MX2007013595A - Compuestos heterociclicos fusionados y composiciones y usos de estos. - Google Patents
Compuestos heterociclicos fusionados y composiciones y usos de estos.Info
- Publication number
- MX2007013595A MX2007013595A MX2007013595A MX2007013595A MX2007013595A MX 2007013595 A MX2007013595 A MX 2007013595A MX 2007013595 A MX2007013595 A MX 2007013595A MX 2007013595 A MX2007013595 A MX 2007013595A MX 2007013595 A MX2007013595 A MX 2007013595A
- Authority
- MX
- Mexico
- Prior art keywords
- substituted
- unsubstituted
- pyrimidin
- tetrahydro
- amine
- Prior art date
Links
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 20
- 239000000203 mixture Substances 0.000 title description 115
- 150000001875 compounds Chemical class 0.000 claims abstract description 235
- 208000002193 Pain Diseases 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 47
- 230000036407 pain Effects 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 241000124008 Mammalia Species 0.000 claims abstract description 20
- 230000002265 prevention Effects 0.000 claims abstract description 17
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 10
- 230000036506 anxiety Effects 0.000 claims abstract description 10
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 10
- 206010061218 Inflammation Diseases 0.000 claims abstract description 9
- 230000004054 inflammatory process Effects 0.000 claims abstract description 9
- 230000000670 limiting effect Effects 0.000 claims abstract description 8
- -1 sulfuric acid ester Chemical class 0.000 claims description 166
- 125000003118 aryl group Chemical group 0.000 claims description 91
- 238000000034 method Methods 0.000 claims description 83
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 58
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 201000010099 disease Diseases 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 33
- 125000002947 alkylene group Chemical group 0.000 claims description 30
- 125000002252 acyl group Chemical group 0.000 claims description 29
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims description 25
- 125000004442 acylamino group Chemical group 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 208000004296 neuralgia Diseases 0.000 claims description 20
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 19
- 229910052760 oxygen Inorganic materials 0.000 claims description 19
- 239000000651 prodrug Substances 0.000 claims description 18
- 229940002612 prodrug Drugs 0.000 claims description 18
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 18
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 125000002837 carbocyclic group Chemical group 0.000 claims description 17
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 229910052717 sulfur Inorganic materials 0.000 claims description 17
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 16
- 230000001404 mediated effect Effects 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 15
- 208000037765 diseases and disorders Diseases 0.000 claims description 15
- 230000000155 isotopic effect Effects 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 150000003462 sulfoxides Chemical class 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 208000021722 neuropathic pain Diseases 0.000 claims description 12
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 208000023275 Autoimmune disease Diseases 0.000 claims description 11
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 11
- 208000003251 Pruritus Diseases 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 206010015037 epilepsy Diseases 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 11
- 208000024891 symptom Diseases 0.000 claims description 11
- 208000011580 syndromic disease Diseases 0.000 claims description 11
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- 206010065390 Inflammatory pain Diseases 0.000 claims description 10
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 claims description 10
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims description 10
- 208000006673 asthma Diseases 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 230000002757 inflammatory effect Effects 0.000 claims description 9
- 208000010125 myocardial infarction Diseases 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
- 206010003246 arthritis Diseases 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 8
- 201000008482 osteoarthritis Diseases 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 206010019233 Headaches Diseases 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 208000008589 Obesity Diseases 0.000 claims description 7
- 206010043269 Tension headache Diseases 0.000 claims description 7
- 208000008548 Tension-Type Headache Diseases 0.000 claims description 7
- 206010046543 Urinary incontinence Diseases 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 208000018912 cluster headache syndrome Diseases 0.000 claims description 7
- 231100000869 headache Toxicity 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
- 201000001119 neuropathy Diseases 0.000 claims description 7
- 235000020824 obesity Nutrition 0.000 claims description 7
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 7
- 125000001174 sulfone group Chemical group 0.000 claims description 7
- 208000006561 Cluster Headache Diseases 0.000 claims description 6
- 208000030814 Eating disease Diseases 0.000 claims description 6
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
- 208000019695 Migraine disease Diseases 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 235000014632 disordered eating Nutrition 0.000 claims description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 6
- 208000017169 kidney disease Diseases 0.000 claims description 6
- 201000006370 kidney failure Diseases 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000019116 sleep disease Diseases 0.000 claims description 6
- 150000003457 sulfones Chemical class 0.000 claims description 6
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 5
- 208000034347 Faecal incontinence Diseases 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 5
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 5
- 206010046542 Urinary hesitation Diseases 0.000 claims description 5
- 208000026935 allergic disease Diseases 0.000 claims description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 5
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 5
- 206010014599 encephalitis Diseases 0.000 claims description 5
- 125000001475 halogen functional group Chemical group 0.000 claims description 5
- 230000009610 hypersensitivity Effects 0.000 claims description 5
- 230000007803 itching Effects 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 230000003959 neuroinflammation Effects 0.000 claims description 5
- 230000000926 neurological effect Effects 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 230000000241 respiratory effect Effects 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 201000009961 allergic asthma Diseases 0.000 claims description 4
- 201000010105 allergic rhinitis Diseases 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 4
- 230000000626 neurodegenerative effect Effects 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 4
- 206010069632 Bladder dysfunction Diseases 0.000 claims description 3
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 claims description 3
- 208000001640 Fibromyalgia Diseases 0.000 claims description 3
- 208000014540 Functional gastrointestinal disease Diseases 0.000 claims description 3
- 208000004983 Phantom Limb Diseases 0.000 claims description 3
- 206010056238 Phantom pain Diseases 0.000 claims description 3
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 3
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 claims description 3
- 201000007637 bowel dysfunction Diseases 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 3
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- ZZRLTCJZOJCIHC-UHFFFAOYSA-N 7-cyclohexyl-1-(cyclohexylamino)-3-morpholin-4-yl-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical compound N1=C(N2CCOCC2)C(C#N)=C2CCN(C3CCCCC3)CC2=C1NC1CCCCC1 ZZRLTCJZOJCIHC-UHFFFAOYSA-N 0.000 claims description 2
- MBPDMPQGMKKBDF-UHFFFAOYSA-N 7-cyclohexyl-1-(cyclohexylamino)-3-piperidin-1-yl-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical compound N1=C(N2CCCCC2)C(C#N)=C2CCN(C3CCCCC3)CC2=C1NC1CCCCC1 MBPDMPQGMKKBDF-UHFFFAOYSA-N 0.000 claims description 2
- 208000001387 Causalgia Diseases 0.000 claims description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000006217 methyl sulfide group Chemical group [H]C([H])([H])S* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 206010029240 Neuritis Diseases 0.000 claims 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 230000007794 irritation Effects 0.000 claims 4
- 208000023504 respiratory system disease Diseases 0.000 claims 4
- 208000036273 reactive airway disease Diseases 0.000 claims 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 2
- RLLPVAHGXHCWKJ-IEBWSBKVSA-N (3-phenoxyphenyl)methyl (1s,3s)-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate Chemical compound CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-IEBWSBKVSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- CJSLXKZWAVSNSS-UHFFFAOYSA-N 3-chloro-7-cyclohexyl-1-(cyclohexylamino)-6,8-dihydro-5h-2,7-naphthyridine-4-carbonitrile Chemical compound C=12CN(C3CCCCC3)CCC2=C(C#N)C(Cl)=NC=1NC1CCCCC1 CJSLXKZWAVSNSS-UHFFFAOYSA-N 0.000 claims 1
- CEKMYRMUKLEDAM-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-(2-phenylethyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C=CC=CC=3)N=CN=C2CC1 CEKMYRMUKLEDAM-UHFFFAOYSA-N 0.000 claims 1
- MCKATWNAHWWXNX-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[2-[3-(trifluoromethyl)phenyl]ethyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C=C(C=CC=3)C(F)(F)F)N=CN=C2CC1 MCKATWNAHWWXNX-UHFFFAOYSA-N 0.000 claims 1
- QCPWBRUFKOYOBO-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[[2-(trifluoromethoxy)phenyl]methyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)OC(F)(F)F)N=CN=C2CC1 QCPWBRUFKOYOBO-UHFFFAOYSA-N 0.000 claims 1
- FMCWYPCITGBOLX-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-n-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=CC(=CC=3)C(F)(F)F)N=CN=C2CC1 FMCWYPCITGBOLX-UHFFFAOYSA-N 0.000 claims 1
- 206010003399 Arthropod bite Diseases 0.000 claims 1
- 201000006390 Brachial Plexus Neuritis Diseases 0.000 claims 1
- 206010006482 Bronchospasm Diseases 0.000 claims 1
- 208000031229 Cardiomyopathies Diseases 0.000 claims 1
- 208000021965 Glossopharyngeal Nerve disease Diseases 0.000 claims 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims 1
- 206010063491 Herpes zoster oticus Diseases 0.000 claims 1
- 241000238631 Hexapoda Species 0.000 claims 1
- 206010049949 Intercostal neuralgia Diseases 0.000 claims 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims 1
- 208000002472 Morton Neuroma Diseases 0.000 claims 1
- 208000020059 Morton neuralgia Diseases 0.000 claims 1
- 206010068106 Occipital neuralgia Diseases 0.000 claims 1
- 206010036105 Polyneuropathy Diseases 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 206010054874 Sphenopalatine neuralgia Diseases 0.000 claims 1
- 208000003589 Spider Bites Diseases 0.000 claims 1
- 241000271897 Viperidae Species 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 230000002146 bilateral effect Effects 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 230000007885 bronchoconstriction Effects 0.000 claims 1
- 229960002504 capsaicin Drugs 0.000 claims 1
- 235000017663 capsaicin Nutrition 0.000 claims 1
- 208000012790 cranial neuralgia Diseases 0.000 claims 1
- 208000004967 femoral neuropathy Diseases 0.000 claims 1
- 239000007789 gas Substances 0.000 claims 1
- 201000011349 geniculate herpes zoster Diseases 0.000 claims 1
- 201000005442 glossopharyngeal neuralgia Diseases 0.000 claims 1
- 230000000968 intestinal effect Effects 0.000 claims 1
- 208000037805 labour Diseases 0.000 claims 1
- 230000005906 menstruation Effects 0.000 claims 1
- 208000032184 meralgia paresthetica Diseases 0.000 claims 1
- DXGORADRDISYAD-UHFFFAOYSA-N n-(cyclohexylmethyl)-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC3CCCCC3)N=CN=C2CC1 DXGORADRDISYAD-UHFFFAOYSA-N 0.000 claims 1
- VOICQPYJFZIJSN-UHFFFAOYSA-N n-[(2,3-difluorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=C(F)C=CC=3)F)N=CN=C2CC1 VOICQPYJFZIJSN-UHFFFAOYSA-N 0.000 claims 1
- WFTRPAANKZLHNU-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)Cl)N=CN=C2CC1 WFTRPAANKZLHNU-UHFFFAOYSA-N 0.000 claims 1
- FIXOWTFOEIUTMF-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 FIXOWTFOEIUTMF-UHFFFAOYSA-N 0.000 claims 1
- NPSGDTBYKGZOCT-UHFFFAOYSA-N n-[(2-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)C)N=CN=C2CC1 NPSGDTBYKGZOCT-UHFFFAOYSA-N 0.000 claims 1
- AGALZLPLRSSCSZ-UHFFFAOYSA-N n-[(3,4-difluorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(F)C(F)=CC=3)N=CN=C2CC1 AGALZLPLRSSCSZ-UHFFFAOYSA-N 0.000 claims 1
- ZFFRYTRFMCOESZ-UHFFFAOYSA-N n-[(3-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(Cl)C=CC=3)N=CN=C2CC1 ZFFRYTRFMCOESZ-UHFFFAOYSA-N 0.000 claims 1
- JOFHBLXBUDVYEL-UHFFFAOYSA-N n-[(3-fluorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(F)C=CC=3)N=CN=C2CC1 JOFHBLXBUDVYEL-UHFFFAOYSA-N 0.000 claims 1
- VRHHZTYCWGFIIU-UHFFFAOYSA-N n-[(3-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound COC1=CC=CC(CNC=2C=3CN(CCC=3N=CN=2)C=2N=CC(C)=CC=2)=C1 VRHHZTYCWGFIIU-UHFFFAOYSA-N 0.000 claims 1
- DLHPMQWXJJUYJE-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=CC(Cl)=CC=3)N=CN=C2CC1 DLHPMQWXJJUYJE-UHFFFAOYSA-N 0.000 claims 1
- NALREZXCDIQRQU-UHFFFAOYSA-N n-[(4-fluoro-3-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C=C(C)C(F)=CC=3)N=CN=C2CC1 NALREZXCDIQRQU-UHFFFAOYSA-N 0.000 claims 1
- CGMKVHOIAYZASS-UHFFFAOYSA-N n-[(4-methoxyphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 CGMKVHOIAYZASS-UHFFFAOYSA-N 0.000 claims 1
- SSYSQHUWGQTOJV-UHFFFAOYSA-N n-[(4-methylphenyl)methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1CNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 SSYSQHUWGQTOJV-UHFFFAOYSA-N 0.000 claims 1
- DUPYPBQTFOKCSC-UHFFFAOYSA-N n-[1-(4-fluorophenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C=1C=C(F)C=CC=1C(C)NC(C=1C2)=NC=NC=1CCN2C1=CC=C(C)C=N1 DUPYPBQTFOKCSC-UHFFFAOYSA-N 0.000 claims 1
- ORRVRGHOSLMGBL-UHFFFAOYSA-N n-[2-(2-chlorophenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCCC=3C(=CC=CC=3)Cl)N=CN=C2CC1 ORRVRGHOSLMGBL-UHFFFAOYSA-N 0.000 claims 1
- GBANCUMWMKNVHG-UHFFFAOYSA-N n-[2-(4-methoxyphenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CCNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 GBANCUMWMKNVHG-UHFFFAOYSA-N 0.000 claims 1
- SVERNLBOIJHNMU-UHFFFAOYSA-N n-[2-(4-methylphenyl)ethyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1CCNC1=NC=NC2=C1CN(C=1N=CC(C)=CC=1)CC2 SVERNLBOIJHNMU-UHFFFAOYSA-N 0.000 claims 1
- QGRXNGVPOGCLCO-UHFFFAOYSA-N n-[[2-(difluoromethoxy)phenyl]methyl]-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N1=CC(C)=CC=C1N1CC2=C(NCC=3C(=CC=CC=3)OC(F)F)N=CN=C2CC1 QGRXNGVPOGCLCO-UHFFFAOYSA-N 0.000 claims 1
- 201000009985 neuronitis Diseases 0.000 claims 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 208000019629 polyneuritis Diseases 0.000 claims 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
- 208000007771 sciatic neuropathy Diseases 0.000 claims 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
- 239000003491 tear gas Substances 0.000 claims 1
- 208000004371 toothache Diseases 0.000 claims 1
- 230000008733 trauma Effects 0.000 claims 1
- 231100000611 venom Toxicity 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- 238000012360 testing method Methods 0.000 description 54
- 125000001424 substituent group Chemical group 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 210000004027 cell Anatomy 0.000 description 39
- 239000000243 solution Substances 0.000 description 36
- 208000004454 Hyperalgesia Diseases 0.000 description 35
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
- 230000004044 response Effects 0.000 description 31
- 150000003254 radicals Chemical class 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 27
- 102000005962 receptors Human genes 0.000 description 27
- 108020003175 receptors Proteins 0.000 description 27
- 239000007787 solid Substances 0.000 description 27
- 125000005309 thioalkoxy group Chemical group 0.000 description 27
- 241001465754 Metazoa Species 0.000 description 26
- 102100040479 P2X purinoceptor 2 Human genes 0.000 description 26
- 101710189968 P2X purinoceptor 2 Proteins 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
- 125000004432 carbon atom Chemical group C* 0.000 description 25
- 150000002431 hydrogen Chemical group 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000000556 agonist Substances 0.000 description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 22
- 238000003786 synthesis reaction Methods 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 125000005843 halogen group Chemical group 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 18
- 210000000287 oocyte Anatomy 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 102100040460 P2X purinoceptor 3 Human genes 0.000 description 17
- 101710189970 P2X purinoceptor 3 Proteins 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 230000002829 reductive effect Effects 0.000 description 16
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 210000003932 urinary bladder Anatomy 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000012267 brine Substances 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 210000002683 foot Anatomy 0.000 description 14
- 229910052736 halogen Inorganic materials 0.000 description 14
- 150000002367 halogens Chemical class 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 13
- 125000005296 thioaryloxy group Chemical group 0.000 description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 125000004423 acyloxy group Chemical group 0.000 description 12
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 229930194542 Keto Natural products 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 238000003556 assay Methods 0.000 description 11
- 125000004429 atom Chemical group 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 11
- 125000005842 heteroatom Chemical group 0.000 description 11
- 125000001183 hydrocarbyl group Chemical group 0.000 description 11
- 125000000468 ketone group Chemical group 0.000 description 11
- 210000005036 nerve Anatomy 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 125000001931 aliphatic group Chemical group 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- 239000000835 fiber Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 210000001032 spinal nerve Anatomy 0.000 description 10
- 125000005415 substituted alkoxy group Chemical group 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 210000000548 hind-foot Anatomy 0.000 description 9
- GTLNHEXHXYAMKA-UHFFFAOYSA-N pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC=C2C(N)=NC=NC2=C1 GTLNHEXHXYAMKA-UHFFFAOYSA-N 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 206010002091 Anaesthesia Diseases 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 230000037005 anaesthesia Effects 0.000 description 8
- 230000008602 contraction Effects 0.000 description 8
- MAKFMOSBBNKPMS-UHFFFAOYSA-N 2,3-dichloropyridine Chemical compound ClC1=CC=CN=C1Cl MAKFMOSBBNKPMS-UHFFFAOYSA-N 0.000 description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
- 108091006146 Channels Proteins 0.000 description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 206010053552 allodynia Diseases 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 229910052791 calcium Inorganic materials 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 6
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 238000009739 binding Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 229910001629 magnesium chloride Inorganic materials 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000007823 neuropathy Effects 0.000 description 6
- 239000002287 radioligand Substances 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 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 5
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 5
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 229910052796 boron Inorganic materials 0.000 description 5
- 239000001110 calcium chloride Substances 0.000 description 5
- 235000011148 calcium chloride Nutrition 0.000 description 5
- 229910001628 calcium chloride Inorganic materials 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 239000010949 copper Substances 0.000 description 5
- 238000006073 displacement reaction Methods 0.000 description 5
- 229960002994 dofetilide Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 229960002725 isoflurane Drugs 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 210000003205 muscle Anatomy 0.000 description 5
- 230000002981 neuropathic effect Effects 0.000 description 5
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000001953 sensory effect Effects 0.000 description 5
- 238000007920 subcutaneous administration Methods 0.000 description 5
- 125000000547 substituted alkyl group Chemical group 0.000 description 5
- 208000009935 visceral pain Diseases 0.000 description 5
- 229910052727 yttrium Inorganic materials 0.000 description 5
- QHKOHEITJANTNS-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-(4-fluorophenyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(F)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 QHKOHEITJANTNS-UHFFFAOYSA-N 0.000 description 4
- UNLAFUDHXQWSDE-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-[4-(trifluoromethylsulfonyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 UNLAFUDHXQWSDE-UHFFFAOYSA-N 0.000 description 4
- 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 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 239000007832 Na2SO4 Substances 0.000 description 4
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001409 amidines Chemical class 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000003447 ipsilateral effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- ISXFZEHIOSXDDM-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-6-yl)-6-(3-methylphenyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(N2CC3=C(NC=4C=C5OCCOC5=CC=4)N=CN=C3CC2)=C1 ISXFZEHIOSXDDM-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- YOTUXZSSJFEIHR-UHFFFAOYSA-N 3,4-dihydro-2h-pyrido[4,3-d]pyrimidin-1-amine Chemical class N1=CC=C2N(N)CNCC2=C1 YOTUXZSSJFEIHR-UHFFFAOYSA-N 0.000 description 3
- LRJANZYRGCLJOT-UHFFFAOYSA-N 4-chloro-6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical compound N1=CC(C)=CC=C1N1CC2=C(Cl)N=CN=C2CC1 LRJANZYRGCLJOT-UHFFFAOYSA-N 0.000 description 3
- XYYZKOFIMYHHAG-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1h-pyrido[4,3-d]pyrimidin-4-one Chemical compound C1CNCC2=C1NC=NC2=O XYYZKOFIMYHHAG-UHFFFAOYSA-N 0.000 description 3
- JVGPRASOJVWZHF-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine Chemical class C1CNCC2=C1N=CN=C2N JVGPRASOJVWZHF-UHFFFAOYSA-N 0.000 description 3
- QIOYDLYXMYJVSO-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-[6-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 QIOYDLYXMYJVSO-UHFFFAOYSA-N 0.000 description 3
- HVOYQKPPHHPFGH-UHFFFAOYSA-N 6-(3-methylphenyl)-n-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC(N2CC3=C(NC=4C=CC(=CC=4)C(F)(F)F)N=CN=C3CC2)=C1 HVOYQKPPHHPFGH-UHFFFAOYSA-N 0.000 description 3
- RPJAAZOTUXKSEV-UHFFFAOYSA-N 6-benzyl-4-chloro-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical compound C1C=2C(Cl)=NC=NC=2CCN1CC1=CC=CC=C1 RPJAAZOTUXKSEV-UHFFFAOYSA-N 0.000 description 3
- UZYHRCWCDFRMDL-UHFFFAOYSA-N 6-phenyl-n-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1CN(C=1C=CC=CC=1)CC2 UZYHRCWCDFRMDL-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 230000003187 abdominal effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 125000001769 aryl amino group Chemical group 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000009460 calcium influx Effects 0.000 description 3
- 235000010418 carrageenan Nutrition 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229920001525 carrageenan Polymers 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 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
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000003372 electrophysiological method Methods 0.000 description 3
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthene Chemical compound C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 3
- 239000011737 fluorine Substances 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
- 239000011521 glass Substances 0.000 description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000004941 influx Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- 230000027939 micturition Effects 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 230000001473 noxious effect Effects 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000005017 substituted alkenyl group Chemical group 0.000 description 3
- 125000004426 substituted alkynyl group Chemical group 0.000 description 3
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical class NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- OSNSWKAZFASRNG-WNFIKIDCSA-N (2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol;hydrate Chemical compound O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O OSNSWKAZFASRNG-WNFIKIDCSA-N 0.000 description 2
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 2
- WFZCJZLWNBAQDW-UHFFFAOYSA-N 1-(3,3-dimethyl-6-nitro-2h-indol-1-yl)ethanone Chemical compound C1=C([N+]([O-])=O)C=C2N(C(=O)C)CC(C)(C)C2=C1 WFZCJZLWNBAQDW-UHFFFAOYSA-N 0.000 description 2
- FDFKETITWKJRNI-UHFFFAOYSA-N 1-(6-amino-3,3-dimethyl-2h-indol-1-yl)ethanone Chemical compound C1=C(N)C=C2N(C(=O)C)CC(C)(C)C2=C1 FDFKETITWKJRNI-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- RADMRAMXLLLVGG-UHFFFAOYSA-N 1h-pyrido[4,3-d]pyrimidin-4-one Chemical group C1=NC=C2C(=O)N=CNC2=C1 RADMRAMXLLLVGG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- UDAIGHZFMLGNDQ-UHFFFAOYSA-N 2-nitroquinoline Chemical class C1=CC=CC2=NC([N+](=O)[O-])=CC=C21 UDAIGHZFMLGNDQ-UHFFFAOYSA-N 0.000 description 2
- JTVMMOAEEVKAGQ-UHFFFAOYSA-N 3,3-dimethyl-6-nitro-1h-indol-2-one Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)C(=O)NC2=C1 JTVMMOAEEVKAGQ-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- TWNMVIMCVYVNFZ-UHFFFAOYSA-N 4-chloro-6-(3-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical compound ClC1=CC=CN=C1N1CC2=C(Cl)N=CN=C2CC1 TWNMVIMCVYVNFZ-UHFFFAOYSA-N 0.000 description 2
- JQURSFJIPOFHBG-UHFFFAOYSA-N 4-chloro-6-pyridin-2-yl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical compound C1C=2C(Cl)=NC=NC=2CCN1C1=CC=CC=N1 JQURSFJIPOFHBG-UHFFFAOYSA-N 0.000 description 2
- FQNBVRGUPKWTOC-UHFFFAOYSA-N 6-(2-methylphenyl)-n-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound CC1=CC=CC=C1N1CC2=C(NC=3C=CC(=CC=3)C(F)(F)F)N=CN=C2CC1 FQNBVRGUPKWTOC-UHFFFAOYSA-N 0.000 description 2
- PEEDOSPNTYUTEZ-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-[4-(difluoromethoxy)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(OC(F)F)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 PEEDOSPNTYUTEZ-UHFFFAOYSA-N 0.000 description 2
- SAFQILJTHSUDDZ-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-phenyl-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound ClC1=CC=CN=C1N1CC2=C(NC=3C=CC=CC=3)N=CN=C2CC1 SAFQILJTHSUDDZ-UHFFFAOYSA-N 0.000 description 2
- KLPXJGNAMPBURC-UHFFFAOYSA-N 6-(3-methylsulfonylpyridin-2-yl)-n-[4-(trifluoromethylsulfonyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound CS(=O)(=O)C1=CC=CN=C1N1CC2=C(NC=3C=CC(=CC=3)S(=O)(=O)C(F)(F)F)N=CN=C2CC1 KLPXJGNAMPBURC-UHFFFAOYSA-N 0.000 description 2
- HFMUODIQKDAGJB-UHFFFAOYSA-N 6-(3-methylsulfonylpyridin-2-yl)-n-[6-(trifluoromethyl)pyridin-3-yl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound CS(=O)(=O)C1=CC=CN=C1N1CC2=C(NC=3C=NC(=CC=3)C(F)(F)F)N=CN=C2CC1 HFMUODIQKDAGJB-UHFFFAOYSA-N 0.000 description 2
- VWSPMHNPEFIUMD-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound N1=CC(C)=CC=C1N1CC(C(=O)NC=N2)=C2CC1 VWSPMHNPEFIUMD-UHFFFAOYSA-N 0.000 description 2
- HGBBNVXZDJSBKS-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidine Chemical class N1=CC(C)=CC=C1N1CC2=CN=CN=C2CC1 HGBBNVXZDJSBKS-UHFFFAOYSA-N 0.000 description 2
- NBTGVWLZXXCVIL-UHFFFAOYSA-N 6-[[6-(3-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-yl]amino]-3,3-dimethyl-1h-indol-2-one Chemical compound C=1C=C2C(C)(C)C(=O)NC2=CC=1NC(C=1C2)=NC=NC=1CCN2C1=NC=CC=C1Cl NBTGVWLZXXCVIL-UHFFFAOYSA-N 0.000 description 2
- IWARVYFPBLDOAK-UHFFFAOYSA-N 6-amino-3,3-dimethyl-1h-indol-2-one Chemical compound NC1=CC=C2C(C)(C)C(=O)NC2=C1 IWARVYFPBLDOAK-UHFFFAOYSA-N 0.000 description 2
- DMRBGCRLTUSKNZ-UHFFFAOYSA-N 6-pyridin-2-yl-4a,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound C1C2C(=O)N=CN=C2CCN1C1=CC=CC=N1 DMRBGCRLTUSKNZ-UHFFFAOYSA-N 0.000 description 2
- HFOCNFPYKJJZPB-UHFFFAOYSA-N 6-pyridin-2-yl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-4-amine Chemical class N1=C(C=CC=C1)N1CC2=C(N=CN=C2N)CC1 HFOCNFPYKJJZPB-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 206010033645 Pancreatitis Diseases 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004697 Polyetherimide Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000002294 Purinergic P2X Receptors Human genes 0.000 description 2
- 108010000836 Purinergic P2X Receptors Proteins 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 230000003185 calcium uptake Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- WDECIBYCCFPHNR-UHFFFAOYSA-N chrysene Chemical compound C1=CC=CC2=CC=C3C4=CC=CC=C4C=CC3=C21 WDECIBYCCFPHNR-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000007850 fluorescent dye Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 229960001031 glucose Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 230000003370 grooming effect Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000000642 iatrogenic effect Effects 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000012423 maintenance Methods 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
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- TXXHDPDFNKHHGW-UHFFFAOYSA-N muconic acid Chemical compound OC(=O)C=CC=CC(O)=O TXXHDPDFNKHHGW-UHFFFAOYSA-N 0.000 description 2
- PGUJIWNAAFTVQV-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-6-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine Chemical compound O1CCOC2=CC(NC=3N=CN=C4CCNCC4=3)=CC=C21 PGUJIWNAAFTVQV-UHFFFAOYSA-N 0.000 description 2
- DESCUSBFAOIJNP-UHFFFAOYSA-N n-(4-tert-butylphenyl)-6-(3-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 DESCUSBFAOIJNP-UHFFFAOYSA-N 0.000 description 2
- UQEHNIONZWRCCR-UHFFFAOYSA-N n-[4-(trifluoromethyl)phenyl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1CNCC2 UQEHNIONZWRCCR-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 230000003040 nociceptive effect Effects 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229920001601 polyetherimide Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000002821 scintillation proximity assay Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000005864 sulfonamidyl group Chemical group 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 2
- 125000005323 thioketone group Chemical group 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 208000014001 urinary system disease Diseases 0.000 description 2
- 238000007879 vasectomy Methods 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
- 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
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- AESJTDNODAZMEA-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrido[4,3-d]pyrimidine Chemical class N1=CC=C2NCNCC2=C1 AESJTDNODAZMEA-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ARBFKKLBTARDKA-UHFFFAOYSA-N 1,4-dioxin-2-amine Chemical compound NC1=COC=CO1 ARBFKKLBTARDKA-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- BJIGPOHHQXLJJG-UHFFFAOYSA-N 1-(3-fluorophenyl)-n-isoquinolin-5-yl-5-methylpyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C3=CC=NC=C3C=CC=2)=NN1C1=CC=CC(F)=C1 BJIGPOHHQXLJJG-UHFFFAOYSA-N 0.000 description 1
- GJKCYSMZYSMYRW-UHFFFAOYSA-N 1-(4-methoxyphenyl)-3-(1-phenylpyrrolidin-3-yl)urea Chemical compound C1=CC(OC)=CC=C1NC(=O)NC1CN(C=2C=CC=CC=2)CC1 GJKCYSMZYSMYRW-UHFFFAOYSA-N 0.000 description 1
- MLZLVMCHKUSCQC-UHFFFAOYSA-N 1-(aminomethyl)-3,3-dimethylcyclohexan-1-ol Chemical compound CC1(C)CCCC(O)(CN)C1 MLZLVMCHKUSCQC-UHFFFAOYSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- DWYHJOLGUSRZSO-UHFFFAOYSA-N 1-phenyl-3-(1-phenylpyrrolidin-3-yl)urea Chemical compound C=1C=CC=CC=1NC(=O)NC(C1)CCN1C1=CC=CC=C1 DWYHJOLGUSRZSO-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- MFJCPDOGFAYSTF-UHFFFAOYSA-N 1H-isochromene Chemical compound C1=CC=C2COC=CC2=C1 MFJCPDOGFAYSTF-UHFFFAOYSA-N 0.000 description 1
- AAQTWLBJPNLKHT-UHFFFAOYSA-N 1H-perimidine Chemical compound N1C=NC2=CC=CC3=CC=CC1=C32 AAQTWLBJPNLKHT-UHFFFAOYSA-N 0.000 description 1
- ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical compound C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- KRIGAYSDVBBXLW-UHFFFAOYSA-N 2-chloro-3-ethylsulfonylpyridine Chemical compound CCS(=O)(=O)C1=CC=CN=C1Cl KRIGAYSDVBBXLW-UHFFFAOYSA-N 0.000 description 1
- KRGYYSGWNZRJPY-UHFFFAOYSA-N 2-chloro-3-methylsulfonylpyridine Chemical compound CS(=O)(=O)C1=CC=CN=C1Cl KRGYYSGWNZRJPY-UHFFFAOYSA-N 0.000 description 1
- VXLYOURCUVQYLN-UHFFFAOYSA-N 2-chloro-5-methylpyridine Chemical compound CC1=CC=C(Cl)N=C1 VXLYOURCUVQYLN-UHFFFAOYSA-N 0.000 description 1
- GUPOZVHRTJYZCX-UHFFFAOYSA-N 2-chloroethanimidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])CCl GUPOZVHRTJYZCX-UHFFFAOYSA-N 0.000 description 1
- 150000005749 2-halopyridines Chemical class 0.000 description 1
- UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- OBRVKOVWGSBITQ-UHFFFAOYSA-N 3,3-dimethyl-6-nitro-1,2-dihydroindole Chemical compound [O-][N+](=O)C1=CC=C2C(C)(C)CNC2=C1 OBRVKOVWGSBITQ-UHFFFAOYSA-N 0.000 description 1
- MLMQPDHYNJCQAO-UHFFFAOYSA-N 3,3-dimethylbutyric acid Chemical compound CC(C)(C)CC(O)=O MLMQPDHYNJCQAO-UHFFFAOYSA-N 0.000 description 1
- XLZYKTYMLBOINK-UHFFFAOYSA-N 3-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C(=O)C=2C=CC(O)=CC=2)=C1 XLZYKTYMLBOINK-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 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
- NDEZTSHWEPQVBX-UHFFFAOYSA-N 4-(difluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)F)C=C1 NDEZTSHWEPQVBX-UHFFFAOYSA-N 0.000 description 1
- GNVFCXUZQGCXPB-UHFFFAOYSA-N 4-(trifluoromethylsulfonyl)aniline Chemical compound NC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 GNVFCXUZQGCXPB-UHFFFAOYSA-N 0.000 description 1
- RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical class C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 1
- GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
- DZXOOWSJLLMRJJ-UHFFFAOYSA-N 5-amino-n-isoquinolin-5-yl-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound NC1=CC(C(=O)NC=2C3=CC=NC=C3C=CC=2)=NN1C1=CC=CC(C(F)(F)F)=C1 DZXOOWSJLLMRJJ-UHFFFAOYSA-N 0.000 description 1
- DEMKNLXJQNYAFY-UHFFFAOYSA-N 5-chloro-2-methylpyridine Chemical compound CC1=CC=C(Cl)C=N1 DEMKNLXJQNYAFY-UHFFFAOYSA-N 0.000 description 1
- WPGKHCFLRHQQBR-UHFFFAOYSA-N 5-methyl-n-(1,2,3,4-tetrahydroisoquinolin-5-yl)-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C=3CCNCC=3C=CC=2)=NN1C1=CC=CC(C(F)(F)F)=C1 WPGKHCFLRHQQBR-UHFFFAOYSA-N 0.000 description 1
- FRCOEAAEFSEYPE-UHFFFAOYSA-N 5-methyl-n-quinolin-3-yl-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C=C3C=CC=CC3=NC=2)=NN1C1=CC=CC(C(F)(F)F)=C1 FRCOEAAEFSEYPE-UHFFFAOYSA-N 0.000 description 1
- QKBBWAFNMUOVAZ-UHFFFAOYSA-N 5-methyl-n-quinolin-5-yl-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C3=CC=CN=C3C=CC=2)=NN1C1=CC=CC(C(F)(F)F)=C1 QKBBWAFNMUOVAZ-UHFFFAOYSA-N 0.000 description 1
- WCUXNKOOMQWXAI-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-(1,3,3-trimethyl-2h-indol-6-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=C2N(C)CC(C)(C)C2=CC=C1NC(C=1C2)=NC=NC=1CCN2C1=NC=CC=C1Cl WCUXNKOOMQWXAI-UHFFFAOYSA-N 0.000 description 1
- FAHCLKAGOJKRSC-UHFFFAOYSA-N 6-(3-chloropyridin-2-yl)-n-(3,3-dimethyl-1,2-dihydroindol-6-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(C=1C2)=NC=NC=1CCN2C1=NC=CC=C1Cl FAHCLKAGOJKRSC-UHFFFAOYSA-N 0.000 description 1
- SXBLISVPZXNYOY-UHFFFAOYSA-N 6-(4-methylphenyl)-n-[4-(trifluoromethyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C)=CC=C1N1CC2=C(NC=3C=CC(=CC=3)C(F)(F)F)N=CN=C2CC1 SXBLISVPZXNYOY-UHFFFAOYSA-N 0.000 description 1
- VERHYUQNBSHEOB-UHFFFAOYSA-N 6-(5-methylpyridin-2-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-2-amine Chemical class N1=CC(C)=CC=C1N1CC2=CN=C(N)N=C2CC1 VERHYUQNBSHEOB-UHFFFAOYSA-N 0.000 description 1
- PVNGDFHKRAIVTC-UHFFFAOYSA-N 6-benzyl-1,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound C1C=2C(=O)N=CNC=2CCN1CC1=CC=CC=C1 PVNGDFHKRAIVTC-UHFFFAOYSA-N 0.000 description 1
- UUBYONJHDUREIJ-UHFFFAOYSA-N 6-benzyl-4a,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one Chemical compound C1C2C(=O)N=CN=C2CCN1CC1=CC=CC=C1 UUBYONJHDUREIJ-UHFFFAOYSA-N 0.000 description 1
- RFHKMMAGPZCRGV-UHFFFAOYSA-N 6-benzyl-n-(2,3-dihydro-1,4-benzodioxin-6-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1CC2=NC=NC(NC=3C=C4OCCOC4=CC=3)=C2CN1CC1=CC=CC=C1 RFHKMMAGPZCRGV-UHFFFAOYSA-N 0.000 description 1
- XWTPEMZDDIDBHV-UHFFFAOYSA-N 6-benzyl-n-(6-tert-butylpyridin-3-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(C)(C)C)=CC=C1NC1=NC=NC2=C1CN(CC=1C=CC=CC=1)CC2 XWTPEMZDDIDBHV-UHFFFAOYSA-N 0.000 description 1
- BJBWBAQOMDBCHF-UHFFFAOYSA-N 6-benzyl-n-[4-(trifluoromethylsulfonyl)phenyl]-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(S(=O)(=O)C(F)(F)F)=CC=C1NC1=NC=NC2=C1CN(CC=1C=CC=CC=1)CC2 BJBWBAQOMDBCHF-UHFFFAOYSA-N 0.000 description 1
- WVIXMWFCKMCQLI-UHFFFAOYSA-N 6-tert-butylpyridin-3-amine Chemical compound CC(C)(C)C1=CC=C(N)C=N1 WVIXMWFCKMCQLI-UHFFFAOYSA-N 0.000 description 1
- 150000005017 7-aminoquinolines Chemical class 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- QGZKDVFQNNGYKY-OUBTZVSYSA-N Ammonia-15N Chemical compound [15NH3] QGZKDVFQNNGYKY-OUBTZVSYSA-N 0.000 description 1
- 102000007347 Apyrase Human genes 0.000 description 1
- 108010007730 Apyrase Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 101150047265 COR2 gene Proteins 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 108091005462 Cation channels Proteins 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
- 108091026890 Coding region Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 238000005361 D2 NMR spectroscopy Methods 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 1
- 206010057671 Female sexual dysfunction Diseases 0.000 description 1
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 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
- 238000012893 Hill function Methods 0.000 description 1
- 101000614332 Homo sapiens P2X purinoceptor 3 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 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 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- TXXHDPDFNKHHGW-CCAGOZQPSA-N Muconic acid Natural products OC(=O)\C=C/C=C\C(O)=O TXXHDPDFNKHHGW-CCAGOZQPSA-N 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 101710189973 P2X purinoceptor 1 Proteins 0.000 description 1
- 102100040444 P2X purinoceptor 1 Human genes 0.000 description 1
- 102100037601 P2X purinoceptor 4 Human genes 0.000 description 1
- 101710189967 P2X purinoceptor 4 Proteins 0.000 description 1
- 102100037603 P2X purinoceptor 5 Human genes 0.000 description 1
- 101710189969 P2X purinoceptor 5 Proteins 0.000 description 1
- 102100037606 P2X purinoceptor 6 Human genes 0.000 description 1
- 101710190089 P2X purinoceptor 6 Proteins 0.000 description 1
- 101710189965 P2X purinoceptor 7 Proteins 0.000 description 1
- 102100037602 P2X purinoceptor 7 Human genes 0.000 description 1
- 229940123304 Phosphodiesterase 7 inhibitor Drugs 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 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
- 101000614338 Rattus norvegicus P2X purinoceptor 3 Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- SLGBZMMZGDRARJ-UHFFFAOYSA-N Triphenylene Natural products C1=CC=C2C3=CC=CC=C3C3=CC=CC=C3C2=C1 SLGBZMMZGDRARJ-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- QVXFGVVYTKZLJN-KHPPLWFESA-N [(z)-hexadec-7-enyl] acetate Chemical compound CCCCCCCC\C=C/CCCCCCOC(C)=O QVXFGVVYTKZLJN-KHPPLWFESA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- JDPAVWAQGBGGHD-UHFFFAOYSA-N aceanthrylene Chemical group C1=CC=C2C(C=CC3=CC=C4)=C3C4=CC2=C1 JDPAVWAQGBGGHD-UHFFFAOYSA-N 0.000 description 1
- 125000004054 acenaphthylenyl group Chemical group C1(=CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- SQFPKRNUGBRTAR-UHFFFAOYSA-N acephenanthrylene Chemical group C1=CC(C=C2)=C3C2=CC2=CC=CC=C2C3=C1 SQFPKRNUGBRTAR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HXGDTGSAIMULJN-UHFFFAOYSA-N acetnaphthylene Natural products C1=CC(C=C2)=C3C2=CC=CC3=C1 HXGDTGSAIMULJN-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 125000000033 alkoxyamino group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 1
- 150000005010 aminoquinolines Chemical class 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- BVUSIQTYUVWOSX-UHFFFAOYSA-N arsindole Chemical compound C1=CC=C2[As]C=CC2=C1 BVUSIQTYUVWOSX-UHFFFAOYSA-N 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- KNNXFYIMEYKHBZ-UHFFFAOYSA-N as-indacene Chemical compound C1=CC2=CC=CC2=C2C=CC=C21 KNNXFYIMEYKHBZ-UHFFFAOYSA-N 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- 239000012148 binding buffer Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000006177 biological buffer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000003461 brachial plexus Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 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
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical group [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 108700010039 chimeric receptor Proteins 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 150000001804 chlorine Chemical class 0.000 description 1
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 230000002060 circadian Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000004186 co-expression Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125890 compound Ia Drugs 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BALGDZWGNCXXES-UHFFFAOYSA-N cyclopentane;propanoic acid Chemical compound CCC(O)=O.C1CCCC1 BALGDZWGNCXXES-UHFFFAOYSA-N 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 231100000223 dermal penetration Toxicity 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- VMMLSJNPNVTYMN-UHFFFAOYSA-N dinitromethylbenzene Chemical group [O-][N+](=O)C([N+]([O-])=O)C1=CC=CC=C1 VMMLSJNPNVTYMN-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000011152 fibreglass Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- HLXVERDKKMHKLD-UHFFFAOYSA-N formylazanium;acetate Chemical compound NC=O.CC(O)=O HLXVERDKKMHKLD-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 238000011990 functional testing Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- VPUGDVKSAQVFFS-UHFFFAOYSA-N hexabenzobenzene Natural products C1=C(C2=C34)C=CC3=CC=C(C=C3)C4=C4C3=CC=C(C=C3)C4=C2C3=C1 VPUGDVKSAQVFFS-UHFFFAOYSA-N 0.000 description 1
- QSQIGGCOCHABAP-UHFFFAOYSA-N hexacene Chemical compound C1=CC=CC2=CC3=CC4=CC5=CC6=CC=CC=C6C=C5C=C4C=C3C=C21 QSQIGGCOCHABAP-UHFFFAOYSA-N 0.000 description 1
- ACGUYXCXAPNIKK-UHFFFAOYSA-N hexachlorophene Chemical compound OC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(O)C(Cl)=CC(Cl)=C1Cl ACGUYXCXAPNIKK-UHFFFAOYSA-N 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000008309 hydrophilic cream Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- AKQZEFRALAUBFS-UHFFFAOYSA-N ilamine Natural products COC(C)C(O)(C(=O)OCC1=CCN2CCCC12)C(C)(C)O AKQZEFRALAUBFS-UHFFFAOYSA-N 0.000 description 1
- 208000008384 ileus Diseases 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229940044173 iodine-125 Drugs 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
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000009200 mechanosensation Effects 0.000 description 1
- 230000007074 memory dysfunction Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 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
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- ZQOJSXUESMTISO-UHFFFAOYSA-N n-(4-tert-butylphenyl)-6-(3-chloropyridin-2-yl)-2-(morpholin-4-ylmethyl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=CC(C(C)(C)C)=CC=C1NC1=NC(CN2CCOCC2)=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 ZQOJSXUESMTISO-UHFFFAOYSA-N 0.000 description 1
- DBSLDADUTINWBP-UHFFFAOYSA-N n-(4-tert-butylphenyl)-6-(3-chloropyridin-2-yl)-2-methoxy-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound N=1C(OC)=NC=2CCN(C=3C(=CC=CN=3)Cl)CC=2C=1NC1=CC=C(C(C)(C)C)C=C1 DBSLDADUTINWBP-UHFFFAOYSA-N 0.000 description 1
- DQBDHDTZQWVDIZ-UHFFFAOYSA-N n-(6-tert-butylpyridin-3-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(C)(C)C)=CC=C1NC1=NC=NC2=C1CNCC2 DQBDHDTZQWVDIZ-UHFFFAOYSA-N 0.000 description 1
- AOPJSINVNQQLBA-UHFFFAOYSA-N n-(6-tert-butylpyridin-3-yl)-6-(3-chloropyridin-2-yl)-7,8-dihydro-5h-pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(C)(C)C)=CC=C1NC1=NC=NC2=C1CN(C=1C(=CC=CN=1)Cl)CC2 AOPJSINVNQQLBA-UHFFFAOYSA-N 0.000 description 1
- SJDMUMDEWSBHIX-UHFFFAOYSA-N n-[3-[2-(diethylamino)ethyl]-4-methyl-2-oxo-1h-quinolin-7-yl]-4-phenylpiperazine-1-carboxamide Chemical compound C1=C2NC(=O)C(CCN(CC)CC)=C(C)C2=CC=C1NC(=O)N(CC1)CCN1C1=CC=CC=C1 SJDMUMDEWSBHIX-UHFFFAOYSA-N 0.000 description 1
- SYTVLMKNHBJTQT-UHFFFAOYSA-N n-[6-(trifluoromethyl)pyridin-3-yl]-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine Chemical compound C1=NC(C(F)(F)F)=CC=C1NC1=NC=NC2=C1CNCC2 SYTVLMKNHBJTQT-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- ULGJQTZESNGVFR-UHFFFAOYSA-N n-isoquinolin-5-yl-1-(3-methoxyphenyl)-5-methylpyrazole-3-carboxamide Chemical compound COC1=CC=CC(N2C(=CC(=N2)C(=O)NC=2C3=CC=NC=C3C=CC=2)C)=C1 ULGJQTZESNGVFR-UHFFFAOYSA-N 0.000 description 1
- CPNKPIYIMJJWTI-UHFFFAOYSA-N n-isoquinolin-5-yl-5-methyl-1-[3-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound CC1=CC(C(=O)NC=2C3=CC=NC=C3C=CC=2)=NN1C1=CC=CC(C(F)(F)F)=C1 CPNKPIYIMJJWTI-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000007971 neurological deficit Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-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
- OVPVGJFDFSJUIG-UHFFFAOYSA-N octalene Chemical compound C1=CC=CC=C2C=CC=CC=CC2=C1 OVPVGJFDFSJUIG-UHFFFAOYSA-N 0.000 description 1
- WTFQBTLMPISHTA-UHFFFAOYSA-N octaphene Chemical compound C1=CC=C2C=C(C=C3C4=CC5=CC6=CC7=CC=CC=C7C=C6C=C5C=C4C=CC3=C3)C3=CC2=C1 WTFQBTLMPISHTA-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- LSQODMMMSXHVCN-UHFFFAOYSA-N ovalene Chemical compound C1=C(C2=C34)C=CC3=CC=C(C=C3C5=C6C(C=C3)=CC=C3C6=C6C(C=C3)=C3)C4=C5C6=C2C3=C1 LSQODMMMSXHVCN-UHFFFAOYSA-N 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 208000005877 painful neuropathy Diseases 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
- PMJHHCWVYXUKFD-UHFFFAOYSA-N penta-1,3-diene Chemical compound CC=CC=C PMJHHCWVYXUKFD-UHFFFAOYSA-N 0.000 description 1
- SLIUAWYAILUBJU-UHFFFAOYSA-N pentacene Chemical compound C1=CC=CC2=CC3=CC4=CC5=CC=CC=C5C=C4C=C3C=C21 SLIUAWYAILUBJU-UHFFFAOYSA-N 0.000 description 1
- GUVXZFRDPCKWEM-UHFFFAOYSA-N pentalene Chemical compound C1=CC2=CC=CC2=C1 GUVXZFRDPCKWEM-UHFFFAOYSA-N 0.000 description 1
- JQQSUOJIMKJQHS-UHFFFAOYSA-N pentaphene Chemical compound C1=CC=C2C=C3C4=CC5=CC=CC=C5C=C4C=CC3=CC2=C1 JQQSUOJIMKJQHS-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- CSHWQDPOILHKBI-UHFFFAOYSA-N peryrene Natural products C1=CC(C2=CC=CC=3C2=C2C=CC=3)=C3C2=CC=CC3=C1 CSHWQDPOILHKBI-UHFFFAOYSA-N 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NQFOGDIWKQWFMN-UHFFFAOYSA-N phenalene Chemical compound C1=CC([CH]C=C2)=C3C2=CC=CC3=C1 NQFOGDIWKQWFMN-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002606 phosphodiesterase VII inhibitor Substances 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- DIJNSQQKNIVDPV-UHFFFAOYSA-N pleiadene Chemical compound C1=C2[CH]C=CC=C2C=C2C=CC=C3[C]2C1=CC=C3 DIJNSQQKNIVDPV-UHFFFAOYSA-N 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- XGBULVIMVCHZSV-UHFFFAOYSA-N pyrrolidin-3-ylurea Chemical class NC(=O)NC1CCNC1 XGBULVIMVCHZSV-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- WEMQMWWWCBYPOV-UHFFFAOYSA-N s-indacene Chemical compound C=1C2=CC=CC2=CC2=CC=CC2=1 WEMQMWWWCBYPOV-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 230000001235 sensitizing effect Effects 0.000 description 1
- 210000000413 sensory ganglia Anatomy 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000003153 stable transfection Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 210000000331 sympathetic ganglia Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 239000003826 tablet Substances 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
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 125000005580 triphenylene group Chemical group 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- 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
- A61P11/02—Nasal agents, e.g. decongestants
-
- 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
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- 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
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Otolaryngology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US67776005P | 2005-05-04 | 2005-05-04 | |
| PCT/US2006/017614 WO2006119504A2 (en) | 2005-05-04 | 2006-05-04 | Fused heterocyclic compounds, and compositions and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007013595A true MX2007013595A (es) | 2008-01-24 |
Family
ID=37308747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2007013595A MX2007013595A (es) | 2005-05-04 | 2006-05-04 | Compuestos heterociclicos fusionados y composiciones y usos de estos. |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US7745451B2 (enExample) |
| EP (1) | EP1885369B1 (enExample) |
| JP (2) | JP5198256B2 (enExample) |
| CA (1) | CA2606760C (enExample) |
| ES (1) | ES2552804T3 (enExample) |
| MX (1) | MX2007013595A (enExample) |
| WO (1) | WO2006119504A2 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006119504A2 (en) * | 2005-05-04 | 2006-11-09 | Renovis, Inc. | Fused heterocyclic compounds, and compositions and uses thereof |
| CA2682162C (en) * | 2007-04-02 | 2016-05-10 | Renovis, Inc. | Pyrid-2-yl fused heterocyclic compounds, and compositions and uses thereof |
| PL2139334T3 (pl) * | 2007-04-17 | 2013-11-29 | Evotec Ag | Skondensowane związki heterocykliczne 2-cyjanofenylu i ich kompozycje i zastosowania |
| WO2009058299A1 (en) | 2007-10-31 | 2009-05-07 | Merck & Co., Inc. | P2x3 receptor antagonists for treatment of pain |
| US8247401B2 (en) | 2007-10-31 | 2012-08-21 | Merck Sharp & Dohme Corp. | P2X3 receptor antagonists for treatment of pain |
| BRPI0906598A2 (pt) | 2008-02-01 | 2015-07-07 | Takeda Pharmaceutical | Oxim derivattivos como inibidores hsp90 |
| MX2010009561A (es) | 2008-02-29 | 2010-09-24 | Renovis Inc | Compuestos amida, composiciones y usos de los mismos. |
| MX2011004570A (es) | 2008-10-31 | 2011-06-17 | Merck Sharp & Dohme | Antagonistas del receptor p2x3 para el tratamiento del dolor. |
| AU2009327349B2 (en) * | 2008-12-19 | 2012-03-15 | Amgen Inc. | Method for the preparation of 1-acetyl-6-amino-3, 3-dimethyl-2, 3 -dihydroindole |
| AU2012202178B2 (en) * | 2008-12-19 | 2012-11-01 | Amgen Inc. | Method for the preparation of 1-acetyl-6-amino-3, 3-dimethyl-2, 3 -dihydroindole |
| PT2399910E (pt) | 2009-02-13 | 2014-05-02 | Shionogi & Co | Novo derivado de triazina e composição farmacéutica que contém o mesmo |
| AU2010229142A1 (en) | 2009-03-23 | 2011-10-13 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
| AU2010229144B2 (en) | 2009-03-23 | 2012-07-12 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
| US8946231B2 (en) | 2009-03-23 | 2015-02-03 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
| UA112517C2 (uk) * | 2010-07-06 | 2016-09-26 | Новартіс Аг | Тетрагідропіридопіримідинові похідні |
| PL2604595T3 (pl) | 2010-08-10 | 2016-09-30 | Pochodna triazyny i związek farmaceutyczny, który ją zawiera i wykazuje aktywność przeciwbólową | |
| US9212130B2 (en) | 2010-08-10 | 2015-12-15 | Shionogi & Co., Ltd. | Heterocyclic derivative and pharmaceutical composition comprising the same |
| WO2012088266A2 (en) | 2010-12-22 | 2012-06-28 | Incyte Corporation | Substituted imidazopyridazines and benzimidazoles as inhibitors of fgfr3 |
| DK2790705T3 (en) | 2011-12-15 | 2018-03-12 | Novartis Ag | Use of inhibitors of the activity or function of PI3K |
| FR2984318B1 (fr) | 2011-12-16 | 2014-06-27 | Oreal | Coupleur de structure 7 amino-1,2,3,4-tetrahydroquinoleines cationiques, composition tinctoriale en comprenant, procedes et utilisations |
| FR2984323B1 (fr) * | 2011-12-16 | 2019-08-30 | L'oreal | Coupleur de structure 7 amino-1,2,3,4-tetrahydroquinoleines, composition tinctoriale en comprenant, procedes et utilisations |
| WO2013118855A1 (ja) | 2012-02-09 | 2013-08-15 | 塩野義製薬株式会社 | 複素環および炭素環誘導体 |
| US9051311B2 (en) | 2012-03-09 | 2015-06-09 | Amgen Inc. | Sulfamide sodium channel inhibitors |
| UA112897C2 (uk) | 2012-05-09 | 2016-11-10 | Байєр Фарма Акцієнгезелльшафт | Біциклічно заміщені урацили та їх застосування для лікування і/або профілактики захворювань |
| ES2984771T3 (es) | 2012-06-13 | 2024-10-31 | Incyte Holdings Corp | Compuestos tricíclicos sustituidos como inhibidores de FGFR |
| WO2014026125A1 (en) | 2012-08-10 | 2014-02-13 | Incyte Corporation | Pyrazine derivatives as fgfr inhibitors |
| US9266892B2 (en) | 2012-12-19 | 2016-02-23 | Incyte Holdings Corporation | Fused pyrazoles as FGFR inhibitors |
| TWI499591B (zh) | 2013-01-11 | 2015-09-11 | Lilly Co Eli | 雙環嘧啶化合物 |
| EA035095B1 (ru) | 2013-04-19 | 2020-04-27 | Инсайт Холдингс Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| TWI637949B (zh) | 2013-06-14 | 2018-10-11 | 塩野義製藥股份有限公司 | 胺基三衍生物及含有其等之醫藥組合物 |
| WO2015103355A1 (en) | 2014-01-01 | 2015-07-09 | Medivation Technologies, Inc. | Compounds and methods of use |
| US10851105B2 (en) | 2014-10-22 | 2020-12-01 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| RS63014B1 (sr) | 2014-12-09 | 2022-04-29 | Bayer Ag | 1,3-tiazol-2-il supstituisani benzamidi |
| US10183937B2 (en) | 2014-12-09 | 2019-01-22 | Bayer Aktiengesellschaft | 1,3-thiazol-2-yl substituted benzamides |
| US9580423B2 (en) | 2015-02-20 | 2017-02-28 | Incyte Corporation | Bicyclic heterocycles as FGFR4 inhibitors |
| MA41551A (fr) | 2015-02-20 | 2017-12-26 | Incyte Corp | Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4 |
| EA038045B1 (ru) | 2015-02-20 | 2021-06-28 | Инсайт Корпорейшн | Бициклические гетероциклы в качестве ингибиторов fgfr |
| AR111960A1 (es) | 2017-05-26 | 2019-09-04 | Incyte Corp | Formas cristalinas de un inhibidor de fgfr y procesos para su preparación |
| CN107597107A (zh) * | 2017-08-30 | 2018-01-19 | 重庆中邦科技有限公司 | 一种2,3‑二氯吡啶生产用催化剂及其制备方法 |
| US11174257B2 (en) | 2018-05-04 | 2021-11-16 | Incyte Corporation | Salts of an FGFR inhibitor |
| RS66310B1 (sr) | 2018-05-04 | 2025-01-31 | Incyte Corp | Čvrsti oblici inhibitora fgfr i procesi za njegovu pripremu |
| AU2019358327B2 (en) * | 2018-10-10 | 2025-04-24 | Glaxosmithkline Intellectual Property (No. 3) Limited | Treatment of pruritus with P2X3 antagonists |
| WO2020174283A1 (en) | 2019-02-25 | 2020-09-03 | Bellus Health Cough Inc. | Treatment with p2x3 modulators |
| KR20210146288A (ko) * | 2019-03-01 | 2021-12-03 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로사이클릴 화합물 및 이의 용도 |
| WO2020185532A1 (en) | 2019-03-08 | 2020-09-17 | Incyte Corporation | Methods of treating cancer with an fgfr inhibitor |
| CN110256420B (zh) * | 2019-05-07 | 2020-04-28 | 江西中医药大学 | 四氢吡啶并嘧啶衍生物及其制备方法和用途 |
| WO2021007269A1 (en) | 2019-07-09 | 2021-01-14 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| WO2021067374A1 (en) | 2019-10-01 | 2021-04-08 | Incyte Corporation | Bicyclic heterocycles as fgfr inhibitors |
| PH12022550892A1 (en) | 2019-10-14 | 2023-05-03 | Incyte Corp | Bicyclic heterocycles as fgfr inhibitors |
| US11566028B2 (en) | 2019-10-16 | 2023-01-31 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| EP4620531A3 (en) | 2019-11-08 | 2025-11-26 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| AU2020395185A1 (en) | 2019-12-04 | 2022-06-02 | Incyte Corporation | Derivatives of an FGFR inhibitor |
| EP4069696A1 (en) | 2019-12-04 | 2022-10-12 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| US12012409B2 (en) | 2020-01-15 | 2024-06-18 | Incyte Corporation | Bicyclic heterocycles as FGFR inhibitors |
| WO2022028506A1 (zh) * | 2020-08-06 | 2022-02-10 | 北京泰德制药股份有限公司 | Sos1抑制剂、包含其的药物组合物及其用途 |
| ES3026782T3 (en) * | 2020-11-27 | 2025-06-12 | Chiesi Farm Spa | (aza)quinoline 4-amines derivatives as p2x3 inhibitors |
| JP2024513575A (ja) | 2021-04-12 | 2024-03-26 | インサイト・コーポレイション | Ｆｇｆｒ阻害剤及びネクチン－４標的化剤を含む併用療法 |
| CN115626922A (zh) * | 2021-04-29 | 2023-01-20 | 苏州恩华生物医药科技有限公司 | 5,6,7,8-四氢吡啶并[4,3-d]嘧啶-4-醇衍生物及其应用 |
| WO2022261160A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| TW202313610A (zh) | 2021-06-09 | 2023-04-01 | 美商英塞特公司 | 作為ｆｇｆｒ抑制劑之三環雜環 |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1197466B (de) | 1962-03-22 | 1965-07-29 | Thomae Gmbh Dr K | Verfahren zur Herstellung von neuen 5, 6, 7, 8-Tetrahydropyrido-[4, 3-d]pyrimidinen |
| US3424760A (en) | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
| US3424761A (en) | 1966-03-07 | 1969-01-28 | Robins Co Inc A H | 3-ureidopyrrolidines |
| DE2502588A1 (de) | 1975-01-23 | 1976-07-29 | Troponwerke Dinklage & Co | Basisch substituierte derivate des 7-amino-2-chinolons, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| JPH04224580A (ja) | 1990-12-25 | 1992-08-13 | Nippon Soda Co Ltd | ピリミジン誘導体、その製造方法及び農園芸用殺菌剤 |
| AU778393B2 (en) | 1999-05-12 | 2004-12-02 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazole carboxamides useful for the treatment of obesity and other disorders |
| AU1071301A (en) | 1999-11-01 | 2001-05-14 | Eli Lilly And Company | Pharmaceutical compounds |
| HK1049338B (en) | 1999-12-17 | 2005-10-21 | Novartis Vaccines & Diagnostics, Inc. | Bicyclic inhibitors of glycogen synthase kinase 3 |
| ATE336492T1 (de) * | 2000-01-14 | 2006-09-15 | Us Gov Health & Human Serv | Methonocarbacycloalkylanaloga von nucleosiden |
| US6531478B2 (en) | 2000-02-24 | 2003-03-11 | Cheryl P. Kordik | Amino pyrazole derivatives useful for the treatment of obesity and other disorders |
| EP1301484A2 (en) | 2000-07-20 | 2003-04-16 | Neurogen Corporation | Capsaicin receptor ligands |
| ATE346064T1 (de) | 2000-09-15 | 2006-12-15 | Vertex Pharma | Pyrazolverbindungen als protein-kinasehemmer |
| ATE354573T1 (de) | 2000-12-21 | 2007-03-15 | Vertex Pharma | ßPYRAZOLVERBINDUNGEN, DIE SICH ALS PROTEINKINASEINHIBITOREN EIGNENß |
| JP4031363B2 (ja) | 2001-01-02 | 2008-01-09 | エフ．ホフマン−ラ ロシュ アーゲー | α−１Ａ／Ｂアドレナリン作動性受容体拮抗薬としてのキナゾロン誘導体 |
| ATE305303T1 (de) * | 2001-02-12 | 2005-10-15 | Hoffmann La Roche | 6-substituierte pyridopyrimidine |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| US7105667B2 (en) | 2001-05-01 | 2006-09-12 | Bristol-Myers Squibb Co. | Fused heterocyclic compounds and use thereof |
| PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| JP4469179B2 (ja) | 2002-01-23 | 2010-05-26 | バイエル ファーマセチカル コーポレーション | Ｒｈｏキナーゼ阻害剤としてのピリミジン誘導体 |
| GB0206033D0 (en) | 2002-03-14 | 2002-04-24 | Pfizer Ltd | Compounds useful in therapy |
| EP1552842A1 (en) | 2002-06-07 | 2005-07-13 | Kyowa Hakko Kogyo Co., Ltd. | Bicyclic pyrimidine derivatives |
| JPWO2004017994A1 (ja) | 2002-08-22 | 2005-12-08 | 協和醗酵工業株式会社 | 喘息の予防および／または治療剤 |
| AU2003262230A1 (en) | 2002-08-22 | 2004-03-11 | Kyowa Hakko Kogyo Co., Ltd. | Preventive and/or therapeutic drugs for itch |
| GB0225908D0 (en) | 2002-11-06 | 2002-12-11 | Pfizer Ltd | Treatment of female sexual dysfunction |
| AU2003299797A1 (en) | 2002-12-19 | 2004-07-14 | Neurogen Corporation | Substituted biphenyl-4-carboxylic acid arylamide analogues as capsaicin receptor modulators |
| EP1608631A4 (en) * | 2003-03-28 | 2008-08-20 | Scios Inc | BICYCLIC PYRIMIDININHIBITORS OF TGF BETA |
| US7232833B2 (en) * | 2003-03-28 | 2007-06-19 | Novexel | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| JPWO2004093912A1 (ja) | 2003-04-23 | 2006-07-13 | 協和醗酵工業株式会社 | 好中球性炎症疾患の予防および／または治療剤 |
| EP1663994B1 (en) * | 2003-08-05 | 2012-03-07 | Vertex Pharmaceuticals Incorporated | Tetrahydroquinazoline compounds as inhibitors of voltage-gated ion channels |
| US7390820B2 (en) | 2003-08-25 | 2008-06-24 | Amgen Inc. | Substituted quinolinone derivatives and methods of use |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| JP2005162673A (ja) | 2003-12-03 | 2005-06-23 | Kyowa Hakko Kogyo Co Ltd | 二環性ピリミジン誘導体 |
| EP1799218A1 (en) | 2004-09-30 | 2007-06-27 | Tibotec Pharmaceuticals Ltd. | Hcv inhibiting bi-cyclic pyrimidines |
| SE0403085D0 (sv) * | 2004-12-17 | 2004-12-17 | Astrazeneca Ab | Novel componds |
| WO2006119504A2 (en) * | 2005-05-04 | 2006-11-09 | Renovis, Inc. | Fused heterocyclic compounds, and compositions and uses thereof |
| JP5400388B2 (ja) | 2005-12-15 | 2014-01-29 | ライジェル ファーマシューティカルズ， インコーポレイテッド | キナーゼインヒビターおよびその利用 |
| WO2013033981A1 (zh) * | 2011-09-06 | 2013-03-14 | 江苏先声药物研究有限公司 | 一类2,7-萘啶衍生物及其制备方法和应用 |
-
2006
- 2006-05-04 WO PCT/US2006/017614 patent/WO2006119504A2/en not_active Ceased
- 2006-05-04 MX MX2007013595A patent/MX2007013595A/es active IP Right Grant
- 2006-05-04 CA CA2606760A patent/CA2606760C/en active Active
- 2006-05-04 US US11/429,026 patent/US7745451B2/en active Active
- 2006-05-04 JP JP2008510301A patent/JP5198256B2/ja active Active
- 2006-05-04 ES ES06770066.6T patent/ES2552804T3/es active Active
- 2006-05-04 EP EP06770066.6A patent/EP1885369B1/en active Active
-
2010
- 2010-03-01 US US12/660,588 patent/US8859545B2/en active Active
-
2012
- 2012-06-12 JP JP2012132675A patent/JP5722280B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US7745451B2 (en) | 2010-06-29 |
| CA2606760C (en) | 2014-12-23 |
| EP1885369B1 (en) | 2015-09-23 |
| JP5722280B2 (ja) | 2015-05-20 |
| US20060258689A1 (en) | 2006-11-16 |
| EP1885369A4 (en) | 2010-04-14 |
| WO2006119504A2 (en) | 2006-11-09 |
| US20100317676A1 (en) | 2010-12-16 |
| US8859545B2 (en) | 2014-10-14 |
| EP1885369A2 (en) | 2008-02-13 |
| WO2006119504A3 (en) | 2009-06-11 |
| JP2012197299A (ja) | 2012-10-18 |
| JP2008546639A (ja) | 2008-12-25 |
| ES2552804T3 (es) | 2015-12-02 |
| JP5198256B2 (ja) | 2013-05-15 |
| CA2606760A1 (en) | 2006-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MX2007013595A (es) | Compuestos heterociclicos fusionados y composiciones y usos de estos. | |
| JP5608655B2 (ja) | Ｐ２ｘ３受容体活性のモジュレーター | |
| JP5916700B2 (ja) | アミド化合物、組成物およびそれらの使用 | |
| US8076345B2 (en) | 2-cyanophenyl-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine compounds, compositions and uses thereof | |
| JP5396379B2 (ja) | ピリド−２−イル縮合複素環式化合物ならびにその組成物および使用 | |
| US7414131B2 (en) | Bicycloheteroarylamine compounds as ion channel ligands and uses thereof | |
| BRPI0619540A2 (pt) | compostos de quinazolinona, seu uso, composição farmacêutica que os compreende e processo para a produção de um composto | |
| HK1140106B (en) | Pyrid-2-yl fused heterocyclic compounds, and compositions and uses thereof | |
| MXPA06007287A (en) | Bicycloheteroarylamine compounds as ion channel ligands and uses thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Grant or registration | ||
| GB | Transfer or rights |