JP4945453B2 - Ｍ４ムスカリン性受容体のアロステリック増強剤としてのチエノピリジン - Google Patents
Ｍ４ムスカリン性受容体のアロステリック増強剤としてのチエノピリジン Download PDFInfo
- Publication number
- JP4945453B2 JP4945453B2 JP2007537951A JP2007537951A JP4945453B2 JP 4945453 B2 JP4945453 B2 JP 4945453B2 JP 2007537951 A JP2007537951 A JP 2007537951A JP 2007537951 A JP2007537951 A JP 2007537951A JP 4945453 B2 JP4945453 B2 JP 4945453B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- group
- compound
- chloro
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 title claims abstract description 24
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 title claims abstract description 24
- 230000003281 allosteric effect Effects 0.000 title abstract description 21
- 229940125670 thienopyridine Drugs 0.000 title 1
- 239000002175 thienopyridine Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 24
- 208000035475 disorder Diseases 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 151
- 230000000694 effects Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 6
- APVXECALWXWTBQ-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(2-morpholin-4-ylethoxy)thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCN1CCOCC1 APVXECALWXWTBQ-UHFFFAOYSA-N 0.000 claims description 5
- CTEGQKDJTBWFHW-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-methoxy-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OC)=NC=2SC=1C(=O)NC1CC1 CTEGQKDJTBWFHW-UHFFFAOYSA-N 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- NJBOUQLKCGARJL-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-oxo-7h-thieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(O)=NC=2SC=1C(=O)NC1CC1 NJBOUQLKCGARJL-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000166 1,3-dioxalanyl group Chemical group 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 208000031091 Amnestic disease Diseases 0.000 claims 1
- ZUUXEGXLNZNKNQ-UHFFFAOYSA-N N-cyclopropylthieno[2,3-b]pyridine-2-carboxamide Chemical group C1(CC1)NC(=O)C1=CC=2C(=NC=CC=2)S1 ZUUXEGXLNZNKNQ-UHFFFAOYSA-N 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 230000006986 amnesia Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 115
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- 239000007787 solid Substances 0.000 description 87
- 239000000243 solution Substances 0.000 description 86
- 239000000203 mixture Substances 0.000 description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 235000019439 ethyl acetate Nutrition 0.000 description 50
- 239000011541 reaction mixture Substances 0.000 description 50
- 238000006243 chemical reaction Methods 0.000 description 43
- 238000007792 addition Methods 0.000 description 36
- 238000000034 method Methods 0.000 description 29
- 239000002244 precipitate Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- 238000001914 filtration Methods 0.000 description 25
- 239000010410 layer Substances 0.000 description 23
- 102000005962 receptors Human genes 0.000 description 23
- 108020003175 receptors Proteins 0.000 description 23
- -1 aliphatic mono- Chemical class 0.000 description 21
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 239000002002 slurry Substances 0.000 description 18
- GJLPQVZOJCFGEX-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-methylsulfinylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(S(C)=O)=NC=2SC=1C(=O)NC1CC1 GJLPQVZOJCFGEX-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 6
- IWAPPICXYVQYRY-UHFFFAOYSA-N 2-[3-amino-5-chloro-2-(cyclopropylcarbamoyl)-4-methylthieno[2,3-b]pyridin-6-yl]oxyacetic acid Chemical compound NC=1C=2C(C)=C(Cl)C(OCC(O)=O)=NC=2SC=1C(=O)NC1CC1 IWAPPICXYVQYRY-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- 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 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 4
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 208000028698 Cognitive impairment Diseases 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 4
- 229960004484 carbachol Drugs 0.000 description 4
- 208000010877 cognitive disease Diseases 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- MEICKJSSGQUWTE-UHFFFAOYSA-N 2,5,6-trichloro-4-methylpyridine-3-carbonitrile Chemical compound CC1=C(Cl)C(Cl)=NC(Cl)=C1C#N MEICKJSSGQUWTE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000026139 Memory disease Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000006984 memory degeneration Effects 0.000 description 3
- 208000023060 memory loss Diseases 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 239000000472 muscarinic agonist Substances 0.000 description 3
- 230000003551 muscarinic effect Effects 0.000 description 3
- MIVRGUPIFGVQQS-UHFFFAOYSA-N n-cyclopropyl-2-sulfanylacetamide Chemical compound SCC(=O)NC1CC1 MIVRGUPIFGVQQS-UHFFFAOYSA-N 0.000 description 3
- 230000003957 neurotransmitter release Effects 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 2
- MRILYUBRJRJWGO-UHFFFAOYSA-N 2,5-dichloro-4-methyl-6-methylsulfanylpyridine-3-carbonitrile Chemical compound CSC1=NC(Cl)=C(C#N)C(C)=C1Cl MRILYUBRJRJWGO-UHFFFAOYSA-N 0.000 description 2
- XYOFNBMNGPNQKP-UHFFFAOYSA-N 2,5-dichloro-4-methyl-6-propan-2-yloxypyridine-3-carbonitrile Chemical compound CC(C)OC1=NC(Cl)=C(C#N)C(C)=C1Cl XYOFNBMNGPNQKP-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- XSPGBPAWYYSUPS-UHFFFAOYSA-N 2-chloro-4-methyl-6-propan-2-yloxypyridine-3-carbonitrile Chemical compound CC(C)OC1=CC(C)=C(C#N)C(Cl)=N1 XSPGBPAWYYSUPS-UHFFFAOYSA-N 0.000 description 2
- UCEUKYCPTWMIAX-UHFFFAOYSA-N 2-chloro-6-(2-methoxyethoxy)-4-methylpyridine-3-carbonitrile Chemical compound COCCOC1=CC(C)=C(C#N)C(Cl)=N1 UCEUKYCPTWMIAX-UHFFFAOYSA-N 0.000 description 2
- LUQWFQHFQWFAII-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-propan-2-yloxythieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OC(C)C)=NC=2SC=1C(=O)NC1CC1 LUQWFQHFQWFAII-UHFFFAOYSA-N 0.000 description 2
- UJGDYAFOVMCJLK-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-(2-hydroxyethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCO)=NC=2SC=1C(=O)NC1CC1 UJGDYAFOVMCJLK-UHFFFAOYSA-N 0.000 description 2
- CDMLTJOYYLHDIN-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-(dimethylamino)-2-oxoethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCC(=O)N(C)C)=NC=2SC=1C(=O)NC1CC1 CDMLTJOYYLHDIN-UHFFFAOYSA-N 0.000 description 2
- LZLJSNRUGDADII-UHFFFAOYSA-N 5,6-dichloro-4-methyl-2-propan-2-yloxypyridine-3-carbonitrile Chemical compound CC(C)OC1=NC(Cl)=C(Cl)C(C)=C1C#N LZLJSNRUGDADII-UHFFFAOYSA-N 0.000 description 2
- BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 2
- IRWHGKWSPQBARJ-UHFFFAOYSA-N 6-chloro-4-methyl-2-propan-2-yloxypyridine-3-carbonitrile Chemical compound CC(C)OC1=NC(Cl)=CC(C)=C1C#N IRWHGKWSPQBARJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical class [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- RSDOPYMFZBJHRL-UHFFFAOYSA-N Oxotremorine Chemical compound O=C1CCCN1CC#CCN1CCCC1 RSDOPYMFZBJHRL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical class OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- 210000001577 neostriatum Anatomy 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
- 229960003081 probenecid Drugs 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- CADKVHDTKJDPMY-UHFFFAOYSA-N s-[2-(cyclopropylamino)-2-oxoethyl] ethanethioate Chemical compound CC(=O)SCC(=O)NC1CC1 CADKVHDTKJDPMY-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229960004793 sucrose Drugs 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical class OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- FLNQAPQQAZVRDA-UHFFFAOYSA-N 1-(2-(2-Hydroxyethoxy)ethyl)piperazine Chemical compound OCCOCCN1CCNCC1 FLNQAPQQAZVRDA-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- BCQVIWRFKUYDMT-UHFFFAOYSA-N 2,5-dichloro-4-methylpyridine-3-carbonitrile Chemical compound CC1=C(Cl)C=NC(Cl)=C1C#N BCQVIWRFKUYDMT-UHFFFAOYSA-N 0.000 description 1
- ROHADJZFOZENIB-UHFFFAOYSA-N 2,5-dichloro-6-(2-methoxyethoxy)-4-methylpyridine-3-carbonitrile Chemical compound COCCOC1=NC(Cl)=C(C#N)C(C)=C1Cl ROHADJZFOZENIB-UHFFFAOYSA-N 0.000 description 1
- FAJSGZKKDBVZAO-UHFFFAOYSA-N 2,5-dichloro-6-methoxy-4-methylpyridine-3-carbonitrile Chemical compound COC1=NC(Cl)=C(C#N)C(C)=C1Cl FAJSGZKKDBVZAO-UHFFFAOYSA-N 0.000 description 1
- LSPMHHJCDSFAAY-UHFFFAOYSA-N 2,6-dichloro-4-methylpyridine-3-carbonitrile Chemical compound CC1=CC(Cl)=NC(Cl)=C1C#N LSPMHHJCDSFAAY-UHFFFAOYSA-N 0.000 description 1
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
- ZPWIVSGEQGESFF-UHFFFAOYSA-N 2-chloro-n-cyclopropylacetamide Chemical compound ClCC(=O)NC1CC1 ZPWIVSGEQGESFF-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- YJHSJERLYWNLQL-UHFFFAOYSA-N 2-hydroxyethyl(dimethyl)azanium;chloride Chemical compound Cl.CN(C)CCO YJHSJERLYWNLQL-UHFFFAOYSA-N 0.000 description 1
- WBBPRCNXBQTYLF-UHFFFAOYSA-N 2-methylthioethanol Chemical compound CSCCO WBBPRCNXBQTYLF-UHFFFAOYSA-N 0.000 description 1
- HMGCGUWFPZVPEK-UHFFFAOYSA-N 2-naphthalen-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C=CC=C2)C2=C1 HMGCGUWFPZVPEK-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- DWPYQDGDWBKJQL-UHFFFAOYSA-N 2-pyridin-4-ylethanol Chemical compound OCCC1=CC=NC=C1 DWPYQDGDWBKJQL-UHFFFAOYSA-N 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- YKKBJKGMEDUVNB-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(2-methylsulfanylethoxy)thieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCSC)=NC=2SC=1C(=O)NC1CC1 YKKBJKGMEDUVNB-UHFFFAOYSA-N 0.000 description 1
- VQMAVAKPBWNTCH-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(2-morpholin-4-ylethoxy)thieno[2,3-b]pyridine-2-carboxamide;hydrochloride Chemical compound Cl.N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCN1CCOCC1 VQMAVAKPBWNTCH-UHFFFAOYSA-N 0.000 description 1
- NTEMIMMUKILTPY-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(2-piperazin-1-ylethoxy)thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCN1CCNCC1 NTEMIMMUKILTPY-UHFFFAOYSA-N 0.000 description 1
- IORGDZHYZGCLMT-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(2-pyridin-4-ylethoxy)thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCC1=CC=NC=C1 IORGDZHYZGCLMT-UHFFFAOYSA-N 0.000 description 1
- YEDKASLHVVTYEJ-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-(3-pyridin-3-ylpropoxy)thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCCC1=CC=CN=C1 YEDKASLHVVTYEJ-UHFFFAOYSA-N 0.000 description 1
- ALVMOKFGVBIMSI-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-(2-morpholin-4-ylethylamino)-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC(=O)NCCN1CCOCC1 ALVMOKFGVBIMSI-UHFFFAOYSA-N 0.000 description 1
- MSXVSICQTXPDHI-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-(2-piperazin-1-ylethoxy)ethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCOCCN1CCNCC1 MSXVSICQTXPDHI-UHFFFAOYSA-N 0.000 description 1
- WUWVJCXXBXHUPR-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound N1=CSC(CCOC=2C(=C(C)C=3C(N)=C(C(=O)NC4CC4)SC=3N=2)Cl)=C1C WUWVJCXXBXHUPR-UHFFFAOYSA-N 0.000 description 1
- XQRPWWTZIGVIEN-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-(pyridine-4-carbonylamino)ethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCCNC(=O)C1=CC=NC=C1 XQRPWWTZIGVIEN-UHFFFAOYSA-N 0.000 description 1
- XLZWAORKOYCVIY-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-[(4-methylpiperazin-1-yl)amino]-2-oxoethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound C1CN(C)CCN1NC(=O)COC(C(=C1C)Cl)=NC2=C1C(N)=C(C(=O)NC1CC1)S2 XLZWAORKOYCVIY-UHFFFAOYSA-N 0.000 description 1
- ZSOBLGRGVBHVMD-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-[2-oxo-2-(2-pyrrolidin-1-ylethylamino)ethoxy]thieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC(=O)NCCN1CCCC1 ZSOBLGRGVBHVMD-UHFFFAOYSA-N 0.000 description 1
- MLCDBSXTPKMRBV-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-4-methyl-6-phenylmethoxythieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC1=CC=CC=C1 MLCDBSXTPKMRBV-UHFFFAOYSA-N 0.000 description 1
- ZGSLJBDAEAYKST-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-(1,3-dioxolan-4-ylmethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC1COCO1 ZGSLJBDAEAYKST-UHFFFAOYSA-N 0.000 description 1
- YJMZPEOXPGASJI-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-(2-methoxyethoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCOC)=NC=2SC=1C(=O)NC1CC1 YJMZPEOXPGASJI-UHFFFAOYSA-N 0.000 description 1
- DTOOFGZHCFIFTM-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-(3-hydroxypropoxy)-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCCO)=NC=2SC=1C(=O)NC1CC1 DTOOFGZHCFIFTM-UHFFFAOYSA-N 0.000 description 1
- MUQSAUMOMFYFPY-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-(2-hydroxyethoxy)ethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCOCCO)=NC=2SC=1C(=O)NC1CC1 MUQSAUMOMFYFPY-UHFFFAOYSA-N 0.000 description 1
- MTMQLYIJIWRRTR-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-(2-hydroxyethylamino)-2-oxoethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCC(=O)NCCO)=NC=2SC=1C(=O)NC1CC1 MTMQLYIJIWRRTR-UHFFFAOYSA-N 0.000 description 1
- YZTWFGRXEGELKR-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-(2-hydroxyethylamino)ethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCNCCO)=NC=2SC=1C(=O)NC1CC1 YZTWFGRXEGELKR-UHFFFAOYSA-N 0.000 description 1
- PYLIVIIBFCAWHU-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-(imidazol-1-ylamino)-2-oxoethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC(=O)NN1C=CN=C1 PYLIVIIBFCAWHU-UHFFFAOYSA-N 0.000 description 1
- DMKGAFIAKIDAGR-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-[2-[(4-fluorophenyl)methylamino]-2-oxoethoxy]-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound N=1C=2SC(C(=O)NC3CC3)=C(N)C=2C(C)=C(Cl)C=1OCC(=O)NCC1=CC=C(F)C=C1 DMKGAFIAKIDAGR-UHFFFAOYSA-N 0.000 description 1
- PPKMGBBMCBGCDZ-UHFFFAOYSA-N 3-amino-5-chloro-n-cyclopropyl-6-ethoxy-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCC)=NC=2SC=1C(=O)NC1CC1 PPKMGBBMCBGCDZ-UHFFFAOYSA-N 0.000 description 1
- BXXFXCFQRRHRLL-UHFFFAOYSA-N 3-amino-6-[2-[bis(2-hydroxyethyl)amino]ethoxy]-5-chloro-n-cyclopropyl-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCN(CCO)CCO)=NC=2SC=1C(=O)NC1CC1 BXXFXCFQRRHRLL-UHFFFAOYSA-N 0.000 description 1
- FVZXYJDGVYLMDB-UHFFFAOYSA-N 3-pyridin-2-ylpropan-1-ol Chemical compound OCCCC1=CC=CC=N1 FVZXYJDGVYLMDB-UHFFFAOYSA-N 0.000 description 1
- ZUGAIMFLQLPTKB-UHFFFAOYSA-N 3-pyridin-3-ylpropan-1-ol Chemical compound OCCCC1=CC=CN=C1 ZUGAIMFLQLPTKB-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 1
- ZMOBMAVJUKZWQR-UHFFFAOYSA-N 5,6-dichloro-2-(2-methoxyethoxy)-4-methylpyridine-3-carbonitrile Chemical compound COCCOC1=NC(Cl)=C(Cl)C(C)=C1C#N ZMOBMAVJUKZWQR-UHFFFAOYSA-N 0.000 description 1
- GEHRSERUQRFUFW-UHFFFAOYSA-N 5-ethylhex-2-ynedioic acid Chemical class CCC(C(O)=O)CC#CC(O)=O GEHRSERUQRFUFW-UHFFFAOYSA-N 0.000 description 1
- PPBBCOZYJYKRKT-UHFFFAOYSA-N 6-(2-acetamidoethoxy)-3-amino-5-chloro-n-cyclopropyl-4-methylthieno[2,3-b]pyridine-2-carboxamide Chemical compound NC=1C=2C(C)=C(Cl)C(OCCNC(=O)C)=NC=2SC=1C(=O)NC1CC1 PPBBCOZYJYKRKT-UHFFFAOYSA-N 0.000 description 1
- HDVPOJWJBSUHSE-UHFFFAOYSA-N 6-chloro-2-(2-methoxyethoxy)-4-methylpyridine-3-carbonitrile Chemical compound COCCOC1=NC(Cl)=CC(C)=C1C#N HDVPOJWJBSUHSE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- XPRYEYJBTFIPRM-UHFFFAOYSA-N C1CC1NC(=O)C2=C(C3=C(S2)N=CC=C3)OCCCC4=CC=CC=N4 Chemical compound C1CC1NC(=O)C2=C(C3=C(S2)N=CC=C3)OCCCC4=CC=CC=N4 XPRYEYJBTFIPRM-UHFFFAOYSA-N 0.000 description 1
- APDUWDQWZPIQHF-UHFFFAOYSA-N CC1=C(CN(C(=C1Cl)OCCOC)Cl)C#N Chemical compound CC1=C(CN(C(=C1Cl)OCCOC)Cl)C#N APDUWDQWZPIQHF-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical class OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical class [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical class OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical class CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical class [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- PVCJKHHOXFKFRP-UHFFFAOYSA-N N-acetylethanolamine Chemical compound CC(=O)NCCO PVCJKHHOXFKFRP-UHFFFAOYSA-N 0.000 description 1
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical class OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical class [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 239000003693 atypical antipsychotic agent Substances 0.000 description 1
- 229940127236 atypical antipsychotics Drugs 0.000 description 1
- 230000010455 autoregulation Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- JOYKCMAPFCSKNO-UHFFFAOYSA-N chloro benzenesulfonate Chemical compound ClOS(=O)(=O)C1=CC=CC=C1 JOYKCMAPFCSKNO-UHFFFAOYSA-N 0.000 description 1
- KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 235000019788 craving Nutrition 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- HWDVTQAXQJQROO-UHFFFAOYSA-N cyclopropylazanide Chemical compound [NH-]C1CC1 HWDVTQAXQJQROO-UHFFFAOYSA-N 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical class CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940074076 glycerol formal Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- TVZISJTYELEYPI-UHFFFAOYSA-N hypodiphosphoric acid Chemical compound OP(O)(=O)P(O)(O)=O TVZISJTYELEYPI-UHFFFAOYSA-N 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 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
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical class [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000005567 liquid scintillation counting Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000010687 lubricating oil Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical class OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical class [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-M methanethiolate Chemical compound [S-]C LSDPWZHWYPCBBB-UHFFFAOYSA-M 0.000 description 1
- QIOHJLDUDDZJPW-UHFFFAOYSA-N methyl 2-[3-amino-5-chloro-2-(cyclopropylcarbamoyl)-4-methylthieno[2,3-b]pyridin-6-yl]oxyacetate Chemical compound NC=1C=2C(C)=C(Cl)C(OCC(=O)OC)=NC=2SC=1C(=O)NC1CC1 QIOHJLDUDDZJPW-UHFFFAOYSA-N 0.000 description 1
- IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229940012189 methyl orange Drugs 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- QVPWDPDVDVVXIB-UHFFFAOYSA-N n-(2-hydroxyethyl)pyridine-4-carboxamide Chemical compound OCCNC(=O)C1=CC=NC=C1 QVPWDPDVDVVXIB-UHFFFAOYSA-N 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-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
- 208000004296 neuralgia Diseases 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940039748 oxalate Drugs 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
- 229940049953 phenylacetate Drugs 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229950009215 phenylbutanoic acid Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000013102 re-test Methods 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 229940116351 sebacate Drugs 0.000 description 1
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000003977 synaptic function Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical class [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 229940071104 xylenesulfonate Drugs 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
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Compression, Expansion, Code Conversion, And Decoders (AREA)
- Measurement Of Velocity Or Position Using Acoustic Or Ultrasonic Waves (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US62178504P | 2004-10-25 | 2004-10-25 | |
| US60/621,785 | 2004-10-25 | ||
| PCT/US2005/037271 WO2006047124A1 (en) | 2004-10-25 | 2005-10-18 | Thienopyridines as allosteric potentiators of the m4 muscarinic receptor |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2008517913A JP2008517913A (ja) | 2008-05-29 |
| JP2008517913A5 JP2008517913A5 (enExample) | 2008-10-23 |
| JP4945453B2 true JP4945453B2 (ja) | 2012-06-06 |
Family
ID=36021809
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007537951A Expired - Fee Related JP4945453B2 (ja) | 2004-10-25 | 2005-10-18 | Ｍ４ムスカリン性受容体のアロステリック増強剤としてのチエノピリジン |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8071776B2 (enExample) |
| EP (1) | EP1807434B1 (enExample) |
| JP (1) | JP4945453B2 (enExample) |
| CN (1) | CN100577666C (enExample) |
| AT (1) | ATE478876T1 (enExample) |
| AU (1) | AU2005299957B2 (enExample) |
| BR (1) | BRPI0517438A (enExample) |
| CA (1) | CA2583550C (enExample) |
| CY (1) | CY1111477T1 (enExample) |
| DE (1) | DE602005023197D1 (enExample) |
| DK (1) | DK1807434T3 (enExample) |
| ES (1) | ES2349416T3 (enExample) |
| MX (1) | MX2007004794A (enExample) |
| PL (1) | PL1807434T3 (enExample) |
| PT (1) | PT1807434E (enExample) |
| WO (1) | WO2006047124A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013126856A1 (en) * | 2012-02-23 | 2013-08-29 | Vanderbilt University | Substituted 5-aminothieno[2,3-c]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
| WO2014035829A1 (en) * | 2012-08-31 | 2014-03-06 | Vanderbilt University | Substituted 3-aminothieno[2,3-c]pyridine-2-carboxamide analogs as positive allosteric modulators |
| US9908893B2 (en) | 2013-06-11 | 2018-03-06 | Latvian Institute Of Organic Synthesis | Thieno [2,3-b] pyridines as multidrug resistance modulators |
| EP3036233A1 (en) | 2013-08-23 | 2016-06-29 | Vanderbilt University | Substituted thieno[2,3-c]pyridazine-6-carboxamide analogs as positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
| ES2789756T3 (es) | 2015-12-23 | 2020-10-26 | Merck Sharp & Dohme | Moduladores alostéricos de 6,7-dihidro-5H-pirrolo[3,4-b]piridin-5-ona del receptor de acetilcolina muscarínico M4 |
| WO2017107089A1 (en) | 2015-12-23 | 2017-06-29 | Merck Sharp & Dohme Corp. | 3- (1h-pyrazol-4-yl) pyridineallosteric modulators of the m4 muscarinic acetylcholine receptor |
| KR102474326B1 (ko) | 2016-06-22 | 2022-12-05 | 반더빌트유니버시티 | 무스카린성 아세틸콜린 수용체 m4의 양성 알로스테릭 조절제 |
| SG11201811712QA (en) | 2016-07-01 | 2019-01-30 | Pfizer | 5,7-dihydro-pyrrolo-pyridine derivatives for treating neurological and neurodegenerative diseases |
| GB201616839D0 (en) | 2016-10-04 | 2016-11-16 | Takeda Pharmaceutical Company Limited | Therapeutic compounds |
| US11008335B2 (en) | 2016-11-07 | 2021-05-18 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor M4 |
| EP3558309B1 (en) | 2016-11-07 | 2023-07-26 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m4 |
| ES2892956T3 (es) | 2016-11-07 | 2022-02-07 | Univ Vanderbilt | Moduladores alostéricos positivos del receptor muscarínico de acetilcolina M4 |
| WO2018112840A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | 6, 5-fused heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor |
| WO2018112842A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | 6,6-fused heteroaryl piperidine ether allosteric modulators of m4 muscarinic acetylcholine receptor |
| WO2018112843A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor |
| FI3642202T3 (fi) | 2017-06-22 | 2023-03-01 | Dihydro-pyrrolo-pyridiinijohdannaisia | |
| WO2019000237A1 (en) | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
| WO2019000238A1 (en) | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | 5- (PYRIDIN-3-YL) OXAZOLE ALLOSTERIC MODULATORS OF M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
| WO2019000236A1 (en) | 2017-06-27 | 2019-01-03 | Merck Sharp & Dohme Corp. | ALLOSTERIC MODULATORS OF 3- (1H-PYRAZOL-4-YL) PYRIDINE FROM THE M4 ACETYLCHOLINE MUSCARINIC RECEPTOR |
| TW201930311A (zh) | 2017-12-05 | 2019-08-01 | 泛德比爾特大學 | 蕈毒鹼型乙醯膽鹼受體m4之正向別構調節劑 |
| CN111406058A (zh) | 2017-12-05 | 2020-07-10 | 范德比尔特大学 | 毒蕈碱型乙酰胆碱受体m4的正向别构调节剂 |
| WO2025201078A1 (zh) * | 2024-03-25 | 2025-10-02 | 四川科伦药物研究院有限公司 | 化合物、包含其的药物组合物及其制备方法和用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3430284A1 (de) * | 1984-08-17 | 1986-02-27 | Troponwerke GmbH & Co KG, 5000 Köln | Neue tryptamin-derivate, ein verfahren zu ihrer herstellung und ihre verwendung |
| NZ290199A (en) * | 1994-07-27 | 1999-06-29 | Sankyo Co | Nitrogen containing heterocyclic compounds, selective allosteric effectors to regulate m1 receptors |
| US6841684B2 (en) * | 1997-12-04 | 2005-01-11 | Allergan, Inc. | Imidiazoles having reduced side effects |
| GB9924962D0 (en) * | 1999-10-21 | 1999-12-22 | Mrc Collaborative Centre | Allosteric sites on muscarinic receptors |
| CN1814596A (zh) * | 2000-04-28 | 2006-08-09 | 阿卡蒂亚药品公司 | 毒蕈碱性激动剂 |
| MXPA04007083A (es) * | 2002-02-20 | 2004-10-29 | Upjohn Co | Compuestos azabiciclicos para el tratamiento de enfermedades. |
| US6974870B2 (en) * | 2002-06-06 | 2005-12-13 | Boehringer Ingelheim Phamaceuticals, Inc. | Substituted 3-amino-thieno [2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses |
-
2005
- 2005-10-18 AU AU2005299957A patent/AU2005299957B2/en not_active Ceased
- 2005-10-18 PL PL05812144T patent/PL1807434T3/pl unknown
- 2005-10-18 DE DE602005023197T patent/DE602005023197D1/de not_active Expired - Lifetime
- 2005-10-18 CA CA2583550A patent/CA2583550C/en not_active Expired - Fee Related
- 2005-10-18 BR BRPI0517438-4A patent/BRPI0517438A/pt not_active IP Right Cessation
- 2005-10-18 MX MX2007004794A patent/MX2007004794A/es active IP Right Grant
- 2005-10-18 AT AT05812144T patent/ATE478876T1/de active
- 2005-10-18 DK DK05812144.3T patent/DK1807434T3/da active
- 2005-10-18 JP JP2007537951A patent/JP4945453B2/ja not_active Expired - Fee Related
- 2005-10-18 WO PCT/US2005/037271 patent/WO2006047124A1/en not_active Ceased
- 2005-10-18 CN CN200580036624A patent/CN100577666C/zh not_active Expired - Fee Related
- 2005-10-18 PT PT05812144T patent/PT1807434E/pt unknown
- 2005-10-18 US US11/577,508 patent/US8071776B2/en not_active Expired - Fee Related
- 2005-10-18 ES ES05812144T patent/ES2349416T3/es not_active Expired - Lifetime
- 2005-10-18 EP EP05812144A patent/EP1807434B1/en not_active Expired - Lifetime
-
2010
- 2010-10-14 CY CY20101100921T patent/CY1111477T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE602005023197D1 (de) | 2010-10-07 |
| AU2005299957B2 (en) | 2011-04-21 |
| JP2008517913A (ja) | 2008-05-29 |
| CN101048413A (zh) | 2007-10-03 |
| AU2005299957A1 (en) | 2006-05-04 |
| DK1807434T3 (da) | 2010-11-22 |
| MX2007004794A (es) | 2007-07-09 |
| US8071776B2 (en) | 2011-12-06 |
| CY1111477T1 (el) | 2015-08-05 |
| CA2583550A1 (en) | 2006-05-04 |
| PT1807434E (pt) | 2010-09-22 |
| CN100577666C (zh) | 2010-01-06 |
| EP1807434A1 (en) | 2007-07-18 |
| WO2006047124A1 (en) | 2006-05-04 |
| PL1807434T3 (pl) | 2011-02-28 |
| CA2583550C (en) | 2013-05-14 |
| ES2349416T3 (es) | 2011-01-03 |
| US20090105244A1 (en) | 2009-04-23 |
| EP1807434B1 (en) | 2010-08-25 |
| ATE478876T1 (de) | 2010-09-15 |
| BRPI0517438A (pt) | 2008-10-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4945453B2 (ja) | Ｍ４ムスカリン性受容体のアロステリック増強剤としてのチエノピリジン | |
| US8697876B2 (en) | Compositions and methods of synthesis of pyridinolypiperidine 5-HT1F agonists | |
| US6586421B2 (en) | Substituted azepino[4,5b]indoline derivatives | |
| NZ547164A (en) | Derivatives of n-[phenyl(piperidine-2-yl)methyl]benzamide, preparation and therapeutic use thereof | |
| EA007966B1 (ru) | Пиридиноилпиперидины как агонисты 5-ht | |
| EA017187B1 (ru) | Конденсированные производные тиазола в качестве ингибиторов киназ | |
| JPWO2015022926A1 (ja) | 新規な縮合ピリミジン化合物又はその塩 | |
| CA3031073A1 (en) | N-(pyridin-2-yl)pyridine-sulfonamide derivatives and their use in the treatment of disease | |
| BR112013021566B1 (pt) | composto, composição farmacêutica e uso de um composto de fórmula (i) | |
| JP2024540080A (ja) | Ｉｒａｋ４分解剤およびその合成 | |
| KR20090114439A (ko) | 아실구아니딘 유도체 | |
| EP3821947A1 (en) | Heterocyclic trpml1 agonists | |
| SI9300438A (en) | Indole and indoline derivates, process for their preparation and use thereof in the treatment | |
| AU2004285855B8 (en) | Novel crystalline forms of {2-[1-(3,5-bis-trifluoromethylbenzyl) -5 -pyridin-4-yl-1H-[1,2,3]triazol-4-yl]-pyridin-3-yl}-(2-chlorophenyl)-methanone | |
| CA2623154A1 (en) | Novel fused pyrrole derivative | |
| KR101279689B1 (ko) | 4-아미노-5-시아노피리미딘 유도체 | |
| KR102607510B1 (ko) | 무스카린 m1 수용체 양성 알로스테릭 조절제로서의 피롤로-피리다진 유도체 | |
| WO2022258007A1 (zh) | 含吡唑多环类衍生物的盐、晶型及其制备方法和应用 | |
| CN110590776A (zh) | 一种联苯衍生物及其制备方法和在医药上的用途 | |
| TW201136938A (en) | Spiropiperidine benzylamines as beta-tryptase inhibitors | |
| CN120020134A (zh) | 杂环羰基类衍生物调节剂、其制备方法和应用 | |
| JP2018083767A (ja) | ヘテロアリールアミド化合物 | |
| WO2021075477A1 (ja) | 運動神経細胞変性阻害剤 | |
| WO2005100355A1 (ja) | 環状アミン化合物 | |
| MXPA00004480A (en) | 5-ht1f |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080901 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080901 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111025 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120124 |
|
| 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: 20120214 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120305 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4945453 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150309 Year of fee payment: 3 |
|
| 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 |
|
| LAPS | Cancellation because of no payment of annual fees |