JP2003535821A - 緑内障を治療するための５−ヒドロキシインダゾール誘導体 - Google Patents
緑内障を治療するための５−ヒドロキシインダゾール誘導体Info
- Publication number
- JP2003535821A JP2003535821A JP2001568911A JP2001568911A JP2003535821A JP 2003535821 A JP2003535821 A JP 2003535821A JP 2001568911 A JP2001568911 A JP 2001568911A JP 2001568911 A JP2001568911 A JP 2001568911A JP 2003535821 A JP2003535821 A JP 2003535821A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- indazol
- halogen
- aminopropyl
- 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.)
- Pending
Links
- 208000010412 Glaucoma Diseases 0.000 title abstract description 15
- ZHDXWEPRYNHNDC-UHFFFAOYSA-N 1h-indazol-5-ol Chemical class OC1=CC=C2NN=CC2=C1 ZHDXWEPRYNHNDC-UHFFFAOYSA-N 0.000 title description 2
- 230000004406 elevated intraocular pressure Effects 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims description 74
- 150000001875 compounds Chemical class 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 150000002431 hydrogen Chemical class 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- -1 2-aminopropyl Chemical group 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- LIRGIBHYEVBULM-UHFFFAOYSA-N [3-(2-aminopropyl)-2h-indazol-5-yl] 2-methylpropanoate Chemical compound C1=C(OC(=O)C(C)C)C=C2C(CC(N)C)=NNC2=C1 LIRGIBHYEVBULM-UHFFFAOYSA-N 0.000 claims description 5
- MUVNPHDJNYIOQP-UHFFFAOYSA-N 3-(2-aminopropyl)-2h-indazol-5-ol Chemical compound C1=C(O)C=C2C(CC(N)C)=NNC2=C1 MUVNPHDJNYIOQP-UHFFFAOYSA-N 0.000 claims description 4
- RVEXITQCEKUGFA-UHFFFAOYSA-N 3-(2-aminopropyl)-6-fluoro-1-methylindazol-5-ol Chemical compound FC1=C(O)C=C2C(CC(N)C)=NN(C)C2=C1 RVEXITQCEKUGFA-UHFFFAOYSA-N 0.000 claims description 3
- ZNYROIPGZTXHCH-UHFFFAOYSA-N 3-(2-aminopropyl)-6-fluoro-2h-indazol-5-ol Chemical compound FC1=C(O)C=C2C(CC(N)C)=NNC2=C1 ZNYROIPGZTXHCH-UHFFFAOYSA-N 0.000 claims description 3
- NVOVVQZEWRKFOQ-UHFFFAOYSA-N 3-(2-aminopropyl)-7-methyl-2h-indazol-5-ol Chemical compound C1=C(O)C=C2C(CC(N)C)=NNC2=C1C NVOVVQZEWRKFOQ-UHFFFAOYSA-N 0.000 claims description 3
- XILORGWKMLOGKF-UHFFFAOYSA-N 4-(diethylamino)-4-oxobutanoic acid Chemical compound CCN(CC)C(=O)CCC(O)=O XILORGWKMLOGKF-UHFFFAOYSA-N 0.000 claims description 3
- UZIBJOVSEWVLOL-UHFFFAOYSA-N [3-(2-aminopropyl)-2h-indazol-5-yl] cyclopropanecarboxylate Chemical compound C1=C2C(CC(N)C)=NNC2=CC=C1OC(=O)C1CC1 UZIBJOVSEWVLOL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 230000004493 normal intraocular pressure Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 5
- YALUWNWLPFRZCR-UHFFFAOYSA-N 3-(2-aminopropyl)-1-methylindazol-5-ol Chemical compound C1=C(O)C=C2C(CC(N)C)=NN(C)C2=C1 YALUWNWLPFRZCR-UHFFFAOYSA-N 0.000 claims 2
- QPBRBJGSIDXXNB-UHFFFAOYSA-N [3-(2-aminopropyl)-2h-indazol-5-yl] 2,2-dimethylpropanoate Chemical compound C1=C(OC(=O)C(C)(C)C)C=C2C(CC(N)C)=NNC2=C1 QPBRBJGSIDXXNB-UHFFFAOYSA-N 0.000 claims 2
- NQJNCNUFJIFXEG-UHFFFAOYSA-N 1-(5-methoxy-2h-indazol-3-yl)propan-2-amine Chemical compound COC1=CC=C2NN=C(CC(C)N)C2=C1 NQJNCNUFJIFXEG-UHFFFAOYSA-N 0.000 claims 1
- YDRACLWXXDIKIW-UHFFFAOYSA-N 3-(2-aminoethyl)-2h-indazol-5-ol Chemical class C1=C(O)C=C2C(CCN)=NNC2=C1 YDRACLWXXDIKIW-UHFFFAOYSA-N 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 22
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 18
- 239000000556 agonist Substances 0.000 description 14
- 238000009472 formulation Methods 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 239000003814 drug Substances 0.000 description 9
- 230000004410 intraocular pressure Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 229940054534 ophthalmic solution Drugs 0.000 description 4
- 150000003906 phosphoinositides Chemical class 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000000862 serotonergic effect Effects 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 150000002989 phenols Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000004382 visual function Effects 0.000 description 3
- NWIUTZDMDHAVTP-KRWDZBQOSA-N (S)-betaxolol Chemical compound C1=CC(OC[C@@H](O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-KRWDZBQOSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- XQAFDTISAVRMTF-UHFFFAOYSA-N 2-(5-phenylmethoxy-2h-indazol-3-yl)acetic acid Chemical compound C=1C2=C(CC(=O)O)NN=C2C=CC=1OCC1=CC=CC=C1 XQAFDTISAVRMTF-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- MQRQYHACXYLPHI-WLHGVMLRSA-N 3-(2-aminopropyl)-1-methylindazol-5-ol;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(O)C=C2C(CC(N)C)=NN(C)C2=C1 MQRQYHACXYLPHI-WLHGVMLRSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- RLJFTICUTYVZDG-UHFFFAOYSA-N Methiothepine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2CC1N1CCN(C)CC1 RLJFTICUTYVZDG-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- SNIXRMIHFOIVBB-UHFFFAOYSA-N N-Hydroxyl-tryptamine Chemical compound C1=CC=C2C(CCNO)=CNC2=C1 SNIXRMIHFOIVBB-UHFFFAOYSA-N 0.000 description 2
- 206010030043 Ocular hypertension Diseases 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- 229960000367 inositol Drugs 0.000 description 2
- 229960004771 levobetaxolol Drugs 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 229940100654 ophthalmic suspension Drugs 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000003478 serotonin 5-HT2 receptor agonist Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- 230000004393 visual impairment Effects 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
- XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- GGUSQTSTQSHJAH-FQEVSTJZSA-N (R)-eliprodil Chemical compound C([C@H](O)C=1C=CC(Cl)=CC=1)N(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-FQEVSTJZSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WBYHTZYHAFNBKW-UHFFFAOYSA-N 1-((s)-2-aminopropyl)-1h-indazol-6-ol Chemical compound C1=C(O)C=C2N(CC(N)C)N=CC2=C1 WBYHTZYHAFNBKW-UHFFFAOYSA-N 0.000 description 1
- NVJMIYVZQAROHV-UHFFFAOYSA-N 1-(1-acetyl-5-phenylmethoxyindazol-3-yl)propan-2-one Chemical compound C1=C2C(CC(=O)C)=NN(C(C)=O)C2=CC=C1OCC1=CC=CC=C1 NVJMIYVZQAROHV-UHFFFAOYSA-N 0.000 description 1
- TTYZMLXYSCHQER-UHFFFAOYSA-N 1-(2h-indazol-3-yl)propan-2-amine Chemical class C1=CC=C2C(CC(N)C)=NNC2=C1 TTYZMLXYSCHQER-UHFFFAOYSA-N 0.000 description 1
- GGUSQTSTQSHJAH-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-[4-(4-fluorobenzyl)piperidin-1-yl]ethanol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1CC1=CC=C(F)C=C1 GGUSQTSTQSHJAH-UHFFFAOYSA-N 0.000 description 1
- JJJDQTSYYHLARV-UHFFFAOYSA-N 1-(5-phenylmethoxy-2h-indazol-3-yl)propan-2-one Chemical compound C1=C2C(CC(=O)C)=NNC2=CC=C1OCC1=CC=CC=C1 JJJDQTSYYHLARV-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- CBYSUDTZYSUMRW-UHFFFAOYSA-N 1-[3-(2-azidopropyl)-5-phenylmethoxyindazol-1-yl]ethanone Chemical compound C1=C2C(CC(C)N=[N+]=[N-])=NN(C(C)=O)C2=CC=C1OCC1=CC=CC=C1 CBYSUDTZYSUMRW-UHFFFAOYSA-N 0.000 description 1
- GCGQUKJGEKWQTC-UHFFFAOYSA-N 1-[3-(2-hydroxypropyl)-5-phenylmethoxyindazol-1-yl]ethanone Chemical compound C1=C2C(CC(O)C)=NN(C(C)=O)C2=CC=C1OCC1=CC=CC=C1 GCGQUKJGEKWQTC-UHFFFAOYSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- YOMBUJAFGMOIGS-UHFFFAOYSA-N 2-fluoro-1-phenylethanone Chemical class FCC(=O)C1=CC=CC=C1 YOMBUJAFGMOIGS-UHFFFAOYSA-N 0.000 description 1
- BXEFQUSYBZYTAE-UHFFFAOYSA-N 2-indol-1-ylethanamine Chemical class C1=CC=C2N(CCN)C=CC2=C1 BXEFQUSYBZYTAE-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- VXOSGHMXAYBBBB-UHFFFAOYSA-N 2h-indazole-3-carbaldehyde Chemical class C1=CC=C2C(C=O)=NNC2=C1 VXOSGHMXAYBBBB-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
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)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19028300P | 2000-03-17 | 2000-03-17 | |
| US60/190,283 | 2000-03-17 | ||
| PCT/US2000/031143 WO2001070701A1 (en) | 2000-03-17 | 2000-11-14 | 5-hydroxy indazole derivatives for treating glaucoma |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003535821A true JP2003535821A (ja) | 2003-12-02 |
| JP2003535821A5 JP2003535821A5 (ko) | 2005-07-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001568911A Pending JP2003535821A (ja) | 2000-03-17 | 2000-11-14 | 緑内障を治療するための５−ヒドロキシインダゾール誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1268439A1 (ko) |
| JP (1) | JP2003535821A (ko) |
| KR (1) | KR20030095183A (ko) |
| CN (1) | CN1450995A (ko) |
| AR (1) | AR026708A1 (ko) |
| AU (2) | AU2001219180B2 (ko) |
| BR (1) | BR0017163A (ko) |
| CA (1) | CA2401959A1 (ko) |
| MX (1) | MXPA02008825A (ko) |
| PL (1) | PL365422A1 (ko) |
| WO (1) | WO2001070701A1 (ko) |
| ZA (1) | ZA200206853B (ko) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
| DK1392292T3 (da) | 2001-06-01 | 2006-05-29 | Alcon Inc | Pyranoindazoler og deres anvendelse til behandling af glaukom |
| TW593302B (en) | 2001-12-20 | 2004-06-21 | Alcon Inc | Novel benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma |
| WO2004043354A2 (en) | 2002-11-08 | 2004-05-27 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| CN100384827C (zh) * | 2002-11-08 | 2008-04-30 | 默克公司 | 用于治疗高眼压症的眼用组合物 |
| US7196082B2 (en) * | 2002-11-08 | 2007-03-27 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| JP2006511556A (ja) | 2002-12-13 | 2006-04-06 | アルコン，インコーポレイテッド | 新規のベンゾピラン類似体及び緑内障の治療のためのそれらの使用 |
| JP2004262812A (ja) * | 2003-02-28 | 2004-09-24 | Rohto Pharmaceut Co Ltd | 眼圧低下剤 |
| US7494983B2 (en) * | 2003-09-04 | 2009-02-24 | Merck & Co. Inc. | Ophthalmic compositions for treating ocular hypertension |
| US7338972B1 (en) | 2003-12-15 | 2008-03-04 | Alcon, Inc. | Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma |
| WO2005058911A2 (en) | 2003-12-15 | 2005-06-30 | Alcon, Inc. | Substituted [1,4]oxazino[2,3-g]indazoles for the treatment of glaucoma |
| US7129257B1 (en) | 2003-12-15 | 2006-10-31 | Alcon, Inc. | Pyrazolo[3,4- e]benzoxazoles for the treatment of glaucoma |
| DK1828182T3 (da) | 2004-11-29 | 2010-05-10 | Warner Lambert Co | Terapeutiske pyrazol[3,4-B]pyridiner og indazoler |
| US7425572B2 (en) | 2004-12-08 | 2008-09-16 | Alcon, Inc. | Use of dioxindoindazoles and dioxoloindazoles for treating glaucoma |
| KR100972921B1 (ko) * | 2009-12-02 | 2010-07-28 | 제이케이이앤씨 주식회사 | 회전 격판식 선회류 세정 및 탈취장치 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2680366B1 (fr) * | 1991-08-13 | 1995-01-20 | Adir | Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
| CN1301161A (zh) * | 1998-05-19 | 2001-06-27 | 艾尔科实验室公司 | 用于治疗眼睛和中枢神经系统障碍的血清素激活的5ht7受体化合物 |
| GB9819020D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds III |
| EP1112106B1 (en) * | 1998-09-18 | 2005-11-23 | Alcon Manufacturing Ltd. | Serotonergic 5ht2 agonists for treating glaucoma |
-
2000
- 2000-11-14 AU AU2001219180A patent/AU2001219180B2/en not_active Ceased
- 2000-11-14 MX MXPA02008825A patent/MXPA02008825A/es unknown
- 2000-11-14 WO PCT/US2000/031143 patent/WO2001070701A1/en not_active Application Discontinuation
- 2000-11-14 AU AU1918001A patent/AU1918001A/xx active Pending
- 2000-11-14 PL PL00365422A patent/PL365422A1/xx not_active Application Discontinuation
- 2000-11-14 CA CA002401959A patent/CA2401959A1/en not_active Abandoned
- 2000-11-14 KR KR1020027011862A patent/KR20030095183A/ko not_active Application Discontinuation
- 2000-11-14 BR BR0017163-8A patent/BR0017163A/pt not_active IP Right Cessation
- 2000-11-14 JP JP2001568911A patent/JP2003535821A/ja active Pending
- 2000-11-14 EP EP00982109A patent/EP1268439A1/en not_active Withdrawn
- 2000-11-14 CN CN00819348A patent/CN1450995A/zh active Pending
- 2000-12-01 AR ARP000106395A patent/AR026708A1/es unknown
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2002
- 2002-08-27 ZA ZA200206853A patent/ZA200206853B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200206853B (en) | 2004-11-02 |
| AU1918001A (en) | 2001-10-03 |
| MXPA02008825A (es) | 2004-10-15 |
| CN1450995A (zh) | 2003-10-22 |
| EP1268439A1 (en) | 2003-01-02 |
| AU2001219180B2 (en) | 2005-04-07 |
| PL365422A1 (en) | 2005-01-10 |
| CA2401959A1 (en) | 2001-09-27 |
| AR026708A1 (es) | 2003-02-26 |
| WO2001070701A1 (en) | 2001-09-27 |
| KR20030095183A (ko) | 2003-12-18 |
| BR0017163A (pt) | 2003-01-14 |
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