HRP20010099A2 - New pharmaceutical uses for nos inhibitors - Google Patents
New pharmaceutical uses for nos inhibitors Download PDFInfo
- Publication number
- HRP20010099A2 HRP20010099A2 HR20010099A HRP20010099A HRP20010099A2 HR P20010099 A2 HRP20010099 A2 HR P20010099A2 HR 20010099 A HR20010099 A HR 20010099A HR P20010099 A HRP20010099 A HR P20010099A HR P20010099 A2 HRP20010099 A2 HR P20010099A2
- Authority
- HR
- Croatia
- Prior art keywords
- formula
- compound
- pyridin
- phenyl
- ylamine
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 368
- 238000000034 method Methods 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 57
- 241000124008 Mammalia Species 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 26
- 239000013543 active substance Substances 0.000 claims description 21
- 230000002401 inhibitory effect Effects 0.000 claims description 19
- 208000002193 Pain Diseases 0.000 claims description 18
- 208000010877 cognitive disease Diseases 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 201000004681 Psoriasis Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 11
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 11
- 208000019116 sleep disease Diseases 0.000 claims description 10
- 230000002829 reductive effect Effects 0.000 claims description 9
- 208000000094 Chronic Pain Diseases 0.000 claims description 8
- 208000005298 acute pain Diseases 0.000 claims description 8
- 230000001684 chronic effect Effects 0.000 claims description 8
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 101000783611 Takifugu rubripes 5-hydroxytryptamine receptor 1D Proteins 0.000 claims description 5
- 208000001407 Vascular Headaches Diseases 0.000 claims description 5
- 239000004084 narcotic analgesic agent Substances 0.000 claims description 5
- 230000006999 cognitive decline Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000000018 receptor agonist Substances 0.000 claims description 4
- 229940044601 receptor agonist Drugs 0.000 claims description 4
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 230000003930 cognitive ability Effects 0.000 claims 2
- -1 nitro, hydroxy, cyano, amino Chemical group 0.000 description 96
- 238000006243 chemical reaction Methods 0.000 description 85
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- 239000002904 solvent Substances 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 125000001424 substituent group Chemical group 0.000 description 58
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 238000010992 reflux Methods 0.000 description 56
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 49
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
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- 229910052739 hydrogen Inorganic materials 0.000 description 36
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- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 35
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 35
- 239000000243 solution Substances 0.000 description 35
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 33
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 125000001624 naphthyl group Chemical group 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
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- 125000003710 aryl alkyl group Chemical group 0.000 description 21
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 229910052757 nitrogen Inorganic materials 0.000 description 21
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
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- 125000003118 aryl group Chemical group 0.000 description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 17
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 16
- 239000003153 chemical reaction reagent Substances 0.000 description 16
- 125000005843 halogen group Chemical group 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
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- 239000003513 alkali Substances 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 14
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- 239000000047 product Substances 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
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- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 229910052794 bromium Inorganic materials 0.000 description 11
- 239000012280 lithium aluminium hydride Substances 0.000 description 11
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
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- 239000003480 eluent Substances 0.000 description 10
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 description 10
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- 229910052763 palladium Inorganic materials 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
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- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 9
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 9
- 125000003282 alkyl amino group Chemical group 0.000 description 9
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 8
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 125000005605 benzo group Chemical group 0.000 description 8
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- 229910052731 fluorine Inorganic materials 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 7
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 7
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 7
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 7
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- 239000007858 starting material Substances 0.000 description 7
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 7
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- 238000005804 alkylation reaction Methods 0.000 description 6
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 6
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
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- MNUHYQZBNHDABI-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-6-amine Chemical group C1NCC2C(N)C21 MNUHYQZBNHDABI-UHFFFAOYSA-N 0.000 description 4
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- JXZYURNNBYDHOH-UHFFFAOYSA-N 2-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=CC=CC=2)=C1C JXZYURNNBYDHOH-UHFFFAOYSA-N 0.000 description 3
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- 238000002648 combination therapy Methods 0.000 description 3
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- OTLDLQZJRFYOJR-LJQANCHMSA-N eletriptan Chemical compound CN1CCC[C@@H]1CC1=CN=C2[C]1C=C(CCS(=O)(=O)C=1C=CC=CC=1)C=C2 OTLDLQZJRFYOJR-LJQANCHMSA-N 0.000 description 3
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- 239000003999 initiator Substances 0.000 description 3
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- BGEQUTBMOCNTSE-UHFFFAOYSA-N n-[1-[2-[4-(6-aminopyridin-2-yl)phenyl]ethyl]pyrrolidin-3-yl]-2-[3-(trifluoromethyl)phenyl]acetamide Chemical compound NC1=CC=CC(C=2C=CC(CCN3CC(CC3)NC(=O)CC=3C=C(C=CC=3)C(F)(F)F)=CC=2)=N1 BGEQUTBMOCNTSE-UHFFFAOYSA-N 0.000 description 1
- BDDKYBPOEPXTOU-UHFFFAOYSA-N n-[1-[2-[4-(6-aminopyridin-2-yl)phenyl]ethyl]pyrrolidin-3-yl]-2-cyclohexylacetamide Chemical compound NC1=CC=CC(C=2C=CC(CCN3CC(CC3)NC(=O)CC3CCCCC3)=CC=2)=N1 BDDKYBPOEPXTOU-UHFFFAOYSA-N 0.000 description 1
- CVQREOITHOPNDI-UHFFFAOYSA-N n-[1-[2-[4-(6-aminopyridin-2-yl)phenyl]ethyl]pyrrolidin-3-yl]-2-phenylacetamide Chemical compound NC1=CC=CC(C=2C=CC(CCN3CC(CC3)NC(=O)CC=3C=CC=CC=3)=CC=2)=N1 CVQREOITHOPNDI-UHFFFAOYSA-N 0.000 description 1
- FONQITKXUUBLDF-UHFFFAOYSA-N n-[2-[4-(6-aminopyridin-2-yl)phenyl]ethyl]-3-oxa-9-azabicyclo[3.3.1]nonan-7-amine Chemical compound NC1=CC=CC(C=2C=CC(CCNC3CC4COCC(N4)C3)=CC=2)=N1 FONQITKXUUBLDF-UHFFFAOYSA-N 0.000 description 1
- IBEOZZWRZGZBGC-UHFFFAOYSA-N n-[6-[2-fluoro-4-(2-oxopyrrolidin-3-yl)phenyl]pyridin-2-yl]-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC(C=2C(=CC(=CC=2)C2C(NCC2)=O)F)=N1 IBEOZZWRZGZBGC-UHFFFAOYSA-N 0.000 description 1
- RLGBZQNTCZYCCC-UHFFFAOYSA-N n-[6-[4-(bromomethyl)-2-propan-2-yloxyphenyl]pyridin-2-yl]-2,2-dimethylpropanamide Chemical compound CC(C)OC1=CC(CBr)=CC=C1C1=CC=CC(NC(=O)C(C)(C)C)=N1 RLGBZQNTCZYCCC-UHFFFAOYSA-N 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000005574 norbornylene group Chemical group 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- HBEQXAKJSGXAIQ-UHFFFAOYSA-N oxopalladium Chemical compound [Pd]=O HBEQXAKJSGXAIQ-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000008533 pain sensitivity Effects 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- JAKNYTQAGPEFJB-UHFFFAOYSA-N piperidin-2-amine Chemical group NC1CCCCN1 JAKNYTQAGPEFJB-UHFFFAOYSA-N 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 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
- 239000011591 potassium Substances 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- KWQRKOSMSFLBTJ-UHFFFAOYSA-N tert-butyl 3-methylsulfonyloxypyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)C1 KWQRKOSMSFLBTJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- VFJYIHQDILEQNR-UHFFFAOYSA-M trimethylsulfanium;iodide Chemical compound [I-].C[S+](C)C VFJYIHQDILEQNR-UHFFFAOYSA-M 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
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Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Psychiatry (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9615298P | 1998-08-11 | 1998-08-11 | |
PCT/IB1999/001389 WO2000009130A2 (en) | 1998-08-11 | 1999-08-05 | New pharmaceutical uses for nos inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20010099A2 true HRP20010099A2 (en) | 2002-02-28 |
Family
ID=22255853
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20010099A HRP20010099A2 (en) | 1998-08-11 | 2001-02-08 | New pharmaceutical uses for nos inhibitors |
Country Status (37)
Country | Link |
---|---|
US (1) | US20020151572A1 (ja) |
EP (1) | EP1109556A2 (ja) |
JP (1) | JP2002522498A (ja) |
KR (1) | KR20010085364A (ja) |
CN (1) | CN1323211A (ja) |
AP (1) | AP2001002067A0 (ja) |
AR (1) | AR020009A1 (ja) |
AU (1) | AU749439B2 (ja) |
BR (1) | BR9912906A (ja) |
CA (1) | CA2340200A1 (ja) |
CO (1) | CO5130011A1 (ja) |
CR (1) | CR6302A (ja) |
CZ (1) | CZ2001486A3 (ja) |
DZ (1) | DZ2867A1 (ja) |
EA (1) | EA200100125A1 (ja) |
EE (1) | EE200100084A (ja) |
GE (1) | GEP20043252B (ja) |
GT (1) | GT199900127A (ja) |
HK (1) | HK1041819A1 (ja) |
HR (1) | HRP20010099A2 (ja) |
HU (1) | HUP0103113A3 (ja) |
ID (1) | ID28227A (ja) |
IL (1) | IL141031A0 (ja) |
IS (1) | IS5814A (ja) |
MA (1) | MA26670A1 (ja) |
NO (1) | NO20010685L (ja) |
NZ (1) | NZ509298A (ja) |
OA (1) | OA11595A (ja) |
PA (1) | PA8479801A1 (ja) |
PE (1) | PE20001025A1 (ja) |
PL (1) | PL346842A1 (ja) |
SK (1) | SK1702001A3 (ja) |
SV (1) | SV1999000121A (ja) |
TN (1) | TNSN99154A1 (ja) |
TR (3) | TR200401803T2 (ja) |
WO (1) | WO2000009130A2 (ja) |
YU (1) | YU9601A (ja) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
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US20010049379A1 (en) | 1997-08-27 | 2001-12-06 | Lowe John Adams | 2-aminopyridines containing fused ring substituents |
EP1267862A2 (en) | 2000-02-22 | 2003-01-02 | Cellegy Canada Inc. | Methods and compositions for improving sleep |
CN100430399C (zh) * | 2002-03-20 | 2008-11-05 | 昆士兰大学 | 包含一氧化氮供体和阿片样物质止痛剂的组合物和方法 |
WO2005007627A1 (ja) * | 2003-07-18 | 2005-01-27 | Nihon Nohyaku Co., Ltd. | フェニルピリジン誘導体、その中間体及びこれを有効成分とする除草剤 |
US9120750B2 (en) | 2013-03-07 | 2015-09-01 | Northwestern University | 2-Aminopyridine-based selective neuronal nitric oxide synthase inhibitors |
US10759791B2 (en) | 2014-11-04 | 2020-09-01 | Northwestern University | Mammalian and bacterial nitric oxide synthase inhibitors |
WO2016073623A2 (en) | 2014-11-04 | 2016-05-12 | Northwestern University | Mammalian and bacterial nitric oxide synthase inhibitors |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CZ291647B6 (cs) * | 1996-03-29 | 2003-04-16 | Pfizer Inc. | 6-Fenylpyridyl-2-aminové deriváty, jejich použití a farmaceutické kompozice na jejich bázi |
HN1997000027A (es) * | 1996-12-06 | 1997-06-05 | Pfizer Prod Inc | Derivados de 6-fenil piridil - 2 amina |
YU35699A (sh) * | 1997-02-10 | 2002-06-19 | Pfizer Products Inc. | 2-amino-6-(2-supstituisan-4-fenoksi)-supstituisani piridini |
HN1998000118A (es) * | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
HN1998000125A (es) * | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
SE9703693D0 (sv) * | 1997-10-10 | 1997-10-10 | Astra Pharma Prod | Novel combination |
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1999
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