DE69922997T2 - Verwendung von isatinderivaten als ionenkanalaktivierende mittel - Google Patents
Verwendung von isatinderivaten als ionenkanalaktivierende mittel Download PDFInfo
- Publication number
- DE69922997T2 DE69922997T2 DE69922997T DE69922997T DE69922997T2 DE 69922997 T2 DE69922997 T2 DE 69922997T2 DE 69922997 T DE69922997 T DE 69922997T DE 69922997 T DE69922997 T DE 69922997T DE 69922997 T2 DE69922997 T2 DE 69922997T2
- Authority
- DE
- Germany
- Prior art keywords
- oxime
- dichloroisatin
- disease
- channels
- methylisatin
- 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.)
- Expired - Lifetime
Links
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical class C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 title claims description 19
- 230000003213 activating effect Effects 0.000 title abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 6
- 201000003883 Cystic fibrosis Diseases 0.000 claims abstract description 6
- 208000036071 Rhinorrhea Diseases 0.000 claims abstract description 6
- 206010039101 Rhinorrhoea Diseases 0.000 claims abstract description 6
- 206010046543 Urinary incontinence Diseases 0.000 claims abstract description 6
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 206010048994 Bladder spasm Diseases 0.000 claims abstract description 5
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- OIKFZVUNSNWSAD-UHFFFAOYSA-N 3-(hydroxyamino)-6,7-dimethylindol-2-one Chemical compound CC1=C(C)C=CC2=C(NO)C(=O)N=C21 OIKFZVUNSNWSAD-UHFFFAOYSA-N 0.000 claims description 4
- CVOUSAVHMDXCKG-UHFFFAOYSA-N 6,7-dichloro-3-(hydroxyamino)indol-2-one Chemical compound C1=CC(Cl)=C(Cl)C2=NC(=O)C(NO)=C21 CVOUSAVHMDXCKG-UHFFFAOYSA-N 0.000 claims description 4
- IGTXKVJLOUTKNB-UHFFFAOYSA-N 6,7-dichloro-3-hydroxyimino-1-methylindol-2-one Chemical compound C1=C(Cl)C(Cl)=C2N(C)C(=O)C(=NO)C2=C1 IGTXKVJLOUTKNB-UHFFFAOYSA-N 0.000 claims description 4
- HJFLMFUUYLJUPD-UHFFFAOYSA-N 6,7-difluoro-3-(hydroxyamino)indol-2-one Chemical compound C1=CC(F)=C(F)C2=C1C(=NO)C(=O)N2 HJFLMFUUYLJUPD-UHFFFAOYSA-N 0.000 claims description 4
- PNSCLWDBNGJLCG-UHFFFAOYSA-N 6-chloro-3-(hydroxyamino)-7-methylindol-2-one Chemical compound CC1=C(Cl)C=CC2=C(NO)C(=O)N=C12 PNSCLWDBNGJLCG-UHFFFAOYSA-N 0.000 claims description 4
- SHFGGAMLXGAYLG-UHFFFAOYSA-N 6-fluoro-3-(hydroxyamino)-7-methylindol-2-one Chemical compound C1=C(F)C(C)=C2NC(=O)C(=NO)C2=C1 SHFGGAMLXGAYLG-UHFFFAOYSA-N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 abstract description 43
- 239000003795 chemical substances by application Substances 0.000 abstract description 16
- 201000010099 disease Diseases 0.000 abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 102000004310 Ion Channels Human genes 0.000 abstract description 6
- 206010010904 Convulsion Diseases 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000003274 myotonic effect Effects 0.000 abstract description 5
- 201000004384 Alopecia Diseases 0.000 abstract description 4
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 4
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 4
- 208000019901 Anxiety disease Diseases 0.000 abstract description 4
- 206010003225 Arteriospasm coronary Diseases 0.000 abstract description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 abstract description 4
- 208000003890 Coronary Vasospasm Diseases 0.000 abstract description 4
- 206010012289 Dementia Diseases 0.000 abstract description 4
- 206010012735 Diarrhoea Diseases 0.000 abstract description 4
- 206010013935 Dysmenorrhoea Diseases 0.000 abstract description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 abstract description 4
- 206010020772 Hypertension Diseases 0.000 abstract description 4
- 206010022562 Intermittent claudication Diseases 0.000 abstract description 4
- 208000019695 Migraine disease Diseases 0.000 abstract description 4
- 206010028980 Neoplasm Diseases 0.000 abstract description 4
- 208000006399 Premature Obstetric Labor Diseases 0.000 abstract description 4
- 208000028017 Psychotic disease Diseases 0.000 abstract description 4
- 208000030886 Traumatic Brain injury Diseases 0.000 abstract description 4
- 206010047163 Vasospasm Diseases 0.000 abstract description 4
- 230000036506 anxiety Effects 0.000 abstract description 4
- 206010003119 arrhythmia Diseases 0.000 abstract description 4
- 230000006793 arrhythmia Effects 0.000 abstract description 4
- 201000011510 cancer Diseases 0.000 abstract description 4
- 230000036461 convulsion Effects 0.000 abstract description 4
- 208000029078 coronary artery disease Diseases 0.000 abstract description 4
- 201000011634 coronary artery vasospasm Diseases 0.000 abstract description 4
- 230000006735 deficit Effects 0.000 abstract description 4
- 230000003676 hair loss Effects 0.000 abstract description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 abstract description 4
- 201000008980 hyperinsulinism Diseases 0.000 abstract description 4
- 208000021156 intermittent vascular claudication Diseases 0.000 abstract description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 abstract description 4
- 208000028867 ischemia Diseases 0.000 abstract description 4
- 208000017169 kidney disease Diseases 0.000 abstract description 4
- 206010027599 migraine Diseases 0.000 abstract description 4
- 210000003205 muscle Anatomy 0.000 abstract description 4
- 208000031225 myocardial ischemia Diseases 0.000 abstract description 4
- 201000003631 narcolepsy Diseases 0.000 abstract description 4
- 208000030761 polycystic kidney disease Diseases 0.000 abstract description 4
- 201000009881 secretory diarrhea Diseases 0.000 abstract description 4
- 208000011580 syndromic disease Diseases 0.000 abstract description 4
- 230000009529 traumatic brain injury Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 206010036600 Premature labour Diseases 0.000 abstract description 2
- 208000026440 premature labor Diseases 0.000 abstract description 2
- 208000005171 Dysmenorrhea Diseases 0.000 abstract 1
- 208000028311 absence seizure Diseases 0.000 abstract 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract 1
- 230000007160 gastrointestinal dysfunction Effects 0.000 abstract 1
- 230000008629 immune suppression Effects 0.000 abstract 1
- 108091006146 Channels Proteins 0.000 description 53
- 239000000203 mixture Substances 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 24
- 238000010992 reflux Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000000243 solution Substances 0.000 description 17
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000011575 calcium Substances 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 125000000217 alkyl group Chemical group 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 239000002552 dosage form Substances 0.000 description 9
- XTXIILHWOQZVAQ-UHFFFAOYSA-N 6,7-dichloro-1h-indole-2,3-dione Chemical compound ClC1=CC=C2C(=O)C(=O)NC2=C1Cl XTXIILHWOQZVAQ-UHFFFAOYSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- -1 carboxy, Acetyl Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- KIFKRDLEAQUAAW-UHFFFAOYSA-N 5,6-dichloro-1h-indole-2,3-dione Chemical compound C1=C(Cl)C(Cl)=CC2=C1C(=O)C(=O)N2 KIFKRDLEAQUAAW-UHFFFAOYSA-N 0.000 description 5
- 108090000862 Ion Channels Proteins 0.000 description 5
- 238000012402 patch clamp technique Methods 0.000 description 5
- BWEXUCVFOHBXSL-UHFFFAOYSA-N 4,5-dichloro-1-methylindole-2,3-dione Chemical compound C1=CC(Cl)=C(Cl)C2=C1N(C)C(=O)C2=O BWEXUCVFOHBXSL-UHFFFAOYSA-N 0.000 description 4
- WWSWHYAXEFLETD-UHFFFAOYSA-N 4,5-dichloro-1h-indole-2,3-dione Chemical compound ClC1=CC=C2NC(=O)C(=O)C2=C1Cl WWSWHYAXEFLETD-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000036982 action potential Effects 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000007937 lozenge Substances 0.000 description 4
- 201000006938 muscular dystrophy Diseases 0.000 description 4
- 210000002569 neuron Anatomy 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- IXMIEQPWCAPGKV-UHFFFAOYSA-N 2-aminooxyacetic acid;hydrochloride Chemical compound Cl.NOCC(O)=O IXMIEQPWCAPGKV-UHFFFAOYSA-N 0.000 description 3
- RVZFBDVLNFODOM-UHFFFAOYSA-N 3h-benzo[e]indole-1,2-dione Chemical compound C1=CC=CC2=C(C(C(=O)N3)=O)C3=CC=C21 RVZFBDVLNFODOM-UHFFFAOYSA-N 0.000 description 3
- SJQHMFFEBMDKME-UHFFFAOYSA-N 5,6-dichloro-1-methylindole-2,3-dione Chemical compound ClC1=C(Cl)C=C2N(C)C(=O)C(=O)C2=C1 SJQHMFFEBMDKME-UHFFFAOYSA-N 0.000 description 3
- MBVCESWADCIXJN-UHFFFAOYSA-N 5-Bromoisatin Chemical compound BrC1=CC=C2NC(=O)C(=O)C2=C1 MBVCESWADCIXJN-UHFFFAOYSA-N 0.000 description 3
- BGLRRLZQCSERCY-UHFFFAOYSA-N 6,7-dichloro-1-methylindole-2,3-dione Chemical compound C1=C(Cl)C(Cl)=C2N(C)C(=O)C(=O)C2=C1 BGLRRLZQCSERCY-UHFFFAOYSA-N 0.000 description 3
- FFHXSUOLKDGHLA-UHFFFAOYSA-N 6,7-difluoro-1h-indole-2,3-dione Chemical compound FC1=CC=C2C(=O)C(=O)NC2=C1F FFHXSUOLKDGHLA-UHFFFAOYSA-N 0.000 description 3
- GVRLEGBOODEAOX-UHFFFAOYSA-N 6,7-dimethyl-1h-indole-2,3-dione Chemical compound CC1=CC=C2C(=O)C(=O)NC2=C1C GVRLEGBOODEAOX-UHFFFAOYSA-N 0.000 description 3
- SFWRUGVSPIELCW-UHFFFAOYSA-N 6-chloro-7-methyl-1h-indole-2,3-dione Chemical compound C1=C(Cl)C(C)=C2NC(=O)C(=O)C2=C1 SFWRUGVSPIELCW-UHFFFAOYSA-N 0.000 description 3
- HTWMONMZWLQDRM-UHFFFAOYSA-N 6-fluoro-3-(hydroxyamino)-7-methoxyindol-2-one Chemical compound C1=C(F)C(OC)=C2NC(=O)C(=NO)C2=C1 HTWMONMZWLQDRM-UHFFFAOYSA-N 0.000 description 3
- SRWISUZBZWZTCI-UHFFFAOYSA-N 6-fluoro-7-methoxy-1h-indole-2,3-dione Chemical compound C1=C(F)C(OC)=C2NC(=O)C(=O)C2=C1 SRWISUZBZWZTCI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 201000006474 Brain Ischemia Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000005946 Xerostomia Diseases 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 208000010643 digestive system disease Diseases 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 206010013781 dry mouth Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000012894 fetal calf serum Substances 0.000 description 3
- 208000018685 gastrointestinal system disease Diseases 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 3
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 2
- 0 *C(C1C(*=C)C2=O)C(*)=C(*)C(*)=C1*2=* Chemical compound *C(C1C(*=C)C2=O)C(*)=C(*)C(*)=C1*2=* 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 2
- WNQDPXTUVQAGCB-UHFFFAOYSA-N 2-(6,7-dichloro-2,3-dioxoindol-1-yl)acetic acid Chemical compound C1=C(Cl)C(Cl)=C2N(CC(=O)O)C(=O)C(=O)C2=C1 WNQDPXTUVQAGCB-UHFFFAOYSA-N 0.000 description 2
- LNMAXZZQNSPQSR-UHFFFAOYSA-N 3-(hydroxyamino)indol-2-one Chemical compound C1=CC=CC2=NC(=O)C(NO)=C21 LNMAXZZQNSPQSR-UHFFFAOYSA-N 0.000 description 2
- ZUVPLKVDZNDZCM-UHFFFAOYSA-N 3-chloro-2-methylaniline Chemical compound CC1=C(N)C=CC=C1Cl ZUVPLKVDZNDZCM-UHFFFAOYSA-N 0.000 description 2
- QKNAAKOLGXLATL-UHFFFAOYSA-N 4,5-dichloro-3-(hydroxyamino)indol-2-one Chemical compound ClC1=C(Cl)C=CC2=NC(=O)C(NO)=C21 QKNAAKOLGXLATL-UHFFFAOYSA-N 0.000 description 2
- KCYTXGNXFVTCKD-UHFFFAOYSA-N 4,5-dichloro-3-hydroxyimino-1-methylindol-2-one Chemical compound C1=CC(Cl)=C(Cl)C2=C1N(C)C(=O)C2=NO KCYTXGNXFVTCKD-UHFFFAOYSA-N 0.000 description 2
- XFKKWKWZFPDVGL-UHFFFAOYSA-N 5,6-dichloro-3-(hydroxyamino)indol-2-one Chemical compound ClC1=C(Cl)C=C2C(=NO)C(=O)NC2=C1 XFKKWKWZFPDVGL-UHFFFAOYSA-N 0.000 description 2
- KWPWCJHCCGGHAR-UHFFFAOYSA-N 5,6-dichloro-3-hydroxyimino-1-methylindol-2-one Chemical compound ClC1=C(Cl)C=C2N(C)C(=O)C(=NO)C2=C1 KWPWCJHCCGGHAR-UHFFFAOYSA-N 0.000 description 2
- APYQTLASEQODSC-UHFFFAOYSA-N 5-bromo-3-(hydroxyamino)indol-2-one Chemical compound C1=C(Br)C=CC2=NC(=O)C(NO)=C21 APYQTLASEQODSC-UHFFFAOYSA-N 0.000 description 2
- SCTZCVLCXNUKGW-UHFFFAOYSA-N 6-fluoro-7-methyl-1h-indole-2,3-dione Chemical compound C1=C(F)C(C)=C2NC(=O)C(=O)C2=C1 SCTZCVLCXNUKGW-UHFFFAOYSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 206010071445 Bladder outlet obstruction Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101000665837 Homo sapiens Protein Red Proteins 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010092555 Large-Conductance Calcium-Activated Potassium Channels Proteins 0.000 description 2
- 102000016469 Large-Conductance Calcium-Activated Potassium Channels Human genes 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 208000003800 Urinary Bladder Neck Obstruction Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- 102000054563 human IK Human genes 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 238000001638 lipofection Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical compound O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 208000007056 sickle cell anemia Diseases 0.000 description 2
- 210000002027 skeletal muscle Anatomy 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 229940075554 sorbate Drugs 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- GTZCVFVGUGFEME-UHFFFAOYSA-N trans-aconitic acid Natural products OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 239000001124 (E)-prop-1-ene-1,2,3-tricarboxylic acid Substances 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- GOFIUEUUROFVMA-UHFFFAOYSA-N 1-(1h-indol-5-yl)ethanone Chemical compound CC(=O)C1=CC=C2NC=CC2=C1 GOFIUEUUROFVMA-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- BRPSAOUFIJSKOT-UHFFFAOYSA-N 2,3-dichloroaniline Chemical compound NC1=CC=CC(Cl)=C1Cl BRPSAOUFIJSKOT-UHFFFAOYSA-N 0.000 description 1
- YCCQGFYAVUTQFK-UHFFFAOYSA-N 2,3-difluoroaniline Chemical compound NC1=CC=CC(F)=C1F YCCQGFYAVUTQFK-UHFFFAOYSA-N 0.000 description 1
- VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical compound CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 description 1
- NGXLTYPELAIUHE-UHFFFAOYSA-N 2-(hydroxyamino)indol-3-one Chemical class C1=CC=C2C(=O)C(NO)=NC2=C1 NGXLTYPELAIUHE-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- PWFDDLWYWJGXGB-UHFFFAOYSA-N 2-aminooxy-1-(4-phenylpiperazin-1-yl)ethanone;hydrochloride Chemical compound Cl.C1CN(C(=O)CON)CCN1C1=CC=CC=C1 PWFDDLWYWJGXGB-UHFFFAOYSA-N 0.000 description 1
- JBIJLHTVPXGSAM-UHFFFAOYSA-N 2-naphthylamine Chemical compound C1=CC=CC2=CC(N)=CC=C21 JBIJLHTVPXGSAM-UHFFFAOYSA-N 0.000 description 1
- SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 1
- RCYMPYMITUEHOJ-UHFFFAOYSA-N 3-fluoro-2-methoxyaniline Chemical compound COC1=C(N)C=CC=C1F RCYMPYMITUEHOJ-UHFFFAOYSA-N 0.000 description 1
- SLDLVGFPFFLYBM-UHFFFAOYSA-N 3-fluoro-2-methyl-aniline Chemical compound CC1=C(N)C=CC=C1F SLDLVGFPFFLYBM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 101710126338 Apamin Proteins 0.000 description 1
- YXSLJKQTIDHPOT-UHFFFAOYSA-N Atracurium Dibesylate Chemical compound C1=C(OC)C(OC)=CC=C1CC1[N+](CCC(=O)OCCCCCOC(=O)CC[N+]2(C)C(C3=CC(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=CC=2)(C)CCC2=CC(OC)=C(OC)C=C21 YXSLJKQTIDHPOT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- RBIHPAASYUYQNM-UHFFFAOYSA-N OCl(=O)(=O)=O.OCl(=O)(=O)=O Chemical compound OCl(=O)(=O)=O.OCl(=O)(=O)=O RBIHPAASYUYQNM-UHFFFAOYSA-N 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108010084455 Zeocin Proteins 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229940091179 aconitate Drugs 0.000 description 1
- 229940091181 aconitic acid Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960001862 atracurium Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- KYKAJFCTULSVSH-UHFFFAOYSA-N chloro(fluoro)methane Chemical compound F[C]Cl KYKAJFCTULSVSH-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- GTZCVFVGUGFEME-IWQZZHSRSA-N cis-aconitic acid Chemical compound OC(=O)C\C(C(O)=O)=C\C(O)=O GTZCVFVGUGFEME-IWQZZHSRSA-N 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- DBKKFIIYQGGHJO-UHFFFAOYSA-N diethyl 2-oxopropanedioate Chemical compound CCOC(=O)C(=O)C(=O)OCC DBKKFIIYQGGHJO-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000002397 epileptogenic effect Effects 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 210000000609 ganglia Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- ZYCMDWDFIQDPLP-UHFFFAOYSA-N hbr bromine Chemical compound Br.Br ZYCMDWDFIQDPLP-UHFFFAOYSA-N 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 1
- 229960001848 lamotrigine Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- YVIIHEKJCKCXOB-STYWVVQQSA-N molport-023-276-178 Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H]2C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(N[C@@H](CSSC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1)=O)CC(C)C)[C@@H](C)O)C(N)=O)C1=CNC=N1 YVIIHEKJCKCXOB-STYWVVQQSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- ZFUNXNSIQZVWSC-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=C(C=CC2=CC=CC=C12)S(=O)(=O)O.C1=C(C=CC2=CC=CC=C12)S(=O)(=O)O ZFUNXNSIQZVWSC-UHFFFAOYSA-N 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- HMROUTPTSBUCNC-UHFFFAOYSA-N o-[[(4-chlorophenyl)methylamino]methyl]hydroxylamine Chemical compound NOCNCC1=CC=C(Cl)C=C1 HMROUTPTSBUCNC-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229960005457 pancuronium Drugs 0.000 description 1
- GVEAYVLWDAFXET-XGHATYIMSA-N pancuronium Chemical compound C[N+]1([C@@H]2[C@@H](OC(C)=O)C[C@@H]3CC[C@H]4[C@@H]5C[C@@H]([C@@H]([C@]5(CC[C@@H]4[C@@]3(C)C2)C)OC(=O)C)[N+]2(C)CCCCC2)CCCCC1 GVEAYVLWDAFXET-XGHATYIMSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 1
- JTEVUCQIVRGWHT-UHFFFAOYSA-N phosphoric acid;phthalic acid Chemical compound OP(O)(O)=O.OC(=O)C1=CC=CC=C1C(O)=O JTEVUCQIVRGWHT-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 230000012481 regulation of membrane potential Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000002020 sage Nutrition 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 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
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- JFJZZMVDLULRGK-URLMMPGGSA-O tubocurarine Chemical compound C([C@H]1[N+](C)(C)CCC=2C=C(C(=C(OC3=CC=C(C=C3)C[C@H]3C=4C=C(C(=CC=4CCN3C)OC)O3)C=21)O)OC)C1=CC=C(O)C3=C1 JFJZZMVDLULRGK-URLMMPGGSA-O 0.000 description 1
- 229960001844 tubocurarine Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA199801608 | 1998-12-04 | ||
| DK160898 | 1998-12-04 | ||
| PCT/DK1999/000679 WO2000033834A1 (en) | 1998-12-04 | 1999-12-03 | Use of isatin derivatives as ion channel activating agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69922997D1 DE69922997D1 (de) | 2005-02-03 |
| DE69922997T2 true DE69922997T2 (de) | 2005-12-15 |
Family
ID=8106503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69922997T Expired - Lifetime DE69922997T2 (de) | 1998-12-04 | 1999-12-03 | Verwendung von isatinderivaten als ionenkanalaktivierende mittel |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US20020016354A1 (https=) |
| EP (1) | EP1135123B1 (https=) |
| JP (1) | JP2002531498A (https=) |
| AT (1) | ATE285769T1 (https=) |
| AU (1) | AU1648600A (https=) |
| DE (1) | DE69922997T2 (https=) |
| WO (1) | WO2000033834A1 (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1736468A3 (en) * | 2000-01-24 | 2007-01-03 | NeuroSearch A/S | Isatin derivatives with neurotrophic activity useful in the treatment of diseases mediated by the nerve growth factor (NGF) activation |
| WO2002000223A1 (en) * | 2000-06-26 | 2002-01-03 | Novo Nordisk A/S | Use of potassium channel agonists for reducing fat food comsumption |
| CA2433041A1 (en) * | 2000-12-28 | 2002-07-11 | Switch Biotech Aktiengesellschaft | Use of intermediate-conductance potassium channels and modulators for diagnosing and treating diseases involving disturbed keratinocyte activiyty |
| EP1361874A1 (en) * | 2001-02-15 | 2003-11-19 | Neurosearch A/S | Treatment of diseases characterized by excessive or insufficient cell death |
| AR033095A1 (es) | 2001-04-04 | 2003-12-03 | Wyeth Corp | Metodos para el tratamiento de motilidad gastrica hiperactiva |
| US7148007B2 (en) * | 2001-07-24 | 2006-12-12 | Kabushiki Kaisha Toshiba | Method for evaluating immunotoxicity of test substance |
| DE10250870A1 (de) * | 2002-10-31 | 2004-05-13 | Switch Biotech Ag | Zusammensetzung enthaltend Aktivatoren von IK-Kaliumkanälen und Calcineurin-Antagonisten und deren Verwendung |
| EP1587486A2 (en) | 2003-01-15 | 2005-10-26 | L'oreal | Care or make-up composition comprising a 2-alkylideneaminooxyacetamide, its use for stimulating the growth of the hair or eyelashes and/or slowing down their loss |
| FR2849773B1 (fr) * | 2003-01-15 | 2006-07-14 | Oreal | Composition capillaire contenant un 2-alkylidene aminooxy-acetamide, son utilisation pour stimuler la pousse des cheveux et/ou freiner leur chute |
| JP4641942B2 (ja) | 2003-10-03 | 2011-03-02 | フェーイレン・ナムローゼ・フェンノートシャップ | ヒトおよび動物におけるｉｇｆ−１血清レベルの低下と関連した種々の疾患状態の治療用の治療用組成物の製造のための血清中ｉｇｆ−１レベルを増加できる化合物の使用 |
| CA2541126A1 (en) | 2003-10-03 | 2005-04-21 | Veijlen N.V. | Animal feed composition |
| WO2008034011A2 (en) | 2006-09-13 | 2008-03-20 | Mcw Research Foundation, Inc. | Methods of modulating cell proliferation and cyst formation in polycystic kidney and liver diseases |
| US8232310B2 (en) * | 2006-12-29 | 2012-07-31 | Georgetown University | Targeting of EWS-FLI1 as anti-tumor therapy |
| JP5305704B2 (ja) * | 2008-03-24 | 2013-10-02 | 富士フイルム株式会社 | 新規化合物、光重合性組成物、カラーフィルタ用光重合性組成物、カラーフィルタ、及びその製造方法、固体撮像素子、並びに、平版印刷版原版 |
| US20120190723A1 (en) * | 2010-12-14 | 2012-07-26 | Fatah Kashanchi | Viral modulators and processes thereof |
| CA2821480A1 (en) | 2010-12-20 | 2012-06-28 | Astrazeneca Ab | 2-carboxamide-4-piperazinyl-benzofuran derivative |
| CN107011242B (zh) | 2012-04-12 | 2020-08-07 | 乔治城大学 | 用于治疗尤文肉瘤家族肿瘤的方法和组合物 |
| AU2014340398A1 (en) * | 2013-10-24 | 2016-06-09 | Georgetown University | Methods and compositions for treating cancer |
| US20170042834A1 (en) * | 2014-04-14 | 2017-02-16 | Flex Pharma, Inc. | Ion channel activators and methods of use |
| WO2015160842A1 (en) * | 2014-04-14 | 2015-10-22 | Flex Pharma, Inc. | Methods and formulatiions of capsaicinoids and capsinoids |
| CN104130175A (zh) * | 2014-06-13 | 2014-11-05 | 天津科技大学 | 不同位置取代吲哚酮类衍生物及其应用 |
| CN107108580B (zh) | 2014-10-09 | 2020-06-30 | 英克特诺治疗公司 | 吲哚酮化合物及其用途 |
| EP3795563B1 (en) | 2016-03-31 | 2024-07-17 | Oncternal Therapeutics, Inc. | Indoline analogs and uses thereof |
| CA3029851A1 (en) | 2016-07-29 | 2018-02-01 | Oncternal Therapeutics, Inc. | Uses of indoline compounds such as tk216 for the treatment of cancer |
| CA3049165A1 (en) | 2017-01-06 | 2018-07-12 | Iovance Biotherapeutics, Inc. | Expansion of tumor infiltrating lymphocytes with potassium channel agonists and therapeutic uses thereof |
| WO2018136943A1 (en) | 2017-01-23 | 2018-07-26 | Flex Pharma, Inc. | Compositions and methods affecting exercise performance |
| CN108017570A (zh) * | 2017-12-21 | 2018-05-11 | 常州大学 | 一种靛红的生产方法 |
| CN108721297A (zh) * | 2018-05-15 | 2018-11-02 | 泰山医学院 | 一种减轻免疫抑制的抗肿瘤药物及其应用 |
| CN108403690A (zh) * | 2018-05-15 | 2018-08-17 | 泰山医学院 | 一种抑制黑色素瘤细胞增殖的药物及其应用 |
| CN113564623A (zh) * | 2021-06-17 | 2021-10-29 | 福建师范大学 | 电化学氧化n-取代吲哚衍生物制备靛红化合物的方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GR65270B (en) * | 1978-10-10 | 1980-07-31 | Fujisawa Pharmaceutical Co | Isatin derivatives and processes for the preparation thereof |
| US4322533A (en) * | 1980-03-17 | 1982-03-30 | Lesher George Y | 1H-Indole-2,3-dione derivatives |
| US4780477A (en) * | 1985-06-08 | 1988-10-25 | Kissei Pharmaceutical Co., Ltd. | Isatin compositions having anti-ulcer activities |
| GB8816944D0 (en) * | 1988-07-15 | 1988-08-17 | Sobio Lab | Compounds |
| IE69677B1 (en) * | 1989-12-11 | 1996-10-02 | Neurosearch As | Isatine derivatives their preparation and use |
| US5192792A (en) * | 1990-12-07 | 1993-03-09 | Warner-Lambert Company | Isatine derivatives, and their method of use |
| US5312928A (en) * | 1991-02-11 | 1994-05-17 | Cambridge Neuroscience | Calcium channel antagonists and methodology for their identification |
| US5514690A (en) * | 1992-11-17 | 1996-05-07 | E. R. Squibb & Sons, Inc. | Aminocarbonyl (thiocarbonyl) and cyanoguanidine derivatives of quinoline and indoline |
| MY128102A (en) * | 1993-02-17 | 2007-01-31 | Chugai Pharmaceutical Co Ltd | Indolin-2-one-derivatives |
| US5565483A (en) * | 1995-06-07 | 1996-10-15 | Bristol-Myers Squibb Company | 3-substituted oxindole derivatives as potassium channel modulators |
| EP1002535A1 (en) * | 1998-10-28 | 2000-05-24 | Hrissanthi Ikonomidou | New use of glutamate antagonists for the treatment of cancer |
-
1999
- 1999-12-03 EP EP99959238A patent/EP1135123B1/en not_active Expired - Lifetime
- 1999-12-03 AT AT99959238T patent/ATE285769T1/de not_active IP Right Cessation
- 1999-12-03 AU AU16486/00A patent/AU1648600A/en not_active Abandoned
- 1999-12-03 DE DE69922997T patent/DE69922997T2/de not_active Expired - Lifetime
- 1999-12-03 WO PCT/DK1999/000679 patent/WO2000033834A1/en not_active Ceased
- 1999-12-03 JP JP2000586327A patent/JP2002531498A/ja active Pending
-
2001
- 2001-05-15 US US09/854,355 patent/US20020016354A1/en not_active Abandoned
-
2002
- 2002-10-16 US US10/270,536 patent/US6969729B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002531498A (ja) | 2002-09-24 |
| US6969729B2 (en) | 2005-11-29 |
| DE69922997D1 (de) | 2005-02-03 |
| EP1135123B1 (en) | 2004-12-29 |
| WO2000033834A1 (en) | 2000-06-15 |
| AU1648600A (en) | 2000-06-26 |
| US20030114513A1 (en) | 2003-06-19 |
| ATE285769T1 (de) | 2005-01-15 |
| EP1135123A1 (en) | 2001-09-26 |
| US20020016354A1 (en) | 2002-02-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69922997T2 (de) | Verwendung von isatinderivaten als ionenkanalaktivierende mittel | |
| DE69924493T2 (de) | Kaliumkanal-blockierende mittel | |
| DE69300532T2 (de) | Naphtylalkylamine, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen. | |
| DE69804273T2 (de) | 5h-Thiazolo[3,2-a]pyrimidinderivate | |
| DE60317348T2 (de) | Pyrimidinderivate und deren verwendung als cb2-modulatoren | |
| EP0242518B1 (de) | Cycloalkano[1,2-b]indol-sulfonamide | |
| DE69332559T2 (de) | 2,3,4,5-tetrahydro-1h-3-benzazepinen mit anti-psychotisch wirkung, und synthese von alfa-substituierten-arylacetamiden | |
| DE69906940T2 (de) | Bizyclische pyrrolverbindungen, deren pharmazeutische zusammensetzungen und ihre verwendung als entzündungshemmende und immunmodulierende mittel | |
| DE602004006891T2 (de) | Derivate von n-äphenyl(pyrrolidin-2-yl)methylübenzamid und n-ä(azepan-2-yl)phenylmethylübenzamid, verfahren zu deren herstellung und deren anwendung in therapeutika | |
| DE10359528A1 (de) | (S)-2-N-Propylamino-5-hydroxytetralin als D3-agonistisches Therapeutikum | |
| DE69914935T2 (de) | 8-azabicyclo[3.2.1]okt-2-en- und -oktanderivate | |
| DE60003911T2 (de) | Heteroaryl-diazacycloalkane, ihre herstellung und verwendung | |
| DE60308699T2 (de) | 2-phenylamino-4-trifluoromethyl-5-(benzyl- oder pyridin-4-ylmethyl)carbamoylpyrimidin-derivate als selektive cb2 cannabinoid-rezeptor modulatoren | |
| DE69920259T2 (de) | Ionenkanal modulatoren | |
| DE2363052A1 (de) | 3-phenyl-3-aminoalkyl-2,6-dioxo-tetraund -hexahydropyridine, verfahren zu ihrer herstellung und ihre verwendung in pharmazeutischen zubereitungen | |
| DE3855520T2 (de) | Methode zur Verbesserung des Schlafes | |
| DE4430091A1 (de) | Verwendung von N-substituierten Phenothiazinen | |
| EP0425906A2 (de) | Substituierte Cycloalkano[b]dihydroindol- und -indolsulfonamide | |
| EP0161599A2 (de) | Neue Benzazepinderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
| DE69922936T2 (de) | Verwendung von indol-2,3-dione-3-oximderivate als ampa-antagonisten | |
| DE60005517T2 (de) | Kaliumkanal-blockierende mittel | |
| DE69514533T2 (de) | Kondensierte indole und chinoxalinderivate, ihre herstellung und verwendung als glutamatantagonisten | |
| DE60020556T2 (de) | Ionenkanal modulierende mittel | |
| DE69030665T2 (de) | (1,2n) und (3,2n)-karbozyklische-2-amino-tetralinderivate | |
| AT396362B (de) | 5,5-dimethyl-3-phenylvinyl-1-aminoalkoxy-iminocyclohex-2-enderivate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |