AU2013229177B2 - Thiazole derivatives as alpha 7 nAChR modulators - Google Patents
Thiazole derivatives as alpha 7 nAChR modulators Download PDFInfo
- Publication number
- AU2013229177B2 AU2013229177B2 AU2013229177A AU2013229177A AU2013229177B2 AU 2013229177 B2 AU2013229177 B2 AU 2013229177B2 AU 2013229177 A AU2013229177 A AU 2013229177A AU 2013229177 A AU2013229177 A AU 2013229177A AU 2013229177 B2 AU2013229177 B2 AU 2013229177B2
- Authority
- AU
- Australia
- Prior art keywords
- substituted
- alkyl
- unsubstituted
- thiazol
- benzenesulfonamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 title description 34
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 title description 34
- 150000007979 thiazole derivatives Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 125000000217 alkyl group Chemical group 0.000 claims description 161
- -1 cyano, hydroxy Chemical group 0.000 claims description 115
- 125000004432 carbon atom Chemical group C* 0.000 claims description 71
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 65
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 63
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 229910052736 halogen Inorganic materials 0.000 claims description 58
- 150000002367 halogens Chemical class 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 31
- 208000035475 disorder Diseases 0.000 claims description 30
- 125000004043 oxo group Chemical group O=* 0.000 claims description 30
- 206010012289 Dementia Diseases 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 208000024827 Alzheimer disease Diseases 0.000 claims description 21
- 208000010877 cognitive disease Diseases 0.000 claims description 21
- 125000004122 cyclic group Chemical group 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 201000000980 schizophrenia Diseases 0.000 claims description 16
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 15
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 15
- 208000002193 Pain Diseases 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 230000009529 traumatic brain injury Effects 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910003600 H2NS Inorganic materials 0.000 claims description 10
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 10
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 10
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 230000004770 neurodegeneration Effects 0.000 claims description 9
- 210000000056 organ Anatomy 0.000 claims description 9
- IUFIXLZAMRLPCO-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,5-dimethylpiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1C(C)CC(C)CN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IUFIXLZAMRLPCO-UHFFFAOYSA-N 0.000 claims description 8
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 8
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 206010040070 Septic Shock Diseases 0.000 claims description 8
- 201000004810 Vascular dementia Diseases 0.000 claims description 8
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 8
- 230000007278 cognition impairment Effects 0.000 claims description 8
- 210000004558 lewy body Anatomy 0.000 claims description 8
- 206010065040 AIDS dementia complex Diseases 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 208000004550 Postoperative Pain Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- 206010003246 arthritis Diseases 0.000 claims description 6
- 210000004204 blood vessel Anatomy 0.000 claims description 6
- 230000006735 deficit Effects 0.000 claims description 6
- 208000026278 immune system disease Diseases 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 238000002054 transplantation Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- IEVWKUXXENKPFC-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2CC3CC3C2)S1 IEVWKUXXENKPFC-UHFFFAOYSA-N 0.000 claims description 5
- 201000010374 Down Syndrome Diseases 0.000 claims description 5
- 208000027626 Neurocognitive disease Diseases 0.000 claims description 5
- 206010044688 Trisomy 21 Diseases 0.000 claims description 5
- 230000001154 acute effect Effects 0.000 claims description 5
- 239000000935 antidepressant agent Substances 0.000 claims description 5
- 229940005513 antidepressants Drugs 0.000 claims description 5
- 239000003693 atypical antipsychotic agent Substances 0.000 claims description 5
- 229940127236 atypical antipsychotics Drugs 0.000 claims description 5
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 5
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- ZKQMQVFMMLVKSO-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-n,n-dimethylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N(C)C)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 ZKQMQVFMMLVKSO-UHFFFAOYSA-N 0.000 claims description 4
- FZVJATOSCCZIAA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-[(2-oxopyrrolidin-1-yl)methyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2C(CCC2)=O)S1 FZVJATOSCCZIAA-UHFFFAOYSA-N 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 208000028698 Cognitive impairment Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 206010033645 Pancreatitis Diseases 0.000 claims description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 4
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 208000005298 acute pain Diseases 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000001149 cognitive effect Effects 0.000 claims description 4
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
- 238000002483 medication Methods 0.000 claims description 4
- DNMVAEYOEHZKQE-UHFFFAOYSA-N n-[4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]phenyl]sulfonylacetamide Chemical compound C1=CC(S(=O)(=O)NC(=O)C)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 DNMVAEYOEHZKQE-UHFFFAOYSA-N 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- WHVQWALJPFZLHW-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chloro-3-methylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(C)=CC(C2=C(SC(=N2)C(=O)N2CC3CC3C2)C=2C=CC(=CC=2)S(N)(=O)=O)=C1 WHVQWALJPFZLHW-UHFFFAOYSA-N 0.000 claims description 3
- GQXVFFJGPNPMEN-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 GQXVFFJGPNPMEN-UHFFFAOYSA-N 0.000 claims description 3
- NEACZCRXQGHXKS-UHFFFAOYSA-N 4-[4-(1-acetyl-2,3-dihydroindol-5-yl)-2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C=1C=C2N(C(=O)C)CCC2=CC=1C=1N=C(C(=O)N2CC3CC3C2)SC=1C1=CC=C(S(N)(=O)=O)C=C1 NEACZCRXQGHXKS-UHFFFAOYSA-N 0.000 claims description 3
- IHGKJDJXIMUVIE-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(2-oxopiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(CCCC2)=O)S1 IHGKJDJXIMUVIE-UHFFFAOYSA-N 0.000 claims description 3
- ZNTASJHFBDFQDH-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,5-dimethylpiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1C(C)CC(C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 ZNTASJHFBDFQDH-UHFFFAOYSA-N 0.000 claims description 3
- PVCWAUMYAZEZEO-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxomorpholin-4-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(COCC2)=O)S1 PVCWAUMYAZEZEO-UHFFFAOYSA-N 0.000 claims description 3
- CPZJSIJYUXTCJT-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4-methylpiperazin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1CN(C)CCN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 CPZJSIJYUXTCJT-UHFFFAOYSA-N 0.000 claims description 3
- HQQDTFLZRUUATI-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-morpholin-4-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCOCC2)S1 HQQDTFLZRUUATI-UHFFFAOYSA-N 0.000 claims description 3
- JGNLVVXJSKGKBU-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-piperidin-1-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCCCC2)S1 JGNLVVXJSKGKBU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 3
- QVQPGNFBJIKHRW-CQSZACIVSA-N C[C@@H]1CN(CCN1C)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 Chemical compound C[C@@H]1CN(CCN1C)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 QVQPGNFBJIKHRW-CQSZACIVSA-N 0.000 claims description 3
- 208000015943 Coeliac disease Diseases 0.000 claims description 3
- 206010065390 Inflammatory pain Diseases 0.000 claims description 3
- 208000002389 Pouchitis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 206010053879 Sepsis syndrome Diseases 0.000 claims description 3
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 3
- 230000006999 cognitive decline Effects 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 230000004112 neuroprotection Effects 0.000 claims description 3
- 201000001245 periodontitis Diseases 0.000 claims description 3
- 201000000306 sarcoidosis Diseases 0.000 claims description 3
- 230000005586 smoking cessation Effects 0.000 claims description 3
- 230000029663 wound healing Effects 0.000 claims description 3
- QAXOZZQNRMADMD-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-3-yl-[4-(4-chlorophenyl)-5-(4-piperidin-1-ylsulfonylphenyl)-1,3-thiazol-2-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C1=C(C=2C=CC(=CC=2)S(=O)(=O)N2CCCCC2)SC(C(=O)N2CC3CC3C2)=N1 QAXOZZQNRMADMD-UHFFFAOYSA-N 0.000 claims description 2
- YBODVHXIBXFWFK-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(2,4-difluorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C(=CC(F)=CC=2)F)N=C(N2CC3CC3C2)S1 YBODVHXIBXFWFK-UHFFFAOYSA-N 0.000 claims description 2
- KHQWCLGAFKODPQ-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CC3C2)S1 KHQWCLGAFKODPQ-UHFFFAOYSA-N 0.000 claims description 2
- QYLGGCFTHMEHQQ-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(2,4-difluorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C(=CC(F)=CC=2)F)N=C(C(=O)N2CC3CC3C2)S1 QYLGGCFTHMEHQQ-UHFFFAOYSA-N 0.000 claims description 2
- UECHVOIVERSJAK-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chloro-2,3-dihydroindol-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(N2C3=C(C(=CC=C3)Cl)CC2)N=C(C(=O)N2CC3CC3C2)S1 UECHVOIVERSJAK-UHFFFAOYSA-N 0.000 claims description 2
- MDNQYKNJVRGIJO-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 MDNQYKNJVRGIJO-UHFFFAOYSA-N 0.000 claims description 2
- YNEIARDZWXOETJ-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-2-methylbenzenesulfonamide Chemical compound C1=C(S(N)(=O)=O)C(C)=CC(C2=C(N=C(S2)C(=O)N2CC3CC3C2)C=2C=CC(Cl)=CC=2)=C1 YNEIARDZWXOETJ-UHFFFAOYSA-N 0.000 claims description 2
- MZMULLDNONLDIF-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 MZMULLDNONLDIF-UHFFFAOYSA-N 0.000 claims description 2
- KXNDOTQEUQJIBV-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-3-methylbenzenesulfonamide Chemical compound CC1=CC(S(N)(=O)=O)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CC3C2)S1 KXNDOTQEUQJIBV-UHFFFAOYSA-N 0.000 claims description 2
- MUHQAGTWFRCHIY-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-cyclopropylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(=CC=2)C2CC2)N=C(C(=O)N2CC3CC3C2)S1 MUHQAGTWFRCHIY-UHFFFAOYSA-N 0.000 claims description 2
- BCWGYJYLROMPDY-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(=CC=2)C(F)(F)F)N=C(C(=O)N2CC3CC3C2)S1 BCWGYJYLROMPDY-UHFFFAOYSA-N 0.000 claims description 2
- BWMVDSCGBQZZFD-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-[6-(trifluoromethyl)pyridin-3-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=NC(=CC=2)C(F)(F)F)N=C(C(=O)N2CC3CC3C2)S1 BWMVDSCGBQZZFD-UHFFFAOYSA-N 0.000 claims description 2
- CGYHQFKLLPPMOE-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-quinolin-8-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C3=NC=CC=C3C=CC=2)N=C(C(=O)N2CC3CC3C2)S1 CGYHQFKLLPPMOE-UHFFFAOYSA-N 0.000 claims description 2
- CFGDAPVRECUXSH-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-5-(4-sulfamoylphenyl)-1,3-thiazol-4-yl]-n,n-dimethylbenzamide Chemical compound C1=CC(C(=O)N(C)C)=CC=C1C1=C(C=2C=CC(=CC=2)S(N)(=O)=O)SC(C(=O)N2CC3CC3C2)=N1 CFGDAPVRECUXSH-UHFFFAOYSA-N 0.000 claims description 2
- ZNNYHMKIPMDMOI-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-5-(4-sulfamoylphenyl)-1,3-thiazol-4-yl]benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C1=C(C=2C=CC(=CC=2)S(N)(=O)=O)SC(C(=O)N2CC3CC3C2)=N1 ZNNYHMKIPMDMOI-UHFFFAOYSA-N 0.000 claims description 2
- HBTVCPINOZYLRB-UHFFFAOYSA-N 4-[2-(4-azaspiro[2.4]heptane-4-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3(CC3)CCC2)S1 HBTVCPINOZYLRB-UHFFFAOYSA-N 0.000 claims description 2
- RQYTUIALCMVIGO-OKILXGFUSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-fluorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(F)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 RQYTUIALCMVIGO-OKILXGFUSA-N 0.000 claims description 2
- HDVJPHGVKBJOLQ-IYBDPMFKSA-N 4-[4-(2,3-dihydro-1h-inden-5-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3CCCC3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 HDVJPHGVKBJOLQ-IYBDPMFKSA-N 0.000 claims description 2
- QHFAVPQTOJLULP-UHFFFAOYSA-N 4-[4-(4-chloro-3-methylphenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(C)=CC(C2=C(SC(=N2)C(=O)N2CCCC2)C=2C=CC(=CC=2)S(N)(=O)=O)=C1 QHFAVPQTOJLULP-UHFFFAOYSA-N 0.000 claims description 2
- SYODNVDXNGZXCD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(2-oxopyrrolidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C(CCC2)=O)S1 SYODNVDXNGZXCD-UHFFFAOYSA-N 0.000 claims description 2
- AOHRWSRNFNZKOD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-1h-isoquinolin-2-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3=CC=CC=C3CC2)S1 AOHRWSRNFNZKOD-UHFFFAOYSA-N 0.000 claims description 2
- SJVXUXCUVBLGGF-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-1h-isoquinoline-2-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3=CC=CC=C3CC2)S1 SJVXUXCUVBLGGF-UHFFFAOYSA-N 0.000 claims description 2
- XKAZMQLDGJPZNL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4-phenylpiperidin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCC(CC2)C=2C=CC=CC=2)S1 XKAZMQLDGJPZNL-UHFFFAOYSA-N 0.000 claims description 2
- JMRPASLWEHEDQD-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(morpholine-4-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCOCC2)S1 JMRPASLWEHEDQD-UHFFFAOYSA-N 0.000 claims description 2
- ZFMBUEKNELBRKL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(piperidine-1-carbonyl)-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCCC2)S1 ZFMBUEKNELBRKL-UHFFFAOYSA-N 0.000 claims description 2
- ZWTPORONWDKZGA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(piperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCCC2)S1 ZWTPORONWDKZGA-UHFFFAOYSA-N 0.000 claims description 2
- OBNPWWMQBOKERA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 OBNPWWMQBOKERA-UHFFFAOYSA-N 0.000 claims description 2
- CNROLYYCONHXGT-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-[(2-oxopiperidin-1-yl)methyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2C(CCCC2)=O)S1 CNROLYYCONHXGT-UHFFFAOYSA-N 0.000 claims description 2
- OPTQOTSMHGTWRS-OKILXGFUSA-N 4-[4-(4-chlorophenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound ClC1=CC=C(C=C1)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C OPTQOTSMHGTWRS-OKILXGFUSA-N 0.000 claims description 2
- STINCJLJSYRNAX-INIZCTEOSA-N 4-[4-(4-chlorophenyl)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2[C@@H](CCC2)C#N)S1 STINCJLJSYRNAX-INIZCTEOSA-N 0.000 claims description 2
- NABONUMFCNUCIL-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(F)C(=CC=2)S(N)(=O)=O)S1 NABONUMFCNUCIL-BETUJISGSA-N 0.000 claims description 2
- PBTFUHYZJJLKKL-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-methylbenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(C)C(=CC=2)S(N)(=O)=O)S1 PBTFUHYZJJLKKL-GASCZTMLSA-N 0.000 claims description 2
- KKACYNBLQLCBEM-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C(=CC(=CC=2)S(N)(=O)=O)F)S1 KKACYNBLQLCBEM-BETUJISGSA-N 0.000 claims description 2
- CPOAHPILTHHLOX-IYBDPMFKSA-N 4-[4-(4-chlorophenyl)-2-[(3r,5s)-3,5-difluoropiperidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C[C@H](F)C[C@H](F)C2)S1 CPOAHPILTHHLOX-IYBDPMFKSA-N 0.000 claims description 2
- RXFBZQNOQLCMSJ-GASCZTMLSA-N 4-[4-(4-cyanophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)C#N)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 RXFBZQNOQLCMSJ-GASCZTMLSA-N 0.000 claims description 2
- DKBGDZQKMHCTRD-IYBDPMFKSA-N C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C(C(Cl)=CC=2)C2CC2)=C(C=2C=C(C)C(=CC=2)S(N)(=O)=O)S1 Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C(C(Cl)=CC=2)C2CC2)=C(C=2C=C(C)C(=CC=2)S(N)(=O)=O)S1 DKBGDZQKMHCTRD-IYBDPMFKSA-N 0.000 claims description 2
- RCUZPZRZXUQSSP-IYBDPMFKSA-N C[C@@H]1CN(C[C@@H](O1)C)C(=O)C=1SC(=C(N1)C1=CC(=NC(=C1)C)C)C1=CC=C(C=C1)S(=O)(=O)N Chemical compound C[C@@H]1CN(C[C@@H](O1)C)C(=O)C=1SC(=C(N1)C1=CC(=NC(=C1)C)C)C1=CC=C(C=C1)S(=O)(=O)N RCUZPZRZXUQSSP-IYBDPMFKSA-N 0.000 claims description 2
- CNBLGUPBSPTTRK-UHFFFAOYSA-N n-[4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-5-(4-sulfamoylphenyl)-1,3-thiazol-4-yl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C1=C(C=2C=CC(=CC=2)S(N)(=O)=O)SC(C(=O)N2CC3CC3C2)=N1 CNBLGUPBSPTTRK-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 26
- 229940124530 sulfonamide Drugs 0.000 claims 3
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- RYMJHHWNDSSIEF-UHFFFAOYSA-N 4-[2-(2,6-dimethylmorpholine-4-carbonyl)-4-pyridin-4-yl-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1C(C)OC(C)CN1C(=O)C1=NC(C=2C=CN=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 RYMJHHWNDSSIEF-UHFFFAOYSA-N 0.000 claims 1
- VNIOUJLTHHFDDZ-YPXDRJKUSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C12CN(CC2C1)C(=O)C=1SC(=C(N1)N1C[C@@H](O[C@@H](C1)C)C)C1=CC=C(C=C1)S(=O)(=O)N VNIOUJLTHHFDDZ-YPXDRJKUSA-N 0.000 claims 1
- XJOJJWZDTJKVNT-UHFFFAOYSA-N 4-[2-(5-azaspiro[2.5]octan-5-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3(CC3)CCC2)S1 XJOJJWZDTJKVNT-UHFFFAOYSA-N 0.000 claims 1
- PKFDOEZPBHUKHR-UHFFFAOYSA-N 4-[2-(5-azaspiro[2.5]octane-5-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3(CC3)CCC2)S1 PKFDOEZPBHUKHR-UHFFFAOYSA-N 0.000 claims 1
- TWPBEZZDBVJXSD-UHFFFAOYSA-N 4-[2-(6-azaspiro[2.5]octan-6-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CCC3(CC3)CC2)S1 TWPBEZZDBVJXSD-UHFFFAOYSA-N 0.000 claims 1
- FDYIEEYOPXIXIK-UHFFFAOYSA-N 4-[2-(6-azaspiro[2.5]octane-6-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCC3(CC3)CC2)S1 FDYIEEYOPXIXIK-UHFFFAOYSA-N 0.000 claims 1
- JAMMKRPUIDPFTG-IYBDPMFKSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(1-methylindol-5-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3C=CN(C)C3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 JAMMKRPUIDPFTG-IYBDPMFKSA-N 0.000 claims 1
- KGTVYBWNGBGBLQ-GASCZTMLSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(1h-indol-5-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3C=CNC3=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 KGTVYBWNGBGBLQ-GASCZTMLSA-N 0.000 claims 1
- HXHCOMLCGVBEMM-IYBDPMFKSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-methylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(C)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 HXHCOMLCGVBEMM-IYBDPMFKSA-N 0.000 claims 1
- MQTUZZYWTJLHLF-GASCZTMLSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-(4-methylsulfonylphenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)S(C)(=O)=O)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 MQTUZZYWTJLHLF-GASCZTMLSA-N 0.000 claims 1
- CCZSJZCJSWRKLZ-OKILXGFUSA-N 4-[2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-4-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)C(F)(F)F)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 CCZSJZCJSWRKLZ-OKILXGFUSA-N 0.000 claims 1
- CMEQUZWIYUHYFF-UHFFFAOYSA-N 4-[2-[2,6-bis(fluoromethyl)morpholine-4-carbonyl]-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC(CF)OC(CF)C2)S1 CMEQUZWIYUHYFF-UHFFFAOYSA-N 0.000 claims 1
- SDUPQAWNTFPSPW-BETUJISGSA-N 4-[4-(2,4-difluorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C(=CC(F)=CC=2)F)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 SDUPQAWNTFPSPW-BETUJISGSA-N 0.000 claims 1
- UEBYLRSONWTNEI-BETUJISGSA-N 4-[4-(3,4-difluorophenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound FC=1C=C(C=CC1F)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C UEBYLRSONWTNEI-BETUJISGSA-N 0.000 claims 1
- GMWBLASSFYGVGG-GASCZTMLSA-N 4-[4-(4-chloro-3-cyclopropylphenyl)-2-[(2R,6S)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound ClC1=C(C=C(C=C1)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)C(=O)N1C[C@H](O[C@H](C1)C)C)C1CC1 GMWBLASSFYGVGG-GASCZTMLSA-N 0.000 claims 1
- QTCVHVBCVNRHRW-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,3-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC(F)(F)CCC2)S1 QTCVHVBCVNRHRW-UHFFFAOYSA-N 0.000 claims 1
- WPXARWUIISVXRJ-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-2h-quinoline-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3=CC=CC=C3CCC2)S1 WPXARWUIISVXRJ-UHFFFAOYSA-N 0.000 claims 1
- FXYICNFGXADGMB-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4,4-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCC(F)(F)CC2)S1 FXYICNFGXADGMB-UHFFFAOYSA-N 0.000 claims 1
- CSXODYWJASTLNM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]-2-fluorobenzenesulfonamide Chemical compound C1=C(F)C(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 CSXODYWJASTLNM-UHFFFAOYSA-N 0.000 claims 1
- HTUMOEGBXYRUNR-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(pyrrolidine-1-carbonyl)-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CCCC2)S1 HTUMOEGBXYRUNR-UHFFFAOYSA-N 0.000 claims 1
- MBDUIIYVTLHJMB-SZPZYZBQSA-N 4-[4-(4-chlorophenyl)-2-[(1r,5s)-1,5-dimethyl-3-azabicyclo[3.1.0]hexan-3-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C([C@]1(C)C[C@@]1(C1)C)N1C(S1)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=C(S(N)(=O)=O)C=C1 MBDUIIYVTLHJMB-SZPZYZBQSA-N 0.000 claims 1
- VBHFPGDISYOVRG-ZRZAMGCNSA-N 4-[4-(4-chlorophenyl)-2-[(1r,5s)-1,5-dimethyl-3-azabicyclo[3.1.0]hexane-3-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C([C@]1(C)C[C@@]1(C1)C)N1C(=O)C(S1)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=C(S(N)(=O)=O)C=C1 VBHFPGDISYOVRG-ZRZAMGCNSA-N 0.000 claims 1
- BFYFDMMQFZWLMA-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-[(2-oxopyrrolidin-1-yl)methyl]-1,3-thiazol-5-yl]-3-fluorobenzenesulfonamide Chemical compound FC1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(CN2C(CCC2)=O)S1 BFYFDMMQFZWLMA-UHFFFAOYSA-N 0.000 claims 1
- BRWNXFPWKXCGTD-OKILXGFUSA-N 4-[4-(4-chlorophenyl)-2-[(2r,6s)-2,6-dimethylmorpholin-4-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 BRWNXFPWKXCGTD-OKILXGFUSA-N 0.000 claims 1
- PIJNYIPTGOMPIA-BETUJISGSA-N 4-[4-(4-chlorophenyl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]-2-(trifluoromethyl)benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=C(C(=CC=2)S(N)(=O)=O)C(F)(F)F)S1 PIJNYIPTGOMPIA-BETUJISGSA-N 0.000 claims 1
- IUFIXLZAMRLPCO-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(3r,5s)-3,5-dimethylpiperidin-1-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)C[C@@H](C)CN1C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IUFIXLZAMRLPCO-GASCZTMLSA-N 0.000 claims 1
- ZNTASJHFBDFQDH-GASCZTMLSA-N 4-[4-(4-chlorophenyl)-2-[(3s,5r)-3,5-dimethylpiperidine-1-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)C[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(Cl)=CC=2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 ZNTASJHFBDFQDH-GASCZTMLSA-N 0.000 claims 1
- IZMPDWSNIQNZSR-IYBDPMFKSA-N 4-[4-[4-(dimethylamino)phenyl]-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=CC(=CC=2)N(C)C)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IZMPDWSNIQNZSR-IYBDPMFKSA-N 0.000 claims 1
- HXPQPAVNQJJRLP-TXEJJXNPSA-N 4-[4-cyclopropyl-2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1(CC1)C=1N=C(SC1C1=CC=C(C=C1)S(=O)(=O)N)N1C[C@@H](O[C@@H](C1)C)C HXPQPAVNQJJRLP-TXEJJXNPSA-N 0.000 claims 1
- AQEIATKGDMRYRX-CQSZACIVSA-N C[C@@H]1CN(CCN1C)C(=O)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 Chemical compound C[C@@H]1CN(CCN1C)C(=O)c1nc(c(s1)-c1ccc(cc1)S(N)(=O)=O)-c1ccc(Cl)cc1 AQEIATKGDMRYRX-CQSZACIVSA-N 0.000 claims 1
- 102100040996 Cochlin Human genes 0.000 claims 1
- 101000748988 Homo sapiens Cochlin Proteins 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 168
- 239000011541 reaction mixture Substances 0.000 description 114
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 72
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 65
- 239000000243 solution Substances 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 50
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- 230000002829 reductive effect Effects 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
- 238000004809 thin layer chromatography Methods 0.000 description 39
- 239000012043 crude product Substances 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
- 239000003480 eluent Substances 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 20
- 238000005859 coupling reaction Methods 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 19
- 229910001873 dinitrogen Inorganic materials 0.000 description 18
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 18
- 229910000027 potassium carbonate Inorganic materials 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 18
- 235000011152 sodium sulphate Nutrition 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 16
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
- 108010009685 Cholinergic Receptors Proteins 0.000 description 15
- 102000034337 acetylcholine receptors Human genes 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000000556 agonist Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000006069 Suzuki reaction reaction Methods 0.000 description 12
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 230000008878 coupling Effects 0.000 description 11
- 238000010168 coupling process Methods 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000011321 prophylaxis Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000015654 memory Effects 0.000 description 9
- 235000011056 potassium acetate Nutrition 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 235000014113 dietary fatty acids Nutrition 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 8
- 239000000194 fatty acid Substances 0.000 description 8
- 229930195729 fatty acid Natural products 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 8
- 239000000376 reactant Substances 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- STYQHICBPYRHQK-UHFFFAOYSA-N 4-bromobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Br)C=C1 STYQHICBPYRHQK-UHFFFAOYSA-N 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 7
- 230000003935 attention Effects 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 6
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 6
- 230000031709 bromination Effects 0.000 description 6
- 238000005893 bromination reaction Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000003599 detergent Substances 0.000 description 6
- 229940113088 dimethylacetamide Drugs 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 201000002832 Lewy body dementia Diseases 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- MKEJZKKVVUZXIS-UHFFFAOYSA-N 2,4-dibromo-1,3-thiazole Chemical compound BrC1=CSC(Br)=N1 MKEJZKKVVUZXIS-UHFFFAOYSA-N 0.000 description 4
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- 102000015696 Interleukins Human genes 0.000 description 4
- 108010063738 Interleukins Proteins 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 4
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 4
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 230000001713 cholinergic effect Effects 0.000 description 4
- 230000019771 cognition Effects 0.000 description 4
- 206010013663 drug dependence Diseases 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229940047122 interleukins Drugs 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000001537 neural effect Effects 0.000 description 4
- 229960002715 nicotine Drugs 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 4
- 210000001428 peripheral nervous system Anatomy 0.000 description 4
- 239000008389 polyethoxylated castor oil Substances 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000003380 propellant Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 210000004515 ventral tegmental area Anatomy 0.000 description 4
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- UXADRPPBRNCNIG-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3CCC2COC3)S1 UXADRPPBRNCNIG-UHFFFAOYSA-N 0.000 description 3
- YRBJUBCAOVBLRM-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3-oxa-8-azabicyclo[3.2.1]octane-8-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3CCC2COC3)S1 YRBJUBCAOVBLRM-UHFFFAOYSA-N 0.000 description 3
- DCXLWPYCCHASCW-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(8-oxa-3-azabicyclo[3.2.1]octane-3-carbonyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CCC(O3)C2)S1 DCXLWPYCCHASCW-UHFFFAOYSA-N 0.000 description 3
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 3
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- RPYWXZCFYPVCNQ-RVDMUPIBSA-N DMXB-A Chemical compound COC1=CC(OC)=CC=C1\C=C/1C(C=2C=NC=CC=2)=NCCC\1 RPYWXZCFYPVCNQ-RVDMUPIBSA-N 0.000 description 3
- 206010012335 Dependence Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 3
- 206010057852 Nicotine dependence Diseases 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 208000025569 Tobacco Use disease Diseases 0.000 description 3
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000003281 allosteric effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 238000006254 arylation reaction Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 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
- 150000008282 halocarbons Chemical class 0.000 description 3
- 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 3
- 230000003287 optical effect Effects 0.000 description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 230000035790 physiological processes and functions Effects 0.000 description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 3
- 229960002646 scopolamine Drugs 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
- 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 2
- PVVDOYLUYGAARG-UHFFFAOYSA-N 1-[benzyl-(3-fluoro-2-hydroxypropyl)amino]-3-fluoropropan-2-ol Chemical compound FCC(O)CN(CC(O)CF)CC1=CC=CC=C1 PVVDOYLUYGAARG-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- FTMXVDOMPAZWLQ-UHFFFAOYSA-N 2,6-dimethylmorpholine-4-carbaldehyde Chemical compound CC1CN(C=O)CC(C)O1 FTMXVDOMPAZWLQ-UHFFFAOYSA-N 0.000 description 2
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 2
- UYIATKBNQOTCMV-UHFFFAOYSA-N 2-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4-(4-chlorophenyl)-1,3-thiazole Chemical compound C1=CC(Cl)=CC=C1C1=CSC(CN2CC3CC3C2)=N1 UYIATKBNQOTCMV-UHFFFAOYSA-N 0.000 description 2
- UTYCJDSZVDYKOO-UHFFFAOYSA-N 2-(3-azabicyclo[3.1.0]hexan-3-ylmethyl)-4-bromo-1,3-thiazole Chemical compound BrC1=CSC(CN2CC3CC3C2)=N1 UTYCJDSZVDYKOO-UHFFFAOYSA-N 0.000 description 2
- OIFAHDAXIUURLN-UHFFFAOYSA-N 2-(fluoromethyl)oxirane Chemical compound FCC1CO1 OIFAHDAXIUURLN-UHFFFAOYSA-N 0.000 description 2
- YSFGGXNLZUSHHS-UHFFFAOYSA-N 2-bromobenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=CC=C1Br YSFGGXNLZUSHHS-UHFFFAOYSA-N 0.000 description 2
- WJXYUEOVOQGJGV-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane;hydrochloride Chemical compound Cl.C1NCC2CC21 WJXYUEOVOQGJGV-UHFFFAOYSA-N 0.000 description 2
- MNILDQSRDHCFJG-UHFFFAOYSA-N 3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2CCC1N2 MNILDQSRDHCFJG-UHFFFAOYSA-N 0.000 description 2
- NZZPVZIOAQKPHI-GASCZTMLSA-N 4-[4-(4-chloro-2,3-dihydroindol-1-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(N2C3=C(C(=CC=C3)Cl)CC2)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 NZZPVZIOAQKPHI-GASCZTMLSA-N 0.000 description 2
- UUBINWDQLDCNHK-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(4,4-difluoropiperidine-1-carbonyl)-1,3-thiazol-5-yl]-2-methylbenzenesulfonamide Chemical compound C1=C(S(N)(=O)=O)C(C)=CC(C2=C(N=C(S2)C(=O)N2CCC(F)(F)CC2)C=2C=CC(Cl)=CC=2)=C1 UUBINWDQLDCNHK-UHFFFAOYSA-N 0.000 description 2
- ORRSAEAVTRLDDG-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CCC(O3)C2)S1 ORRSAEAVTRLDDG-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- KCBOFZCQZNTPPY-UHFFFAOYSA-N 5-azaspiro[2.5]octane;hydrobromide Chemical compound Br.C1CC11CNCCC1 KCBOFZCQZNTPPY-UHFFFAOYSA-N 0.000 description 2
- MBVHOEVCNOFJRL-UHFFFAOYSA-N 8-(4-bromo-1,3-thiazol-2-yl)-3-oxa-8-azabicyclo[3.2.1]octane Chemical compound BrC1=CSC(N2C3CCC2COC3)=N1 MBVHOEVCNOFJRL-UHFFFAOYSA-N 0.000 description 2
- URAKZDHXGOIQQL-UHFFFAOYSA-N 8-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1=CC(Cl)=CC=C1C1=CSC(N2C3CCC2COC3)=N1 URAKZDHXGOIQQL-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000008811 Agoraphobia Diseases 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 238000011765 DBA/2 mouse Methods 0.000 description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 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
- 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
- 101000822103 Homo sapiens Neuronal acetylcholine receptor subunit alpha-7 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 102100021511 Neuronal acetylcholine receptor subunit alpha-7 Human genes 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-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
- 241000700159 Rattus Species 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- 208000028810 Shared psychotic disease Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003502 anti-nociceptive effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- RBEUYGBXYIJAEZ-UHFFFAOYSA-N benzyl 5-azaspiro[2.5]octane-5-carboxylate Chemical compound C1CCC2(CC2)CN1C(=O)OCC1=CC=CC=C1 RBEUYGBXYIJAEZ-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000005621 boronate group Chemical class 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 125000005945 imidazopyridyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000018937 joint inflammation Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- XXZNFWHGOMHWCO-UHFFFAOYSA-N n,n-diethylthiohydroxylamine Chemical compound CCN(S)CC XXZNFWHGOMHWCO-UHFFFAOYSA-N 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 235000021313 oleic acid Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 239000008180 pharmaceutical surfactant Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000006977 prepulse inhibition Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 230000009151 sensory gating Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 239000000344 soap Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- 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
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-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
- POOPWPIOIMBTOH-OLQVQODUSA-N (1s,5r)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NC[C@@]2([H])CC[C@]1([H])O2 POOPWPIOIMBTOH-OLQVQODUSA-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
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-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
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- YNBXNVUZXFMNSJ-UHFFFAOYSA-N (4-bromophenyl) 1,4-diazabicyclo[3.2.2]nonane-4-carboxylate;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1OC(=O)N1C(CC2)CCN2CC1 YNBXNVUZXFMNSJ-UHFFFAOYSA-N 0.000 description 1
- AKSXQPCIAOIJGP-UHFFFAOYSA-N (4-sulfamoylphenyl)boronic acid Chemical compound NS(=O)(=O)C1=CC=C(B(O)O)C=C1 AKSXQPCIAOIJGP-UHFFFAOYSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
- TYAGAVRSOFABFO-VIFPVBQESA-N (5s)-spiro[1,3-oxazolidine-5,3'-1-azabicyclo[2.2.2]octane]-2-one Chemical compound O1C(=O)NC[C@]11C(CC2)CCN2C1 TYAGAVRSOFABFO-VIFPVBQESA-N 0.000 description 1
- VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
- FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
- CEIIEALEIHQDBX-UHFFFAOYSA-N 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methyl-3-isoxazolyl)urea Chemical compound C1=C(Cl)C(OC)=CC(OC)=C1NC(=O)NC1=NOC(C)=C1 CEIIEALEIHQDBX-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- XGNXSYSIPMUOAF-UHFFFAOYSA-N 1-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]methyl]pyrrolidin-2-one Chemical compound C1=CC(Cl)=CC=C1C1=CSC(CN2C(CCC2)=O)=N1 XGNXSYSIPMUOAF-UHFFFAOYSA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- STHHLVCQSLRQNI-UHFFFAOYSA-N 1-azabicyclo[3.2.1]octane Chemical compound C1C2CCN1CCC2 STHHLVCQSLRQNI-UHFFFAOYSA-N 0.000 description 1
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004565 2,3-dihydrobenzofuran-4-yl group Chemical group O1CCC2=C1C=CC=C2* 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
- QUHMUJDBEBZWHJ-UHFFFAOYSA-N 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-(2,4-difluorophenyl)-1,3-thiazole Chemical compound FC1=CC(F)=CC=C1C1=CSC(N2CC3CC3C2)=N1 QUHMUJDBEBZWHJ-UHFFFAOYSA-N 0.000 description 1
- GTWQDMPRIJBDLI-UHFFFAOYSA-N 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-bromo-1,3-thiazole Chemical compound BrC1=CSC(N2CC3CC3C2)=N1 GTWQDMPRIJBDLI-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-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
- MOQVHOPVBREXLY-UHFFFAOYSA-N 3h-dioxol-4-ylmethanol Chemical compound OCC1=COOC1 MOQVHOPVBREXLY-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- RKSARRKTQRGCPY-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.1.0]hexane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]-5,6,7,8-tetrahydronaphthalene-1-sulfonamide Chemical compound C1=2CCCCC=2C(S(=O)(=O)N)=CC=C1C=1SC(C(=O)N2CC3CC3C2)=NC=1C1=CC=C(Cl)C=C1 RKSARRKTQRGCPY-UHFFFAOYSA-N 0.000 description 1
- MIAZICXDLFGPCN-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.2.1]octan-3-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2CC3CCC(C3)C2)S1 MIAZICXDLFGPCN-UHFFFAOYSA-N 0.000 description 1
- HHPRYROIORWJNO-UHFFFAOYSA-N 4-[2-(3-azabicyclo[3.2.1]octane-3-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2CC3CCC(C3)C2)S1 HHPRYROIORWJNO-UHFFFAOYSA-N 0.000 description 1
- MFYGYYLTOHYNNM-UHFFFAOYSA-N 4-[2-(8-azabicyclo[3.2.1]octan-8-yl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3CCC2CCC3)S1 MFYGYYLTOHYNNM-UHFFFAOYSA-N 0.000 description 1
- QABSWFDRJDYHHS-UHFFFAOYSA-N 4-[2-(8-azabicyclo[3.2.1]octane-8-carbonyl)-4-(4-chlorophenyl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(C(=O)N2C3CCC2CCC3)S1 QABSWFDRJDYHHS-UHFFFAOYSA-N 0.000 description 1
- IFKBWQYSWMSHJE-IYBDPMFKSA-N 4-[4-(1-acetyl-2,3-dihydroindol-5-yl)-2-[(2s,6r)-2,6-dimethylmorpholine-4-carbonyl]-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(=O)C1=NC(C=2C=C3CCN(C3=CC=2)C(C)=O)=C(C=2C=CC(=CC=2)S(N)(=O)=O)S1 IFKBWQYSWMSHJE-IYBDPMFKSA-N 0.000 description 1
- AULNCWIVHQPAQL-UHFFFAOYSA-N 4-[4-(4-chlorophenyl)-2-(3,4-dihydro-2h-quinolin-1-yl)-1,3-thiazol-5-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(C=2C=CC(Cl)=CC=2)N=C(N2C3=CC=CC=C3CCC2)S1 AULNCWIVHQPAQL-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
- AYUAEJPYEJEHJN-UHFFFAOYSA-N 4-bromo-1,3-thiazole-2-carboxylic acid Chemical compound OC(=O)C1=NC(Br)=CS1 AYUAEJPYEJEHJN-UHFFFAOYSA-N 0.000 description 1
- FSYGAHNNOFHTHA-UHFFFAOYSA-N 4-bromo-2-(bromomethyl)-1,3-thiazole Chemical compound BrCC1=NC(Br)=CS1 FSYGAHNNOFHTHA-UHFFFAOYSA-N 0.000 description 1
- IGHNKNGPWJLEQN-UHFFFAOYSA-N 4-bromo-2-(bromomethyl)-5-methyl-1,3-thiazole Chemical compound CC=1SC(CBr)=NC=1Br IGHNKNGPWJLEQN-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
- HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- OGTSCXDENOXSGN-UHFFFAOYSA-N 8-[5-bromo-4-(4-chlorophenyl)-1,3-thiazol-2-yl]-3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1=CC(Cl)=CC=C1C1=C(Br)SC(N2C3CCC2COC3)=N1 OGTSCXDENOXSGN-UHFFFAOYSA-N 0.000 description 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000021465 Brief psychotic disease Diseases 0.000 description 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241001466804 Carnivora Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010063094 Cerebral malaria Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 201000007336 Cryptococcosis Diseases 0.000 description 1
- 241000221204 Cryptococcus neoformans Species 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010014612 Encephalitis viral Diseases 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- NLPRAJRHRHZCQQ-UHFFFAOYSA-N Epibatidine Natural products C1=NC(Cl)=CC=C1C1C(N2)CCC2C1 NLPRAJRHRHZCQQ-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 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 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 102000000849 HMGB Proteins Human genes 0.000 description 1
- 108010001860 HMGB Proteins Proteins 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 206010058558 Hypoperfusion Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- 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 1
- 241000283953 Lagomorpha Species 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- WECKJONDRAUFDD-ZDUSSCGKSA-N N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-4-chlorobenzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)N[C@@H]1C(CC2)CCN2C1 WECKJONDRAUFDD-ZDUSSCGKSA-N 0.000 description 1
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 206010036105 Polyneuropathy Diseases 0.000 description 1
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 208000030988 Schizoid Personality disease Diseases 0.000 description 1
- 208000020186 Schizophreniform disease Diseases 0.000 description 1
- 208000024791 Schizotypal Personality disease Diseases 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- 208000019568 Shared Paranoid disease Diseases 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 208000027520 Somatoform disease Diseases 0.000 description 1
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 1
- 201000002661 Spondylitis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000002667 Subdural Hematoma Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241001493546 Suina Species 0.000 description 1
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical class OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000000323 Tourette Syndrome Diseases 0.000 description 1
- 208000016620 Tourette disease Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
- IOSLINNLJFQMFF-XMMPIXPASA-N [(2R)-1-[[4-[[3-[(4-fluorophenyl)methylsulfanyl]phenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound FC1=CC=C(CSC=2C=C(OCC3=CC=C(CN4[C@H](CCC4)CO)C=C3)C=CC=2)C=C1 IOSLINNLJFQMFF-XMMPIXPASA-N 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
- PGMHAGJAACRSNR-UHFFFAOYSA-N [4-(4-chlorophenyl)-1,3-thiazol-2-yl]-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone Chemical compound C1=CC(Cl)=CC=C1C1=CSC(C(=O)N2C3CCC2COC3)=N1 PGMHAGJAACRSNR-UHFFFAOYSA-N 0.000 description 1
- DFJBLYBDGRUTEO-UHFFFAOYSA-N [4-(4-chlorophenyl)-1,3-thiazol-2-yl]-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone Chemical compound C1=CC(Cl)=CC=C1C1=CSC(C(=O)N2CC3CCC(O3)C2)=N1 DFJBLYBDGRUTEO-UHFFFAOYSA-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
- 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
- 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
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003192 autonomic ganglia Anatomy 0.000 description 1
- 210000003403 autonomic nervous system Anatomy 0.000 description 1
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- DFLLABDAFZKLMX-UHFFFAOYSA-N benzyl 3-methylidenepiperidine-1-carboxylate Chemical compound C1C(=C)CCCN1C(=O)OCC1=CC=CC=C1 DFLLABDAFZKLMX-UHFFFAOYSA-N 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- JAPMJSVZDUYFKL-UHFFFAOYSA-N bicyclo[3.1.0]hexane Chemical group C1CCC2CC21 JAPMJSVZDUYFKL-UHFFFAOYSA-N 0.000 description 1
- SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical group C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
- AWYMFBJJKFTCFO-UHFFFAOYSA-N bicyclo[3.2.0]heptane Chemical class C1CCC2CCC21 AWYMFBJJKFTCFO-UHFFFAOYSA-N 0.000 description 1
- GNTFBMAGLFYMMZ-UHFFFAOYSA-N bicyclo[3.2.2]nonane Chemical group C1CC2CCC1CCC2 GNTFBMAGLFYMMZ-UHFFFAOYSA-N 0.000 description 1
- WNTGVOIBBXFMLR-UHFFFAOYSA-N bicyclo[3.3.1]nonane Chemical group C1CCC2CCCC1C2 WNTGVOIBBXFMLR-UHFFFAOYSA-N 0.000 description 1
- WMRPOCDOMSNXCQ-UHFFFAOYSA-N bicyclo[3.3.2]decane Chemical group C1CCC2CCCC1CC2 WMRPOCDOMSNXCQ-UHFFFAOYSA-N 0.000 description 1
- KVLCIHRZDOKRLK-UHFFFAOYSA-N bicyclo[4.2.1]nonane Chemical group C1C2CCC1CCCC2 KVLCIHRZDOKRLK-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 208000019664 bone resorption disease Diseases 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 229950003210 bradanicline Drugs 0.000 description 1
- OXKRFEWMSWPKKV-RXVVDRJESA-N bradanicline Chemical compound C([C@@H]1N2CCC(CC2)[C@@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-RXVVDRJESA-N 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000006172 buffering agent 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
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 229910021386 carbon form Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 230000037410 cognitive enhancement Effects 0.000 description 1
- 230000006998 cognitive state Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940127271 compound 49 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229940126545 compound 53 Drugs 0.000 description 1
- 229940127113 compound 57 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 229940126179 compound 72 Drugs 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 206010061811 demyelinating polyneuropathy Diseases 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000005959 diazepanyl group Chemical group 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- NLPRAJRHRHZCQQ-IVZWLZJFSA-N epibatidine Chemical compound C1=NC(Cl)=CC=C1[C@@H]1[C@H](N2)CC[C@H]2C1 NLPRAJRHRHZCQQ-IVZWLZJFSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000009540 excitatory neurotransmission Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000000848 glutamatergic effect Effects 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 230000009997 humoral pathway Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000009539 inhibitory neurotransmission Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000010220 ion permeability Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000012947 ischemia reperfusion injury Diseases 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000005969 isothiazolinyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000003367 kinetic assay Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000004758 lung carcinogenesis Effects 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001343 mnemonic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 201000005518 mononeuropathy Diseases 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- KADXVMRYQRCLAH-UHFFFAOYSA-N n'-iodobutanediamide Chemical compound NC(=O)CCC(=O)NI KADXVMRYQRCLAH-UHFFFAOYSA-N 0.000 description 1
- SSRDSYXGYPJKRR-ZDUSSCGKSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-7-chloro-1-benzothiophene-2-carboxamide Chemical compound C1N(CC2)CCC2[C@H]1NC(=O)C1=CC(C=CC=C2Cl)=C2S1 SSRDSYXGYPJKRR-ZDUSSCGKSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000010004 neural pathway Effects 0.000 description 1
- 230000001703 neuroimmune Effects 0.000 description 1
- 230000004751 neurological system process Effects 0.000 description 1
- 210000000715 neuromuscular junction Anatomy 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 201000003077 normal pressure hydrocephalus Diseases 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000002889 oleic acids Chemical class 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 235000015205 orange juice Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
- 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 208000027753 pain disease Diseases 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 208000021090 palsy Diseases 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 208000024817 paranoid personality disease Diseases 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 238000011302 passive avoidance test Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 230000007824 polyneuropathy Effects 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 201000000196 pseudobulbar palsy Diseases 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000000246 remedial effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 208000022610 schizoaffective disease Diseases 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 230000031893 sensory processing Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-N sodium;2-[dodecanoyl(methyl)amino]acetic acid Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC(O)=O KSAVQLQVUXSOCR-UHFFFAOYSA-N 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 230000006886 spatial memory Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- FOEYMRPOKBCNCR-UHFFFAOYSA-N spiro[2.5]octane Chemical compound C1CC11CCCCC1 FOEYMRPOKBCNCR-UHFFFAOYSA-N 0.000 description 1
- VRQDPNKOUPEWOC-UHFFFAOYSA-N spiro[bicyclo[2.2.2]octane-3,3'-piperidine] Chemical compound C1CCNCC21C(CC1)CCC1C2 VRQDPNKOUPEWOC-UHFFFAOYSA-N 0.000 description 1
- CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- NXZIGGBPLGAPTI-UHFFFAOYSA-N tert-butyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2OC21 NXZIGGBPLGAPTI-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
- 208000032471 type 1 spinal muscular atrophy Diseases 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
- 229960004751 varenicline Drugs 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 201000002498 viral encephalitis Diseases 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- XCHIZTUBUXZESJ-UHFFFAOYSA-N way-317,538 Chemical compound C=1C=C(C=2C=NC=CC=2)C=CC=1NC(=O)CCCCN1CCOCC1 XCHIZTUBUXZESJ-UHFFFAOYSA-N 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN237KO2012 | 2012-03-06 | ||
| IN235KO2012 | 2012-03-06 | ||
| IN235/KOL/2012 | 2012-03-06 | ||
| IN236/KOL/2012 | 2012-03-06 | ||
| IN236KO2012 | 2012-03-06 | ||
| IN237/KOL/2012 | 2012-03-06 | ||
| IN1307KO2012 | 2012-11-12 | ||
| IN1307/KOL/2012 | 2012-11-12 | ||
| PCT/IB2013/051455 WO2013132380A1 (en) | 2012-03-06 | 2013-02-22 | Thiazole derivatives as alpha 7 nachr modulators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2013229177A1 AU2013229177A1 (en) | 2014-09-18 |
| AU2013229177B2 true AU2013229177B2 (en) | 2017-03-23 |
Family
ID=54261190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2013229177A Expired - Fee Related AU2013229177B2 (en) | 2012-03-06 | 2013-02-22 | Thiazole derivatives as alpha 7 nAChR modulators |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US9388196B2 (enExample) |
| EP (1) | EP2822946A1 (enExample) |
| AU (1) | AU2013229177B2 (enExample) |
| CA (1) | CA2866015A1 (enExample) |
| IN (1) | IN2014MN01756A (enExample) |
| NZ (1) | NZ629453A (enExample) |
| SG (1) | SG11201405239WA (enExample) |
| WO (1) | WO2013132380A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104603118B (zh) * | 2012-05-31 | 2017-10-03 | 菲尼克斯药品股份公司 | 作为孤儿核受体RORγ调节物的经甲酰胺或磺酰胺取代的噻唑及相关衍生物 |
| US20150299178A1 (en) * | 2012-11-12 | 2015-10-22 | Lupin Limited | Thiazole Derivatives as Alpha 7 NACHR Modulators |
| US9617210B2 (en) | 2013-03-13 | 2017-04-11 | Lupin Limited | Pyrrole derivatives as alpha 7 NACHR modulators |
| TW201446243A (zh) | 2013-06-03 | 2014-12-16 | Lupin Ltd | 4-(5-(4-氯苯基)-2-(2-環丙基乙醯基)-1,4-二甲基-1氫-吡咯-3-基)苯磺醯胺作為α7尼古丁乙醯膽鹼受體調節劑 |
| WO2014203150A1 (en) | 2013-06-17 | 2014-12-24 | Lupin Limited | Pyrrole derivatives as alpha 7 nachr modulators |
| MX395534B (es) * | 2014-07-03 | 2025-03-25 | Celgene Quanticel Res Inc | Inhibidores de demetilasa-1 especifica de lisina. |
| US10183938B2 (en) | 2014-12-16 | 2019-01-22 | Axovant Sciences Gmbh | Geminal substituted quinuclidine amide compounds as agonists of α-7 nicotonic acetylcholine receptors |
| JP2018516973A (ja) | 2015-06-10 | 2018-06-28 | フォーラム・ファーマシューティカルズ・インコーポレイテッドＦｏｒｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． | α７−ニコチン性アセチルコリン受容体のアゴニストとしてのアミノベンゾイソオキサゾール化合物 |
| US10844051B2 (en) | 2015-07-22 | 2020-11-24 | The Royal Institution For The Advancement Of Learning/Mcgill University | Substituted oxazoles for the treatment of cancer |
| EP3334740A4 (en) | 2015-08-12 | 2019-02-06 | Axovant Sciences GmbH | GEMINAL SUBSTITUTED AMINOBENZISOXAZOLE COMPOUNDS AS AGONISTS OF ALPHA 7-NICOTINIC ACETYLCHOLINE RECEPTORS |
| CN108101860B (zh) * | 2018-02-08 | 2021-11-23 | 苏州敬业医药化工有限公司 | 顺式-2，6-二甲基吗啉的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5668161A (en) * | 1994-07-27 | 1997-09-16 | G.D. Searle & Co. | Substituted thiazoles for the treatment of inflammation |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3953596A (en) | 1973-06-14 | 1976-04-27 | Ici United States Inc. | 8-Oxa-3-azabicyclo(3.2.1)octane analgesic compositions and method of alleviating pain in animals |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5608082A (en) | 1994-07-28 | 1997-03-04 | Agouron Pharmaceuticals, Inc. | Compounds useful as antiproliferative agents and GARFT inhibitors |
| JP4290872B2 (ja) | 1997-09-12 | 2009-07-08 | メルク フロスト カナダ リミテツド | シクロオキシゲナーゼ−２阻害薬としての２，３，５−トリ置換ピリジン類 |
| TWI262917B (en) | 2002-02-01 | 2006-10-01 | Dainippon Sumitomo Pharma Co | 2-Furancarboxylic hydrazides and pharmaceutical compositions containing the same |
| FR2840303B1 (fr) | 2002-05-31 | 2005-07-15 | Rhodia Chimie Sa | Procede d'arylation ou de vinylation ou d'alcylynation d'un compose nucleophile |
| SE0201938D0 (sv) | 2002-06-20 | 2002-06-20 | Astrazeneca Ab | New process |
| DE10244810A1 (de) | 2002-09-26 | 2004-04-08 | Bayer Ag | Neue Morpholin-überbrückte Indazolderivate |
| US7129235B2 (en) | 2003-07-11 | 2006-10-31 | Abbott Laboratories | Amides useful for treating pain |
| US7442805B2 (en) | 2003-09-25 | 2008-10-28 | Wyeth | Substituted sulfonamide-indoles |
| GB0403038D0 (en) | 2004-02-11 | 2004-03-17 | Novartis Ag | Organic compounds |
| WO2005092843A1 (en) | 2004-03-29 | 2005-10-06 | Neurosearch A/S | Novel urea derivatives and their medical use |
| ITTO20040264A1 (it) | 2004-04-28 | 2004-07-28 | Rotta Res Lab Spa | Nuovi derivati pirrolici ad attivita' angiotensina-ii antagonista |
| EP1790640A4 (en) | 2004-09-09 | 2009-07-29 | Chugai Pharmaceutical Co Ltd | NEW IMIDAZOLIDINE DERIVATIVE AND APPLICATION THEREOF |
| US20060142349A1 (en) | 2004-12-23 | 2006-06-29 | Pfizer Inc | Methods of modulating the activities of alpha-7 nicotinic acetylcholine receptor |
| EP1866314B1 (en) | 2005-02-16 | 2010-09-15 | NeuroSearch A/S | Novel diazabicyclic aryl derivatives and their medical use |
| FR2885616B1 (fr) | 2005-05-12 | 2007-06-22 | Servier Lab | Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2007019251A2 (en) | 2005-08-04 | 2007-02-15 | Apogee Biotechnology Corporation | Sphingosine kinase inhibitors and methods of their use |
| JP5341516B2 (ja) | 2005-09-13 | 2013-11-13 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ２−アニリン−４−アリール置換チアゾール誘導体 |
| EP1984360B1 (en) | 2006-02-03 | 2014-01-15 | Eli Lilly & Company | Compounds and methods for modulating FX-receptors |
| DE602007004307D1 (de) | 2006-02-16 | 2010-03-04 | Neurosearch As | Enantiomerenreine chinuclidinyloxy-pyridazine und ihre verwendung als nikotin-acetylcholin-rezeptorliganden |
| JO3019B1 (ar) | 2006-04-19 | 2016-09-05 | Janssen Pharmaceutica Nv | ثلاثي مستبدل 4،2،1-ثلاثي زولات |
| AU2007265116A1 (en) | 2006-06-27 | 2008-01-03 | Abbott Laboratories | Pyrrole derivatives and their methods of use |
| MX2008016336A (es) | 2006-06-27 | 2009-01-16 | Abbott Lab | Derivados de tiazolina y oxazolina y sus metodos de uso. |
| JP2010509216A (ja) | 2006-11-02 | 2010-03-25 | メルク エンド カムパニー インコーポレーテッド | ヘテロシクリル置換抗高コレステロール血症化合物 |
| US20080287479A1 (en) | 2006-12-20 | 2008-11-20 | Pfizer Inc | Inhibitors of serine palmitoyltransferase |
| US8110588B2 (en) | 2007-08-08 | 2012-02-07 | Neurosearch A/S | 1,2,3-triazole derivatives useful as modulators of nicotinic acetylcholine receptors |
| GB0718735D0 (en) | 2007-09-25 | 2007-11-07 | Prolysis Ltd | Antibacterial agents |
| MX2010003155A (es) | 2007-10-04 | 2010-04-01 | Hoffmann La Roche | Derivados de ciclopropil aril amida y uso de los mismos. |
| MX2010003156A (es) | 2007-10-04 | 2010-04-01 | Hoffmann La Roche | Derivados de aril amida substituida con tetrazol y usos de los mismos. |
| JO2784B1 (en) | 2007-10-18 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | 5,3,1 - Triazole substitute derivative |
| MY152486A (en) | 2008-03-19 | 2014-10-15 | Janssen Pharmaceutica Nv | Trisubstituted 1,2,4 - triazoles as nicotinic acetylcholine receptor modulators |
| US7786171B2 (en) | 2008-04-04 | 2010-08-31 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
| JP2011516598A (ja) | 2008-04-17 | 2011-05-26 | グラクソ グループ リミテッド | ニコチン性アセチルコリン受容体サブタイプアルファ−７１のモジュレータとしてのインドール |
| BRPI0912196A2 (pt) | 2008-05-09 | 2015-10-06 | Janssen Pharmaceutica Nv | pirazóis trissubstituídos como moduladores do receptor de acetilcolina. |
| WO2010083444A1 (en) | 2009-01-15 | 2010-07-22 | Anvyl, Llc | Alpha7 nicotinic acetylcholine receptor allosteric modulators, their derivatives and uses thereof |
| WO2010120854A1 (en) | 2009-04-15 | 2010-10-21 | Glaxosmithkline Llc | Chemical compounds |
| WO2010130768A1 (en) | 2009-05-14 | 2010-11-18 | Neurosearch A/S | Novel 1,4-diaza-bicyclo[3.2.1]octane derivatives useful as nicotinic acetylcholine receptor modulators |
| JO3250B1 (ar) | 2009-09-22 | 2018-09-16 | Novartis Ag | إستعمال منشطات مستقبل نيكوتينيك أسيتيل كولين ألفا 7 |
| JO3078B1 (ar) | 2009-11-27 | 2017-03-15 | Janssen Pharmaceutica Nv | مورفولينوثيازولات بصفتها منظمات الوستيرية نوع الفا 7 موجبة |
| AU2012213086B2 (en) | 2011-02-03 | 2016-05-05 | Lupin Limited | Pyrrole derivatives used as modulators of alpha7 nAChR |
| KR20140026378A (ko) | 2011-02-23 | 2014-03-05 | 루핀 리미티드 | 알파 7 ｎａｃｈｒ 조절자로서 헤테로아릴 유도체 |
| AU2012235779B2 (en) | 2011-03-31 | 2017-03-02 | Lupin Limited | Pyrrole derivatives as nicotinic acetylcholine receptor modulators for use in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease |
| US8946432B2 (en) | 2011-07-05 | 2015-02-03 | Lupin Limited | Biaryl derivatives as nAChR modulators |
-
2013
- 2013-02-22 EP EP13711972.3A patent/EP2822946A1/en not_active Withdrawn
- 2013-02-22 WO PCT/IB2013/051455 patent/WO2013132380A1/en not_active Ceased
- 2013-02-22 CA CA2866015A patent/CA2866015A1/en not_active Abandoned
- 2013-02-22 US US14/379,134 patent/US9388196B2/en not_active Expired - Fee Related
- 2013-02-22 NZ NZ629453A patent/NZ629453A/en not_active IP Right Cessation
- 2013-02-22 SG SG11201405239WA patent/SG11201405239WA/en unknown
- 2013-02-22 AU AU2013229177A patent/AU2013229177B2/en not_active Expired - Fee Related
- 2013-02-22 IN IN1756MUN2014 patent/IN2014MN01756A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5668161A (en) * | 1994-07-27 | 1997-09-16 | G.D. Searle & Co. | Substituted thiazoles for the treatment of inflammation |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013132380A1 (en) | 2013-09-12 |
| NZ629453A (en) | 2016-04-29 |
| US9388196B2 (en) | 2016-07-12 |
| IN2014MN01756A (enExample) | 2015-07-03 |
| EP2822946A1 (en) | 2015-01-14 |
| SG11201405239WA (en) | 2014-09-26 |
| US20150291617A1 (en) | 2015-10-15 |
| CA2866015A1 (en) | 2013-09-12 |
| AU2013229177A1 (en) | 2014-09-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2013229177B2 (en) | Thiazole derivatives as alpha 7 nAChR modulators | |
| AU2012235779B2 (en) | Pyrrole derivatives as nicotinic acetylcholine receptor modulators for use in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's disease | |
| US8946432B2 (en) | Biaryl derivatives as nAChR modulators | |
| US9617210B2 (en) | Pyrrole derivatives as alpha 7 NACHR modulators | |
| WO2012104782A1 (en) | Pyrrole derivatives used as modulators of alpha7 nachr | |
| US9504680B2 (en) | Pyrrole derivatives as alpha 7 nAChR modulators | |
| EP2945941B1 (en) | Pyrrole derivatives as alpha 7 nachr modulators | |
| US20150299178A1 (en) | Thiazole Derivatives as Alpha 7 NACHR Modulators | |
| NZ615583B2 (en) | Pyrrole derivatives as nicotinic acetylcholine receptor modulators for use in the treatment of neurodegenerative disorders such as alzheimer's and parkinson's disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK25 | Application lapsed reg. 22.2i(2) - failure to pay acceptance fee |