JP6297655B2 - 多環式化合物及びその使用方法 - Google Patents
多環式化合物及びその使用方法 Download PDFInfo
- Publication number
- JP6297655B2 JP6297655B2 JP2016191898A JP2016191898A JP6297655B2 JP 6297655 B2 JP6297655 B2 JP 6297655B2 JP 2016191898 A JP2016191898 A JP 2016191898A JP 2016191898 A JP2016191898 A JP 2016191898A JP 6297655 B2 JP6297655 B2 JP 6297655B2
- Authority
- JP
- Japan
- Prior art keywords
- optionally substituted
- compound
- synthesis
- acid
- mmol
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 249
- 125000003367 polycyclic group Chemical group 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 383
- 230000015572 biosynthetic process Effects 0.000 claims description 176
- 239000000203 mixture Substances 0.000 claims description 124
- 229910052739 hydrogen Inorganic materials 0.000 claims description 79
- 239000001257 hydrogen Substances 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 49
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 8
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 6
- YYPNNBPPDFTQFX-UHFFFAOYSA-N 2-thiophen-3-ylethanol Chemical compound OCCC=1C=CSC=1 YYPNNBPPDFTQFX-UHFFFAOYSA-N 0.000 claims description 4
- 238000003821 enantio-separation Methods 0.000 claims description 4
- 238000001212 derivatisation Methods 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- HUMIEJNVCICTPJ-UHFFFAOYSA-N 2,2-dimethoxy-n-methylethanamine Chemical compound CNCC(OC)OC HUMIEJNVCICTPJ-UHFFFAOYSA-N 0.000 claims 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 description 172
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 112
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- -1 propen-1-yl Chemical group 0.000 description 85
- 125000000217 alkyl group Chemical group 0.000 description 67
- 125000003118 aryl group Chemical group 0.000 description 66
- 239000000243 solution Substances 0.000 description 66
- 125000000623 heterocyclic group Chemical group 0.000 description 65
- 208000002193 Pain Diseases 0.000 description 64
- 125000004429 atom Chemical group 0.000 description 63
- 239000011734 sodium Substances 0.000 description 60
- 208000035475 disorder Diseases 0.000 description 57
- 125000001072 heteroaryl group Chemical group 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 201000010099 disease Diseases 0.000 description 54
- 125000000753 cycloalkyl group Chemical group 0.000 description 53
- 230000036407 pain Effects 0.000 description 53
- 239000002552 dosage form Substances 0.000 description 52
- 235000019439 ethyl acetate Nutrition 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 48
- 125000004103 aminoalkyl group Chemical group 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 238000004440 column chromatography Methods 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 42
- 239000012267 brine Substances 0.000 description 41
- 239000012043 crude product Substances 0.000 description 41
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
- 239000004480 active ingredient Substances 0.000 description 40
- 125000003342 alkenyl group Chemical group 0.000 description 39
- 208000024891 symptom Diseases 0.000 description 39
- 125000003545 alkoxy group Chemical group 0.000 description 37
- 125000000304 alkynyl group Chemical group 0.000 description 36
- 125000003710 aryl alkyl group Chemical group 0.000 description 36
- 208000012902 Nervous system disease Diseases 0.000 description 34
- 238000001914 filtration Methods 0.000 description 32
- 208000028017 Psychotic disease Diseases 0.000 description 31
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 31
- 201000000980 schizophrenia Diseases 0.000 description 31
- 239000008194 pharmaceutical composition Substances 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 239000003814 drug Substances 0.000 description 29
- 125000005843 halogen group Chemical group 0.000 description 29
- 238000003756 stirring Methods 0.000 description 29
- 150000003840 hydrochlorides Chemical class 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- 239000000546 pharmaceutical excipient Substances 0.000 description 25
- 0 *C1SC(*C*CCOC2(*)CC(*)(N(*)*)I)C2=C1* Chemical compound *C1SC(*C*CCOC2(*)CC(*)(N(*)*)I)C2=C1* 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 21
- 229940079593 drug Drugs 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 208000004296 neuralgia Diseases 0.000 description 19
- 230000006977 prepulse inhibition Effects 0.000 description 19
- 208000004454 Hyperalgesia Diseases 0.000 description 18
- 208000021722 neuropathic pain Diseases 0.000 description 18
- 206010010904 Convulsion Diseases 0.000 description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 125000003107 substituted aryl group Chemical group 0.000 description 16
- 239000000460 chlorine Substances 0.000 description 15
- 235000019441 ethanol Nutrition 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 14
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 14
- 125000005842 heteroatom Chemical group 0.000 description 14
- 150000002430 hydrocarbons Chemical group 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 125000003386 piperidinyl group Chemical group 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 208000018737 Parkinson disease Diseases 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 12
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 12
- 208000025966 Neurological disease Diseases 0.000 description 11
- 150000001721 carbon Chemical group 0.000 description 11
- 208000024714 major depressive disease Diseases 0.000 description 11
- 208000033808 peripheral neuropathy Diseases 0.000 description 11
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- 239000003826 tablet Substances 0.000 description 11
- 208000024827 Alzheimer disease Diseases 0.000 description 10
- 206010012289 Dementia Diseases 0.000 description 10
- 208000035154 Hyperesthesia Diseases 0.000 description 10
- 208000019022 Mood disease Diseases 0.000 description 10
- 238000013270 controlled release Methods 0.000 description 10
- 239000007884 disintegrant Substances 0.000 description 10
- 206010015037 epilepsy Diseases 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 125000002883 imidazolyl group Chemical group 0.000 description 10
- 208000015122 neurodegenerative disease Diseases 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- 230000002265 prevention Effects 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 208000020925 Bipolar disease Diseases 0.000 description 9
- 102100028728 Bone morphogenetic protein 1 Human genes 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 208000010877 cognitive disease Diseases 0.000 description 9
- 230000006378 damage Effects 0.000 description 9
- 238000003818 flash chromatography Methods 0.000 description 9
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 239000006186 oral dosage form Substances 0.000 description 9
- 239000006201 parenteral dosage form Substances 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- 208000019901 Anxiety disease Diseases 0.000 description 8
- 208000000094 Chronic Pain Diseases 0.000 description 8
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 8
- 208000023105 Huntington disease Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- 206010053552 allodynia Diseases 0.000 description 8
- 238000010171 animal model Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 208000013403 hyperactivity Diseases 0.000 description 8
- 208000014674 injury Diseases 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 230000004770 neurodegeneration Effects 0.000 description 8
- 230000000069 prophylactic effect Effects 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 208000012672 seasonal affective disease Diseases 0.000 description 8
- 208000011117 substance-related disease Diseases 0.000 description 8
- 208000030507 AIDS Diseases 0.000 description 7
- 208000028698 Cognitive impairment Diseases 0.000 description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 7
- 208000005793 Restless legs syndrome Diseases 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 230000036506 anxiety Effects 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 238000012377 drug delivery Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 238000007726 management method Methods 0.000 description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 7
- 239000008108 microcrystalline cellulose Substances 0.000 description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 description 7
- 125000002757 morpholinyl group Chemical group 0.000 description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 201000001119 neuropathy Diseases 0.000 description 7
- 230000007823 neuropathy Effects 0.000 description 7
- 208000020016 psychiatric disease Diseases 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 125000005017 substituted alkenyl group Chemical group 0.000 description 7
- 125000005415 substituted alkoxy group Chemical group 0.000 description 7
- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- 125000004426 substituted alkynyl group Chemical group 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- QENGPZGAWFQWCZ-UHFFFAOYSA-N 3-Methylthiophene Chemical compound CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 description 6
- 206010001497 Agitation Diseases 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 6
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 206010065390 Inflammatory pain Diseases 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 208000019695 Migraine disease Diseases 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 201000001880 Sexual dysfunction Diseases 0.000 description 6
- 206010041349 Somnolence Diseases 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 235000010443 alginic acid Nutrition 0.000 description 6
- 229920000615 alginic acid Polymers 0.000 description 6
- 239000000164 antipsychotic agent Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000011230 binding agent Substances 0.000 description 6
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 230000001684 chronic effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000004064 dysfunction Effects 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 125000004404 heteroalkyl group Chemical group 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000000314 lubricant Substances 0.000 description 6
- 206010027599 migraine Diseases 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 230000036278 prepulse Effects 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- 231100000872 sexual dysfunction Toxicity 0.000 description 6
- 239000012453 solvate Substances 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- 230000008448 thought Effects 0.000 description 6
- 238000003828 vacuum filtration Methods 0.000 description 6
- 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 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 5
- 206010013654 Drug abuse Diseases 0.000 description 5
- 208000001640 Fibromyalgia Diseases 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- 208000016285 Movement disease Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 208000004983 Phantom Limb Diseases 0.000 description 5
- 206010056238 Phantom pain Diseases 0.000 description 5
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 238000013019 agitation Methods 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 230000036461 convulsion Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 5
- 206010013663 drug dependence Diseases 0.000 description 5
- 208000024732 dysthymic disease Diseases 0.000 description 5
- 239000000945 filler Substances 0.000 description 5
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 206010022437 insomnia Diseases 0.000 description 5
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 201000006417 multiple sclerosis Diseases 0.000 description 5
- RTPZVGYRAUUZTD-UHFFFAOYSA-N n-methyl-1-(4h-thieno[3,2-c]chromen-4-yl)methanamine Chemical compound CNCC1OC2=CC=CC=C2C2=C1C=CS2 RTPZVGYRAUUZTD-UHFFFAOYSA-N 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000002093 peripheral effect Effects 0.000 description 5
- 150000003335 secondary amines Chemical class 0.000 description 5
- 208000019116 sleep disease Diseases 0.000 description 5
- 230000024188 startle response Effects 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 4
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 4
- VMJOFTHFJMLIKL-UHFFFAOYSA-N 2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1 VMJOFTHFJMLIKL-UHFFFAOYSA-N 0.000 description 4
- CBKDCOKSXCTDAA-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1C=CS2 CBKDCOKSXCTDAA-UHFFFAOYSA-N 0.000 description 4
- 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 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 208000000044 Amnesia Diseases 0.000 description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 208000001387 Causalgia Diseases 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229920000881 Modified starch Polymers 0.000 description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- 239000008156 Ringer's lactate solution Substances 0.000 description 4
- 206010070834 Sensitisation Diseases 0.000 description 4
- 206010040021 Sensory abnormalities Diseases 0.000 description 4
- 235000021355 Stearic acid Nutrition 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 239000000783 alginic acid Substances 0.000 description 4
- 229960001126 alginic acid Drugs 0.000 description 4
- 150000004781 alginic acids Chemical class 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 239000007894 caplet Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229960003920 cocaine Drugs 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 229910052805 deuterium Inorganic materials 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 208000002173 dizziness Diseases 0.000 description 4
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
- 239000003889 eye drop Substances 0.000 description 4
- 229940012356 eye drops Drugs 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 4
- 229960001375 lactose Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 230000013016 learning Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000015654 memory Effects 0.000 description 4
- 230000003340 mental effect Effects 0.000 description 4
- OSZVCAAHYJXXAJ-UHFFFAOYSA-N n-methyl-1-(3-methyl-4,5,6,7-tetrahydro-1-benzothiophen-4-yl)methanamine Chemical compound CNCC1CCCC2=C1C(C)=CS2 OSZVCAAHYJXXAJ-UHFFFAOYSA-N 0.000 description 4
- UEZSTRCEDCIBSS-UHFFFAOYSA-N n-methyl-1-(3-methyl-5,6-dihydro-4h-cyclopenta[b]thiophen-6-yl)methanamine Chemical compound CC1=CSC2=C1CCC2CNC UEZSTRCEDCIBSS-UHFFFAOYSA-N 0.000 description 4
- HPGXWUUGOKBNNJ-UHFFFAOYSA-N n-methyl-1-(4h-thieno[2,3-c]chromen-4-yl)methanamine Chemical compound CNCC1OC2=CC=CC=C2C2=C1SC=C2 HPGXWUUGOKBNNJ-UHFFFAOYSA-N 0.000 description 4
- XIUQDJTZLRPVDS-UHFFFAOYSA-N n-methyl-8-phenyl-1,2,3,4-tetrahydrodibenzothiophen-4-amine Chemical compound CNC1CCCC(C2=C3)=C1SC2=CC=C3C1=CC=CC=C1 XIUQDJTZLRPVDS-UHFFFAOYSA-N 0.000 description 4
- 201000003631 narcolepsy Diseases 0.000 description 4
- 210000005036 nerve Anatomy 0.000 description 4
- 230000002981 neuropathic effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 208000022821 personality disease Diseases 0.000 description 4
- 208000028173 post-traumatic stress disease Diseases 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 230000000698 schizophrenic effect Effects 0.000 description 4
- 230000035807 sensation Effects 0.000 description 4
- 230000008313 sensitization Effects 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 208000020685 sleep-wake disease Diseases 0.000 description 4
- 208000020431 spinal cord injury Diseases 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000008117 stearic acid Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 230000000451 tissue damage Effects 0.000 description 4
- 231100000827 tissue damage Toxicity 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- 206010044652 trigeminal neuralgia Diseases 0.000 description 4
- LVPYWMBNEWEIQH-IMTBSYHQSA-N (1s)-1-[(4s)-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl]ethanamine Chemical compound C[C@H](N)[C@H]1OCCC2=C1C=CS2 LVPYWMBNEWEIQH-IMTBSYHQSA-N 0.000 description 3
- PHVGLOWYWQNSRM-UHFFFAOYSA-N (2-ethyl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound NCC1OCCC2=C1C=C(CC)S2 PHVGLOWYWQNSRM-UHFFFAOYSA-N 0.000 description 3
- XXGOWWQYQBPPPW-VHSXEESVSA-N (2s)-2-[(7r)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]pyrrolidine Chemical compound C1CCN[C@@H]1[C@@H]1C(SC=C2)=C2CCO1 XXGOWWQYQBPPPW-VHSXEESVSA-N 0.000 description 3
- SSJZHZQJKGFVHY-UHFFFAOYSA-N (3-methyl-4,5,6,7-tetrahydro-1-benzothiophen-4-yl)methanamine Chemical compound C1CCC(CN)C2=C1SC=C2C SSJZHZQJKGFVHY-UHFFFAOYSA-N 0.000 description 3
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- FFYSKGQMTMUMEM-UHFFFAOYSA-N 1-(3-chloro-5,6-dihydro-4h-cyclopenta[b]thiophen-4-yl)-n-methylmethanamine Chemical compound S1C=C(Cl)C2=C1CCC2CNC FFYSKGQMTMUMEM-UHFFFAOYSA-N 0.000 description 3
- HJKLEAOXCZIMPI-UHFFFAOYSA-N 2,2-diethoxyethanamine Chemical compound CCOC(CN)OCC HJKLEAOXCZIMPI-UHFFFAOYSA-N 0.000 description 3
- YYJBWYBULYUKMR-UHFFFAOYSA-N 2-bromo-3-methylthiophene Chemical compound CC=1C=CSC=1Br YYJBWYBULYUKMR-UHFFFAOYSA-N 0.000 description 3
- RBIGKSZIQCTIJF-UHFFFAOYSA-N 3-formylthiophene Chemical compound O=CC=1C=CSC=1 RBIGKSZIQCTIJF-UHFFFAOYSA-N 0.000 description 3
- YAOWNFAXUDSXQA-UHFFFAOYSA-N 3-methyl-6-(nitromethyl)-5,6-dihydro-4h-cyclopenta[b]thiophene Chemical compound [O-][N+](=O)CC1CCC2=C1SC=C2C YAOWNFAXUDSXQA-UHFFFAOYSA-N 0.000 description 3
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- SNYURIHMNFPQFL-UHFFFAOYSA-N 5-chloro-1-benzothiophene Chemical compound ClC1=CC=C2SC=CC2=C1 SNYURIHMNFPQFL-UHFFFAOYSA-N 0.000 description 3
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 3
- BJHKTBMMYSYOLJ-UHFFFAOYSA-N 5-phenyl-1-benzothiophene Chemical compound C=1C=C2SC=CC2=CC=1C1=CC=CC=C1 BJHKTBMMYSYOLJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 208000017194 Affective disease Diseases 0.000 description 3
- 208000031091 Amnestic disease Diseases 0.000 description 3
- 206010003805 Autism Diseases 0.000 description 3
- 208000020706 Autistic disease Diseases 0.000 description 3
- 206010058019 Cancer Pain Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 3
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
- 206010012239 Delusion Diseases 0.000 description 3
- 206010012335 Dependence Diseases 0.000 description 3
- 208000020401 Depressive disease Diseases 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 3
- 206010052804 Drug tolerance Diseases 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 208000004547 Hallucinations Diseases 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000001456 Jet Lag Syndrome Diseases 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 229910010082 LiAlH Inorganic materials 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 208000000112 Myalgia Diseases 0.000 description 3
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 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 3
- ODHCTXKNWHHXJC-UHFFFAOYSA-N acide pyroglutamique Natural products OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229940025084 amphetamine Drugs 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000561 anti-psychotic effect Effects 0.000 description 3
- 229940005529 antipsychotics Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- BMLSTPRTEKLIPM-UHFFFAOYSA-I calcium;potassium;disodium;hydrogen carbonate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].OC([O-])=O BMLSTPRTEKLIPM-UHFFFAOYSA-I 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000005687 corn oil Nutrition 0.000 description 3
- 239000002285 corn oil Substances 0.000 description 3
- 235000012343 cottonseed oil Nutrition 0.000 description 3
- 239000002385 cottonseed oil Substances 0.000 description 3
- 239000013058 crude material Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 3
- 230000006735 deficit Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 231100000868 delusion Toxicity 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 230000008451 emotion Effects 0.000 description 3
- 201000003104 endogenous depression Diseases 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 235000012208 gluconic acid Nutrition 0.000 description 3
- 229950006191 gluconic acid Drugs 0.000 description 3
- 230000026781 habituation Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000009610 hypersensitivity Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000008297 liquid dosage form Substances 0.000 description 3
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000036651 mood Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000008904 neural response Effects 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000003368 psychostimulant agent Substances 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 239000008159 sesame oil Substances 0.000 description 3
- 235000011803 sesame oil Nutrition 0.000 description 3
- 201000002859 sleep apnea Diseases 0.000 description 3
- 239000008354 sodium chloride injection Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- BOOFCAWXWFFTOF-UHFFFAOYSA-N tert-butyl n-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1OCCC2=C1C=CS2 BOOFCAWXWFFTOF-UHFFFAOYSA-N 0.000 description 3
- FDRALHHLTUIOSZ-UHFFFAOYSA-N tert-butyl n-[(2-bromo-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1OCCC2=C1C=C(Br)S2 FDRALHHLTUIOSZ-UHFFFAOYSA-N 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- 238000000844 transformation Methods 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- KHZWAHOZGFRRNO-APPZFPTMSA-N (1r)-1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylethanamine Chemical compound CN[C@H](C)[C@@H]1OCCC2=C1SC=C2 KHZWAHOZGFRRNO-APPZFPTMSA-N 0.000 description 2
- RJKFJOKFGIHYEE-SVRRBLITSA-N (1r)-1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]ethanamine Chemical compound C[C@@H](N)[C@@H]1OCCC2=C1SC=C2 RJKFJOKFGIHYEE-SVRRBLITSA-N 0.000 description 2
- SSCWSCUCEZCNJT-UHFFFAOYSA-N (2-bromo-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound NCC1OCCC2=C1C=C(Br)S2 SSCWSCUCEZCNJT-UHFFFAOYSA-N 0.000 description 2
- BOJYRNFSHPAZBL-UHFFFAOYSA-N (2-bromothiophen-3-yl)methanol Chemical compound OCC=1C=CSC=1Br BOJYRNFSHPAZBL-UHFFFAOYSA-N 0.000 description 2
- HWNPTXNCWWHZEW-UHFFFAOYSA-N (2-fluoro-3-methyl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound C1COC(CN)C2=C1SC(F)=C2C HWNPTXNCWWHZEW-UHFFFAOYSA-N 0.000 description 2
- NQSCGFNDMBODNB-UHFFFAOYSA-N (3-bromo-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound NCC1OCCC2=C1C(Br)=CS2 NQSCGFNDMBODNB-UHFFFAOYSA-N 0.000 description 2
- UYEBWPIRYKGCOU-UHFFFAOYSA-N (3-methyl-5,6-dihydro-4h-cyclopenta[b]thiophen-6-yl)methanamine Chemical compound NCC1CCC2=C1SC=C2C UYEBWPIRYKGCOU-UHFFFAOYSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
- JKRYSONDYRROQO-UHFFFAOYSA-N 1-(2-bromo-3-chloro-5,6-dihydro-4h-cyclopenta[b]thiophen-4-yl)-n-methylmethanamine Chemical compound S1C(Br)=C(Cl)C2=C1CCC2CNC JKRYSONDYRROQO-UHFFFAOYSA-N 0.000 description 2
- HSVFEOWFFWPULX-UHFFFAOYSA-N 1-(3-chloro-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl)-n-methylmethanamine Chemical compound CNCC1OCCC2=C1SC=C2Cl HSVFEOWFFWPULX-UHFFFAOYSA-N 0.000 description 2
- PPLSPIZQQHAHBA-UHFFFAOYSA-N 1-(5,6-dihydro-4h-cyclopenta[b]thiophen-4-yl)-n-methylmethanamine Chemical compound S1C=CC2=C1CCC2CNC PPLSPIZQQHAHBA-UHFFFAOYSA-N 0.000 description 2
- POTLHQVUZAJAMW-UHFFFAOYSA-N 1-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)-n-methylcyclohexan-1-amine Chemical compound O1CCC=2SC=CC=2C1C1(NC)CCCCC1 POTLHQVUZAJAMW-UHFFFAOYSA-N 0.000 description 2
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- GWQOOADXMVQEFT-UHFFFAOYSA-N 2,5-Dimethylthiophene Chemical compound CC1=CC=C(C)S1 GWQOOADXMVQEFT-UHFFFAOYSA-N 0.000 description 2
- JYNOXEBITOGCMQ-UHFFFAOYSA-N 2,5-dibromo-3-phenylthiophene Chemical compound S1C(Br)=CC(C=2C=CC=CC=2)=C1Br JYNOXEBITOGCMQ-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- GPAIEIFXXXKXEH-UHFFFAOYSA-N 2-(4-bromothiophen-2-yl)ethanol Chemical compound OCCC1=CC(Br)=CS1 GPAIEIFXXXKXEH-UHFFFAOYSA-N 0.000 description 2
- BYKQZKUBMDJFOY-UHFFFAOYSA-N 2-(4-methylthiophen-2-yl)ethanol Chemical compound CC1=CSC(CCO)=C1 BYKQZKUBMDJFOY-UHFFFAOYSA-N 0.000 description 2
- LCZBURNPKZNQFE-UHFFFAOYSA-N 2-(4-phenylthiophen-3-yl)ethanol Chemical compound OCCC1=CSC=C1C1=CC=CC=C1 LCZBURNPKZNQFE-UHFFFAOYSA-N 0.000 description 2
- KIJUQVMAPUFEAZ-UHFFFAOYSA-N 2-(5-bromo-4-iodothiophen-2-yl)ethoxy-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(I)=C(Br)S1 KIJUQVMAPUFEAZ-UHFFFAOYSA-N 0.000 description 2
- IHOCRMPRADFCNM-UHFFFAOYSA-N 2-(5-bromothiophen-2-yl)ethanol Chemical compound OCCC1=CC=C(Br)S1 IHOCRMPRADFCNM-UHFFFAOYSA-N 0.000 description 2
- TWBHKELSPUYCCE-UHFFFAOYSA-N 2-(5-bromothiophen-2-yl)ethoxy-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC=C(Br)S1 TWBHKELSPUYCCE-UHFFFAOYSA-N 0.000 description 2
- FXHRBUQMWOTKRI-UHFFFAOYSA-N 2-(5-ethylthiophen-2-yl)ethanol Chemical compound CCC1=CC=C(CCO)S1 FXHRBUQMWOTKRI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- GUHABYPYCGXANA-UHFFFAOYSA-N 2-fluorospiro[6,7-dihydrothieno[3,2-c]pyran-4,3'-pyrrolidine] Chemical compound S1C(F)=CC2=C1CCOC21CCNC1 GUHABYPYCGXANA-UHFFFAOYSA-N 0.000 description 2
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 2
- VCRSXSFOKOVCRV-UHFFFAOYSA-N 2-thiophen-3-ylphenol Chemical compound OC1=CC=CC=C1C1=CSC=C1 VCRSXSFOKOVCRV-UHFFFAOYSA-N 0.000 description 2
- OLVHNXAWFVEGDN-UHFFFAOYSA-N 3-(4-methylthiophen-2-yl)-4-nitrobutanoic acid Chemical compound CC1=CSC(C(CC(O)=O)C[N+]([O-])=O)=C1 OLVHNXAWFVEGDN-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- XCMISAPCWHTVNG-UHFFFAOYSA-N 3-bromothiophene Chemical compound BrC=1C=CSC=1 XCMISAPCWHTVNG-UHFFFAOYSA-N 0.000 description 2
- LRFMGESCOZAPTQ-UHFFFAOYSA-N 3-methyl-6-(nitromethyl)-5,6-dihydrocyclopenta[b]thiophen-4-one Chemical compound [O-][N+](=O)CC1CC(=O)C2=C1SC=C2C LRFMGESCOZAPTQ-UHFFFAOYSA-N 0.000 description 2
- DEWAOGITEZGETP-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophen-4-ylmethanamine Chemical compound NCC1CCCC2=C1C=CS2 DEWAOGITEZGETP-UHFFFAOYSA-N 0.000 description 2
- QAHUKUVYNAQQIX-UHFFFAOYSA-N 4-(5-phenyl-1-benzothiophen-3-yl)butanoic acid Chemical compound C1=C2C(CCCC(=O)O)=CSC2=CC=C1C1=CC=CC=C1 QAHUKUVYNAQQIX-UHFFFAOYSA-N 0.000 description 2
- BUWSEZUSGNBMJN-UHFFFAOYSA-N 4-(nitromethyl)-4,5-dihydrocyclopenta[b]thiophen-6-one Chemical compound S1C=CC2=C1C(=O)CC2C[N+](=O)[O-] BUWSEZUSGNBMJN-UHFFFAOYSA-N 0.000 description 2
- SPIAULWVSNOTEL-UHFFFAOYSA-N 4-(nitromethyl)-4h-thieno[3,2-c]chromene Chemical compound [O-][N+](=O)CC1OC2=CC=CC=C2C2=C1C=CS2 SPIAULWVSNOTEL-UHFFFAOYSA-N 0.000 description 2
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- HVXCGIPRXBJIRK-UHFFFAOYSA-N 4-methylthiophene-2-carbaldehyde Chemical compound CC1=CSC(C=O)=C1 HVXCGIPRXBJIRK-UHFFFAOYSA-N 0.000 description 2
- VVOASXXDMVSWTK-UHFFFAOYSA-N 4-nitro-3-thiophen-3-ylbutanoic acid Chemical compound OC(=O)CC(C[N+]([O-])=O)C=1C=CSC=1 VVOASXXDMVSWTK-UHFFFAOYSA-N 0.000 description 2
- QUOGANUQCIWVBF-UHFFFAOYSA-N 4-oxo-4-(5-phenyl-1-benzothiophen-3-yl)butanoic acid Chemical compound C1=C2C(C(=O)CCC(=O)O)=CSC2=CC=C1C1=CC=CC=C1 QUOGANUQCIWVBF-UHFFFAOYSA-N 0.000 description 2
- KFSODTRTXWHIKA-UHFFFAOYSA-N 4h-thieno[3,2-c]chromen-4-ylmethanamine Chemical compound NCC1OC2=CC=CC=C2C2=C1C=CS2 KFSODTRTXWHIKA-UHFFFAOYSA-N 0.000 description 2
- WXVOJUGDSMHYNX-UHFFFAOYSA-N 5-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)-n,n,2-trimethylimidazole-1-sulfonamide Chemical compound CN(C)S(=O)(=O)N1C(C)=NC=C1C1C(C=CS2)=C2CCO1 WXVOJUGDSMHYNX-UHFFFAOYSA-N 0.000 description 2
- GJEKNELSXNSYAQ-UHFFFAOYSA-N 6,7-dihydro-5h-1-benzothiophen-4-one Chemical compound O=C1CCCC2=C1C=CS2 GJEKNELSXNSYAQ-UHFFFAOYSA-N 0.000 description 2
- DAHQJNJKSDLOPD-UHFFFAOYSA-N 8-phenyl-2,3-dihydro-1h-dibenzothiophen-4-one Chemical compound O=C1CCCC(C2=C3)=C1SC2=CC=C3C1=CC=CC=C1 DAHQJNJKSDLOPD-UHFFFAOYSA-N 0.000 description 2
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 206010001488 Aggression Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 2
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 206010012218 Delirium Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 208000027534 Emotional disease Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000011688 Generalised anxiety disease Diseases 0.000 description 2
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 2
- 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 2
- 206010020772 Hypertension Diseases 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 208000001294 Nociceptive Pain Diseases 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-GSVOUGTGSA-N Pyroglutamic acid Natural products OC(=O)[C@H]1CCC(=O)N1 ODHCTXKNWHHXJC-GSVOUGTGSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000019568 Shared Paranoid disease Diseases 0.000 description 2
- 208000028810 Shared psychotic disease Diseases 0.000 description 2
- 208000032140 Sleepiness 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 208000011963 Substance-induced psychotic disease Diseases 0.000 description 2
- 231100000393 Substance-induced psychotic disorder Toxicity 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 208000000323 Tourette Syndrome Diseases 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 208000018839 Wilson disease Diseases 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 208000005298 acute pain Diseases 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000006986 amnesia Effects 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- 239000008135 aqueous vehicle Substances 0.000 description 2
- 230000037007 arousal Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 125000003725 azepanyl group Chemical group 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 229960002903 benzyl benzoate Drugs 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 208000028683 bipolar I disease Diseases 0.000 description 2
- 208000025307 bipolar depression Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 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
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 2
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 229960004170 clozapine Drugs 0.000 description 2
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229960002887 deanol Drugs 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000008355 dextrose injection Substances 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- 239000002027 dichloromethane extract Substances 0.000 description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 238000007876 drug discovery Methods 0.000 description 2
- 201000002545 drug psychosis Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- JVKOMXUTXGBJFC-ONEGZZNKSA-N ethyl (e)-3-thiophen-3-ylprop-2-enoate Chemical compound CCOC(=O)\C=C\C=1C=CSC=1 JVKOMXUTXGBJFC-ONEGZZNKSA-N 0.000 description 2
- FBQKXCVUIJDJCQ-UHFFFAOYSA-N ethyl 4-(4-methylthiophen-2-yl)butanoate Chemical compound CCOC(=O)CCCC1=CC(C)=CS1 FBQKXCVUIJDJCQ-UHFFFAOYSA-N 0.000 description 2
- ZUSSQACKXMCGFT-UHFFFAOYSA-N ethyl 4-nitro-3-thiophen-3-ylbutanoate Chemical compound CCOC(=O)CC(C[N+]([O-])=O)C=1C=CSC=1 ZUSSQACKXMCGFT-UHFFFAOYSA-N 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 208000033699 familial Guillain-Barre syndrome Diseases 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 208000029364 generalized anxiety disease Diseases 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229960000448 lactic acid Drugs 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 229940098895 maleic acid Drugs 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 229940099690 malic acid Drugs 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- 229960001252 methamphetamine Drugs 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 2
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 2
- GDGREFAMRJKVLP-UHFFFAOYSA-N n-methyl-1-(2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-7-yl)methanamine Chemical compound CNCC1CCCC2=C1SC(C)=N2 GDGREFAMRJKVLP-UHFFFAOYSA-N 0.000 description 2
- WIAVLWYUZKLCJA-UHFFFAOYSA-N n-methyl-1-(3-phenyl-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl)methanamine Chemical compound C=1SC=2C(CNC)OCCC=2C=1C1=CC=CC=C1 WIAVLWYUZKLCJA-UHFFFAOYSA-N 0.000 description 2
- LEIJIFSKDBIFJW-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1-benzothiophen-4-yl)methanamine Chemical compound CNCC1CCCC2=C1C=CS2 LEIJIFSKDBIFJW-UHFFFAOYSA-N 0.000 description 2
- QFMGONGWMDRQGW-UHFFFAOYSA-N n-methyl-1-(4,5,6,7-tetrahydro-1-benzothiophen-7-yl)methanamine Chemical compound CNCC1CCCC2=C1SC=C2 QFMGONGWMDRQGW-UHFFFAOYSA-N 0.000 description 2
- FZSCLOWORZHKMH-UHFFFAOYSA-N n-methyl-4-(methylaminomethyl)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine Chemical compound CNCC1CCCC2=C1N=C(NC)S2 FZSCLOWORZHKMH-UHFFFAOYSA-N 0.000 description 2
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 230000003955 neuronal function Effects 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000002687 nonaqueous vehicle Substances 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- 230000001473 noxious effect Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229960005152 pentetrazol Drugs 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 230000006461 physiological response Effects 0.000 description 2
- 229920001451 polypropylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 150000003235 pyrrolidines Chemical class 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 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 2
- 229960002646 scopolamine Drugs 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical compound OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- 230000009155 sensory pathway Effects 0.000 description 2
- 208000012201 sexual and gender identity disease Diseases 0.000 description 2
- 208000015891 sexual disease Diseases 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 230000037321 sleepiness Effects 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 238000003419 tautomerization reaction Methods 0.000 description 2
- GKYVFBVUIZKTPT-UHFFFAOYSA-N tert-butyl 3-hydroxy-3-[2-(2-hydroxyphenyl)thiophen-3-yl]pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1(O)C1=C(C=2C(=CC=CC=2)O)SC=C1 GKYVFBVUIZKTPT-UHFFFAOYSA-N 0.000 description 2
- JHXQRPUXSBWNHR-UHFFFAOYSA-N tert-butyl 3-hydroxy-3-thiophen-3-ylpyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1(O)C1=CSC=C1 JHXQRPUXSBWNHR-UHFFFAOYSA-N 0.000 description 2
- HLFRLJXPKWUEDP-UHFFFAOYSA-N tert-butyl n-[(2-iodo-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1OCCC2=C1C=C(I)S2 HLFRLJXPKWUEDP-UHFFFAOYSA-N 0.000 description 2
- AGDQXAFPUYUSBI-UHFFFAOYSA-N tert-butyl n-[(2-pyridin-3-yl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methyl]carbamate Chemical compound C=1C=2C(CNC(=O)OC(C)(C)C)OCCC=2SC=1C1=CC=CN=C1 AGDQXAFPUYUSBI-UHFFFAOYSA-N 0.000 description 2
- GYIHKJQTALKIBR-UHFFFAOYSA-N tert-butyl spiro[pyrrolidine-3,4'-thieno[3,2-c]chromene]-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC21C(C=CS1)=C1C1=CC=CC=C1O2 GYIHKJQTALKIBR-UHFFFAOYSA-N 0.000 description 2
- JMYJXOAXVNGFKO-UHFFFAOYSA-N tert-butyl-dimethyl-[2-(4-methylthiophen-2-yl)ethoxy]silane Chemical compound CC1=CSC(CCO[Si](C)(C)C(C)(C)C)=C1 JMYJXOAXVNGFKO-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- CHXZRHMQQRUVHF-UHFFFAOYSA-N thiophene A Natural products CC#CC1=CC=C(C#CC#CC=C)S1 CHXZRHMQQRUVHF-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000003901 trigeminal nerve Anatomy 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 230000001457 vasomotor Effects 0.000 description 2
- 208000009935 visceral pain Diseases 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000008136 water-miscible vehicle Substances 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- YOECCLZXTDYJSL-UHFFFAOYSA-N (1,3-dimethyl-6,7-dihydro-4h-thieno[3,4-c]pyran-4-yl)methanamine Chemical compound NCC1OCCC2=C(C)SC(C)=C21 YOECCLZXTDYJSL-UHFFFAOYSA-N 0.000 description 1
- CMKMQAYGTUPDRW-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methanol Chemical compound OCC1CCCC2=C1N=C(N)S2 CMKMQAYGTUPDRW-UHFFFAOYSA-N 0.000 description 1
- CJXBGHVVRHSHPH-UHFFFAOYSA-N (2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-4-yl)methyl methanesulfonate Chemical compound CS(=O)(=O)OCC1CCCC2=C1N=C(N)S2 CJXBGHVVRHSHPH-UHFFFAOYSA-N 0.000 description 1
- SAADYZLXEVGUKG-UHFFFAOYSA-N (2-fluoro-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound NCC1OCCC2=C1C=C(F)S2 SAADYZLXEVGUKG-UHFFFAOYSA-N 0.000 description 1
- YDMRDHQUQIVWBE-UHFFFAOYSA-N (2-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1O YDMRDHQUQIVWBE-UHFFFAOYSA-N 0.000 description 1
- JUBQYMFJKKQDIL-UHFFFAOYSA-N (2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-7-yl)methanamine Chemical compound C1CCC(CN)C2=C1N=C(C)S2 JUBQYMFJKKQDIL-UHFFFAOYSA-N 0.000 description 1
- BBADFWSFNOQECA-UHFFFAOYSA-N (2-piperidin-1-yl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound C=1C=2C(CN)OCCC=2SC=1N1CCCCC1 BBADFWSFNOQECA-UHFFFAOYSA-N 0.000 description 1
- WLNLFCUFBJDLLM-UHFFFAOYSA-N (2-pyridin-3-yl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound C=1C=2C(CN)OCCC=2SC=1C1=CC=CN=C1 WLNLFCUFBJDLLM-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- LOMFOPQMKQJGMX-UHFFFAOYSA-N (3-pyridin-3-yl-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)methanamine Chemical compound C1=2C(CN)OCCC=2SC=C1C1=CC=CN=C1 LOMFOPQMKQJGMX-UHFFFAOYSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
- NGRIHWBDQMEDHK-UHFFFAOYSA-N 1-(2-bromo-3-chloro-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl)-n-methylmethanamine Chemical compound CNCC1OCCC2=C1SC(Br)=C2Cl NGRIHWBDQMEDHK-UHFFFAOYSA-N 0.000 description 1
- WBWIZZNDPKHYTO-UHFFFAOYSA-N 1-(2-bromo-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl)-n-methylmethanamine Chemical compound CNCC1OCCC2=C1SC(Br)=C2 WBWIZZNDPKHYTO-UHFFFAOYSA-N 0.000 description 1
- QXJQGRZYZOXBDT-UHFFFAOYSA-N 1-(2-bromothiophen-3-yl)-2-nitroethanol Chemical compound [O-][N+](=O)CC(O)C=1C=CSC=1Br QXJQGRZYZOXBDT-UHFFFAOYSA-N 0.000 description 1
- RQPKRDCFGLCWNM-UHFFFAOYSA-N 1-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)cyclohexan-1-amine Chemical compound O1CCC=2SC=CC=2C1C1(N)CCCCC1 RQPKRDCFGLCWNM-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- JTSKSTQQTIICTJ-UHFFFAOYSA-N 1-[2-bromo-3-(trifluoromethyl)-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl]-n-methylmethanamine Chemical compound CNCC1OCCC2=C1C(C(F)(F)F)=C(Br)S2 JTSKSTQQTIICTJ-UHFFFAOYSA-N 0.000 description 1
- HGHXSASHYCILOM-UHFFFAOYSA-N 1-chloro-4-(2,2-dimethoxyethylsulfanyl)benzene Chemical compound COC(OC)CSC1=CC=C(Cl)C=C1 HGHXSASHYCILOM-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-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
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
- WAQFYSJKIRRXLP-UHFFFAOYSA-N 2,4-dibromothiophene Chemical compound BrC1=CSC(Br)=C1 WAQFYSJKIRRXLP-UHFFFAOYSA-N 0.000 description 1
- WOEIQMDZRCPWRS-UHFFFAOYSA-N 2,5-dibromo-3-ethyl-4-phenylthiophene Chemical compound CCC1=C(Br)SC(Br)=C1C1=CC=CC=C1 WOEIQMDZRCPWRS-UHFFFAOYSA-N 0.000 description 1
- XSJNRKCAVIWOGV-UHFFFAOYSA-N 2-(2-bromothiophen-3-yl)ethanol Chemical compound OCCC=1C=CSC=1Br XSJNRKCAVIWOGV-UHFFFAOYSA-N 0.000 description 1
- OJKAJJJGSHQYTR-UHFFFAOYSA-N 2-(4,5,6,7-tetrahydro-1-benzothiophen-3-yl)ethanol Chemical compound C1CCCC2=C1SC=C2CCO OJKAJJJGSHQYTR-UHFFFAOYSA-N 0.000 description 1
- MFTUBMVRULFRJU-UHFFFAOYSA-N 2-(5-chloro-1-benzothiophen-2-yl)ethanol Chemical compound ClC1=CC=C2SC(CCO)=CC2=C1 MFTUBMVRULFRJU-UHFFFAOYSA-N 0.000 description 1
- MSDNQSCVLOKBEE-UHFFFAOYSA-N 2-(5-fluorothiophen-2-yl)ethoxy-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC=C(F)S1 MSDNQSCVLOKBEE-UHFFFAOYSA-N 0.000 description 1
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
- UIPDHRPWNWVZQV-UHFFFAOYSA-N 2-[5-bromo-4-(trifluoromethyl)thiophen-2-yl]ethoxy-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC(C(F)(F)F)=C(Br)S1 UIPDHRPWNWVZQV-UHFFFAOYSA-N 0.000 description 1
- FUSFWUFSEJXMRQ-UHFFFAOYSA-N 2-bromo-1,1-dimethoxyethane Chemical compound COC(CBr)OC FUSFWUFSEJXMRQ-UHFFFAOYSA-N 0.000 description 1
- GOHSKRBVVFCLDO-UHFFFAOYSA-N 2-bromo-2-chloro-2-fluoroacetic acid Chemical compound OC(=O)C(F)(Cl)Br GOHSKRBVVFCLDO-UHFFFAOYSA-N 0.000 description 1
- MMCOTLPKJZWVQI-UHFFFAOYSA-N 2-bromo-5-chloro-1-benzothiophene Chemical compound ClC1=CC=C2SC(Br)=CC2=C1 MMCOTLPKJZWVQI-UHFFFAOYSA-N 0.000 description 1
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 1
- MMEGVQIGIBCTHI-UHFFFAOYSA-N 2-bromothiophene-3-carbaldehyde Chemical compound BrC=1SC=CC=1C=O MMEGVQIGIBCTHI-UHFFFAOYSA-N 0.000 description 1
- OVXJWSYBABKZMD-UHFFFAOYSA-N 2-chloro-1,1-diethoxyethane Chemical compound CCOC(CCl)OCC OVXJWSYBABKZMD-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- JCCCMAAJYSNBPR-UHFFFAOYSA-N 2-ethylthiophene Chemical compound CCC1=CC=CS1 JCCCMAAJYSNBPR-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- FFUDKNPQBLHKFG-UHFFFAOYSA-N 2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazole-7-carbonitrile Chemical compound C1CCC(C#N)C2=C1N=C(C)S2 FFUDKNPQBLHKFG-UHFFFAOYSA-N 0.000 description 1
- QFTUPSZZEJQOJX-UHFFFAOYSA-N 2-methyl-5,6-dihydro-4h-1,3-benzothiazol-7-one Chemical compound C1CCC(=O)C2=C1N=C(C)S2 QFTUPSZZEJQOJX-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- BOWIFWCBNWWZOG-UHFFFAOYSA-N 3-Thiophenemethanol Chemical compound OCC=1C=CSC=1 BOWIFWCBNWWZOG-UHFFFAOYSA-N 0.000 description 1
- TVYQEDUVSABWTO-UHFFFAOYSA-N 3-bromo-4,5,6,7-tetrahydro-1-benzothiophene Chemical compound C1CCCC2=C1SC=C2Br TVYQEDUVSABWTO-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- YVRKWORZQDNEFG-UHFFFAOYSA-N 3-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carbonitrile Chemical compound C1CCC(C#N)C2=C1SC=C2C YVRKWORZQDNEFG-UHFFFAOYSA-N 0.000 description 1
- BECAJEAHWWQBBH-UHFFFAOYSA-N 3-methyl-6,7-dihydro-5h-1-benzothiophen-4-one Chemical compound C1CCC(=O)C2=C1SC=C2C BECAJEAHWWQBBH-UHFFFAOYSA-N 0.000 description 1
- ZDQZVKVIYAPRON-UHFFFAOYSA-N 3-phenylthiophene Chemical compound S1C=CC(C=2C=CC=CC=2)=C1 ZDQZVKVIYAPRON-UHFFFAOYSA-N 0.000 description 1
- BQFZLZCBCSKUPL-UHFFFAOYSA-N 3-thiophen-2-ylpropan-1-ol Chemical compound OCCCC1=CC=CS1 BQFZLZCBCSKUPL-UHFFFAOYSA-N 0.000 description 1
- ZBQGJRGOKSUHEI-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophen-7-ylmethanamine Chemical compound NCC1CCCC2=C1SC=C2 ZBQGJRGOKSUHEI-UHFFFAOYSA-N 0.000 description 1
- IQCDWMKOBOPLEN-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene-4-carbonitrile Chemical compound N#CC1CCCC2=C1C=CS2 IQCDWMKOBOPLEN-UHFFFAOYSA-N 0.000 description 1
- NAEABLQWNLNRLH-UHFFFAOYSA-N 4,5,6,7-tetrahydro-1-benzothiophene-7-carbonitrile Chemical compound N#CC1CCCC2=C1SC=C2 NAEABLQWNLNRLH-UHFFFAOYSA-N 0.000 description 1
- PEOXTJAJKCCOPZ-UHFFFAOYSA-N 4-(4-methylthiophen-2-yl)butanoic acid Chemical compound CC1=CSC(CCCC(O)=O)=C1 PEOXTJAJKCCOPZ-UHFFFAOYSA-N 0.000 description 1
- VBDQFINPZKKLIK-UHFFFAOYSA-N 4-(aminomethyl)-4,5,6,7-tetrahydro-1,3-benzothiazol-2-amine Chemical compound NCC1CCCC2=C1N=C(N)S2 VBDQFINPZKKLIK-UHFFFAOYSA-N 0.000 description 1
- AYTKKMCQQCDLET-UHFFFAOYSA-N 4-(aminomethyl)-6,7-dihydro-5h-1-benzothiophen-4-ol Chemical compound NCC1(O)CCCC2=C1C=CS2 AYTKKMCQQCDLET-UHFFFAOYSA-N 0.000 description 1
- GSVMDXQGXUCKDN-UHFFFAOYSA-N 4-(chloromethyl)-6,7-dihydro-4h-thieno[3,2-c]pyran Chemical compound ClCC1OCCC2=C1C=CS2 GSVMDXQGXUCKDN-UHFFFAOYSA-N 0.000 description 1
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- WRFYIYOXJWKONR-UHFFFAOYSA-N 4-bromo-2-methoxyaniline Chemical compound COC1=CC(Br)=CC=C1N WRFYIYOXJWKONR-UHFFFAOYSA-N 0.000 description 1
- PHFOMDABIOSBIP-UHFFFAOYSA-N 4-hydroxy-6,7-dihydro-5h-1-benzothiophene-4-carbonitrile Chemical compound N#CC1(O)CCCC2=C1C=CS2 PHFOMDABIOSBIP-UHFFFAOYSA-N 0.000 description 1
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 1
- 125000005986 4-piperidonyl group Chemical group 0.000 description 1
- QICKSFILIHOSPO-UHFFFAOYSA-N 4-thiophen-3-ylbutanoic acid Chemical compound OC(=O)CCCC=1C=CSC=1 QICKSFILIHOSPO-UHFFFAOYSA-N 0.000 description 1
- DYTVRYMZZQQKPG-UHFFFAOYSA-N 4h-thieno[2,3-c]chromen-4-ylmethanamine Chemical compound NCC1OC2=CC=CC=C2C2=C1SC=C2 DYTVRYMZZQQKPG-UHFFFAOYSA-N 0.000 description 1
- JEJQJCKVMQVOHZ-UHFFFAOYSA-N 5,6-dihydro-4h-1-benzothiophen-7-one Chemical compound O=C1CCCC2=C1SC=C2 JEJQJCKVMQVOHZ-UHFFFAOYSA-N 0.000 description 1
- VMANPYMZMLYRPY-UHFFFAOYSA-N 5,6-dihydro-4h-cyclopenta[b]thiophen-4-ylmethanamine Chemical compound S1C=CC2=C1CCC2CN VMANPYMZMLYRPY-UHFFFAOYSA-N 0.000 description 1
- BSTYEWVPNPQKAI-UHFFFAOYSA-N 5-(5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl)-n,n,2-trimethylimidazole-1-sulfonamide Chemical compound CN(C)S(=O)(=O)N1C(C)=NC=C1C1C(SC=C2)=C2CCO1 BSTYEWVPNPQKAI-UHFFFAOYSA-N 0.000 description 1
- FATNNNCLTSHUQL-UHFFFAOYSA-N 5-bromo-4-methylthiophene-2-carbaldehyde Chemical compound CC=1C=C(C=O)SC=1Br FATNNNCLTSHUQL-UHFFFAOYSA-N 0.000 description 1
- WQPHBGBXYRHVHQ-UHFFFAOYSA-N 5-formyl-n,n,2-trimethylimidazole-1-sulfonamide Chemical compound CN(C)S(=O)(=O)N1C(C)=NC=C1C=O WQPHBGBXYRHVHQ-UHFFFAOYSA-N 0.000 description 1
- PILKAXDAYOOPHC-UHFFFAOYSA-N 6,7-dihydro-4h-thieno[3,4-c]pyran-4-ylmethanamine Chemical compound NCC1OCCC2=CSC=C12 PILKAXDAYOOPHC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- HJUXXCOVGMCKQL-AWEZNQCLSA-N 9h-fluoren-9-ylmethyl (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound OC[C@@H]1CCCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 HJUXXCOVGMCKQL-AWEZNQCLSA-N 0.000 description 1
- ZYMWYFMERGYVAM-NPMXOYFQSA-N 9h-fluoren-9-ylmethyl n-[(1s)-1-[(4s)-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl]ethyl]carbamate Chemical compound O([C@@H]1[C@@H](NC(=O)OCC2C3=CC=CC=C3C3=CC=CC=C32)C)CCC2=C1C=CS2 ZYMWYFMERGYVAM-NPMXOYFQSA-N 0.000 description 1
- GIZCEJUGNDJXMH-LBPRGKRZSA-N 9h-fluoren-9-ylmethyl n-[(2s)-1-hydroxypropan-2-yl]carbamate Chemical compound C1=CC=C2C(COC(=O)N[C@H](CO)C)C3=CC=CC=C3C2=C1 GIZCEJUGNDJXMH-LBPRGKRZSA-N 0.000 description 1
- ULGIGDIOTZVEMJ-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-[1-(hydroxymethyl)cyclohexyl]carbamate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC1(CO)CCCCC1 ULGIGDIOTZVEMJ-UHFFFAOYSA-N 0.000 description 1
- 101150010783 Aard gene Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- BZBAYMUKLAYQEO-UHFFFAOYSA-N Bc1ccccc1 Chemical compound Bc1ccccc1 BZBAYMUKLAYQEO-UHFFFAOYSA-N 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- RDSIMGKJEYNNLF-UHFFFAOYSA-N Brc(cc1)cc2c1[s]cc2 Chemical compound Brc(cc1)cc2c1[s]cc2 RDSIMGKJEYNNLF-UHFFFAOYSA-N 0.000 description 1
- SJWIONFDUXLPLT-UHFFFAOYSA-N C(C(CCC1)c2c1[s]cc2)N1CCCCC1 Chemical compound C(C(CCC1)c2c1[s]cc2)N1CCCCC1 SJWIONFDUXLPLT-UHFFFAOYSA-N 0.000 description 1
- NIBDYNBWJDEMKA-UHFFFAOYSA-N CC1(CN)OCCc2c1cc[s]2 Chemical compound CC1(CN)OCCc2c1cc[s]2 NIBDYNBWJDEMKA-UHFFFAOYSA-N 0.000 description 1
- QYAKDSPIRNDQQT-UHFFFAOYSA-N CCCOC(NCC(CC1)c2c1[s]cc2)=O Chemical compound CCCOC(NCC(CC1)c2c1[s]cc2)=O QYAKDSPIRNDQQT-UHFFFAOYSA-N 0.000 description 1
- YROKMZXMUQVNCL-UHFFFAOYSA-N CCNCC1Oc(cccc2)c2-c2c1cc[s]2 Chemical compound CCNCC1Oc(cccc2)c2-c2c1cc[s]2 YROKMZXMUQVNCL-UHFFFAOYSA-N 0.000 description 1
- NKMBPHQKTQXAEA-UHFFFAOYSA-N CCNCC1[O](C2)C2c(cccc2)c2-c2c1[s]cc2 Chemical compound CCNCC1[O](C2)C2c(cccc2)c2-c2c1[s]cc2 NKMBPHQKTQXAEA-UHFFFAOYSA-N 0.000 description 1
- XAGNBZCWQQDYKN-UHFFFAOYSA-N CCOC(CCC(O)Cl)=O Chemical compound CCOC(CCC(O)Cl)=O XAGNBZCWQQDYKN-UHFFFAOYSA-N 0.000 description 1
- UTNILOISSJIBBI-ONGXEEELSA-N CC[O](CC1)[C@@H]([C@H](C)NC)c2c1cc[s]2 Chemical compound CC[O](CC1)[C@@H]([C@H](C)NC)c2c1cc[s]2 UTNILOISSJIBBI-ONGXEEELSA-N 0.000 description 1
- OWQHQSMBZDCQQE-UHFFFAOYSA-N CN(C)CC1[O](C2)C2CCc2c1[s]cc2 Chemical compound CN(C)CC1[O](C2)C2CCc2c1[s]cc2 OWQHQSMBZDCQQE-UHFFFAOYSA-N 0.000 description 1
- DGUTVARAUDGJCP-UHFFFAOYSA-N CNCC1OCCCCc2c1[s]cc2Cl Chemical compound CNCC1OCCCCc2c1[s]cc2Cl DGUTVARAUDGJCP-UHFFFAOYSA-N 0.000 description 1
- LEIJIFSKDBIFJW-MRVPVSSYSA-N CNC[C@@H](CCC1)c2c1[s]cc2 Chemical compound CNC[C@@H](CCC1)c2c1[s]cc2 LEIJIFSKDBIFJW-MRVPVSSYSA-N 0.000 description 1
- LEIJIFSKDBIFJW-QMMMGPOBSA-N CNC[C@H](CCC1)c2c1[s]cc2 Chemical compound CNC[C@H](CCC1)c2c1[s]cc2 LEIJIFSKDBIFJW-QMMMGPOBSA-N 0.000 description 1
- CNHALALZKXTYNZ-ZETCQYMHSA-N C[C@@H](Cc1c(CCO)cc[s]1)N Chemical compound C[C@@H](Cc1c(CCO)cc[s]1)N CNHALALZKXTYNZ-ZETCQYMHSA-N 0.000 description 1
- RJKFJOKFGIHYEE-XPUUQOCRSA-N C[C@@H]([C@@H]1OCCc2c1[s]cc2)N Chemical compound C[C@@H]([C@@H]1OCCc2c1[s]cc2)N RJKFJOKFGIHYEE-XPUUQOCRSA-N 0.000 description 1
- KHZWAHOZGFRRNO-IONNQARKSA-N C[C@@H]([C@H]1OCCc2c1[s]cc2)NC Chemical compound C[C@@H]([C@H]1OCCc2c1[s]cc2)NC KHZWAHOZGFRRNO-IONNQARKSA-N 0.000 description 1
- GKTZPLKWQFDZOS-MRVPVSSYSA-N C[C@H](Cc1c(CCO)cc[s]1)NC Chemical compound C[C@H](Cc1c(CCO)cc[s]1)NC GKTZPLKWQFDZOS-MRVPVSSYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- SIQIZMRCDPCDLJ-UHFFFAOYSA-N Cc1c[s]c(C=[U])c1 Chemical compound Cc1c[s]c(C=[U])c1 SIQIZMRCDPCDLJ-UHFFFAOYSA-N 0.000 description 1
- ZOTUVBXMCVFEMX-UHFFFAOYSA-N Cc1c[s]c(CCC2)c1C2=[U] Chemical compound Cc1c[s]c(CCC2)c1C2=[U] ZOTUVBXMCVFEMX-UHFFFAOYSA-N 0.000 description 1
- GSBJUDNVLJRVPX-UHFFFAOYSA-N Cc1c[s]c2c1C(CN1CCCCC1)CCC2 Chemical compound Cc1c[s]c2c1C(CN1CCCCC1)CCC2 GSBJUDNVLJRVPX-UHFFFAOYSA-N 0.000 description 1
- ZMHCXWXSVCESEW-MRVPVSSYSA-N Cc1c[s]c2c1CCO[C@@H]2CN Chemical compound Cc1c[s]c2c1CCO[C@@H]2CN ZMHCXWXSVCESEW-MRVPVSSYSA-N 0.000 description 1
- UOYYYKLMJHZPKQ-VIFPVBQESA-N Cc1c[s]c2c1CCO[C@H]2CNC Chemical compound Cc1c[s]c2c1CCO[C@H]2CNC UOYYYKLMJHZPKQ-VIFPVBQESA-N 0.000 description 1
- YQWDJSHLJXHUKM-UHFFFAOYSA-N Cc1ccc2[s]c(CCOC3CN)c3c2c1 Chemical compound Cc1ccc2[s]c(CCOC3CN)c3c2c1 YQWDJSHLJXHUKM-UHFFFAOYSA-N 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 206010008025 Cerebellar ataxia Diseases 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010057645 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 208000022497 Cocaine-Related disease Diseases 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010010947 Coordination abnormal Diseases 0.000 description 1
- 102000012437 Copper-Transporting ATPases Human genes 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 208000024254 Delusional disease Diseases 0.000 description 1
- 206010012374 Depressed mood Diseases 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 201000010374 Down Syndrome Diseases 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
- 241000206672 Gelidium Species 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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 206010020400 Hostility Diseases 0.000 description 1
- 208000004044 Hypesthesia Diseases 0.000 description 1
- 206010021403 Illusion Diseases 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 206010028570 Myelopathy Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- LXLPDUNFMGIHRH-UHFFFAOYSA-N NC(CCC1)c2c1c(cc(cc1)-c3ccccc3)c1[s]2 Chemical compound NC(CCC1)c2c1c(cc(cc1)-c3ccccc3)c1[s]2 LXLPDUNFMGIHRH-UHFFFAOYSA-N 0.000 description 1
- GXNYKQMLUHGYIS-UHFFFAOYSA-N NCC1OCCc2c1[s]c1c2CCCC1 Chemical compound NCC1OCCc2c1[s]c1c2CCCC1 GXNYKQMLUHGYIS-UHFFFAOYSA-N 0.000 description 1
- DHNMZCCPYCESAV-UHFFFAOYSA-N NCC1[O]#Cc(cccc2)c2-c2c1[s]cc2 Chemical compound NCC1[O]#Cc(cccc2)c2-c2c1[s]cc2 DHNMZCCPYCESAV-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 206010057852 Nicotine dependence Diseases 0.000 description 1
- 229910003849 O-Si Inorganic materials 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
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 206010033425 Pain in extremity Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000027099 Paranoid disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 208000029808 Psychomotor disease Diseases 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 206010040030 Sensory loss Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010072005 Spinal pain Diseases 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 208000025569 Tobacco Use disease Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010044688 Trisomy 21 Diseases 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 208000027093 acute inflammatory demyelinating polyradiculoneuropathy Diseases 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 229960000250 adipic acid Drugs 0.000 description 1
- 208000012826 adjustment disease Diseases 0.000 description 1
- 210000003766 afferent neuron Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- AEMOLEFTQBMNLQ-WAXACMCWSA-N alpha-D-glucuronic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-WAXACMCWSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229960004977 anhydrous lactose Drugs 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000009118 appropriate response Effects 0.000 description 1
- 150000004982 aromatic amines Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 125000005870 benzindolyl group Chemical group 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960004365 benzoic acid Drugs 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
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 210000004958 brain cell Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 201000006145 cocaine dependence Diseases 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 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
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000008356 dextrose and sodium chloride injection Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 description 1
- 125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000003027 ear inner Anatomy 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000004970 emotional disturbance Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- XALDUAUTMGZSQG-UHFFFAOYSA-N ethyl 2-(2,5-dimethylthiophen-3-yl)-2-oxoacetate Chemical compound CCOC(=O)C(=O)C=1C=C(C)SC=1C XALDUAUTMGZSQG-UHFFFAOYSA-N 0.000 description 1
- NNEBHSVVRNIDMV-UHFFFAOYSA-N ethyl 2-amino-4,5,6,7-tetrahydro-1,3-benzothiazole-4-carboxylate Chemical compound CCOC(=O)C1CCCC2=C1N=C(N)S2 NNEBHSVVRNIDMV-UHFFFAOYSA-N 0.000 description 1
- OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 1
- QWNCQKOFHALYOH-UHFFFAOYSA-N ethyl 3-(4-methylthiophen-2-yl)-4-nitrobutanoate Chemical compound CCOC(=O)CC(C[N+]([O-])=O)C1=CC(C)=CS1 QWNCQKOFHALYOH-UHFFFAOYSA-N 0.000 description 1
- VKCMWLOBUILIOQ-UHFFFAOYSA-N ethyl 3-bromo-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCCC(Br)C1=O VKCMWLOBUILIOQ-UHFFFAOYSA-N 0.000 description 1
- KRAJFDPIKIMZDW-UHFFFAOYSA-N ethyl 4-oxo-4-(5-phenyl-1-benzothiophen-3-yl)butanoate Chemical compound C1=C2C(C(=O)CCC(=O)OCC)=CSC2=CC=C1C1=CC=CC=C1 KRAJFDPIKIMZDW-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- FBWNOMOLQXFMGR-UHFFFAOYSA-N ethyl n-[1-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)cyclohexyl]carbamate Chemical compound O1CCC=2SC=CC=2C1C1(NC(=O)OCC)CCCCC1 FBWNOMOLQXFMGR-UHFFFAOYSA-N 0.000 description 1
- GSYRJZLRSLSZQQ-UHFFFAOYSA-N ethyl n-[1-(6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl)cyclopropyl]carbamate Chemical compound O1CCC=2SC=CC=2C1C1(NC(=O)OCC)CC1 GSYRJZLRSLSZQQ-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 210000001061 forehead Anatomy 0.000 description 1
- 150000004675 formic acid derivatives Chemical class 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 125000003844 furanonyl group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 229960005219 gentisic acid Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 244000144993 groups of animals Species 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229960003878 haloperidol Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229960000443 hydrochloric acid Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 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
- 208000034783 hypoesthesia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=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
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical class IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 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
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000003151 isocoumarinyl group Chemical group C1(=O)OC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 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
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 208000028756 lack of coordination Diseases 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229940033355 lauric acid Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000006742 locomotor activity Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000002175 menstrual effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VPUJEVPRVCLHAP-UHFFFAOYSA-N methyl 1-(9h-fluoren-9-ylmethoxycarbonylamino)cyclohexane-1-carboxylate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC1(C(=O)OC)CCCCC1 VPUJEVPRVCLHAP-UHFFFAOYSA-N 0.000 description 1
- OZXFOIUFQYDOMN-UHFFFAOYSA-N methyl 1-(9h-fluoren-9-ylmethoxycarbonylamino)cyclopropane-1-carboxylate Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)NC1(C(=O)OC)CC1 OZXFOIUFQYDOMN-UHFFFAOYSA-N 0.000 description 1
- CSHMCEYIMFSLSS-UHFFFAOYSA-N methyl 1-aminocyclopropane-1-carboxylate Chemical compound COC(=O)C1(N)CC1 CSHMCEYIMFSLSS-UHFFFAOYSA-N 0.000 description 1
- GQJCAQADCPTHKN-UHFFFAOYSA-N methyl 2,2-difluoro-2-fluorosulfonylacetate Chemical compound COC(=O)C(F)(F)S(F)(=O)=O GQJCAQADCPTHKN-UHFFFAOYSA-N 0.000 description 1
- IVBHFRNHMUYYEM-UHFFFAOYSA-N methyl 2-formylpyrrolidine-1-carboxylate Chemical compound COC(=O)N1CCCC1C=O IVBHFRNHMUYYEM-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- XZKIIXAYFWZZPB-UHFFFAOYSA-N n,n,2-trimethylimidazole-1-sulfonamide Chemical compound CN(C)S(=O)(=O)N1C=CN=C1C XZKIIXAYFWZZPB-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-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
- YFTVTBIOFNDYGT-UHFFFAOYSA-N n-methyl-1-[3-(trifluoromethyl)-6,7-dihydro-4h-thieno[3,2-c]pyran-4-yl]methanamine Chemical compound CNCC1OCCC2=C1C(C(F)(F)F)=CS2 YFTVTBIOFNDYGT-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
- 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 229960005017 olanzapine Drugs 0.000 description 1
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940041672 oral gel Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 229960005010 orotic acid Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 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
- 125000003544 oxime group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 208000002851 paranoid schizophrenia Diseases 0.000 description 1
- 230000008289 pathophysiological mechanism Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 125000005327 perimidinyl group Chemical group N1C(=NC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 230000004793 poor memory Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000002442 prefrontal cortex Anatomy 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- HVVNJUAVDAZWCB-UHFFFAOYSA-N prolinol Chemical compound OCC1CCCN1 HVVNJUAVDAZWCB-UHFFFAOYSA-N 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000001107 psychogenic effect Effects 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 description 1
- RGCGYSDYLDVWAO-UHFFFAOYSA-N pyrrolidine;2-pyrrolidin-1-ylethanol Chemical compound C1CCNC1.OCCN1CCCC1 RGCGYSDYLDVWAO-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- ZTHJULTYCAQOIJ-WXXKFALUSA-N quetiapine fumarate Chemical compound [H+].[H+].[O-]C(=O)\C=C\C([O-])=O.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12.C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 ZTHJULTYCAQOIJ-WXXKFALUSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 210000004761 scalp Anatomy 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
- 238000012216 screening Methods 0.000 description 1
- 229940116353 sebacic acid Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 229940035004 seroquel Drugs 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 230000011273 social behavior Effects 0.000 description 1
- 230000003997 social interaction Effects 0.000 description 1
- 230000004036 social memory Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- NXWWZQRTUBGQGS-UHFFFAOYSA-N tert-butyl 3-(2-bromothiophen-3-yl)-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1(O)C1=C(Br)SC=C1 NXWWZQRTUBGQGS-UHFFFAOYSA-N 0.000 description 1
- JSOMVCDXPUXKIC-UHFFFAOYSA-N tert-butyl 3-oxopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)C1 JSOMVCDXPUXKIC-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
- VMTGLWYUSHIMAW-UHFFFAOYSA-N tert-butyl-[2-(5-fluoro-4-methylthiophen-2-yl)ethoxy]-dimethylsilane Chemical compound CC=1C=C(CCO[Si](C)(C)C(C)(C)C)SC=1F VMTGLWYUSHIMAW-UHFFFAOYSA-N 0.000 description 1
- QCUZVCFKJUVWLS-UHFFFAOYSA-N tert-butyl-[2-(5-fluorothiophen-2-yl)ethoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCC1=CC=C(F)S1 QCUZVCFKJUVWLS-UHFFFAOYSA-N 0.000 description 1
- 125000001940 tetracyclic carbocycle group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- GYICYQJEVCIYJY-UHFFFAOYSA-N thiophen-1-ylidenemethanone Chemical compound O=C=S1C=CC=C1 GYICYQJEVCIYJY-UHFFFAOYSA-N 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000003440 toxic substance Substances 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
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- PXQSEZAMRRQEQN-UHFFFAOYSA-N tri(propan-2-yl)-(2-thiophen-2-ylethoxy)silane Chemical compound CC(C)[Si](C(C)C)(C(C)C)OCCC1=CC=CS1 PXQSEZAMRRQEQN-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000003936 working memory Effects 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 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
- 125000004933 β-carbolinyl group Chemical group C1(=NC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered 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
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or 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
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/76—Dibenzothiophenes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/20—Spiro-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Reproductive Health (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Pregnancy & Childbirth (AREA)
- Otolaryngology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Description
本出願は、その内容が全体として引用により本明細書中に組み込まれている、2009年12月4日に出願された米国仮特許出願第61/266,880号の優先権を主張するものである。
精神病及び統合失調症を含むが、これらに限定されない、様々な神経障害を治療するのに有用な多環式化合物、該化合物を含む組成物、及びその使用方法を本明細書で提供する。
中枢神経系障害は、異なる重症度で広範な集団に影響を及ぼす。通常、このクラスの障害の主な特徴は、以前の機能レベルからの著しい悪化を示す認知又は記憶の顕著な障害を含む。
式(I)の化合物、又は医薬として許容し得るその塩もしくは立体異性体を本明細書で提供する。
特に定義しない限り、本明細書で使用される全ての技術用語及び科学用語は、当業者によって一般に理解されるものと同じ意味を有する。特定の実施態様では、略語は、J. Org. Chem. 2007, 72, 23Aに定義されている通りである。本明細書で言及されている全ての刊行物及び特許は、引用によりその全体が本明細書に組み込まれる。
本明細書及び添付の特許請求の範囲で使用される場合、不定冠詞「a」及び「an」、並びに定冠詞「the」は、文脈から明らかにそうでないことが示されない限り、複数形及び単数形の指示対象を含む。
一実施態様では、式(I)の化合物、又は医薬として許容し得るその塩もしくは立体異性体を本明細書で提供する。
X及びYのうちの一方はOであり、かつもう一方はCH2であるか;又はX及びYは両方ともCH2であり;
Z1、Z2、及びZ3のうちの1つはSであり;かつ(i)Z1、Z2、及びZ3のうちの2つはCであるか;又は(ii)Z1、Z2、及びZ3のうちの1つはCであり、かつZ1、Z2、及びZ3のうちの1つはNであり;
R1及びR2は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R8(式中、R8は、その各々が任意に置換されている、SO2アルキルもしくはSO2アリールである)であるか;又は(iii)R1及びR2は、それらが結合している窒素原子とともに、任意に置換されたヘテロシクリルもしくはヘテロアリールを形成し;
R3及びR4は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R9(式中、R9は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R3及びR4は、それらが結合している炭素原子とともに、任意に置換されたシクロアルキルもしくはヘテロシクリルを形成するか;又は(iv)R3及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し、かつR4は(i)もしくは(ii)であるか;又は(v)R3及びR4は一緒に組み合わされて、二重結合を形成し、R1及び/又はR2並びにそれらが結合している原子とともに、任意に置換されたヘテロアリール(例えば、イミダゾリルもしくはチアゾリル)を形成し、;
R5は、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキルであるか;又は(ii)−(CH2)p−R10(式中、R10は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R5及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し;
R6及びR7は、各々独立に、(i)その各々が任意に置換されている、水素、ハロ、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R11(式中、R11は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、シクロアルコキシル、ヘテロアリール、もしくはヘテロシクリルである)であるか;又は(iii)R6及びR7は、それらが結合している原子とともに、任意に置換されたアリール、ヘテロアリール、シクロアルキル、もしくはヘテロシクリル環を形成し;但し、Z1、Z2、及びZ3のうちの1つがNであるとき、R7は存在せず;
mは、0、1、又は2であり;
nは、0、1、又は2であり;かつ
pの各々の出現は、独立に、0、1、又は2である。
式中、
X及びYのうちの一方はOであり、かつもう一方はCH2であるか;又はX及びYは両方ともCH2であり;
Z1、Z2、及びZ3のうちの2つはCであり、かつZ1、Z2、及びZ3のうちの1つはSであり;
R1及びR2は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R8(式中、R8は、その各々が任意に置換されている、SO2アルキルもしくはSO2アリールである)であるか;又は(iii)R1及びR2は、それらが結合している窒素原子とともに、任意に置換されたヘテロシクリルもしくはヘテロアリールを形成し;
R3及びR4は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキルである)であるか;又は(ii)−(CH2)p−R9(式中、R9は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R3及びR4は、それらが結合している炭素原子とともに、任意に置換されたシクロアルキルもしくはヘテロシクリルを形成するか;又は(iv)R3及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し、かつR4は(i)もしくは(ii)であるか;又は(v)R3及びR4は一緒に組み合わされて、二重結合を形成し、R1及び/又はR2並びにそれらが結合している原子とともに、任意に置換されたヘテロアリール(例えば、イミダゾリルもしくはチアゾリル)を形成し;
R5は、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキルであるか;又は(ii)−(CH2)p−R10(式中、R10は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R5及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し;
R6及びR7は、各々独立に、(i)その各々が任意に置換されている、水素、ハロ、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R11(式中、R11は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、シクロアルコキシル、ヘテロアリール、もしくはヘテロシクリルである)であるか;又は(iii)R6及びR7は、それらが結合している原子とともに、任意に置換されたアリール、ヘテロアリール、シクロアルキル、もしくはヘテロシクリル環を形成し;
mは、0、1、又は2であり;
nは、0、1、又は2であり;かつ
pの各々の出現は、独立に、0、1、又は2である。
R1及びR2は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R8(式中、R8は、その各々が任意に置換されている、SO2アルキルもしくはSO2アリールである)であるか;又は(iii)R1及びR2は、それらが結合している窒素原子とともに、任意に置換されたヘテロシクリルもしくはヘテロアリールを形成し;
R3及びR4は、各々独立に、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R9(式中、R9は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R3及びR4は、それらが結合している炭素原子とともに、任意に置換されたシクロアルキルもしくはヘテロシクリルを形成するか;又は(iv)R3及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し、かつR4は(i)もしくは(ii)であるか;又は(v)R3及びR4は一緒に組み合わされて、二重結合を形成し、かつR1及び/もしくはR2並びにそれらが結合している原子とともに、任意に置換されたヘテロアリールを形成し;
R5は、(i)その各々が任意に置換されている、水素、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R10(式中、R10は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、もしくはシクロアルコキシルである)であるか;又は(iii)R5及びR1は、それらが結合している原子とともに、任意に置換されたヘテロシクリルを形成し;
R6及びR7は、各々独立に、(i)その各々が任意に置換されている、水素、ハロ、アルキル、アルコキシル、アミノアルキル、アルケニル、アルキニル、シクロアルキル、シクロアルキルアルキル、アリール、もしくはアラルキル;又は(ii)−(CH2)p−R11(式中、R11は、その各々が任意に置換されている、CF3、CN、ニトロ、アミノ、ヒドロキシル、シクロアルコキシル、ヘテロアリール、もしくはヘテロシクリルである)であるか;又は(iii)R6及びR7は、それらが結合している原子とともに、任意に置換されたアリール、ヘテロアリール、シクロアルキル、もしくはヘテロシクリル環を形成し;かつ
mは、0、1、又は2であり;
pの各々の出現は、独立に、0、1、又は2である。
以下のスキームは、本明細書で提供される化合物の調製のための例示的な合成方法を提供する。当業者であれば、同様の方法を用いて、本明細書で提供される化合物を調製することができることを理解するであろう。言い換えると、当業者であれば、試薬、保護基、反応条件、及び反応シーケンスの好適な調整を用いて、所望の実施態様を調製することができることを認識するであろう。反応は、調製すべき材料の量に合わせてスケールを上下させることができる。
一実施態様では、本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体を当技術分野で公知の疾患モデルで投与する方法を本明細書で提供する。一実施態様では、該疾患モデルは動物モデルである。一実施態様では、本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体を、ヒトでの特定の疾患の治療における有効性を予測する動物モデルで投与する方法を本明細書で提供する。該方法は、対象において、本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体を投与することを含む。一実施態様では、該方法は、対象において、治療的有効量の本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体を投与することを含む。一実施態様では、該方法は、本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体による試験対象(例えば、マウス又はラット)の治療を含む。一実施態様では、該方法は、別々の動物群(例えば、対照群に参照化合物を投与し、試験群に本明細書で提供される化合物を投与する)か、又は同じ動物群(例えば、併用療法として)かのいずれかでの、本明細書で提供される化合物、又は医薬として許容し得るその塩もしくは立体異性体、及び参照化合物による試験対象(例えば、マウス又はラット)の治療を含む。一実施態様では、本明細書で提供される化合物のインビボ活性は用量依存的である。
一実施態様では、神経障害を含むが、これに限定されない、様々な障害を治療、予防、及び/又は管理する方法を本明細書で提供する。一実施態様では、神経障害の1以上の症状を治療、予防、及び/又は管理する方法を本明細書で提供する。一実施態様では、該方法は、対象(例えば、ヒト)に、治療的又は予防的有効用量の本明細書で提供される組成物もしくは化合物、又は医薬として許容し得るその塩もしくは立体異性体を投与することを含む。一実施態様では、対象はヒトである。一実施態様では、対象は動物である。一実施態様では、本明細書で提供される化合物は、対象の脳によく浸透する。特定の実施態様では、本明細書で提供される化合物の有効濃度は、10nM未満、100nM未満、1μM未満、10μM未満、100μM未満、又は1mM未満である。一実施態様では、化合物の活性は、本明細書中の他の場所に記載されているか又は文献で知られているような、当技術分野で認められている様々な動物モデルで評価することができる。
医薬組成物は、個々の、単一単位剤形の調製に用いることができる。本明細書で提供される医薬組成物及び剤形は、本明細書で提供される化合物、又は医薬として許容し得るその塩、立体異性体、クラスレート、もしくはプロドラッグを含む。医薬組成物及び剤形は、1種以上の賦形剤をさらに含むことができる。
経口投与に好適な医薬組成物は、個別の剤形、例えば、限定するものではないが、錠剤(例えば、チュアブル錠)、カプレット剤、カプセル剤、及び液剤(例えば、味付きシロップ剤)などとして提供することができる。そのような剤形は所定量の活性成分を含み、当業者に周知の薬学の方法により調製することができる。一般的には、「レミントンの薬学の科学及び実務(Remington’s The Science and Practice of Pharmacy)」(第21版, Lippincott Williams & Wilkins(2005))を参照されたい。
本明細書で提供される活性成分は、制御放出手段によるか、又は当業者に周知の送達装置によって投与することができる。例としては、各々引用により本明細書に組み込まれる米国特許第3,845,770号;同第3,916,899号;同第3,536,809号;同第3,598,123号;及び同第4,008,719号、同第5,674,533号、同第5,059,595号、同第5,591,767号、第5,120,548号、同第5,073,543号、同第5,639,476号、同第5,354,556号、及び同第5,733,566号に記載されているものが挙げられるが、これらに限定されない。そのような剤形を用いて、例えば、ヒドロプロピルメチルセルロース、他のポリマーマトリックス、ゲル、透過膜、浸透システム、多層コーティング、微粒子、リポソーム、微小球、又はこれらの組合せを用いて1種以上の活性成分の緩徐放出又は制御放出を提供し、様々な比率の所望の放出プロファイルを提供することができる。本明細書で提供される活性剤とともに使用するために、本明細書に記載されているものを含む、当業者に公知の好適な制御放出製剤を容易に選択することができる。一実施態様では、限定するものではないが、制御放出に適している錠剤、カプセル剤、ゲルキャップ剤、及びカプレット剤などの経口投与に好適な単一単位剤形を本明細書で提供する。
非経口剤形は、皮下、静脈内(ボーラス注入を含む)、筋肉内、及び動脈内を含むが、これらに限定されない、様々な経路によって患者に投与することができる。いくつかの実施態様では、非経口剤形の投与は、汚染物質に対する患者の自然な防御機構を迂回し、したがって、これらの実施態様では、非経口剤形は、滅菌性であるか、又は患者への投与の前に滅菌可能である。非経口剤形の例としては、注射可能な溶液、注射用の医薬として許容し得るビヒクルにすぐに溶解又は懸濁可能な乾燥製品、注射可能な懸濁液、及び乳剤が挙げられるが、これらに限定されない。
本明細書で提供される局所及び粘膜剤形としては、スプレー剤、エアゾール剤、液剤、乳剤、懸濁剤、点眼薬もしくは他の眼科用調製物、又は当業者に公知の他の形態が挙げられるが、これらに限定されない。例えば、「レミントンの製薬科学(Remington’s Pharmaceutical Sciences)」(第21版, Lippincott Williams & Wilkins(2005));並びに「医薬剤形入門(Introduction to Pharmaceutical Dosage Forms)」(第4版, Lea & Febiger, Philadelphia(1985))を参照されたい。口腔内の粘膜組織を治療するのに好適な剤形は、洗口液として、又は口腔ゲルとして調剤することができる。
一実施態様では、本明細書で提供される活性成分は、同時に、又は同じ投与経路で患者に投与されない。別の実施態様では、適量の活性成分の投与を簡略化することができるキットを提供する。
特定の実施態様を以下の非限定的な実施例によって説明する。
下記の実施例において、特に指示しない限り、温度は全て摂氏温度で示され、部及びパーセンテージは全て重量によるものである。試薬は、Sigma−Aldrich(登録商標)Chemical Companyなどの商業的供給業者から購入することができ、かつ特に指示しない限り、さらに精製することなく使用することができる。試薬は、当業者に公知の標準的な文献手順に従って調製することもできる。溶媒は、Sure−Seal(登録商標)ボトルとしてSigma−Aldrich(登録商標)から購入し、受け取った状態のまま使用することができる。特に指示しない限り、溶媒は全て、当業者に公知の標準的な方法を用いて精製することができる。
上記の環状ケトン(1.0g、6.6mmol)のMeOH(330mL)及びDMSO(10mL)溶液に、Tosmic(1.7g、8.7mmol)、次いでKOtBu(2.5g、26.3mmol)を少しずつ添加した。得られた混合物を25℃で36時間撹拌した。36時間の時点で、大半の揮発性物質を真空中で除去した。該反応混合物をEtOAc及びH2Oで希釈した。有機物をNH4Cl(飽和水溶液)、ブラインで洗浄し、Na2SO4上で乾燥させ、濃縮し、カラムクロマトグラフィー(ヘキサン中の0〜30%EtOAc)で精製すると、所望のニトリル化合物が得られた。
得られたニトリル(0.3g、1.8mmol)を、10mLのさらなるTHFで20mLに希釈した過剰のBH3・THF(10mL、10mmol)を用いて一級アミンに還元した。該反応混合物を25℃で1時間撹拌した。1時間の時点で、K2CO3(飽和水溶液)の注意深い添加を用いて、該反応液をクエンチした。EtOAcを添加し、有機層をNaHCO3及びブラインで洗浄し、Na2SO4上で乾燥させ、濾過した。得られた黄色の油をRP−HPLCでさらに精製すると、一級アミン化合物が得られた。
該一級アミンを、10%NEt3のMeOH溶液中の過剰のBOC2Oで保護した。該反応混合物を25℃で1時間撹拌した。1時間の時点で、全ての揮発性物質を真空中で除去した。該粗物質を10mLのTHFに溶解させた。THF中の20mLの1MLAHを滴加し、該反応混合物を25℃で2時間撹拌した。2時間の時点で、K2CO3(飽和水溶液)の注意深い添加を用いて、該反応液をクエンチした。EtOAcを添加し、有機層をNaHCO3で洗浄し、ブラインで乾燥させ、Na2SO4上で乾燥させ、濾過した。得られた黄色の油をRP−HPLCでさらに精製すると、二級アミン化合物が得られた。
Chiral TechnologiesのAS、AD、OJ、及びODカラム、並びに指定の溶媒系を用いて、本明細書に開示されたラセミ化合物の順相キラル分離を実施した。
統合失調症のPCP多動及びプレパルス抑制(PPI)モデルを用いて、化合物の抗精神病様活性をマウスで評価した。
動物:Jackson Laboratories(Bar Harbor, Maine)からの雄C57Bl/6Jマウスを用いた。受け取った後、マウスに固有の識別番号を割り当て(尾部にマーキングする)、ケージ当たりのマウスを4匹としてOptiMICE換気ケージ内で集団飼育した。試験の残りの期間中、全ての動物を4匹の群で飼育し続けた。全てのマウスを、試験前に少なくとも2週間、コロニー部屋に慣れさせた。環境順応の期間中、マウスを定期的に検査し、手で触れ、計量して、適切な健康状態及び適性を保証した。動物を12時間/12時間明暗周期で維持した。室温を20〜23℃に維持し、相対湿度を30%〜70%に維持した。試験期間中は、餌と水を不断給餌した。各試験において、動物を処置群に無作為に割り当てた。
オープンフィールド(OF)チャンバーは、水平方向及び垂直方向の活動を測定するための赤外光線(16×16×16)で囲まれたPlexiglasスクエアチャンバー(27.3×27.3×20.3cm;Med Associates Inc., St Albans, VT)であった。解析は、オープンフィールドを中央及び周辺域に分割するように構成した。移動距離は、マウスが移動したときの水平ビームの中断から測定したのに対し、後肢立ち(rearing)活動は垂直ビームの中断から測定した。
聴覚性驚愕は、外部からの聴覚刺激に対する無条件反射応答である。驚愕のプレパルス抑制(PPI)とは、驚愕刺激前の低強度聴覚刺激の提示により生じる驚愕応答の低下を意味する。ヒトと齧歯類での研究の結果が類似しているため、PPIパラダイムは、統合失調症及び抗精神病作用の研究に用いられる。PPIは、統合失調症で認められる感覚−運動ゲーティングの欠陥の評価のためのツールとして、及び潜在的な抗精神病薬をスクリーニングするために用いられている。PCPなどの様々な精神異常発現薬はPPIを破壊することができる。マウスにおいて、クロザピンなどの抗精神病薬は、PCPによって誘発されたPPIの破壊を逆転させることができる。
上記の実施態様は、単に例示的なものであることが意図され、当業者であれば、特定の化合物、材料、及び手順の多くの等価物を認識するか、又はルーチンの実験を用いて、これらを確認することができるであろう。そのような等価物は全て、本開示の範囲内にあると考えられ、かつ添付の特許請求の範囲によって包含される。
Claims (28)
- 式(IVa):
で示される化合物または医薬として許容し得るその塩もしくは立体異性体の製造方法であって、下記の工程(a)を含む方法:
(a)式(i):
で示されるヒドロキシアルキルチオフェンをアミノ−アルデヒドアセタールおよび酸で処理し、式(IVa)の化合物
(式中、
mは0であり;
nは1であり
R1およびR2は、各々独立に、水素またはC1−C4アルキルであり;
R3およびR4は、各々独立に、水素またはC1−C4アルキルであり;
R5は、水素であり;および
R6およびR7は、各々独立に、水素、ハロ、またはC1−C4アルキルである)
または医薬として許容し得るその塩もしくは立体異性体を製造する工程。 - 前記アミノ−アルデヒドアセタールが、アミノ−アルデヒドジエチルアセタールを含む、請求項1記載の方法。
- 前記酸が、トリフルオロメチルスルホン酸を含む、請求項1〜3のいずれか一項に記載の方法。
- ヒドロキシアルキルチオフェンのアミノ−アルデヒドアセタールおよび酸での処理が、エーテル溶媒中で行われる、請求項1〜4のいずれか一項に記載の方法。
- 前記エーテル溶媒が、1,4−ジオキサンである、請求項5記載の方法。
- (b)工程(a)の生成物を塩基で処理する工程をさらに含む、請求項1〜6のいずれか一項に記載の方法。
- 前記塩基が、水酸化カリウムを含む、請求項7記載の方法。
- 前記塩基が、水酸化カリウム水溶液である、請求項8記載の方法。
- 式(IVa)の化合物の少なくとも1つの立体異性体を製造する、請求項1〜9のいずれか一項に記載の方法。
- 式(IVa)の化合物の1つ以上の立体異性体を含む混合物を製造する、請求項10記載の方法。
- (c)混合物の分割によって式(IVa)の化合物の1つの立体異性体または医薬として許容し得るその塩を単離する工程をさらに含む、請求項11記載の方法。
- 前記分割が、少なくとも1つのキラルクロマトグラフィー、再結晶化、ジアステレオマー塩形成、または式(IVa)の化合物の1つ以上の立体異性体のジアステレオマー付加物への誘導体化と、その後の分離を含む、請求項12記載の方法。
- 前記分割が、ジアステレオマー塩形成を含む、請求項13記載の方法。
- 式(IVa)の化合物または医薬として許容し得るその塩が、医薬として許容し得る塩を含む、請求項1〜14のいずれか一項に記載の方法。
- 式(IVa)の化合物または医薬として許容し得るその塩が、塩酸塩を含む、請求項15記載の方法。
- R3およびR4が、各々、水素であり、かつR6およびR7が、各々独立に、水素またはC1−C4アルキルである、請求項1〜16のいずれか一項に記載の方法。
- R 2 、R 3 、R 4 、R 5 、R 6 、およびR 7 が各々、水素である、請求項1〜17のいずれか一項に記載の方法。
- R 1 がメチルである、請求項19記載の方法。
- 前記分割が、キラルクロマトグラフィーを用いて行われる、請求項25記載の方法。
- 前記分割が、キラルクロマトグラフィーを用いて行われる、請求項27記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26688009P | 2009-12-04 | 2009-12-04 | |
US61/266,880 | 2009-12-04 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016131247A Division JP6028310B1 (ja) | 2009-12-04 | 2016-07-01 | 多環式化合物及びその使用方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018028819A Division JP2018104454A (ja) | 2009-12-04 | 2018-02-21 | 多環式化合物及びその使用方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017031198A JP2017031198A (ja) | 2017-02-09 |
JP6297655B2 true JP6297655B2 (ja) | 2018-03-20 |
Family
ID=44115515
Family Applications (7)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012542219A Active JP5778168B2 (ja) | 2009-12-04 | 2010-12-03 | 多環式化合物及びその使用方法 |
JP2014253082A Active JP5710064B1 (ja) | 2009-12-04 | 2014-12-15 | 多環式化合物及びその使用方法 |
JP2015136603A Active JP6005807B2 (ja) | 2009-12-04 | 2015-07-08 | 多環式化合物及びその使用方法 |
JP2016131247A Active JP6028310B1 (ja) | 2009-12-04 | 2016-07-01 | 多環式化合物及びその使用方法 |
JP2016191898A Active JP6297655B2 (ja) | 2009-12-04 | 2016-09-29 | 多環式化合物及びその使用方法 |
JP2018028819A Pending JP2018104454A (ja) | 2009-12-04 | 2018-02-21 | 多環式化合物及びその使用方法 |
JP2020108727A Active JP7104746B2 (ja) | 2009-12-04 | 2020-06-24 | 多環式化合物及びその使用方法 |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012542219A Active JP5778168B2 (ja) | 2009-12-04 | 2010-12-03 | 多環式化合物及びその使用方法 |
JP2014253082A Active JP5710064B1 (ja) | 2009-12-04 | 2014-12-15 | 多環式化合物及びその使用方法 |
JP2015136603A Active JP6005807B2 (ja) | 2009-12-04 | 2015-07-08 | 多環式化合物及びその使用方法 |
JP2016131247A Active JP6028310B1 (ja) | 2009-12-04 | 2016-07-01 | 多環式化合物及びその使用方法 |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018028819A Pending JP2018104454A (ja) | 2009-12-04 | 2018-02-21 | 多環式化合物及びその使用方法 |
JP2020108727A Active JP7104746B2 (ja) | 2009-12-04 | 2020-06-24 | 多環式化合物及びその使用方法 |
Country Status (20)
Country | Link |
---|---|
US (7) | US8710245B2 (ja) |
EP (2) | EP3252057B1 (ja) |
JP (7) | JP5778168B2 (ja) |
KR (7) | KR102074089B1 (ja) |
CN (5) | CN111560025A (ja) |
AU (3) | AU2010325925B2 (ja) |
BR (2) | BR122021013836B1 (ja) |
CA (1) | CA2781716A1 (ja) |
DK (2) | DK3252057T3 (ja) |
ES (1) | ES2625330T3 (ja) |
FI (1) | FI3252057T3 (ja) |
HK (2) | HK1212969A1 (ja) |
IL (6) | IL272376B1 (ja) |
MX (2) | MX2012006326A (ja) |
NZ (5) | NZ767139A (ja) |
PT (1) | PT2507245T (ja) |
RU (3) | RU2707067C2 (ja) |
SG (3) | SG181498A1 (ja) |
WO (1) | WO2011069063A2 (ja) |
ZA (1) | ZA201203533B (ja) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ767139A (en) * | 2009-12-04 | 2022-08-26 | Sunovion Pharmaceuticals Inc | Multicyclic compounds and methods of use thereof |
WO2013066152A1 (en) * | 2011-10-31 | 2013-05-10 | N.V. Nutricia | Method for improving executive function |
US10189825B2 (en) | 2012-02-08 | 2019-01-29 | Sunovion Pharmaceuticals Inc. | Heteroaryl compounds and methods of use thereof |
CN103755727B (zh) * | 2013-12-20 | 2015-12-30 | 南京华威医药科技开发有限公司 | 布林佐胺中间体制备方法 |
WO2015112902A2 (en) * | 2014-01-23 | 2015-07-30 | Sova Pharmaceuticals, Inc. | CYSTATHIONINE-(gamma)-LYASE (CSE) INHIBITORS FOR TREATING PAIN |
CN106715444B (zh) | 2014-08-27 | 2019-07-12 | 普雷克斯顿医疗股份公司 | 新型色酮肟衍生物以及其作为代谢型谷氨酸受体的别构调节剂的用途 |
CN104193722A (zh) * | 2014-08-27 | 2014-12-10 | 湖南华腾制药有限公司 | 一种n-叔丁氧羰基-3-甲胺噻吩的制备方法 |
US9856238B2 (en) * | 2015-02-11 | 2018-01-02 | Sunovion Pharmaceuticals Inc. | 1-heterocyclyl isochromanyl compounds and analogs for treating CNS disorders |
MX371197B (es) * | 2015-02-11 | 2020-01-22 | Sunovion Pharmaceuticals Inc | Compuestos de dihidro-4h-pirazolo [5,1-c] [1,4] oxazinilo y análogos para el tratamiento de trastornos del sistema nervioso central (snc). |
HUE047531T2 (hu) | 2015-08-27 | 2020-04-28 | Prexton Therapeutics Sa | Levodopa indukálta diszkinézia kezelésére alkalmas, agyba bejutni képes kromon oxim-származék |
JO3638B1 (ar) * | 2015-09-09 | 2020-08-27 | Lilly Co Eli | مركبات مفيدة في تثبيط ror - جاما- t |
DK3407888T3 (da) * | 2016-01-26 | 2021-04-06 | Intra Cellular Therapies Inc | Pyridopyrroloquinoxalinforbindelser, deres sammensætninger og anvendelser |
WO2017144341A1 (de) | 2016-02-23 | 2017-08-31 | Bayer Cropscience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
KR20190065246A (ko) | 2016-07-29 | 2019-06-11 | 선오비온 파마슈티컬스 인코포레이티드 | 화합물 및 조성물 및 이들의 용도 |
CN116514761A (zh) * | 2016-07-29 | 2023-08-01 | 赛诺维信制药公司 | 化合物、组合物及其用途 |
EP3582815A1 (en) | 2017-02-16 | 2019-12-25 | Sunovion Pharmaceuticals Inc. | Methods of treating schizophrenia |
WO2018166855A1 (en) | 2017-03-16 | 2018-09-20 | Basf Se | Heterobicyclic substituted dihydroisoxazoles |
SG11202000669VA (en) | 2017-08-02 | 2020-02-27 | Sunovion Pharmaceuticals Inc | Isochroman compounds and uses thereof |
JP2021513972A (ja) * | 2018-02-16 | 2021-06-03 | サノビオン ファーマシューティカルズ インクSunovion Pharmaceuticals Inc. | 社会的機能障害の治療方法 |
CN112135827B (zh) | 2018-02-16 | 2024-01-12 | 赛诺维信制药公司 | 盐、晶型及其制备方法 |
EP3890726A1 (en) | 2018-12-06 | 2021-10-13 | Sunovion Pharmaceuticals Inc. | Methods of treating neurological and psychiatric disorders |
CA3130849A1 (en) | 2019-03-14 | 2020-09-17 | Sunovion Pharmaceuticals Inc. | Salts of a isochromanyl compound and crystalline forms, processes for preparing, therapeutic uses, and pharmaceutical compositions thereof |
CN110894195A (zh) * | 2019-12-09 | 2020-03-20 | 门希国 | 一种新的2-噻吩乙酸的制备新方法 |
JP2023519882A (ja) | 2020-03-27 | 2023-05-15 | ソム、イノベーション、バイオテック、ソシエダッド、アノニマ | シヌクレイノパチーの治療に有用な化合物 |
KR20230003503A (ko) | 2020-04-14 | 2023-01-06 | 선오비온 파마슈티컬스 인코포레이티드 | 신경학적 및 정신의학적 장애의 치료를 위한 (S)-(4,5-디히드로-7H-티에노[2,3-c]피란-7-일)-N-메틸메탄아민 |
WO2022060758A1 (en) | 2020-09-16 | 2022-03-24 | Teva Pharmaceuticals International Gmbh | Solid state forms of sep-363856 and process for preparation thereof |
KR20230162058A (ko) * | 2021-03-29 | 2023-11-28 | 슈징 바이오파마 컴퍼니 리미티드 | 스피로 함유 유도체, 이를 위한 제조 방법 및 이의 용도 |
TW202304926A (zh) * | 2021-04-10 | 2023-02-01 | 日商住友製藥股份有限公司 | 二環性吡啶衍生物 |
CN115677718A (zh) * | 2021-07-30 | 2023-02-03 | 武汉思瓴生物科技有限公司 | 甲基甲胺类衍生物制剂、药物组合物及其应用 |
AU2022348905A1 (en) | 2021-09-23 | 2024-04-11 | Sumitomo Pharma America, Inc. | Methods of treating metabolic disorders |
WO2023078392A1 (zh) | 2021-11-04 | 2023-05-11 | 上海翰森生物医药科技有限公司 | 2-(芳基-2-基)吗啉及其氘代衍生物、制备方法和应用 |
CN114324369B (zh) * | 2022-03-11 | 2022-06-07 | 北京新研创能科技有限公司 | 双极板表面划痕检测系统及方法 |
WO2023246872A1 (zh) * | 2022-06-24 | 2023-12-28 | 山东绿叶制药有限公司 | 作为taar1配体激动剂的杂环化合物 |
WO2024050323A1 (en) | 2022-08-30 | 2024-03-07 | Sunovion Pharmaceuticals Inc. | Ulotaront for the adjuvant treatment of major depressive disorder |
WO2024067542A1 (zh) * | 2022-09-27 | 2024-04-04 | 上海枢境生物科技有限公司 | 一种含螺环类衍生物的盐、晶型及其制备方法和应用 |
WO2024081828A1 (en) | 2022-10-13 | 2024-04-18 | Sunovion Pharmaceuticals Inc. | Methods of reducing physical dependence to neuropsychiatric treatments |
CN115677719A (zh) * | 2022-10-27 | 2023-02-03 | 复旦大学 | 一种芳基并杂环化合物及其制备方法和用途 |
WO2024092070A1 (en) | 2022-10-28 | 2024-05-02 | Sumitomo Pharma America, Inc. | Ulotaront for treating anxiety and associated conditions |
WO2024107681A1 (en) | 2022-11-15 | 2024-05-23 | Sumitomo Pharma America, Inc. | Methods of switching neuropsychiatric medications using ulotaront |
Family Cites Families (142)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US402145A (en) * | 1889-04-30 | Combined trough and rack | ||
US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
US4036842A (en) * | 1972-05-16 | 1977-07-19 | American Home Products Corporation | Process for preparing polycyclic heterocycles having a pyran ring |
US4021451A (en) * | 1972-05-16 | 1977-05-03 | American Home Products Corporation | Process for preparing polycyclic heterocycles having a pyran ring |
US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US4021452A (en) | 1975-04-23 | 1977-05-03 | American Cyanamid Company | 2,5-Dihydro-2,5-dialkoxyfuran derivatives |
US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
US4127665A (en) | 1978-01-18 | 1978-11-28 | Pfizer Inc. | Thienohydantoin derivatives |
US4147797A (en) * | 1978-08-11 | 1979-04-03 | Pfizer Inc. | Spiro-furanohydantoin derivatives |
FR2459239A1 (fr) * | 1979-06-20 | 1981-01-09 | Logeais Labor Jacques | Nouveaux derives amines du benzothiazole, leur procede de preparation et leur application en therapeutique |
GB8333512D0 (en) * | 1983-12-16 | 1984-01-25 | Erba Farmitalia | Tetrahydropyrano derivatives |
IE58110B1 (en) | 1984-10-30 | 1993-07-14 | Elan Corp Plc | Controlled release powder and process for its preparation |
NZ219646A (en) * | 1986-03-27 | 1990-10-26 | Merck Sharp & Dohme | Oxadiazole derivatives of azacyclics for treating cns disorders |
PH30676A (en) * | 1986-07-22 | 1997-09-16 | Boehringer Ingelhein Kg | Hetrazepine compounds which have useful pharmaceutical utility |
PT90001B (pt) | 1988-03-16 | 1994-06-30 | Zambeletti Spa L | Processo para a preparacao de derivados heterociclicos de etilenodiamina |
US5073543A (en) | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
DE3827727A1 (de) | 1988-08-16 | 1990-02-22 | Boehringer Ingelheim Kg | Anellierte tetrahydropyridinessigsaeurederivate, verfahren zu deren herstellung und verwendung solcher verbindungen zur kardioprotektion |
GB8824400D0 (en) | 1988-10-18 | 1988-11-23 | Glaxo Group Ltd | Chemical compounds |
EP0368175A1 (de) * | 1988-11-06 | 1990-05-16 | Boehringer Ingelheim Kg | 3S,7S-3-(Morpholinocarbonyl)-5-(2-chlorphenyl)-7,10-dimethyl-3,4-dihydro-2H,7H-cyclopenta[4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin. |
GB8827479D0 (en) | 1988-11-24 | 1988-12-29 | Zambeletti Spa L | Novel compounds |
IT1229203B (it) | 1989-03-22 | 1991-07-25 | Bioresearch Spa | Impiego di acido 5 metiltetraidrofolico, di acido 5 formiltetraidrofolico e dei loro sali farmaceuticamente accettabili per la preparazione di composizioni farmaceutiche in forma a rilascio controllato attive nella terapia dei disturbi mentali organici e composizioni farmaceutiche relative. |
EP0416740A3 (en) | 1989-08-08 | 1991-08-28 | Beecham Group P.L.C. | Novel compounds with renin-inhibiting activity |
JPH0735373B2 (ja) | 1989-08-11 | 1995-04-19 | 三共株式会社 | カルボン酸アミド化合物 |
US5120548A (en) | 1989-11-07 | 1992-06-09 | Merck & Co., Inc. | Swelling modulated polymeric drug delivery device |
GB8926560D0 (en) | 1989-11-24 | 1990-01-17 | Zambeletti Spa L | Pharmaceuticals |
GB8927872D0 (en) | 1989-12-08 | 1990-02-14 | Beecham Group Plc | Pharmaceuticals |
US5032598A (en) | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Nitrogens containing heterocyclic compounds as class III antiarrhythmic agents |
JPH03223277A (ja) | 1989-12-29 | 1991-10-02 | Yoshitomi Pharmaceut Ind Ltd | ベンゾチオフェン誘導体 |
KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
ZA912744B (en) | 1990-03-23 | 1992-02-26 | Zambeletti Spa L | Pharmaceuticals |
JPH049367A (ja) | 1990-04-26 | 1992-01-14 | Zeria Pharmaceut Co Ltd | アリールアルカノイル誘導体,該化合物の製造中間体及びそれらを含有する医薬 |
US5733566A (en) | 1990-05-15 | 1998-03-31 | Alkermes Controlled Therapeutics Inc. Ii | Controlled release of antiparasitic agents in animals |
GB9018139D0 (en) * | 1990-08-17 | 1990-10-03 | Pfizer Ltd | Therapeutic agents |
NZ240155A (en) | 1990-10-29 | 1992-10-28 | Ishihara Sangyo Kaisha | Heterocyclyl acyl and (hexahydro) indanyl acyl substituted hydrazine derivatives, preparation thereof and pesticidal compositions |
DE4104257A1 (de) | 1991-02-13 | 1992-08-20 | Boehringer Ingelheim Kg | Verwendung von anellierten tetrahydropyridinessigsaeurederivaten fuer die behandlung neurologischer erkrankungen |
GB9104839D0 (en) | 1991-03-07 | 1991-04-17 | Zambeletti Spa L | Novel compounds |
NZ243065A (en) | 1991-06-13 | 1995-07-26 | Lundbeck & Co As H | Piperidine derivatives and pharmaceutical compositions |
US5580578A (en) | 1992-01-27 | 1996-12-03 | Euro-Celtique, S.A. | Controlled release formulations coated with aqueous dispersions of acrylic polymers |
PH31294A (en) | 1992-02-13 | 1998-07-06 | Thomae Gmbh Dr K | Benzimidazolyl derivatives, pharmaceutical compositions containing these compounds and process for preparing them. |
JP3223277B2 (ja) | 1992-04-10 | 2001-10-29 | カシオ計算機株式会社 | 楽音制御装置 |
FR2692264B1 (fr) | 1992-06-12 | 1994-08-05 | Adir | Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les contenant. |
IT1255178B (it) | 1992-06-26 | 1995-10-20 | Pierrel Spa | N(eter0)-aril-n(etero)-tetralinalchil piperazine aventi attivita' serotoninergica,dopaminergica e adrenergica |
EP0600836B1 (de) | 1992-12-02 | 1998-08-05 | Novartis AG | Selektiv-herbizides Mittel |
US5591767A (en) | 1993-01-25 | 1997-01-07 | Pharmetrix Corporation | Liquid reservoir transdermal patch for the administration of ketorolac |
TW334423B (en) * | 1993-10-22 | 1998-06-21 | Hoffmann La Roche | Tricyclic 1-aminoethylpyrrole-derivatives |
JP3163068B2 (ja) | 1993-12-27 | 2001-05-08 | 日本建工株式会社 | 野縁取付け金具 |
IT1270594B (it) | 1994-07-07 | 1997-05-07 | Recordati Chem Pharm | Composizione farmaceutica a rilascio controllato di moguisteina in sospensione liquida |
FR2723091B1 (fr) | 1994-07-29 | 1996-11-08 | Esteve Labor Dr | Tetrahydropyridine-(6,4-hydroxypiperidine) alkylazoles |
FR2734819B1 (fr) | 1995-05-31 | 1997-07-04 | Adir | Nouveaux composes de la piperazine, de la piperidine et de la 1,2,5,6-tetrahydropyridine, leur procede de preparation et les compositions pharmaceutiques les contenant |
PL342816A1 (en) * | 1998-03-12 | 2001-07-02 | Novo Nordisk As | Modulators of proteinous thyrosinic phosphatase (ptpase) |
WO1999046267A1 (en) | 1998-03-12 | 1999-09-16 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (ptpases) |
US6262044B1 (en) * | 1998-03-12 | 2001-07-17 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases (PTPASES) |
EP1080068A1 (en) * | 1998-03-12 | 2001-03-07 | Novo Nordisk A/S | Modulators of protein tyrosine phosphatases |
WO2000023445A1 (en) | 1998-10-21 | 2000-04-27 | Novo Nordisk A/S | New compounds, their preparation and use |
AU768652B2 (en) | 1998-12-14 | 2003-12-18 | Astellas Pharma Inc. | Piperazine derivatives |
WO2000043397A1 (en) | 1999-01-19 | 2000-07-27 | Neurosearch A/S | Fused heterocyclic compounds and their use in the treatment of neurodegenerative diseases |
US6313309B1 (en) * | 1999-04-05 | 2001-11-06 | Ortho-Mcneil Pharmaceutical, Inc. | 4-thionaphthyl—1H—imidazoles which are usefulα22-adrenoceptoR agonists/ antagonists |
AU4589800A (en) | 1999-05-05 | 2000-11-21 | Darwin Discovery Limited | 9-(1,2,3,4-tetrahydronaphthalen-1-yl)-1,9-dihydropurin-6-one derivatives as pde7inhibitors |
JP2003503453A (ja) | 1999-07-02 | 2003-01-28 | ワーナー−ランバート・カンパニー | 相乗作用組成物:ガバペンチンおよびプレガバリン |
AU7476800A (en) | 1999-09-10 | 2001-04-10 | Novo Nordisk A/S | Method of inhibiting protein tyrosine phosphatase 1b and/or t-cell protein tyrosine phosphatase and/or other ptpases with an asp residue at position 48 |
JP2003509430A (ja) * | 1999-09-10 | 2003-03-11 | ノボ ノルディスク アクティーゼルスカブ | プロテインチロシンホスファターゼ(ptpアーゼ)のモジュレーター |
WO2001032610A1 (fr) | 1999-10-29 | 2001-05-10 | Kaken Pharmaceutical Co., Ltd. | Derive d'uree, son procede de production, et produit pharmaceutique contenant ce derive d'uree |
AR030537A1 (es) | 1999-11-05 | 2003-08-27 | Abbott Lab | Acidos quinolincarboxilicos y naftiridincarboxilico antibacterianos |
DE69912808T2 (de) * | 1999-12-08 | 2004-09-30 | Centre National De La Recherche Scientifique (C.N.R.S.) | Verwendung von Hymenialdisin und dessen Derivaten zur Herstellung therapeutischer Mittel |
AU2001277731A1 (en) | 2000-08-09 | 2002-02-18 | Welfide Corporation | Fused bicyclic amide compounds and medicinal use thereof |
WO2002022614A1 (fr) | 2000-09-12 | 2002-03-21 | Sankyo Company,Limited | Derives de quinolizine |
WO2002102387A1 (en) | 2001-06-18 | 2002-12-27 | H. Lundbeck A/S | Treatment of neuropathic pain |
US20040180883A1 (en) * | 2001-07-11 | 2004-09-16 | Jeremy Gilmore | Pharmaceutical compounds with serotonin receptor activity |
WO2003006455A1 (en) * | 2001-07-11 | 2003-01-23 | Eli Lilly And Company | Pharmaceutical compounds with serotonin receptor activity |
IL161576A0 (en) | 2001-10-26 | 2004-09-27 | Aventis Pharma Inc | Benzimidazoles and analogues and their use as protein kinases inhibitors |
JP2003261566A (ja) | 2002-03-11 | 2003-09-19 | Sankyo Co Ltd | キノリジンを含有する医薬 |
TW200930291A (en) | 2002-04-29 | 2009-07-16 | Bayer Cropscience Ag | Pesticidal heterocycles |
US7276522B2 (en) | 2002-05-21 | 2007-10-02 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones, 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
US7358269B2 (en) | 2002-05-21 | 2008-04-15 | Allergan, Inc. | 2-((2-Thioxo-2,3-dihydro-1H-imidazol-4-yl)methyl)-3,4-dihydronapthalen-1(2H)-one |
US7091232B2 (en) | 2002-05-21 | 2006-08-15 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
US7323485B2 (en) | 2002-05-21 | 2008-01-29 | Allergan, Inc. | 4-(substituted cycloalkylmethyl) imidazole-2-thiones, 4-(substituted cycloalkenylmethyl) imidazole-2-thiones, 4-(substituted cycloalkylmethyl) imidazol-2-ones and 4-(substituted cycloalkenylmethyl) imidazol-2-ones and related compounds |
SE0202134D0 (sv) | 2002-07-08 | 2002-07-08 | Astrazeneca Ab | Therapeutic agents |
CA2502541A1 (en) | 2002-10-16 | 2004-04-29 | Isis Innovation Limited | Asparaginyl hydroxylases and modulators thereof |
DE10252667A1 (de) * | 2002-11-11 | 2004-05-27 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
AU2003278529A1 (en) * | 2002-11-21 | 2004-06-15 | Pfizer Products Inc. | 3-amino-piperidine derivatives and processes for their preparation |
EP1587482A4 (en) | 2003-01-31 | 2010-08-25 | Technion Res & Dev Foundation | ANTI-INFLAMMATORY COMPOSITIONS AND USES THEREOF |
EP2527326B1 (en) | 2003-03-07 | 2014-10-08 | Santen Pharmaceutical Co., Ltd | Novel compounds having 4-pyridylalkylthio group as substituent |
JP2004269449A (ja) | 2003-03-11 | 2004-09-30 | Ishihara Sangyo Kaisha Ltd | ベンズアミド誘導体、それらの製造方法及びそれらを含有する有害生物防除剤 |
US7205318B2 (en) | 2003-03-18 | 2007-04-17 | Bristol-Myers Squibb Company | Lactam-containing cyclic diamines and derivatives as a factor Xa inhibitors |
CN100475793C (zh) | 2003-03-31 | 2009-04-08 | 大正制药株式会社 | 喹唑啉衍生物及其制备药物的用途 |
JP2005145859A (ja) | 2003-11-13 | 2005-06-09 | Nippon Steel Chem Co Ltd | 脱水素化方法及び芳香族複素環化合物の製造方法 |
DE10360793A1 (de) * | 2003-12-23 | 2005-07-28 | Grünenthal GmbH | Spirocyclische Cyclohexan-Derivate |
AU2005208938A1 (en) | 2004-01-29 | 2005-08-11 | Elixir Pharmaceuticals, Inc | Anti-viral therapeutics |
DE102004004974A1 (de) | 2004-01-31 | 2005-08-18 | Aventis Pharma Deutschland Gmbh | Thieno-Iminosäure-Derivate als Inhibitoren von Matrix-Metalloproteinasen |
KR100553398B1 (ko) * | 2004-03-12 | 2006-02-16 | 한미약품 주식회사 | 티에노[3,2-c]피리딘 유도체의 제조 방법 및 이에사용되는 중간체 |
KR20070046150A (ko) | 2004-07-28 | 2007-05-02 | 아이알엠 엘엘씨 | 스테로이드 호르몬 핵 수용체의 조절제로서의 화합물 및조성물 |
SE0401970D0 (sv) | 2004-08-02 | 2004-08-02 | Astrazeneca Ab | Novel compounds |
SE0401971D0 (sv) | 2004-08-02 | 2004-08-02 | Astrazeneca Ab | Piperidne derivatives |
EP1634873A1 (en) | 2004-08-27 | 2006-03-15 | Laboratorios Del Dr. Esteve, S.A. | Sigma receptor inhibitors |
FR2875230A1 (fr) | 2004-09-13 | 2006-03-17 | Sanofi Aventis Sa | Derives de pyrazole condense, leur preparation et leur application en therapeutique |
JP2006117568A (ja) | 2004-10-20 | 2006-05-11 | Mitsubishi Pharma Corp | チオフェン環を有する新規アミド誘導体及びその医薬としての用途 |
US7214704B2 (en) | 2004-11-15 | 2007-05-08 | Bristol-Myers Squibb Company | 2-Amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
AU2006214233A1 (en) * | 2005-02-17 | 2006-08-24 | Wyeth | Cycloalkylfused indole, benzothiophene, benzofuran and indene derivatives |
TW200642683A (en) | 2005-04-22 | 2006-12-16 | Sankyo Co | Heterocyclic compound |
KR20080030630A (ko) | 2005-06-27 | 2008-04-04 | 이 아이 듀폰 디 네모아 앤드 캄파니 | 전기 전도성 중합체 조성물 |
WO2007001939A1 (en) | 2005-06-27 | 2007-01-04 | Janssen Pharmaceutica N.V. | Tetrahydro-pyranopyrazole compounds displaying cannabinoid modulating activities |
JP2009505948A (ja) * | 2005-07-11 | 2009-02-12 | デブジェン エヌブイ | キナーゼ阻害剤としてのアミド誘導体 |
US8846742B2 (en) | 2006-02-14 | 2014-09-30 | The Trustees Of Columbia University In The City Of New York | Neuronal pain pathway modulators |
EP1986638A2 (en) | 2006-02-21 | 2008-11-05 | Ampla Pharmaceuticals Inc. | Cb1 antagonists and inverse agonists |
EP1829869A1 (en) * | 2006-03-02 | 2007-09-05 | Laboratorios Del Dr. Esteve, S.A. | 4,5,6,7-Tetrahydrobenzo[b]thiophene derivatives and their use as sigma receptor ligands |
EP2017275A4 (en) * | 2006-04-28 | 2011-06-22 | Eisai R&D Man Co Ltd | BENZISOXAZOLE COMPOUND |
MX2009003761A (es) | 2006-10-04 | 2009-06-30 | Schering Corp | Derivados biciclicos y triciclicos como antagonistas del receptor de trombina. |
US7960569B2 (en) | 2006-10-17 | 2011-06-14 | Bristol-Myers Squibb Company | Indole antagonists of P2Y1 receptor useful in the treatment of thrombotic conditions |
US20100137294A1 (en) | 2006-11-15 | 2010-06-03 | Genetic Technologies Limited | Compounds, compositions and methods for controlling invertebrate pests |
WO2009008906A2 (en) | 2007-02-06 | 2009-01-15 | The Trustees Of The University Of Pennsylvania | Therapeutic compounds for blocking dna synthesis of pox viruses |
US7598417B2 (en) | 2007-04-12 | 2009-10-06 | Allergan, Inc. | Substituted fluoroethyl ureas as alpha 2 adrenergic agents |
EP1982987A1 (en) * | 2007-04-16 | 2008-10-22 | Laboratorios del Dr. Esteve S.A. | Spiro-pyrano-pyrazole derivatives |
EP1982714A1 (en) * | 2007-04-16 | 2008-10-22 | Laboratorios del Dr. Esteve S.A. | Pyrano-pyrazole-amines |
EP2020414A1 (en) | 2007-06-20 | 2009-02-04 | Laboratorios del Dr. Esteve S.A. | spiro[piperidine-4,4'-thieno[3,2-c]pyran] derivatives and related compounds as inhibitors of the sigma receptor for the treatment of psychosis |
US8338623B2 (en) | 2007-07-09 | 2012-12-25 | Abbvie Inc. | Compounds as cannabinoid receptor ligands |
ES2469824T3 (es) | 2007-11-21 | 2014-06-20 | Janssen Pharmaceutica N.V. | Espiropiperidinas para su uso como inhibidores de la triptasa |
US7973051B2 (en) | 2007-11-30 | 2011-07-05 | Hoffman-La Roche Inc. | Aminothiazoles as FBPase inhibitors for diabetes |
US8268754B2 (en) | 2007-12-07 | 2012-09-18 | Nissan Chemical Industries, Ltd. | Substituted dihydroazole compound and pest control agent |
WO2009085256A1 (en) | 2007-12-27 | 2009-07-09 | Panacos Pharmaceuticals, Inc. | Anti-hiv compounds |
CN101759710B (zh) | 2008-10-06 | 2011-10-05 | 山东轩竹医药科技有限公司 | 含有取代的氮杂环的头孢菌素衍生物 |
US9776963B2 (en) | 2008-11-10 | 2017-10-03 | The Trustees Of The University Of Pennsylvania | Small molecule CD4 mimetics and uses thereof |
AR075442A1 (es) | 2009-02-16 | 2011-03-30 | Abbott Gmbh & Co Kg | Derivados de aminotetralina, composiciones farmaceuticas que las contienen y sus usos en terapia |
TW201038569A (en) | 2009-02-16 | 2010-11-01 | Abbott Gmbh & Co Kg | Heterocyclic compounds, pharmaceutical compositions containing them, and their use in therapy |
WO2011036889A1 (ja) | 2009-09-25 | 2011-03-31 | 武田薬品工業株式会社 | 複素環化合物 |
JP5723381B2 (ja) * | 2009-11-16 | 2015-05-27 | イーライ リリー アンド カンパニー | Orl−1受容体アンタゴニストとしてのスピロピペリジン化合物 |
UA107943C2 (en) * | 2009-11-16 | 2015-03-10 | Lilly Co Eli | Compounds of spiropiperidines as antagonists of the orl-1 receptors |
NZ767139A (en) | 2009-12-04 | 2022-08-26 | Sunovion Pharmaceuticals Inc | Multicyclic compounds and methods of use thereof |
AU2010339271B2 (en) | 2009-12-28 | 2015-09-03 | General Incorporated Association Pharma Valley Project Supporting Organization | 1,3,4-oxadiazole-2-carboxamide compound |
EP2377850A1 (en) | 2010-03-30 | 2011-10-19 | Pharmeste S.r.l. | TRPV1 vanilloid receptor antagonists with a bicyclic portion |
EP2560636A4 (en) | 2010-04-23 | 2013-11-27 | Kineta Inc | ANTIVIRAL COMPOUNDS |
US8883839B2 (en) | 2010-08-13 | 2014-11-11 | Abbott Laboratories | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US9051280B2 (en) | 2010-08-13 | 2015-06-09 | AbbVie Deutschland GmbH & Co. KG | Tetraline and indane derivatives, pharmaceutical compositions containing them, and their use in therapy |
US8569339B2 (en) | 2011-03-10 | 2013-10-29 | Boehringer Ingelheim International Gmbh | Soluble guanylate cyclase activators |
CN102731574B (zh) | 2011-03-30 | 2016-03-02 | 中国人民解放军军事医学科学院毒物药物研究所 | 噻吩并吡啶类α-胺基苄基膦酸酯、其制备方法及用途 |
WO2013010453A1 (en) | 2011-07-15 | 2013-01-24 | Abbott Laboratories | Chemoking receptor antagonists |
CN106537488B (zh) | 2014-07-23 | 2019-06-07 | 夏普株式会社 | 显示装置及其驱动方法 |
EP3582815A1 (en) | 2017-02-16 | 2019-12-25 | Sunovion Pharmaceuticals Inc. | Methods of treating schizophrenia |
JP2021513972A (ja) | 2018-02-16 | 2021-06-03 | サノビオン ファーマシューティカルズ インクSunovion Pharmaceuticals Inc. | 社会的機能障害の治療方法 |
CN112135827B (zh) | 2018-02-16 | 2024-01-12 | 赛诺维信制药公司 | 盐、晶型及其制备方法 |
EP3890726A1 (en) | 2018-12-06 | 2021-10-13 | Sunovion Pharmaceuticals Inc. | Methods of treating neurological and psychiatric disorders |
-
2010
- 2010-12-03 NZ NZ767139A patent/NZ767139A/en unknown
- 2010-12-03 US US13/513,176 patent/US8710245B2/en active Active
- 2010-12-03 CN CN202010422479.3A patent/CN111560025A/zh active Pending
- 2010-12-03 BR BR122021013836-2A patent/BR122021013836B1/pt active IP Right Grant
- 2010-12-03 JP JP2012542219A patent/JP5778168B2/ja active Active
- 2010-12-03 FI FIEP17160203.0T patent/FI3252057T3/fi active
- 2010-12-03 DK DK17160203.0T patent/DK3252057T3/da active
- 2010-12-03 KR KR1020187012385A patent/KR102074089B1/ko active IP Right Grant
- 2010-12-03 EP EP17160203.0A patent/EP3252057B1/en active Active
- 2010-12-03 CA CA2781716A patent/CA2781716A1/en active Pending
- 2010-12-03 NZ NZ626068A patent/NZ626068A/en unknown
- 2010-12-03 SG SG2012040895A patent/SG181498A1/en unknown
- 2010-12-03 EP EP10835185.9A patent/EP2507245B1/en active Active
- 2010-12-03 SG SG10201510665WA patent/SG10201510665WA/en unknown
- 2010-12-03 IL IL272376A patent/IL272376B1/en unknown
- 2010-12-03 CN CN202410181638.3A patent/CN118165002A/zh active Pending
- 2010-12-03 WO PCT/US2010/058884 patent/WO2011069063A2/en active Application Filing
- 2010-12-03 NZ NZ731621A patent/NZ731621A/en unknown
- 2010-12-03 AU AU2010325925A patent/AU2010325925B2/en active Active
- 2010-12-03 SG SG10201401661RA patent/SG10201401661RA/en unknown
- 2010-12-03 KR KR1020167017387A patent/KR101772834B1/ko active IP Right Grant
- 2010-12-03 KR KR1020127017294A patent/KR101637247B1/ko active IP Right Grant
- 2010-12-03 KR KR1020217030661A patent/KR102505085B1/ko active IP Right Grant
- 2010-12-03 DK DK10835185.9T patent/DK2507245T3/en active
- 2010-12-03 RU RU2018100098A patent/RU2707067C2/ru active
- 2010-12-03 MX MX2012006326A patent/MX2012006326A/es active IP Right Grant
- 2010-12-03 NZ NZ600008A patent/NZ600008A/en unknown
- 2010-12-03 BR BR112012013431-0A patent/BR112012013431B1/pt active IP Right Grant
- 2010-12-03 KR KR1020177023257A patent/KR101855471B1/ko active IP Right Grant
- 2010-12-03 NZ NZ711802A patent/NZ711802A/en unknown
- 2010-12-03 RU RU2012127770/04A patent/RU2557059C2/ru active
- 2010-12-03 KR KR1020157019665A patent/KR101637246B1/ko active IP Right Grant
- 2010-12-03 ES ES10835185.9T patent/ES2625330T3/es active Active
- 2010-12-03 CN CN201410333332.1A patent/CN104193761B/zh active Active
- 2010-12-03 PT PT108351859T patent/PT2507245T/pt unknown
- 2010-12-03 CN CN201610836552.5A patent/CN106883246B/zh active Active
- 2010-12-03 RU RU2015119926A patent/RU2641648C1/ru active
- 2010-12-03 KR KR1020207002216A patent/KR102307413B1/ko active IP Right Grant
- 2010-12-03 CN CN201080062822.2A patent/CN102762575B/zh active Active
-
2012
- 2012-05-15 ZA ZA2012/03533A patent/ZA201203533B/en unknown
- 2012-06-01 MX MX2020012825A patent/MX2020012825A/es unknown
- 2012-06-04 IL IL220173A patent/IL220173A0/en active IP Right Grant
-
2014
- 2014-03-12 US US14/205,859 patent/US9351954B2/en active Active
- 2014-12-15 JP JP2014253082A patent/JP5710064B1/ja active Active
-
2015
- 2015-06-09 HK HK15105471.0A patent/HK1212969A1/zh unknown
- 2015-07-08 JP JP2015136603A patent/JP6005807B2/ja active Active
- 2015-11-24 US US14/950,834 patent/US10085968B2/en active Active
- 2015-12-10 IL IL243018A patent/IL243018B/en active IP Right Grant
- 2015-12-10 IL IL243015A patent/IL243015B/en active IP Right Grant
- 2015-12-10 IL IL243019A patent/IL243019B/en active IP Right Grant
- 2015-12-10 IL IL243021A patent/IL243021B/en active IP Right Grant
-
2016
- 2016-01-27 AU AU2016200448A patent/AU2016200448C1/en active Active
- 2016-07-01 JP JP2016131247A patent/JP6028310B1/ja active Active
- 2016-09-29 JP JP2016191898A patent/JP6297655B2/ja active Active
-
2017
- 2017-10-20 AU AU2017248551A patent/AU2017248551B2/en active Active
-
2018
- 2018-02-21 JP JP2018028819A patent/JP2018104454A/ja active Pending
- 2018-05-31 HK HK18107195.8A patent/HK1247911A1/zh unknown
- 2018-08-30 US US16/117,450 patent/US20190125722A1/en not_active Abandoned
-
2020
- 2020-02-14 US US16/791,118 patent/US10894033B2/en active Active
- 2020-06-24 JP JP2020108727A patent/JP7104746B2/ja active Active
- 2020-11-19 US US16/952,401 patent/US20210267938A1/en not_active Abandoned
-
2022
- 2022-01-13 US US17/574,702 patent/US20220387382A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6297655B2 (ja) | 多環式化合物及びその使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20170921 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171003 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180104 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180123 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180221 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6297655 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |