000 abstract description 8
- 206010038923 Retinopathy Diseases 0.000 abstract description 6
- 208000027866 inflammatory disease Diseases 0.000 abstract description 6
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 6
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 6
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 208000024172 Cardiovascular disease Diseases 0.000 abstract description 2
- 208000026278 immune system disease Diseases 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 24
- 238000011282 treatment Methods 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 21
- 230000008728 vascular permeability Effects 0.000 description 18
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- 230000002792 vascular Effects 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 102000009076 src-Family Kinases Human genes 0.000 description 12
- 108010087686 src-Family Kinases Proteins 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- 239000005022 packaging material Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 206010030113 Oedema Diseases 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 102000001253 Protein Kinase Human genes 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 108060006633 protein kinase Proteins 0.000 description 7
- 235000020945 retinal Nutrition 0.000 description 7
- 230000002207 retinal effect Effects 0.000 description 7
- 238000011200 topical administration Methods 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 230000008482 dysregulation Effects 0.000 description 6
- 239000012091 fetal bovine serum Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 230000011664 signaling Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000004888 barrier function Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 208000017442 Retinal disease Diseases 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 230000003831 deregulation Effects 0.000 description 4
- 229960003699 evans blue Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229940054534 ophthalmic solution Drugs 0.000 description 4
- 239000002997 ophthalmic solution Substances 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- 238000012384 transportation and delivery Methods 0.000 description 4
- 230000035899 viability Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000001344 Macular Edema Diseases 0.000 description 3
- 206010025415 Macular oedema Diseases 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 208000010668 atopic eczema Diseases 0.000 description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000001516 cell proliferation assay Methods 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 201000011190 diabetic macular edema Diseases 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000003349 gelling agent Substances 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 230000002601 intratumoral effect Effects 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 201000010230 macular retinal edema Diseases 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 230000037361 pathway Effects 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 150000003246 quinazolines Chemical class 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- OWQPOVKKUWUEKE-UHFFFAOYSA-N 1,2,3-benzotriazine Chemical compound N1=NN=CC2=CC=CC=C21 OWQPOVKKUWUEKE-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- IJXKEDDKGGBSBX-UHFFFAOYSA-N 6-bromoquinazolin-2-amine Chemical compound C1=C(Br)C=CC2=NC(N)=NC=C21 IJXKEDDKGGBSBX-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 208000036487 Arthropathies Diseases 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000012659 Joint disease Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000004115 adherent culture Methods 0.000 description 2
- 230000001464 adherent effect Effects 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 239000003732 agents acting on the eye Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000004155 blood-retinal barrier Anatomy 0.000 description 2
- 230000004378 blood-retinal barrier Effects 0.000 description 2
- 239000001045 blue dye Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000006677 mitochondrial metabolism Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940023490 ophthalmic product Drugs 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 229940021747 therapeutic vaccine Drugs 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 208000026726 vitreous disease Diseases 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- TYRDPAITJGOXCX-UHFFFAOYSA-N 1-[4-[[6-(2,6-dimethylphenyl)quinazolin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(=CC=2)N2C(N(CCN3CCCC3)CC2)=O)N=C2)C2=C1 TYRDPAITJGOXCX-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- OIQOAYVCKAHSEJ-UHFFFAOYSA-N 2-[2,3-bis(2-hydroxyethoxy)propoxy]ethanol;hexadecanoic acid;octadecanoic acid Chemical compound OCCOCC(OCCO)COCCO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O OIQOAYVCKAHSEJ-UHFFFAOYSA-N 0.000 description 1
- DKDSOJOOGBYVHM-JOCHJYFZSA-N 2-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenoxy]-1-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]ethanone Chemical compound C1[C@H](N(C)C)CCN1C(=O)COC(C=C1)=CC=C1NC1=NC=C(C=C(C=C2C)C=3C(=CC=C(O)C=3)Cl)C2=N1 DKDSOJOOGBYVHM-JOCHJYFZSA-N 0.000 description 1
- MZHYKEMGPNRRNY-OAQYLSRUSA-N 2-[4-[[6-(2-chloro-5-hydroxyphenyl)quinazolin-2-yl]amino]phenoxy]-1-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]ethanone Chemical compound C1[C@H](N(C)C)CCN1C(=O)COC(C=C1)=CC=C1NC1=NC=C(C=C(C=C2)C=3C(=CC=C(O)C=3)Cl)C2=N1 MZHYKEMGPNRRNY-OAQYLSRUSA-N 0.000 description 1
- 150000003930 2-aminopyridines Chemical class 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- WWINACYDRQWTQL-UHFFFAOYSA-N 2-pyridin-2-ylquinazoline Chemical class N1=CC=CC=C1C1=NC=C(C=CC=C2)C2=N1 WWINACYDRQWTQL-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- XNURRHDXCWKBOG-UHFFFAOYSA-N 6-(2,6-dimethylphenyl)-n-(4-piperazin-1-ylphenyl)quinazolin-2-amine Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(=CC=2)N2CCNCC2)N=C2)C2=C1 XNURRHDXCWKBOG-UHFFFAOYSA-N 0.000 description 1
- IKBSPYGANZLZMV-UHFFFAOYSA-N 6-(2,6-dimethylphenyl)quinazolin-2-amine Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(N)N=C2)C2=C1 IKBSPYGANZLZMV-UHFFFAOYSA-N 0.000 description 1
- UNGQOAOOFFOHMM-UHFFFAOYSA-N 6-(2-chloro-5-methoxyphenyl)quinazolin-2-amine Chemical compound COC1=CC=C(Cl)C(C=2C=C3C=NC(N)=NC3=CC=2)=C1 UNGQOAOOFFOHMM-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241001076939 Artines Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000004736 B-Cell Leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 1
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
- 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 201000010183 Papilledema Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 208000035106 Primate disease Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- YDWKSSWZGXRQET-UHFFFAOYSA-N Pyrrolidine, 1-[2-(4-bromophenoxy)ethyl]- Chemical compound C1=CC(Br)=CC=C1OCCN1CCCC1 YDWKSSWZGXRQET-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical compound C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 206010038886 Retinal oedema Diseases 0.000 description 1
- 206010038903 Retinal vascular occlusion Diseases 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 108700014220 acyltransferase activity proteins Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 239000013011 aqueous formulation Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000023402 cell communication Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000017455 cell-cell adhesion Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000007073 chemical hydrolysis Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000012912 drug discovery process Methods 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 102000058223 human VEGFA Human genes 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000000021 kinase assay Methods 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 238000001499 laser induced fluorescence spectroscopy Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000013332 literature search Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000001620 monocyclic carbocycle group Chemical group 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 208000026113 non-human primate disease Diseases 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000771 oncological effect Effects 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001987 poloxamine Polymers 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical class C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 1
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical class N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 150000003726 retinal derivatives Chemical class 0.000 description 1
- 201000011195 retinal edema Diseases 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000003026 viability measurement method Methods 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08360043 | 2008-12-29 | ||
| PCT/EP2009/067494 WO2010076238A1 (en) | 2008-12-29 | 2009-12-18 | Substituted quinazoline compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2011007064A true MX2011007064A (es) | 2012-01-20 |
Family
ID=41735344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2011007064A MX2011007064A (es) | 2008-12-29 | 2009-12-18 | Compuestos de quinazolina substituidos. |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8389530B2 (enExample) |
| EP (1) | EP2381943A1 (enExample) |
| JP (1) | JP2012514020A (enExample) |
| KR (1) | KR20110120878A (enExample) |
| CN (1) | CN102333533A (enExample) |
| AU (1) | AU2009334869A1 (enExample) |
| BR (1) | BRPI0924067A2 (enExample) |
| CA (1) | CA2748319A1 (enExample) |
| CO (1) | CO6390105A2 (enExample) |
| CR (1) | CR20110368A (enExample) |
| DO (1) | DOP2011000209A (enExample) |
| EA (1) | EA019110B1 (enExample) |
| EC (1) | ECSP11011204A (enExample) |
| IL (1) | IL213742A0 (enExample) |
| MA (1) | MA32968B1 (enExample) |
| MX (1) | MX2011007064A (enExample) |
| NI (1) | NI201100134A (enExample) |
| NZ (1) | NZ593949A (enExample) |
| PE (1) | PE20120424A1 (enExample) |
| SG (1) | SG172415A1 (enExample) |
| TN (1) | TN2011000319A1 (enExample) |
| WO (1) | WO2010076238A1 (enExample) |
| ZA (1) | ZA201104777B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201204723A (en) | 2010-06-22 | 2012-02-01 | Fovea Pharmaceuticals | Heterocyclic compounds, their preparation and their therapeutic application |
| BR112015000653A2 (pt) | 2012-07-11 | 2019-11-05 | Blueprint Medicines Corp | compostos inibidores do receptor de fator de crescimento de fibroblasto, sua composição farmacêutica e seus usos |
| DK3395814T3 (da) | 2013-10-25 | 2022-07-04 | Blueprint Medicines Corp | Hæmmere af fibroblastvækstfaktorreceptoren |
| WO2015108992A1 (en) | 2014-01-15 | 2015-07-23 | Blueprint Medicines Corporation | Heterobicyclic compounds and their use as fgfr4 receptor inhibitors |
| KR101715448B1 (ko) * | 2014-07-16 | 2017-03-20 | 주식회사 큐리언트 | 염증성 질환 치료용 화합물 |
| JP6385584B2 (ja) | 2014-12-24 | 2018-09-05 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖの処置のための縮合ピリミジン化合物 |
| TWI770552B (zh) | 2014-12-24 | 2022-07-11 | 美商基利科學股份有限公司 | 喹唑啉化合物 |
| PT3237397T (pt) | 2014-12-24 | 2019-02-08 | Gilead Sciences Inc | Compostos de isoquinolina para o tratamento de hiv |
| CN112239459B (zh) * | 2019-07-19 | 2021-11-26 | 中国科学院上海药物研究所 | 稠环嘧啶氨基化合物、其制备方法、药物组合物及应用 |
| CN115916759B (zh) * | 2020-06-19 | 2025-07-15 | 泰州红云制药有限公司 | 取代喹唑啉类化合物、其制备方法、药物组合及应用 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0015718A (pt) * | 1999-11-22 | 2002-07-23 | Warner Lambert Co | Quinazolinas e seu uso para inibição de enzimas de cinase dependente de ciclina |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| CA2542329A1 (en) | 2003-10-16 | 2005-04-28 | Chiron Corporation | 2,6-disubstituted quinazolines, quinoxalines, quinolines and isoquinolines as inhibitors of raf kinase for treatment of cancer |
| EP2543376A1 (en) | 2004-04-08 | 2013-01-09 | Targegen, Inc. | Benzotriazine inhibitors of kinases |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| US20070054916A1 (en) * | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| MX2007011500A (es) | 2005-03-16 | 2007-11-21 | Targegen Inc | Compuestos pirimidina y metodos de uso. |
| EP1878727A4 (en) * | 2005-04-28 | 2013-11-13 | Kyowa Hakko Kirin Co Ltd | 2-AMINOQUINAZOLINE DERIVATIVES |
| JP2008543775A (ja) | 2005-06-08 | 2008-12-04 | ターゲジェン インコーポレーティッド | 眼の障害を治療するための方法および組成物 |
| TW200808739A (en) * | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
| CA2673003A1 (en) * | 2006-12-22 | 2008-07-03 | Novartis Ag | Quinazolines for pdk1 inhibition |
-
2009
- 2009-12-18 CN CN2009801575427A patent/CN102333533A/zh active Pending
- 2009-12-18 WO PCT/EP2009/067494 patent/WO2010076238A1/en not_active Ceased
- 2009-12-18 AU AU2009334869A patent/AU2009334869A1/en not_active Abandoned
- 2009-12-18 JP JP2011544017A patent/JP2012514020A/ja active Pending
- 2009-12-18 CA CA2748319A patent/CA2748319A1/en not_active Abandoned
- 2009-12-18 EA EA201101012A patent/EA019110B1/ru not_active IP Right Cessation
- 2009-12-18 BR BRPI0924067A patent/BRPI0924067A2/pt not_active IP Right Cessation
- 2009-12-18 KR KR1020117017495A patent/KR20110120878A/ko not_active Withdrawn
- 2009-12-18 US US13/142,333 patent/US8389530B2/en not_active Expired - Fee Related
- 2009-12-18 NZ NZ593949A patent/NZ593949A/xx not_active IP Right Cessation
- 2009-12-18 MA MA34018A patent/MA32968B1/fr unknown
- 2009-12-18 EP EP09799340A patent/EP2381943A1/en not_active Withdrawn
- 2009-12-18 PE PE2011001296A patent/PE20120424A1/es not_active Application Discontinuation
- 2009-12-18 MX MX2011007064A patent/MX2011007064A/es active IP Right Grant
- 2009-12-18 SG SG2011047339A patent/SG172415A1/en unknown
-
2011
- 2011-06-23 IL IL213742A patent/IL213742A0/en unknown
- 2011-06-27 TN TN2011000319A patent/TN2011000319A1/fr unknown
- 2011-06-27 CR CR20110368A patent/CR20110368A/es not_active Application Discontinuation
- 2011-06-28 ZA ZA2011/04777A patent/ZA201104777B/en unknown
- 2011-06-29 CO CO11081323A patent/CO6390105A2/es not_active Application Discontinuation
- 2011-06-29 NI NI201100134A patent/NI201100134A/es unknown
- 2011-06-29 DO DO2011000209A patent/DOP2011000209A/es unknown
- 2011-07-14 EC EC2011011204A patent/ECSP11011204A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA201104777B (en) | 2012-03-28 |
| CO6390105A2 (es) | 2012-02-29 |
| US20120004210A1 (en) | 2012-01-05 |
| MA32968B1 (fr) | 2012-01-02 |
| ECSP11011204A (es) | 2011-10-31 |
| CN102333533A (zh) | 2012-01-25 |
| TN2011000319A1 (en) | 2012-12-17 |
| AU2009334869A1 (en) | 2011-07-14 |
| EA201101012A1 (ru) | 2012-01-30 |
| AU2009334869A2 (en) | 2011-09-29 |
| CR20110368A (es) | 2011-12-02 |
| IL213742A0 (en) | 2011-07-31 |
| NZ593949A (en) | 2013-08-30 |
| EA019110B1 (ru) | 2014-01-30 |
| US8389530B2 (en) | 2013-03-05 |
| EP2381943A1 (en) | 2011-11-02 |
| NI201100134A (es) | 2012-03-06 |
| SG172415A1 (en) | 2011-07-28 |
| PE20120424A1 (es) | 2012-05-04 |
| BRPI0924067A2 (pt) | 2016-01-26 |
| WO2010076238A1 (en) | 2010-07-08 |
| CA2748319A1 (en) | 2010-07-08 |
| DOP2011000209A (es) | 2011-09-30 |
| KR20110120878A (ko) | 2011-11-04 |
| JP2012514020A (ja) | 2012-06-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2011007064A (es) | Compuestos de quinazolina substituidos. | |
| US20120041195A1 (en) | Heterocyclic compounds | |
| CN104903321B (zh) | 作为激酶抑制剂的经取代三环苯并咪唑 | |
| JP2013533237A (ja) | 複素環化合物、それらの調製およびそれらの療法的適用 | |
| AU2006224605B2 (en) | Potassium channel modulating agents and their medical use | |
| CN110240629B (zh) | 蛋白降解靶向bcr-abl化合物及其抗肿瘤应用 | |
| CN104356136A (zh) | 作为蛋白酶c抑制剂的3-酰氨基-吡咯并[3,4-c]吡唑-5(1h,4h,6h)甲醛衍生物 | |
| JP2010522186A (ja) | 化合物 | |
| AU4333299A (en) | Quinazolinone inhibitors of cgmp phosphodiesterase | |
| WO2020233618A1 (zh) | 一类细胞程序性坏死抑制剂及其制备方法和用途 | |
| EP1863796A1 (en) | Pyrazolyl-pyrimidines as potassium channel modulating agents and their medical use | |
| WO2023213211A9 (zh) | 2,4-二取代-5-氟嘧啶衍生物及其制备方法和应用 | |
| AU2011211410B2 (en) | [1,2,4] triazolo [1,5-A] pyridines as kinase inhibitors | |
| CN117164590A (zh) | 稠合嘧啶类衍生物及其应用 | |
| ES2371358T3 (es) | Compuesto de benzoimidazol capaz de inhibir prostaglandina d sintetasa. | |
| OA16290A (en) | Heterocyclic compounds, their preparation and their therapeutic application. | |
| DE102004022383A1 (de) | Neue Pyridopyrazine und deren Verwendung als Modulatoren von Kinasen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration |