NZ563191A - Substituted indole compounds having NOS inhibitory activity - Google Patents
Substituted indole compounds having NOS inhibitory activityInfo
- Publication number
- NZ563191A NZ563191A NZ563191A NZ56319106A NZ563191A NZ 563191 A NZ563191 A NZ 563191A NZ 563191 A NZ563191 A NZ 563191A NZ 56319106 A NZ56319106 A NZ 56319106A NZ 563191 A NZ563191 A NZ 563191A
- Authority
- NZ
- New Zealand
- Prior art keywords
- optionally substituted
- compound
- alkyl
- integer
- heterocyclyl
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title claims description 9
- 230000002401 inhibitory effect Effects 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 259
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 147
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 71
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 67
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 67
- 208000002193 Pain Diseases 0.000 claims abstract description 54
- 206010027599 migraine Diseases 0.000 claims abstract description 52
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 50
- 230000036407 pain Effects 0.000 claims abstract description 44
- 208000004454 Hyperalgesia Diseases 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 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 claims abstract description 26
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 25
- 208000004296 neuralgia Diseases 0.000 claims abstract description 22
- 208000021722 neuropathic pain Diseases 0.000 claims abstract description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 19
- 206010053552 allodynia Diseases 0.000 claims abstract description 18
- 230000006378 damage Effects 0.000 claims abstract description 17
- 125000001424 substituent group Chemical group 0.000 claims abstract description 17
- 208000006011 Stroke Diseases 0.000 claims abstract description 16
- 230000001684 chronic effect Effects 0.000 claims abstract description 16
- 206010019233 Headaches Diseases 0.000 claims abstract description 15
- 206010029350 Neurotoxicity Diseases 0.000 claims abstract description 15
- 206010044221 Toxic encephalopathy Diseases 0.000 claims abstract description 15
- 206010015037 epilepsy Diseases 0.000 claims abstract description 15
- 229960005181 morphine Drugs 0.000 claims abstract description 15
- 230000007135 neurotoxicity Effects 0.000 claims abstract description 15
- 231100000228 neurotoxicity Toxicity 0.000 claims abstract description 15
- 208000035154 Hyperesthesia Diseases 0.000 claims abstract description 13
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims abstract description 12
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 11
- 208000008548 Tension-Type Headache Diseases 0.000 claims abstract description 11
- 230000000926 neurological effect Effects 0.000 claims abstract description 11
- 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 10
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 claims abstract description 9
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 9
- 206010019196 Head injury Diseases 0.000 claims abstract description 9
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 9
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 8
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 8
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 8
- 206010007625 cardiogenic shock Diseases 0.000 claims abstract description 8
- 206010013663 drug dependence Diseases 0.000 claims abstract description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 7
- 206010012289 Dementia Diseases 0.000 claims abstract description 7
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 7
- 230000036506 anxiety Effects 0.000 claims abstract description 7
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 7
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims abstract description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims abstract description 6
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims abstract description 6
- 230000001154 acute effect Effects 0.000 claims abstract description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims abstract description 6
- 208000033679 diabetic kidney disease Diseases 0.000 claims abstract description 6
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 6
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 5
- 208000020431 spinal cord injury Diseases 0.000 claims abstract description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
- 208000030507 AIDS Diseases 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 4
- 206010044652 trigeminal neuralgia Diseases 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 113
- -1 propoxylphene Chemical compound 0.000 claims description 103
- 125000000623 heterocyclic group Chemical group 0.000 claims description 74
- 125000003118 aryl group Chemical group 0.000 claims description 57
- 239000003112 inhibitor Substances 0.000 claims description 48
- 108010008858 Nitric Oxide Synthase Type I Proteins 0.000 claims description 42
- 102000006538 Nitric Oxide Synthase Type I Human genes 0.000 claims description 41
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 239000000935 antidepressant agent Substances 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 25
- 229940005513 antidepressants Drugs 0.000 claims description 24
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 23
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 22
- 230000001430 anti-depressive effect Effects 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 239000000556 agonist Substances 0.000 claims description 17
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- KQKPFRSPSRPDEB-UHFFFAOYSA-N sumatriptan Chemical compound CNS(=O)(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 KQKPFRSPSRPDEB-UHFFFAOYSA-N 0.000 claims description 17
- 239000005557 antagonist Substances 0.000 claims description 16
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 16
- 229960003708 sumatriptan Drugs 0.000 claims description 16
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims description 14
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims description 14
- 108010075520 Nitric Oxide Synthase Type III Proteins 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 229940127221 norepinephrine reuptake inhibitor Drugs 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 10
- 102000004257 Potassium Channel Human genes 0.000 claims description 10
- 108020001213 potassium channel Proteins 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims description 8
- GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 claims description 8
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 claims description 8
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical group O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 claims description 8
- 229960002430 atomoxetine Drugs 0.000 claims description 8
- 229960000600 milnacipran Drugs 0.000 claims description 8
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 8
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims description 8
- 229960001158 nortriptyline Drugs 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229960002702 piroxicam Drugs 0.000 claims description 8
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 8
- 229940076279 serotonin Drugs 0.000 claims description 8
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- MVVJINIUPYKZHR-UHFFFAOYSA-N 3-[[4-[5-(methoxymethyl)-2-oxo-1,3-oxazolidin-3-yl]phenoxy]methyl]benzonitrile Chemical compound O=C1OC(COC)CN1C(C=C1)=CC=C1OCC1=CC=CC(C#N)=C1 MVVJINIUPYKZHR-UHFFFAOYSA-N 0.000 claims description 6
- QPGGEKPRGVJKQB-UHFFFAOYSA-N 5-[2-(dimethylamino)ethyl]-11-methyl-6-benzo[b][1,4]benzodiazepinone Chemical compound O=C1N(CCN(C)C)C2=CC=CC=C2N(C)C2=CC=CC=C21 QPGGEKPRGVJKQB-UHFFFAOYSA-N 0.000 claims description 6
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 229960003148 adinazolam Drugs 0.000 claims description 6
- GJSLOMWRLALDCT-UHFFFAOYSA-N adinazolam Chemical compound C12=CC(Cl)=CC=C2N2C(CN(C)C)=NN=C2CN=C1C1=CC=CC=C1 GJSLOMWRLALDCT-UHFFFAOYSA-N 0.000 claims description 6
- 229960000959 amineptine Drugs 0.000 claims description 6
- VDPUXONTAVMIKZ-UHFFFAOYSA-N amineptine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2C([NH2+]CCCCCCC(=O)O)C2=CC=CC=C21 VDPUXONTAVMIKZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000001961 anticonvulsive agent Substances 0.000 claims description 6
- KRNDIPHOJLIHRI-UHFFFAOYSA-N bazinaprine Chemical group N#CC1=CC(C=2C=CC=CC=2)=NN=C1NCCN1CCOCC1 KRNDIPHOJLIHRI-UHFFFAOYSA-N 0.000 claims description 6
- 229950005683 bazinaprine Drugs 0.000 claims description 6
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- WZXHSWVDAYOFPE-UHFFFAOYSA-N brofaromine Chemical compound C=1C2=CC(OC)=CC(Br)=C2OC=1C1CCNCC1 WZXHSWVDAYOFPE-UHFFFAOYSA-N 0.000 claims description 6
- 229950004068 brofaromine Drugs 0.000 claims description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 229950001660 cimoxatone Drugs 0.000 claims description 6
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims description 6
- SEDQWOMFMIJKCU-UHFFFAOYSA-N demexiptiline Chemical compound C1=CC2=CC=CC=C2C(=NOCCNC)C2=CC=CC=C21 SEDQWOMFMIJKCU-UHFFFAOYSA-N 0.000 claims description 6
- 229950010189 demexiptiline Drugs 0.000 claims description 6
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 claims description 6
- 229960004193 dextropropoxyphene Drugs 0.000 claims description 6
- 229960003075 dibenzepin Drugs 0.000 claims description 6
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 6
- 229960001393 dosulepin Drugs 0.000 claims description 6
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims description 6
- 229960004801 imipramine Drugs 0.000 claims description 6
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 claims description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 6
- 230000002441 reversible effect Effects 0.000 claims description 6
- 229960004394 topiramate Drugs 0.000 claims description 6
- PHTUQLWOUWZIMZ-GZTJUZNOSA-N trans-dothiepin Chemical compound C1SC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 PHTUQLWOUWZIMZ-GZTJUZNOSA-N 0.000 claims description 6
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 5
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 claims description 5
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical group C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 claims description 5
- ULFYMTMZNITFSB-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-3-(4-methylsulfonylphenyl)cyclopent-2-en-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(F)C=C(F)C=2)C(=O)CC1 ULFYMTMZNITFSB-UHFFFAOYSA-N 0.000 claims description 5
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 claims description 5
- JICJBGPOMZQUBB-UHFFFAOYSA-N 7-[(3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid Chemical compound O=S1(=O)N(C)C2=CC=CC=C2C(NCCCCCCC(O)=O)C2=CC=C(Cl)C=C21 JICJBGPOMZQUBB-UHFFFAOYSA-N 0.000 claims description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 5
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 claims description 5
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 claims description 5
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 5
- ALFGKMXHOUSVAD-UHFFFAOYSA-N Ketobemidone Chemical compound C=1C=CC(O)=CC=1C1(C(=O)CC)CCN(C)CC1 ALFGKMXHOUSVAD-UHFFFAOYSA-N 0.000 claims description 5
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 claims description 5
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 5
- KTDZCOWXCWUPEO-UHFFFAOYSA-N NS-398 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCCC1 KTDZCOWXCWUPEO-UHFFFAOYSA-N 0.000 claims description 5
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 5
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 5
- 229960000836 amitriptyline Drugs 0.000 claims description 5
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical group C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 claims description 5
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 5
- 229960000590 celecoxib Drugs 0.000 claims description 5
- 229960001653 citalopram Drugs 0.000 claims description 5
- 229960004606 clomipramine Drugs 0.000 claims description 5
- WAZQAZKAZLXFMK-UHFFFAOYSA-N deracoxib Chemical compound C1=C(F)C(OC)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 WAZQAZKAZLXFMK-UHFFFAOYSA-N 0.000 claims description 5
- 229960003314 deracoxib Drugs 0.000 claims description 5
- 229960003914 desipramine Drugs 0.000 claims description 5
- 229960000616 diflunisal Drugs 0.000 claims description 5
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 claims description 5
- 229960005426 doxepin Drugs 0.000 claims description 5
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 claims description 5
- 230000009977 dual effect Effects 0.000 claims description 5
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 claims description 5
- 229960004945 etoricoxib Drugs 0.000 claims description 5
- 229960001419 fenoprofen Drugs 0.000 claims description 5
- 229960001680 ibuprofen Drugs 0.000 claims description 5
- 229960002844 iprindole Drugs 0.000 claims description 5
- PLIGPBGDXASWPX-UHFFFAOYSA-N iprindole Chemical compound C1CCCCCC2=C1N(CCCN(C)C)C1=CC=CC=C12 PLIGPBGDXASWPX-UHFFFAOYSA-N 0.000 claims description 5
- 229960003029 ketobemidone Drugs 0.000 claims description 5
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 5
- 229960000991 ketoprofen Drugs 0.000 claims description 5
- 229960002813 lofepramine Drugs 0.000 claims description 5
- SAPNXPWPAUFAJU-UHFFFAOYSA-N lofepramine Chemical compound C12=CC=CC=C2CCC2=CC=CC=C2N1CCCN(C)CC(=O)C1=CC=C(Cl)C=C1 SAPNXPWPAUFAJU-UHFFFAOYSA-N 0.000 claims description 5
- 229960004090 maprotiline Drugs 0.000 claims description 5
- QSLMDECMDJKHMQ-GSXCWMCISA-N maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 claims description 5
- 229960003464 mefenamic acid Drugs 0.000 claims description 5
- 229960001929 meloxicam Drugs 0.000 claims description 5
- YXVZOBVWVRFPTE-UHFFFAOYSA-N metapramine Chemical compound CNC1CC2=CC=CC=C2N(C)C2=CC=CC=C12 YXVZOBVWVRFPTE-UHFFFAOYSA-N 0.000 claims description 5
- 229950006180 metapramine Drugs 0.000 claims description 5
- 229960001785 mirtazapine Drugs 0.000 claims description 5
- 229960002009 naproxen Drugs 0.000 claims description 5
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 229960000482 pethidine Drugs 0.000 claims description 5
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- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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| PCT/IB2006/003873 WO2007063418A2 (en) | 2005-04-13 | 2006-04-13 | Substituted indole compounds having nos inhibitory activity |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8173813B2 (en) | 2007-03-23 | 2012-05-08 | Neuraxon, Inc. | Quinolone and tetrahydroquinolone and related compounds having NOS inhibitory activity |
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| GB0400895D0 (en) * | 2004-01-15 | 2004-02-18 | Smithkline Beecham Corp | Chemical compounds |
| TW200616967A (en) | 2004-06-24 | 2006-06-01 | Smithkline Beecham Corp | Novel indazole carboxamides and their use |
| BRPI0607517A2 (pt) * | 2005-04-13 | 2009-09-08 | Neuraxon Inc | compostos de indol substituìdo, composição farmacêutica compreendendo o mesmo, método para tratar e uso do mesmo |
| US8063071B2 (en) | 2007-10-31 | 2011-11-22 | GlaxoSmithKline, LLC | Chemical compounds |
| US7605122B2 (en) * | 2005-07-29 | 2009-10-20 | Millennium Medical Spa | Human chorionic gonadotropin (hCG) formulations for facilitating weight loss and body contouring |
| RU2008110908A (ru) * | 2005-08-25 | 2009-09-27 | Шеринг Корпорейшн (US) | Производные имидазола в качестве функционально селективных агонистов альфа2с адренорецепторов |
| MX2008009655A (es) * | 2006-02-07 | 2008-09-03 | Lundbeck & Co As H | Metodo para tratar o reducir los sintomas de la esquizofrenia. |
| US20080031822A1 (en) * | 2006-04-13 | 2008-02-07 | Frank Porreca | Methods of modeling migraine pain and identifying candidate compounds for the treatment of migraine |
| TW200808780A (en) * | 2006-04-13 | 2008-02-16 | Neuraxon Inc | 1,5 and 3,6- substituted indole compounds having NOS inhibitory activity |
| AR065804A1 (es) | 2007-03-23 | 2009-07-01 | Smithkline Beecham Corp | Compuesto de indol carboxamida, composicion farmaceutica que lo comprende y uso de dicho compuesto para preparar un medicamento |
| US20100166660A1 (en) * | 2007-03-23 | 2010-07-01 | Frank Porreca | Methods of modeling migraine pain and identifying candidate compounds for the treatment of migraine |
| EP2018854A1 (en) * | 2007-07-27 | 2009-01-28 | Merz Pharma GmbH & Co. KGaA | Novel combinations of neramexane for the treatment of neurodegenerative disorders |
| WO2009062318A1 (en) * | 2007-11-16 | 2009-05-22 | Neuraxon, Inc. | 3,5-substituted indole compounds having nos and norepinephrine reuptake inhibitory activity |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8173813B2 (en) | 2007-03-23 | 2012-05-08 | Neuraxon, Inc. | Quinolone and tetrahydroquinolone and related compounds having NOS inhibitory activity |
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