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 |
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| JP2003535821A true JP2003535821A (ja) | 2003-12-02 |
| JP2003535821A5 JP2003535821A5 (enExample) | 2005-07-28 |
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| JP (1) | JP2003535821A (enExample) |
| KR (1) | KR20030095183A (enExample) |
| CN (1) | CN1450995A (enExample) |
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| CA (1) | CA2401959A1 (enExample) |
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| PL (1) | PL365422A1 (enExample) |
| WO (1) | WO2001070701A1 (enExample) |
| ZA (1) | ZA200206853B (enExample) |
Families Citing this family (16)
| 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 |
| WO2002098350A2 (en) | 2001-06-01 | 2002-12-12 | Alcon, Inc. | Pyranoindazoles and their use for the treatment of glaucoma |
| TW593302B (en) | 2001-12-20 | 2004-06-21 | Alcon Inc | Novel benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma |
| US7196082B2 (en) | 2002-11-08 | 2007-03-27 | 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 |
| CA2505127A1 (en) * | 2002-11-08 | 2004-05-27 | James B. Doherty | Ophthalmic compositions for treating ocular hypertension |
| EP1581209A4 (en) | 2002-12-13 | 2009-03-11 | Alcon Inc | NEW BENZOPYRAN ANALOGUE AND ITS USE FOR THE TREATMENT OF GLAUKOM |
| JP2004262812A (ja) * | 2003-02-28 | 2004-09-24 | Rohto Pharmaceut Co Ltd | 眼圧低下剤 |
| AU2004271978B2 (en) * | 2003-09-04 | 2009-02-05 | Merck & Co., Inc. | Ophthalmic compositions for treating ocular hypertension |
| AR046890A1 (es) | 2003-12-15 | 2005-12-28 | Alcon Inc | [1,4] oxazino [2,3-g] indazoles sustituidos para el tratamiento del glaucoma. |
| US7129257B1 (en) | 2003-12-15 | 2006-10-31 | Alcon, Inc. | Pyrazolo[3,4- e]benzoxazoles for the treatment of glaucoma |
| US7338972B1 (en) | 2003-12-15 | 2008-03-04 | Alcon, Inc. | Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma |
| AU2005308523B2 (en) | 2004-11-29 | 2010-01-07 | Warner-Lambert Company Llc | Therapeutic pyrazolo[3,4-b] pyridines and indazoles |
| 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 |
| WO2025000053A1 (en) * | 2023-06-28 | 2025-01-02 | Psylo Pty Ltd | Compounds |
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. |
| WO1999059499A2 (en) * | 1998-05-19 | 1999-11-25 | Alcon Laboratories, Inc. | Serotonergic 5ht7 receptor compounds for treating ocular and cns disorders |
| GB9819020D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds III |
| AU755119B2 (en) * | 1998-09-18 | 2002-12-05 | Alcon Laboratories, Inc. | Serotonergic 5HT2 agonists for treating glaucoma |
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2000
- 2000-11-14 WO PCT/US2000/031143 patent/WO2001070701A1/en not_active Ceased
- 2000-11-14 JP JP2001568911A patent/JP2003535821A/ja active Pending
- 2000-11-14 KR KR1020027011862A patent/KR20030095183A/ko not_active Ceased
- 2000-11-14 AU AU2001219180A patent/AU2001219180B2/en not_active Ceased
- 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 CN CN00819348A patent/CN1450995A/zh active Pending
- 2000-11-14 MX MXPA02008825A patent/MXPA02008825A/es unknown
- 2000-11-14 BR BR0017163-8A patent/BR0017163A/pt not_active IP Right Cessation
- 2000-11-14 EP EP00982109A patent/EP1268439A1/en not_active Withdrawn
- 2000-11-14 AU AU1918001A patent/AU1918001A/xx active Pending
- 2000-12-01 AR ARP000106395A patent/AR026708A1/es unknown
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- 2002-08-27 ZA ZA200206853A patent/ZA200206853B/en unknown
Also Published As
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| MXPA02008825A (es) | 2004-10-15 |
| PL365422A1 (en) | 2005-01-10 |
| EP1268439A1 (en) | 2003-01-02 |
| WO2001070701A1 (en) | 2001-09-27 |
| AU2001219180B2 (en) | 2005-04-07 |
| AR026708A1 (es) | 2003-02-26 |
| AU1918001A (en) | 2001-10-03 |
| KR20030095183A (ko) | 2003-12-18 |
| BR0017163A (pt) | 2003-01-14 |
| ZA200206853B (en) | 2004-11-02 |
| CA2401959A1 (en) | 2001-09-27 |
| CN1450995A (zh) | 2003-10-22 |
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