KR20080077652A - 로 키나제-매개 질환 및 증상 치료용 (인다졸-5-일)피라진및 (1,3-디하이드로인돌-2-온)피라진 - Google Patents
로 키나제-매개 질환 및 증상 치료용 (인다졸-5-일)피라진및 (1,3-디하이드로인돌-2-온)피라진Info
- Publication number
- KR20080077652A KR20080077652A KR1020087015628A KR20087015628A KR20080077652A KR 20080077652 A KR20080077652 A KR 20080077652A KR 1020087015628 A KR1020087015628 A KR 1020087015628A KR 20087015628 A KR20087015628 A KR 20087015628A KR 20080077652 A KR20080077652 A KR 20080077652A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- alkyl
- independently
- membered ring
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 12
- 230000001404 mediated effect Effects 0.000 title claims abstract description 11
- 201000010099 disease Diseases 0.000 title claims abstract description 10
- 108010041788 rho-Associated Kinases Proteins 0.000 title claims abstract description 9
- 102000000568 rho-Associated Kinases Human genes 0.000 title claims abstract description 9
- UMRCHZNOQHLOGW-UHFFFAOYSA-N 1,3-dihydroindol-2-one;pyrazine Chemical class C1=CN=CC=N1.C1=CC=C2NC(=O)CC2=C1 UMRCHZNOQHLOGW-UHFFFAOYSA-N 0.000 title abstract description 5
- GTHRBGRAVFPOMM-UHFFFAOYSA-N 5-pyrazin-2-yl-1h-indazole Chemical class C1=C2C=NNC2=CC=C1C1=CN=CC=N1 GTHRBGRAVFPOMM-UHFFFAOYSA-N 0.000 title abstract description 5
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 33
- 239000000203 mixture Substances 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 21
- 230000004410 intraocular pressure Effects 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 16
- -1 amino, hydroxyl Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 108091000080 Phosphotransferase Proteins 0.000 claims description 7
- 102000020233 phosphotransferase Human genes 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 claims description 5
- 239000002876 beta blocker Substances 0.000 claims description 5
- 229940097320 beta blocking agent Drugs 0.000 claims description 5
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 150000003180 prostaglandins Chemical class 0.000 claims description 5
- 239000003981 vehicle Substances 0.000 claims description 5
- 239000000556 agonist Substances 0.000 claims description 4
- 239000004090 neuroprotective agent Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 230000001276 controlling effect Effects 0.000 claims description 3
- 239000003623 enhancer Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 239000003349 gelling agent Substances 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 1
- 230000002209 hydrophobic effect Effects 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 230000035515 penetration Effects 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 11
- 208000030533 eye disease Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 229940043355 kinase inhibitor Drugs 0.000 description 9
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 9
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- PBSHSOGGJFGOLH-UHFFFAOYSA-N 5-bromo-3-methyl-1-(phenylmethoxymethyl)indazole Chemical compound C12=CC=C(Br)C=C2C(C)=NN1COCC1=CC=CC=C1 PBSHSOGGJFGOLH-UHFFFAOYSA-N 0.000 description 4
- XDJNHYAQZWCIAH-UHFFFAOYSA-N 5-bromo-3-methyl-2h-indazole Chemical compound C1=CC(Br)=CC2=C(C)NN=C21 XDJNHYAQZWCIAH-UHFFFAOYSA-N 0.000 description 4
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229960000686 benzalkonium chloride Drugs 0.000 description 4
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 4
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- 229940124274 edetate disodium Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229940068968 polysorbate 80 Drugs 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010030043 Ocular hypertension Diseases 0.000 description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- OASPGGSWQLTGFB-UHFFFAOYSA-N 5-[6-[(2-amino-3-phenylpropyl)amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C=1N=CC(C=2C=C3CC(=O)NC3=CC=2)=NC=1NCC(N)CC1=CC=CC=C1 OASPGGSWQLTGFB-UHFFFAOYSA-N 0.000 description 2
- OASPGGSWQLTGFB-KRWDZBQOSA-N 5-[6-[[(2s)-2-amino-3-phenylpropyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C([C@@H](CNC=1N=C(C=NC=1)C=1C=C2CC(=O)NC2=CC=1)N)C1=CC=CC=C1 OASPGGSWQLTGFB-KRWDZBQOSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 206010067013 Normal tension glaucoma Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 208000005107 Premature Birth Diseases 0.000 description 2
- 206010036590 Premature baby Diseases 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 101000729528 Rattus norvegicus Rho-associated protein kinase 2 Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 102100039314 Rho-associated protein kinase 2 Human genes 0.000 description 2
- 229940121742 Serine/threonine kinase inhibitor Drugs 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000003915 cell function Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 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
- 230000006378 damage Effects 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000004406 elevated intraocular pressure Effects 0.000 description 2
- 230000004438 eyesight Effects 0.000 description 2
- 238000002875 fluorescence polarization Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 201000002978 low tension glaucoma Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000003836 peripheral circulation Effects 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 2
- 230000004382 visual function Effects 0.000 description 2
- 230000004393 visual impairment Effects 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- DFRNGPOBNCSWQM-KRWDZBQOSA-N (2s)-1-n-[6-(1h-indazol-5-yl)pyrazin-2-yl]-3-phenylpropane-1,2-diamine Chemical compound C([C@@H](CNC=1N=C(C=NC=1)C=1C=C2C=NNC2=CC=1)N)C1=CC=CC=C1 DFRNGPOBNCSWQM-KRWDZBQOSA-N 0.000 description 1
- RFPWFCWAYZTJJQ-INIZCTEOSA-N (2s)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-[2-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@H](N)CNC=1C=NC=C(N=1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1C(F)(F)F RFPWFCWAYZTJJQ-INIZCTEOSA-N 0.000 description 1
- MMGWEPPKARLEGJ-KRWDZBQOSA-N (2s)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-[4-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C([C@H](N)CNC=1C=NC=C(N=1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(C(F)(F)F)C=C1 MMGWEPPKARLEGJ-KRWDZBQOSA-N 0.000 description 1
- JBGRZWNLARISEG-KRWDZBQOSA-N (2s)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-phenylpropane-1,2-diamine Chemical compound C([C@H](N)CNC=1C=NC=C(N=1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1 JBGRZWNLARISEG-KRWDZBQOSA-N 0.000 description 1
- GVAWTAGXPYDKCT-RMRYJAPISA-N (2s)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-phenylpropane-1,2-diamine;dihydrochloride Chemical compound Cl.Cl.C([C@H](N)CNC=1C=NC=C(N=1)C1=CC=C2NN=C(C2=C1)C)C1=CC=CC=C1 GVAWTAGXPYDKCT-RMRYJAPISA-N 0.000 description 1
- CZRLMUVCBFZDOT-KRWDZBQOSA-N (2s)-3-(4-bromophenyl)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]propane-1,2-diamine Chemical compound C([C@H](N)CNC=1C=NC=C(N=1)C1=CC=C2NN=C(C2=C1)C)C1=CC=C(Br)C=C1 CZRLMUVCBFZDOT-KRWDZBQOSA-N 0.000 description 1
- XNRQIHIOKXQSPG-UHFFFAOYSA-N 1-(5-bromo-2-fluorophenyl)ethanone Chemical compound CC(=O)C1=CC(Br)=CC=C1F XNRQIHIOKXQSPG-UHFFFAOYSA-N 0.000 description 1
- DFRNGPOBNCSWQM-UHFFFAOYSA-N 1-n-[6-(1h-indazol-5-yl)pyrazin-2-yl]-3-phenylpropane-1,2-diamine Chemical compound C=1N=CC(C=2C=C3C=NNC3=CC=2)=NC=1NCC(N)CC1=CC=CC=C1 DFRNGPOBNCSWQM-UHFFFAOYSA-N 0.000 description 1
- MMGWEPPKARLEGJ-UHFFFAOYSA-N 1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-[4-(trifluoromethyl)phenyl]propane-1,2-diamine Chemical compound C1=C2C(C)=NNC2=CC=C1C(N=1)=CN=CC=1NCC(N)CC1=CC=C(C(F)(F)F)C=C1 MMGWEPPKARLEGJ-UHFFFAOYSA-N 0.000 description 1
- JBGRZWNLARISEG-UHFFFAOYSA-N 1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]-3-phenylpropane-1,2-diamine Chemical compound C1=C2C(C)=NNC2=CC=C1C(N=1)=CN=CC=1NCC(N)CC1=CC=CC=C1 JBGRZWNLARISEG-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 1
- GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
- CZRLMUVCBFZDOT-UHFFFAOYSA-N 3-(4-bromophenyl)-1-n-[6-(3-methyl-2h-indazol-5-yl)pyrazin-2-yl]propane-1,2-diamine Chemical compound C1=C2C(C)=NNC2=CC=C1C(N=1)=CN=CC=1NCC(N)CC1=CC=C(Br)C=C1 CZRLMUVCBFZDOT-UHFFFAOYSA-N 0.000 description 1
- IDALZVDRIDQUEZ-UHFFFAOYSA-N 5-[5-amino-6-[(2-amino-3-phenylpropyl)amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound N=1C(C=2C=C3CC(=O)NC3=CC=2)=CN=C(N)C=1NCC(N)CC1=CC=CC=C1 IDALZVDRIDQUEZ-UHFFFAOYSA-N 0.000 description 1
- IDALZVDRIDQUEZ-INIZCTEOSA-N 5-[5-amino-6-[[(2s)-2-amino-3-phenylpropyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C([C@@H](CNC=1C(=NC=C(N=1)C=1C=C2CC(=O)NC2=CC=1)N)N)C1=CC=CC=C1 IDALZVDRIDQUEZ-INIZCTEOSA-N 0.000 description 1
- RWBCRCMATUTEOQ-UHFFFAOYSA-N 5-[6-[(2-amino-4-methylpentyl)amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound CC(C)CC(N)CNC1=CN=CC(C=2C=C3CC(=O)NC3=CC=2)=N1 RWBCRCMATUTEOQ-UHFFFAOYSA-N 0.000 description 1
- IYLPVRFPNUHKNN-KRWDZBQOSA-N 5-[6-[[(2s)-2-amino-3-(4-bromophenyl)propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C([C@@H](CNC=1N=C(C=NC=1)C=1C=C2CC(=O)NC2=CC=1)N)C1=CC=C(Br)C=C1 IYLPVRFPNUHKNN-KRWDZBQOSA-N 0.000 description 1
- BFKYZFHYFWREAG-INIZCTEOSA-N 5-[6-[[(2s)-2-amino-3-[2-(trifluoromethyl)phenyl]propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C([C@@H](CNC=1N=C(C=NC=1)C=1C=C2CC(=O)NC2=CC=1)N)C1=CC=CC=C1C(F)(F)F BFKYZFHYFWREAG-INIZCTEOSA-N 0.000 description 1
- PABNPKQOPCCHOW-KRWDZBQOSA-N 5-[6-[[(2s)-2-amino-3-[4-(trifluoromethyl)phenyl]propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C([C@@H](CNC=1N=C(C=NC=1)C=1C=C2CC(=O)NC2=CC=1)N)C1=CC=C(C(F)(F)F)C=C1 PABNPKQOPCCHOW-KRWDZBQOSA-N 0.000 description 1
- RWBCRCMATUTEOQ-AWEZNQCLSA-N 5-[6-[[(2s)-2-amino-4-methylpentyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound CC(C)C[C@H](N)CNC1=CN=CC(C=2C=C3CC(=O)NC3=CC=2)=N1 RWBCRCMATUTEOQ-AWEZNQCLSA-N 0.000 description 1
- IYLPVRFPNUHKNN-UHFFFAOYSA-N 5-[6-[[2-amino-3-(4-bromophenyl)propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C=1N=CC(C=2C=C3CC(=O)NC3=CC=2)=NC=1NCC(N)CC1=CC=C(Br)C=C1 IYLPVRFPNUHKNN-UHFFFAOYSA-N 0.000 description 1
- BFKYZFHYFWREAG-UHFFFAOYSA-N 5-[6-[[2-amino-3-[2-(trifluoromethyl)phenyl]propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C=1N=CC(C=2C=C3CC(=O)NC3=CC=2)=NC=1NCC(N)CC1=CC=CC=C1C(F)(F)F BFKYZFHYFWREAG-UHFFFAOYSA-N 0.000 description 1
- PABNPKQOPCCHOW-UHFFFAOYSA-N 5-[6-[[2-amino-3-[4-(trifluoromethyl)phenyl]propyl]amino]pyrazin-2-yl]-1,3-dihydroindol-2-one Chemical compound C=1N=CC(C=2C=C3CC(=O)NC3=CC=2)=NC=1NCC(N)CC1=CC=C(C(F)(F)F)C=C1 PABNPKQOPCCHOW-UHFFFAOYSA-N 0.000 description 1
- MMFGGDVQLQQQRX-UHFFFAOYSA-N 5-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C=C1C=O MMFGGDVQLQQQRX-UHFFFAOYSA-N 0.000 description 1
- LPSHGKVAJCQEAA-UHFFFAOYSA-N 6-(1h-indazol-5-yl)pyrazin-2-amine Chemical compound NC1=CN=CC(C=2C=C3C=NNC3=CC=2)=N1 LPSHGKVAJCQEAA-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010066470 Amniorrhoea Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101100322915 Caenorhabditis elegans akt-1 gene Proteins 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102100030011 Endoribonuclease Human genes 0.000 description 1
- 101710199605 Endoribonuclease Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 1
- 101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 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 description 1
- 239000003810 Jones reagent Substances 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010027417 Metabolic acidosis Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
- 101710088493 Rho-associated protein kinase 2 Proteins 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- 101710113029 Serine/threonine-protein kinase Proteins 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- GLYOPNLBKCBTMI-UHFFFAOYSA-N [2-chloro-2-(1-chloro-2-phenylethoxy)ethyl]benzene Chemical compound C=1C=CC=CC=1CC(Cl)OC(Cl)CC1=CC=CC=C1 GLYOPNLBKCBTMI-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 150000005347 biaryls Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 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
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- LBOVMDOAMWYGHK-UHFFFAOYSA-N ethanol;methylsulfinylmethane Chemical compound CCO.CS(C)=O LBOVMDOAMWYGHK-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 210000000720 eyelash Anatomy 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 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
- 230000036543 hypotension Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical class C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 description 1
- GZZCYMXZJQCAJU-UHFFFAOYSA-N isoquinoline-1-sulfonamide Chemical class C1=CC=C2C(S(=O)(=O)N)=NC=CC2=C1 GZZCYMXZJQCAJU-UHFFFAOYSA-N 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940042472 mineral oil Drugs 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002241 neurite Anatomy 0.000 description 1
- 230000004493 normal intraocular pressure Effects 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical class NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000011535 reaction buffer Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000003590 rho kinase inhibitor Substances 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000003351 stiffener Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000004078 waterproofing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
- A61K31/4965—Non-condensed pyrazines
-
- 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75313605P | 2005-12-22 | 2005-12-22 | |
| US60/753,136 | 2005-12-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20080077652A true KR20080077652A (ko) | 2008-08-25 |
Family
ID=37963712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087015628A Ceased KR20080077652A (ko) | 2005-12-22 | 2006-12-19 | 로 키나제-매개 질환 및 증상 치료용 (인다졸-5-일)피라진및 (1,3-디하이드로인돌-2-온)피라진 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US7655662B2 (https=) |
| EP (1) | EP1962853A1 (https=) |
| JP (1) | JP2009521494A (https=) |
| KR (1) | KR20080077652A (https=) |
| CN (1) | CN101340912A (https=) |
| AR (1) | AR058618A1 (https=) |
| BR (1) | BRPI0620463A2 (https=) |
| CA (1) | CA2629342A1 (https=) |
| MX (1) | MX2008008328A (https=) |
| RU (1) | RU2008130111A (https=) |
| TW (1) | TW200733964A (https=) |
| UY (1) | UY30058A1 (https=) |
| WO (1) | WO2007076360A1 (https=) |
| ZA (1) | ZA200804497B (https=) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007008942A2 (en) * | 2005-07-11 | 2007-01-18 | Aerie Pharmaceuticals, Inc. | Phenylamino-acetic acid [1-(pyridin-4-yl)-methylidene]-hydrazide derivatives and related compounds as modulators of g protein-coupled receptor kinases for the treatment of eye diseases |
| WO2007008926A1 (en) * | 2005-07-11 | 2007-01-18 | Aerie Pharmaceuticals, Inc. | Isoquinoline compounds |
| WO2008036540A2 (en) | 2006-09-20 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| WO2008041118A2 (en) * | 2006-10-04 | 2008-04-10 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| US20100022517A1 (en) * | 2006-12-18 | 2010-01-28 | Richards Lori A | Ophthalmic formulation of rho kinase inhibitor compound |
| US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
| US8455514B2 (en) | 2008-01-17 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-and 7-amino isoquinoline compounds and methods for making and using the same |
| WO2009155209A1 (en) * | 2008-06-18 | 2009-12-23 | Inspire Pharmaceuticals, Inc. | Ophthalmic formulation of rho kinase inhibitor compound |
| US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
| KR20170015566A (ko) | 2008-11-10 | 2017-02-08 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｒ 키나제의 억제제로서 유용한 화합물 |
| ES2663222T3 (es) | 2008-12-19 | 2018-04-11 | Vertex Pharmaceuticals Incorporated | Derivados de pirazina útiles como inhibidores de la quinasa ATR |
| EP3053913B1 (en) | 2009-05-01 | 2018-03-07 | Aerie Pharmaceuticals, Inc. | Dual mechanism inhibitors for the treatment of disease |
| CN102822170B (zh) | 2009-12-21 | 2014-12-10 | 阵列生物制药公司 | 作为cFMS抑制剂的取代的N-(1H-吲唑-4-基)咪唑并[1,2-a]吡啶-3-羧酰胺化合物 |
| JP5856151B2 (ja) | 2010-05-12 | 2016-02-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼ阻害剤として有用な２−アミノピリジン誘導体 |
| US9630956B2 (en) | 2010-05-12 | 2017-04-25 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP2013526540A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| JP2013529200A (ja) | 2010-05-12 | 2013-07-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| US8969356B2 (en) | 2010-05-12 | 2015-03-03 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP2013526539A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用なピラジン |
| CA2803802A1 (en) | 2010-06-23 | 2011-12-29 | Vertex Pharmaceuticals Incorporated | Pyrrolo- pyrazine derivatives useful as inhibitors of atr kinase |
| JP2014510151A (ja) | 2011-04-05 | 2014-04-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ（ｔｒａｋｉｎａｓｅ）阻害剤として有用なアミノピラジン化合物 |
| WO2012178125A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| EP2723745A1 (en) | 2011-06-22 | 2014-04-30 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| WO2012178124A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| SG10201606774UA (en) | 2011-09-30 | 2016-10-28 | Vertex Pharma | Processes for making compounds useful as inhibitors of atr kinase |
| KR20140084112A (ko) | 2011-09-30 | 2014-07-04 | 버텍스 파마슈티칼스 인코포레이티드 | Ａｔｒ 키나제의 억제제로서 유용한 화합물 |
| WO2013049859A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors |
| WO2013049719A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| US8853217B2 (en) | 2011-09-30 | 2014-10-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8841337B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8841450B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2013071094A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071088A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| WO2013071085A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Pyrazine compounds useful as inhibitors of atr kinase |
| CA2869309C (en) | 2012-04-05 | 2021-02-09 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase and combination therapies thereof |
| US8999632B2 (en) | 2012-10-04 | 2015-04-07 | Vertex Pharmaceuticals Incorporated | Method for measuring ATR inhibition mediated increases in DNA damage |
| US8912198B2 (en) | 2012-10-16 | 2014-12-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
| DK3811943T3 (da) | 2013-03-15 | 2023-04-03 | Aerie Pharmaceuticals Inc | Forbindelse til anvendelse til behandling af øjenlidelser |
| US9328200B2 (en) * | 2013-07-17 | 2016-05-03 | Ultrasci Discovery Llp | Branched polymeric quaternary ammonium compounds and their uses |
| DK3077397T3 (da) | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| PL3152212T3 (pl) | 2014-06-05 | 2020-06-15 | Vertex Pharmaceuticals Inc. | Radioznakowane pochodne związku 2-amino-6-fluoro-n-[5-fluoro-piridyn-3-ylo]-pirazolo[1,5-a]pirymidino-3-karboksamidu przydatne jako inhibitor kinazy atr, wytwarzanie tego związku i jego różnych postaci stałych |
| LT3157566T (lt) | 2014-06-17 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Vėžio gydymo būdas, panaudojant chk1 ir atr inhibitorių derinį |
| HK1258570A1 (zh) | 2015-09-30 | 2019-11-15 | Vertex Pharmaceuticals Inc. | 使用dna损伤剂及atr抑制剂的组合治疗癌症的方法 |
| US10550087B2 (en) | 2015-11-17 | 2020-02-04 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
| US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
| KR102568079B1 (ko) | 2016-08-31 | 2023-08-17 | 에어리 파마슈티컬즈, 인코포레이티드 | 안과용 조성물 |
| KR20190135027A (ko) | 2017-03-31 | 2019-12-05 | 에어리 파마슈티컬즈, 인코포레이티드 | 아릴 시클로프로필-아미노-이소퀴놀리닐 아미드 화합물 |
| GEP20237548B (en) | 2018-07-05 | 2023-10-10 | Incyte Corp | Fused pyrazine derivatives as a2a /a2b inhibitors |
| AU2019337703B2 (en) | 2018-09-14 | 2023-02-02 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| TWI829857B (zh) | 2019-01-29 | 2024-01-21 | 美商英塞特公司 | 作為a2a / a2b抑制劑之吡唑并吡啶及三唑并吡啶 |
| US12064376B2 (en) * | 2020-06-03 | 2024-08-20 | Glaukos Corporation | Rho kinase inhibitor releasing implants and related methods of use |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0492903A1 (en) * | 1990-12-21 | 1992-07-01 | MERCK SHARP & DOHME LTD. | Substituted pyrazines, pyrimidines and pyridazines for use in the treatment of glaucoma |
| PT868186E (pt) | 1995-12-21 | 2005-05-31 | Alcon Lab Inc | Utilizacao de certos compostos de isoquinolinossulfonilo para tratamento de glaucoma e isquemia ocular |
| US6586425B2 (en) | 1996-02-21 | 2003-07-01 | Wisconsin Alumni Research Foundation | Cytoskeletal active agents for glaucoma therapy |
| US5798380A (en) | 1996-02-21 | 1998-08-25 | Wisconsin Alumni Research Foundation | Cytoskeletal active agents for glaucoma therapy |
| NZ513800A (en) | 1996-08-12 | 2001-09-28 | Welfide Corp | Treatment of diseases using Rho kinase inhibitors |
| CA2214841A1 (en) | 1997-10-31 | 1999-04-30 | Lisa Mckerracher | Rho antagonists and their use to block inhibition of neurite outgrowth |
| AU5198199A (en) | 1998-08-17 | 2000-03-06 | Senju Pharmaceutical Co., Ltd. | Preventives/remedies for glaucoma |
| EP1177796B1 (en) | 1999-04-27 | 2011-04-27 | Mitsubishi Tanabe Pharma Corporation | Medicament for prevention or therapeutic treatment of liver disease |
| JP3430254B2 (ja) | 2000-03-13 | 2003-07-28 | 独立行政法人産業技術総合研究所 | β−ジケトナートを有する金属錯体及びその製法、光電変換素子並びに、光化学電池 |
| JP4776136B2 (ja) | 2000-03-16 | 2011-09-21 | 田辺三菱製薬株式会社 | アミド化合物およびその用途 |
| AU2001236006A1 (en) | 2000-03-31 | 2001-10-15 | Mitsubishi Pharma Corporation | Preventives/remedies for kidney diseases |
| JPWO2002100833A1 (ja) | 2001-06-12 | 2004-09-24 | 住友製薬株式会社 | Ｒｈｏキナーゼ阻害剤 |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| DE60320933D1 (de) | 2002-01-10 | 2008-06-26 | Bayer Healthcare Ag | Rho-kinase inhibitoren |
| MXPA04007196A (es) | 2002-01-23 | 2005-06-08 | Bayer Pharmaceuticals Corp | Inhibidores de rho-quinasa. |
| GB0206860D0 (en) * | 2002-03-22 | 2002-05-01 | Glaxo Group Ltd | Compounds |
| US7015227B2 (en) | 2002-06-21 | 2006-03-21 | Cgi Pharmaceuticals, Inc. | Certain amino-substituted monocycles as kinase modulators |
| AU2003281623B8 (en) | 2002-07-22 | 2009-06-11 | Asahi Kasei Pharma Corporation | 5-substituted isoquinoline derivative |
| EP1550660A1 (en) | 2002-09-12 | 2005-07-06 | Kirin Beer Kabushiki Kaisha | Isoquinoline derivatives having kinasae inhibitory activity and drugs containing the same |
| WO2004084824A2 (en) | 2003-03-24 | 2004-10-07 | Merck & Co., Inc. | Biaryl substituted 6-membered heterocyles as sodium channel blockers |
| GB2400101A (en) | 2003-03-28 | 2004-10-06 | Biofocus Discovery Ltd | Compounds capable of binding to the active site of protein kinases |
| CA2530389A1 (en) * | 2003-07-02 | 2005-01-13 | Biofocus Discovery Limited | Pyrazine and pyridine derivatives as rho kinase inhibitors |
| AU2004278382B2 (en) | 2003-09-30 | 2008-09-18 | Amgen Inc. | Vanilloid receptor ligands and their use in treatments |
| WO2006071548A2 (en) * | 2004-12-27 | 2006-07-06 | Alcon, Inc. | Aminopyrazine analogs for treating glaucoma and other rho kinase-mediated diseases |
-
2006
- 2006-12-19 EP EP06846689A patent/EP1962853A1/en not_active Withdrawn
- 2006-12-19 ZA ZA200804497A patent/ZA200804497B/xx unknown
- 2006-12-19 WO PCT/US2006/062307 patent/WO2007076360A1/en not_active Ceased
- 2006-12-19 JP JP2008547727A patent/JP2009521494A/ja active Pending
- 2006-12-19 CA CA002629342A patent/CA2629342A1/en not_active Abandoned
- 2006-12-19 US US11/612,894 patent/US7655662B2/en not_active Expired - Fee Related
- 2006-12-19 CN CNA2006800482845A patent/CN101340912A/zh active Pending
- 2006-12-19 MX MX2008008328A patent/MX2008008328A/es active IP Right Grant
- 2006-12-19 KR KR1020087015628A patent/KR20080077652A/ko not_active Ceased
- 2006-12-19 BR BRPI0620463-5A patent/BRPI0620463A2/pt not_active IP Right Cessation
- 2006-12-19 RU RU2008130111/04A patent/RU2008130111A/ru unknown
- 2006-12-21 UY UY30058A patent/UY30058A1/es not_active Application Discontinuation
- 2006-12-21 TW TW095148175A patent/TW200733964A/zh unknown
- 2006-12-21 AR ARP060105725A patent/AR058618A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| TW200733964A (en) | 2007-09-16 |
| US7655662B2 (en) | 2010-02-02 |
| EP1962853A1 (en) | 2008-09-03 |
| ZA200804497B (en) | 2009-10-28 |
| RU2008130111A (ru) | 2010-01-27 |
| BRPI0620463A2 (pt) | 2011-11-16 |
| JP2009521494A (ja) | 2009-06-04 |
| AR058618A1 (es) | 2008-02-13 |
| US20070149548A1 (en) | 2007-06-28 |
| MX2008008328A (es) | 2008-09-15 |
| CN101340912A (zh) | 2009-01-07 |
| CA2629342A1 (en) | 2007-07-05 |
| UY30058A1 (es) | 2007-03-30 |
| WO2007076360A1 (en) | 2007-07-05 |
| WO2007076360A8 (en) | 2007-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7655662B2 (en) | (Indazol-5-yl)-pyrazines and (1,3-dihydro-indol-2-one)-pyrazines for treating glaucoma and controlling intraocular pressure | |
| US7820670B2 (en) | 6-aminoimidazo[1,2-b]pyridazine analogs as rho kinase inhibitors for the treatment of rho kinase-mediated diseases and conditions | |
| KR100994173B1 (ko) | 녹내장 및 다른 로 키나아제-매개 질환 치료용아미노피라진 유사체 | |
| JP7081850B2 (ja) | 眼科用製剤 | |
| ES2374336T3 (es) | Agente profiláctico o terapéutico para una enfermedad ocular posterior que comprende un agonista selectivo no ergótico del receptor d2 como principio activo. | |
| US20070142376A1 (en) | Control of intraocular pressure using alk5 modulation agents | |
| KR20110042054A (ko) | 축성 근시의 예방 또는 치료제 | |
| EA001752B1 (ru) | Терапевтическое лечение глазных заболеваний, связанных с фактором роста сосудистого эндотелия | |
| CN100353942C (zh) | 用于视网膜神经疾病的含有烷基醚衍生物或其盐的预防剂/治疗剂 | |
| CN117551073A (zh) | 用于治疗皮肤疾病噻吩基苯胺化合物 | |
| US9861593B2 (en) | Method for treating or preventing dry eye disorders using alkylamino-polyhydroxyalkanes | |
| KR20200044873A (ko) | 안구 제약학적 조성물 | |
| JP4175801B2 (ja) | 消炎鎮痛点眼剤 | |
| KR20210049857A (ko) | 안과 질환 치료용 약물 조성물 및 치료 방법 | |
| JP2003520245A5 (https=) | ||
| US7867999B1 (en) | Hydroxyamino- and amino-substituted pyridine analogs for treating rho kinase-mediated diseases and conditions | |
| EP3320904B1 (en) | Preventative and/or therapeutic agent containing pyridyl aminoacetic acid compound for treating a disease involving a greatly elevated intraocular pressure | |
| AU2006330599B2 (en) | (indazol-5-yl)-pyrazines and (1,3-dihydro-indol-2-one)- pyrazines for treating rho kinase-mediated diseases and conditions | |
| US7060704B2 (en) | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders | |
| JPH06102664B2 (ja) | 局所的に有効なカルボニツクアンヒドラーゼ阻害剤としての５―カルバモイルチエノ〔２，３―ｂ〕チオフエン―２―スルホンアミド類及び製造方法 | |
| CN112409360B (zh) | 杂芳基乙烯基黄嘌呤衍生物及其用途 | |
| US20160008333A1 (en) | Prophylactic or therapeutic agent for posterior ocular disease containing tetrahydropyranylaminocyclopentylcarbonyltetrahydropyridopyridine derivative as effective ingredient | |
| KR20070121791A (ko) | 각결막 장애 치료제 | |
| CN106456641A (zh) | 眼后段疾病的预防或治疗剂 | |
| HK1232476A1 (zh) | 眼後段疾病的预防或治疗剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20080627 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20100204 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20110920 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20120530 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20110920 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |