IL133871A - Derivatives of prostaglandin without side effects for the treatment of glaucoma - Google Patents

Derivatives of prostaglandin without side effects for the treatment of glaucoma

Info

Publication number: IL133871A
Authority: IL; Israel
Prior art keywords: cycloalkyl; alkyl; aryl; hydroxy; alkyl group
Prior art date: 1997-07-11

Application number

IL13387198A

Other languages

English (en)

Hebrew (he)

Other versions

IL133871A0 (en

Original Assignee

Pharmacia & Upjohn Ab

Priority date (The priority date 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 date listed.)

1997-07-11

Filing date

1998-07-10

Publication date

2004-09-27

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=20407743&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=IL133871(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1998-07-10 Application filed by Pharmacia & Upjohn Ab filed Critical Pharmacia & Upjohn Ab

2001-04-30 Publication of IL133871A0 publication Critical patent/IL133871A0/xx

2004-09-27 Publication of IL133871A publication Critical patent/IL133871A/en

Links

150000003180 prostaglandins Chemical class 0.000 title claims abstract description 31
208000010412 Glaucoma Diseases 0.000 title claims abstract description 10
230000000694 effects Effects 0.000 title claims abstract description 9
239000000203 mixture Substances 0.000 claims abstract description 43
-1 hydroxy, methyl Chemical group 0.000 claims abstract description 32
125000000217 alkyl group Chemical group 0.000 claims abstract description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 26
125000003118 aryl group Chemical group 0.000 claims abstract description 22
150000001875 compounds Chemical class 0.000 claims abstract description 22
229920006395 saturated elastomer Chemical group 0.000 claims abstract description 21
125000004417 unsaturated alkyl group Chemical group 0.000 claims abstract description 21
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 20
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
239000001257 hydrogen Substances 0.000 claims abstract description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 11
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 10
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 10
125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 10
125000005842 heteroatom Chemical group 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
239000001301 oxygen Substances 0.000 claims abstract description 10
229910052717 sulfur Inorganic materials 0.000 claims abstract description 10
239000011593 sulfur Chemical group 0.000 claims abstract description 10
206010030043 Ocular hypertension Diseases 0.000 claims abstract description 8
150000002148 esters Chemical class 0.000 claims abstract description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims abstract description 8
239000000556 agonist Substances 0.000 claims abstract description 7
229910052736 halogen Chemical group 0.000 claims abstract description 7
150000002367 halogens Chemical group 0.000 claims abstract description 7
230000003061 melanogenesis Effects 0.000 claims abstract description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
229910014033 C-OH Inorganic materials 0.000 claims abstract description 5
229910014570 C—OH Inorganic materials 0.000 claims abstract description 5
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 5
VNWKTOKETHGBQD-AKLPVKDBSA-N carbane Chemical compound [15CH4] VNWKTOKETHGBQD-AKLPVKDBSA-N 0.000 claims abstract description 5
229910052799 carbon Inorganic materials 0.000 claims abstract description 5
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 5
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 4
125000001424 substituent group Chemical group 0.000 claims abstract description 4
125000006531 (C2-C5) alkyl group Chemical group 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 6
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract 2
229960002986 dinoprostone Drugs 0.000 claims description 14
230000004410 intraocular pressure Effects 0.000 claims description 13
230000001603 reducing effect Effects 0.000 claims description 8
102000017953 prostanoid receptors Human genes 0.000 claims description 7
108050007059 prostanoid receptors Proteins 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
229940094443 oxytocics prostaglandins Drugs 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 3
125000005907 alkyl ester group Chemical group 0.000 claims 3
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
235000019439 ethyl acetate Nutrition 0.000 description 38
239000000243 solution Substances 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
239000000741 silica gel Substances 0.000 description 28
229910002027 silica gel Inorganic materials 0.000 description 28
229960001866 silicon dioxide Drugs 0.000 description 28
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
238000012544 monitoring process Methods 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000003921 oil Substances 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
239000003480 eluent Substances 0.000 description 15
239000011541 reaction mixture Substances 0.000 description 15
102000005962 receptors Human genes 0.000 description 15
108020003175 receptors Proteins 0.000 description 15
239000012267 brine Substances 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
238000005481 NMR spectroscopy Methods 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
239000000047 product Substances 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
150000004702 methyl esters Chemical class 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 8
108020004999 messenger RNA Proteins 0.000 description 8
102000015433 Prostaglandin Receptors Human genes 0.000 description 7
108010050183 Prostaglandin Receptors Proteins 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
210000002752 melanocyte Anatomy 0.000 description 7
102100024448 Prostaglandin E2 receptor EP2 subtype Human genes 0.000 description 6
BORBLDJNKYHVJP-FXBDTBDDSA-N dolichodial Chemical compound C[C@H]1CC[C@H](C(=C)C=O)[C@@H]1C=O BORBLDJNKYHVJP-FXBDTBDDSA-N 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
102100024447 Prostaglandin E2 receptor EP3 subtype Human genes 0.000 description 5
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 5
239000002299 complementary DNA Substances 0.000 description 5
238000000034 method Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
241000282693 Cercopithecidae Species 0.000 description 4
241000282326 Felis catus Species 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
150000002431 hydrogen Chemical group 0.000 description 4
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
XLUXAKJPHJEFKL-UHFFFAOYSA-N 1-ethylcyclobutane-1-carboxylic acid Chemical compound CCC1(C(O)=O)CCC1 XLUXAKJPHJEFKL-UHFFFAOYSA-N 0.000 description 3
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
DAPZSGCXUJECAI-UHFFFAOYSA-N 4-[tert-butyl(dimethyl)silyl]oxycyclopent-2-en-1-one Chemical compound CC(C)(C)[Si](C)(C)OC1CC(=O)C=C1 DAPZSGCXUJECAI-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
101150053131 PTGER3 gene Proteins 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 description 3
238000003556 assay Methods 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000012634 fragment Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
229940086542 triethylamine Drugs 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
206010018307 Glaucoma and ocular hypertension Diseases 0.000 description 2
102100034343 Integrase Human genes 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
238000012300 Sequence Analysis Methods 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
108090000300 Thromboxane Receptors Proteins 0.000 description 2
102000003938 Thromboxane Receptors Human genes 0.000 description 2
239000011543 agarose gel Substances 0.000 description 2
238000010171 animal model Methods 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Inorganic materials [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
229940126214 compound 3 Drugs 0.000 description 2
239000000284 extract Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
WMWSRIHFAVOHSW-UHFFFAOYSA-N lithium;ethane-1,2-diamine;ethyne Chemical compound [Li+].[C-]#C.NCCN WMWSRIHFAVOHSW-UHFFFAOYSA-N 0.000 description 2
230000003101 melanogenic effect Effects 0.000 description 2
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 description 2
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
235000011007 phosphoric acid Nutrition 0.000 description 2
230000019612 pigmentation Effects 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
239000000018 receptor agonist Substances 0.000 description 2
229940044601 receptor agonist Drugs 0.000 description 2
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
238000003756 stirring Methods 0.000 description 2
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 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
KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical compound CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
SCBZBMXPJYMXRC-UHFFFAOYSA-N 1-(bromomethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CBr)=C1 SCBZBMXPJYMXRC-UHFFFAOYSA-N 0.000 description 1
UOWIYNWMROWVDG-UHFFFAOYSA-N 1-dimethoxyphosphorylpropan-2-one Chemical compound COP(=O)(OC)CC(C)=O UOWIYNWMROWVDG-UHFFFAOYSA-N 0.000 description 1
FOBVMYJQWZOGGJ-XYRJXBATSA-N 17-phenyl-18,19,20-trinor-prostaglandin E2 Chemical compound C([C@H](O)\C=C\[C@@H]1[C@H](C(=O)C[C@H]1O)C\C=C/CCCC(O)=O)CC1=CC=CC=C1 FOBVMYJQWZOGGJ-XYRJXBATSA-N 0.000 description 1
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
CPVNCBJFUQQXSU-UHFFFAOYSA-O 4-carboxybutyl(triphenyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 CPVNCBJFUQQXSU-UHFFFAOYSA-O 0.000 description 1
MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
238000001712 DNA sequencing Methods 0.000 description 1
102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
241000790917 Dioxys <bee> Species 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
101001117519 Homo sapiens Prostaglandin E2 receptor EP2 subtype Proteins 0.000 description 1
101000836978 Homo sapiens Sperm-associated antigen 11B Proteins 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
239000004367 Lipase Substances 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
241000282567 Macaca fascicularis Species 0.000 description 1
WCZKTUCDHDAAGU-UHFFFAOYSA-L N1=CC=CC=C1.[Cr](=O)(=O)(Cl)Cl Chemical compound N1=CC=CC=C1.[Cr](=O)(=O)(Cl)Cl WCZKTUCDHDAAGU-UHFFFAOYSA-L 0.000 description 1
208000007950 Ocular Hypotension Diseases 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
FPABVZYYTCHNMK-YNRDDPJXSA-N PGF2alpha isopropyl ester Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(=O)OC(C)C FPABVZYYTCHNMK-YNRDDPJXSA-N 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
108050008995 Prostaglandin F receptors Proteins 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
IXYRGLOAGUSEMY-UHFFFAOYSA-N [4-(3-fluorophenyl)-4-methyl-2-oxopentyl]phosphonic acid Chemical compound OP(=O)(O)CC(=O)CC(C)(C)C1=CC=CC(F)=C1 IXYRGLOAGUSEMY-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical group C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
UOKRBSXOBUKDGE-UHFFFAOYSA-N butylphosphonic acid Chemical compound CCCCP(O)(O)=O UOKRBSXOBUKDGE-UHFFFAOYSA-N 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
238000010367 cloning Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940125833 compound 23 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
210000004087 cornea Anatomy 0.000 description 1
210000004748 cultured cell Anatomy 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000012530 fluid Substances 0.000 description 1
229920002674 hyaluronan Polymers 0.000 description 1
229960003160 hyaluronic acid Drugs 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
239000005457 ice water Substances 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
238000002955 isolation Methods 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000005259 measurement Methods 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
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
239000002674 ointment Substances 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
238000007427 paired t-test Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000000049 pigment Substances 0.000 description 1
229960001416 pilocarpine Drugs 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
238000003752 polymerase chain reaction Methods 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229940068968 polysorbate 80 Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000013641 positive control Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
238000012163 sequencing technique Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000012353 t test Methods 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
210000001177 vas deferen Anatomy 0.000 description 1
230000000007 visual effect Effects 0.000 description 1

Classifications

- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- 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

Landscapes

Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Ophthalmology & Optometry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

IL13387198A 1997-07-11 1998-07-10 Derivatives of prostaglandin without side effects for the treatment of glaucoma IL133871A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9702706A SE9702706D0 (sv)	1997-07-11	1997-07-11	Prostaglandin derivatives devoid of side-effects for the treatment of glaucoma
PCT/SE1998/001368 WO1999002165A1 (en)	1997-07-11	1998-07-10	Prostaglandin derivatives devoid of side-effects for the treatment of glaucoma

Publications (2)

Publication Number	Publication Date
IL133871A0 IL133871A0 (en)	2001-04-30
IL133871A true IL133871A (en)	2004-09-27

Family

ID=20407743

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL13387198A IL133871A (en)	1997-07-11	1998-07-10	Derivatives of prostaglandin without side effects for the treatment of glaucoma

Country Status (18)

Country	Link
EP (1)	EP1014991A1 (is)
JP (1)	JP2002509543A (is)
KR (1)	KR20010021682A (is)
CN (1)	CN1169528C (is)
AU (1)	AU739828B2 (is)
BR (1)	BR9815501A (is)
CA (1)	CA2294779A1 (is)
HU (1)	HUP0003106A3 (is)
IL (1)	IL133871A (is)
IS (1)	IS5333A (is)
NO (1)	NO20000062D0 (is)
NZ (1)	NZ501834A (is)
PL (1)	PL337940A1 (is)
RU (1)	RU2207858C2 (is)
SE (1)	SE9702706D0 (is)
SK (1)	SK183499A3 (is)
TR (1)	TR200000008T2 (is)
WO (1)	WO1999002165A1 (is)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9803761D0 (sv) *	1998-11-04	1998-11-04	Synphora Ab	Method to avoid increased iridial pigmentation during prostaglandin treatment
CA2364948C (en)	1999-03-05	2011-04-26	Duke University	C16 unsaturated fp-selective prostaglandins analogs
US6894175B1 (en)	1999-08-04	2005-05-17	The Procter & Gamble Company	2-Decarboxy-2-phosphinico prostaglandin derivatives and methods for their preparation and use
US20020037914A1 (en)	2000-03-31	2002-03-28	Delong Mitchell Anthony	Compositions and methods for treating hair loss using C16-C20 aromatic tetrahydro prostaglandins
US20020013294A1 (en)	2000-03-31	2002-01-31	Delong Mitchell Anthony	Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives
US20020172693A1 (en)	2000-03-31	2002-11-21	Delong Michell Anthony	Compositions and methods for treating hair loss using non-naturally occurring prostaglandins
US6531504B2 (en) *	2001-05-17	2003-03-11	Allergan, Inc.	Prostanoic acid derivatives as agents for lowering intraocular pressure
GB0112699D0 (en)	2001-05-24	2001-07-18	Resolution Chemicals Ltd	Process for the preparation of prostglandins and analogues thereof
US6713268B2 (en) *	2001-06-26	2004-03-30	Allergan, Inc.	Methods of identifying ocular hypotensive compounds having reduced hyperpigmentation
US7456274B2 (en) *	2002-09-16	2008-11-25	Texas Tech University System	Inhibition of metallo-β-lactamase
US7091231B2 (en) *	2004-12-10	2006-08-15	Allergan, Inc.	12-Aryl prostaglandin analogs
GB0501192D0 (en)	2005-01-20	2005-03-02	Resolution Chemicals Ltd	Stable prostaglandin-containing compositions
PL212658B1 (pl) *	2005-04-18	2012-11-30	Inst Farmaceutyczny	Sposób otrzymywania pochodnych 13,14-dihydro-PGF<sub>2</sub><sub>α</sub>
US8455513B2 (en)	2007-01-10	2013-06-04	Aerie Pharmaceuticals, Inc.	6-aminoisoquinoline compounds
JPWO2009133863A1 (ja)	2008-04-28	2011-09-01	国立大学法人浜松医科大学	Ｅｐ１アゴニストを含有してなる免疫増強剤
US8450344B2 (en)	2008-07-25	2013-05-28	Aerie Pharmaceuticals, Inc.	Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
WO2010126626A2 (en)	2009-05-01	2010-11-04	Aerie Pharmaceuticals, Inc.	Dual mechanism inhibitors for the treatment of disease
US8901319B2 (en)	2009-10-16	2014-12-02	Cayman Chemical Company, Incorporated	Process for the preparation of F-series prostaglandins
HRP20160908T1 (hr)	2012-03-28	2016-09-23	Merck Patent Gmbh	Biciklički derivati pirazinona
JP2012246301A (ja) *	2012-08-10	2012-12-13	Cayman Chemical Co Inc	Ｆ系プロスタグランジン類を調製する方法
ES2776199T3 (es)	2013-03-15	2020-07-29	Aerie Pharmaceuticals Inc	Conjugados de compuestos de isoquinolina y prostaglandinas
US9643927B1 (en)	2015-11-17	2017-05-09	Aerie Pharmaceuticals, Inc.	Process for the preparation of kinase inhibitors and intermediates thereof
WO2018045091A1 (en)	2016-08-31	2018-03-08	Aerie Pharmaceuticals, Inc.	Ophthalmic compositions
CA3057872A1 (en)	2017-03-31	2018-10-04	Aerie Pharmaceuticals, Inc.	Aryl cyclopropyl-amino-isoquinolinyl amide compounds
AU2019337703B2 (en)	2018-09-14	2023-02-02	Aerie Pharmaceuticals, Inc.	Aryl cyclopropyl-amino-isoquinolinyl amide compounds

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4085272A (en) *	1977-03-30	1978-04-18	American Cyanamid Company	11-(2-Hydroxyethylthio)prostenoic acid E2 series derivatives
US4132738A (en) *	1978-02-23	1979-01-02	Miles Laboratories, Inc.	Preparation of 15-deoxy-16-hydroxyprostaglandins
US4311707A (en) *	1979-02-12	1982-01-19	American Cyanamid Company	Process for topically producing cutaneous vasodilation for the treatment of vasospastic or ischemic conditions
ES2105333T3 (es) *	1992-10-13	1997-10-16	Alcon Lab Inc	Combinaciones de prostaglandinas y derivados de clonidina para el tratamiento del glaucoma.

1997
- 1997-07-11 SE SE9702706A patent/SE9702706D0/xx unknown
1998
- 1998-07-10 TR TR2000/00008T patent/TR200000008T2/xx unknown
- 1998-07-10 PL PL98337940A patent/PL337940A1/xx unknown
- 1998-07-10 IL IL13387198A patent/IL133871A/en not_active IP Right Cessation
- 1998-07-10 AU AU83683/98A patent/AU739828B2/en not_active Ceased
- 1998-07-10 JP JP50856099A patent/JP2002509543A/ja not_active Withdrawn
- 1998-07-10 WO PCT/SE1998/001368 patent/WO1999002165A1/en not_active Ceased
- 1998-07-10 SK SK1834-99A patent/SK183499A3/sk unknown
- 1998-07-10 BR BR9815501-6A patent/BR9815501A/pt not_active IP Right Cessation
- 1998-07-10 HU HU0003106A patent/HUP0003106A3/hu unknown
- 1998-07-10 NZ NZ501834A patent/NZ501834A/en unknown
- 1998-07-10 EP EP98934082A patent/EP1014991A1/en not_active Ceased
- 1998-07-10 CA CA002294779A patent/CA2294779A1/en not_active Abandoned
- 1998-07-10 RU RU2000103224/14A patent/RU2207858C2/ru not_active IP Right Cessation
- 1998-07-10 CN CNB988070456A patent/CN1169528C/zh not_active Ceased
- 1998-07-10 KR KR1020007000240A patent/KR20010021682A/ko not_active Ceased
2000
- 2000-01-06 NO NO20000062A patent/NO20000062D0/no unknown
- 2000-01-07 IS IS5333A patent/IS5333A/is unknown

Also Published As

Publication number	Publication date
WO1999002165A1 (en)	1999-01-21
HUP0003106A2 (hu)	2001-01-29
CN1169528C (zh)	2004-10-06
NO20000062L (no)	2000-01-06
CN1262623A (zh)	2000-08-09
SE9702706D0 (sv)	1997-07-11
HK1029942A1 (en)	2001-04-20
KR20010021682A (ko)	2001-03-15
IS5333A (is)	2000-01-07
SK183499A3 (en)	2000-07-11
NO20000062D0 (no)	2000-01-06
EP1014991A1 (en)	2000-07-05
JP2002509543A (ja)	2002-03-26
RU2207858C2 (ru)	2003-07-10
TR200000008T2 (tr)	2000-05-22
BR9815501A (pt)	2001-07-17
HUP0003106A3 (en)	2002-12-28
AU739828B2 (en)	2001-10-18
CA2294779A1 (en)	1999-01-21
AU8368398A (en)	1999-02-08
IL133871A0 (en)	2001-04-30
NZ501834A (en)	2002-05-31
PL337940A1 (en)	2000-09-11

Legal Events

Date	Code	Title
2005-02-20	FF	Patent granted
2005-03-20	KB	Patent renewed
2009-08-31	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
AU739828B2 (en)	2001-10-18	Prostaglandin derivatives devoid of side-effects for the treatment of glaucoma
Peng et al.	2017	Recent advances in asymmetric total synthesis of prostaglandins
FI92690C (fi)	1994-12-27	Menetelmä farmakologisesti aktiivisten 13,14-dihydro-17-fenyyli-18,19,20-trinor-PGF2 -alkyyliestereiden valmistamiseksi
KR0167745B1 (ko)	1999-01-15	15-케토-프로스타글란딘 i 화합물을 함유하는 뇌기능 보호제
US20010023258A1 (en)	2001-09-20	Use of cloprostenol and fluprostenol analogues to treat glaucoma and ocular hypertension
NO308993B1 (no)	2000-11-27	Middel for behandling av lever- og gallesykdommer samt forbindelser som kan anvendes i midlet
JP2011037861A (ja)	2011-02-24	Ｃ１６不飽和ｆｐ−選択的プロスタグランジン類縁体
KR101561171B1 (ko)	2015-10-19	Ｆ-계열 프로스타글란딘의 제조 방법
US6172109B1 (en)	2001-01-09	13-Thia prostaglandins for use in glaucoma therapy
KR100195430B1 (ko)	1999-06-15	15-케토-프로스타글란딘 화합물에 의한 염증성 질환 치료
KR20000053228A (ko)	2000-08-25	안압강하제로서의 프로스타글란딘의 시스-δ⁴ 유사체
WO1998057930A1 (en)	1998-12-23	Keto-substituted tetrahydrofuran analogs of prostaglandins as ocular hypotensives
JP2002538138A (ja)	2002-11-12	Ｃ１６不飽和ｆｐ−選択的プロスタグランジン類縁体
AU2139600A (en)	2000-07-24	Method and composition for treatment of female sexual dysfunction
CN101146541B (zh)	2012-04-11	用于治疗中枢神经系统疾病的方法和组合物
HUT62874A (en)	1993-06-28	Process for the synthesis of prostaglandin derivatives
HK1252353A1 (zh)	2019-05-24	治疗精神分裂症的方法
CZ200084A3 (cs)	2000-08-16	Prostaglandinové deriváty pro léčení glaukomu, bez vedlejších účinků
HK1196278A (en)	2014-12-12	Method for treating schizophrenia
HK1029942B (en)	2005-03-24	Prostaglandin derivatives devoid of side-effects for the treatment of glaucoma
MXPA00000403A (en)	2001-12-04	Prostaglandin derivatives devoid of side-effects for the treatment of glaucoma