AU2006335174B2 - Tetralone-based monoamine reuptake inhibitors - Google Patents
Tetralone-based monoamine reuptake inhibitors Download PDFInfo
- Publication number
- AU2006335174B2 AU2006335174B2 AU2006335174A AU2006335174A AU2006335174B2 AU 2006335174 B2 AU2006335174 B2 AU 2006335174B2 AU 2006335174 A AU2006335174 A AU 2006335174A AU 2006335174 A AU2006335174 A AU 2006335174A AU 2006335174 B2 AU2006335174 B2 AU 2006335174B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- pharmaceutically acceptable
- substituted
- mixture
- solvate
- 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.)
- Ceased
Links
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 title abstract description 23
- 239000003112 inhibitor Substances 0.000 title description 7
- 230000000407 monoamine reuptake Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 223
- 239000000203 mixture Substances 0.000 claims abstract description 136
- 238000000034 method Methods 0.000 claims abstract description 64
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 33
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims abstract description 30
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960002748 norepinephrine Drugs 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 16
- 229960003638 dopamine Drugs 0.000 claims abstract description 15
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims abstract description 14
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
- 230000000946 synaptic effect Effects 0.000 claims abstract description 13
- 101710164184 Synaptic vesicular amine transporter Proteins 0.000 claims abstract description 9
- 102100034333 Synaptic vesicular amine transporter Human genes 0.000 claims abstract description 9
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 7
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 78
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 239000003814 drug Substances 0.000 claims description 37
- 239000012453 solvate Substances 0.000 claims description 31
- 208000002193 Pain Diseases 0.000 claims description 20
- 208000015114 central nervous system disease Diseases 0.000 claims description 18
- 108010078791 Carrier Proteins Proteins 0.000 claims description 17
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 claims description 15
- 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 claims description 15
- 208000012902 Nervous system disease Diseases 0.000 claims description 15
- 229940076279 serotonin Drugs 0.000 claims description 14
- 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 claims description 13
- 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 claims description 11
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 claims description 11
- 239000003981 vehicle Substances 0.000 claims description 10
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 208000012672 seasonal affective disease Diseases 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 6
- 230000036506 anxiety Effects 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 208000001640 Fibromyalgia Diseases 0.000 claims description 5
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 5
- 206010013954 Dysphoria Diseases 0.000 claims description 4
- 208000005793 Restless legs syndrome Diseases 0.000 claims description 4
- 201000002859 sleep apnea Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 230000000626 neurodegenerative effect Effects 0.000 claims 1
- 150000001412 amines Chemical class 0.000 abstract description 29
- 238000011282 treatment Methods 0.000 abstract description 20
- 210000003169 central nervous system Anatomy 0.000 abstract description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
- -1 cyclic hydrocarbon radical Chemical class 0.000 description 76
- 239000000243 solution Substances 0.000 description 72
- 230000015572 biosynthetic process Effects 0.000 description 70
- 238000003786 synthesis reaction Methods 0.000 description 69
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
- 125000000217 alkyl group Chemical group 0.000 description 50
- 125000003118 aryl group Chemical group 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 40
- 125000001072 heteroaryl group Chemical group 0.000 description 37
- 125000004404 heteroalkyl group Chemical group 0.000 description 35
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 32
- 229910052739 hydrogen Inorganic materials 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 125000001424 substituent group Chemical group 0.000 description 28
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 27
- 229940079593 drug Drugs 0.000 description 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 23
- 241000282414 Homo sapiens Species 0.000 description 23
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 22
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 22
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 21
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 20
- 235000019253 formic acid Nutrition 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 18
- 125000004429 atom Chemical group 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 235000019441 ethanol Nutrition 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 230000014759 maintenance of location Effects 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 238000003556 assay Methods 0.000 description 16
- 239000002552 dosage form Substances 0.000 description 16
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 16
- 229910052736 halogen Inorganic materials 0.000 description 16
- 150000002367 halogens Chemical class 0.000 description 16
- KCKZIWSINLBROE-UHFFFAOYSA-N 3,4-dihydro-1h-naphthalen-2-one Chemical class C1=CC=C2CC(=O)CCC2=C1 KCKZIWSINLBROE-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 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 14
- 230000005764 inhibitory process Effects 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 229960001866 silicon dioxide Drugs 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 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 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
- 239000000872 buffer Substances 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 210000003568 synaptosome Anatomy 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- CUAMEZDGVVKYAA-NBFOKTCDSA-N 1-[(4s)-4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-2-yl]ethanamine Chemical compound C1([C@H]2C3=CC=CC=C3C=C(C2)C(N)C)=CC=C(Cl)C(Cl)=C1 CUAMEZDGVVKYAA-NBFOKTCDSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000002009 diols Chemical class 0.000 description 12
- 238000011534 incubation Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- JGMBHJNMQVKDMW-NSHDSACASA-N (4s)-4-(3,4-dichlorophenyl)-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@H]1C2=CC=CC=C2C(=O)CC1 JGMBHJNMQVKDMW-NSHDSACASA-N 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 238000013270 controlled release Methods 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 10
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 229910052722 tritium Inorganic materials 0.000 description 10
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 230000009471 action Effects 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 9
- 150000002923 oximes Chemical class 0.000 description 9
- 208000020016 psychiatric disease Diseases 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 description 8
- FKRLHQFRKFCLTN-TWONFVHBSA-N 1-[(2s,4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]ethanamine Chemical compound C1([C@@H]2C[C@@H](CC3=CC=CC=C32)C(N)C)=CC=C(Cl)C(Cl)=C1 FKRLHQFRKFCLTN-TWONFVHBSA-N 0.000 description 8
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 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 8
- 229930006000 Sucrose Natural products 0.000 description 8
- 238000004296 chiral HPLC Methods 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 229960002464 fluoxetine Drugs 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 230000009871 nonspecific binding Effects 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000005720 sucrose Substances 0.000 description 8
- BSMNRYCSBFHEMQ-KCJUWKMLSA-N (1r,5s)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane Chemical compound C1=C(Cl)C(Cl)=CC=C1[C@]1(CNC2)[C@@H]2C1 BSMNRYCSBFHEMQ-KCJUWKMLSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 238000006722 reduction reaction Methods 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 6
- IRHVHIDULBEOHN-LLJXTTFASA-N 1-[(2s,4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-n,n-dimethylethanamine Chemical compound C1([C@@H]2C[C@@H](CC3=CC=CC=C32)C(C)N(C)C)=CC=C(Cl)C(Cl)=C1 IRHVHIDULBEOHN-LLJXTTFASA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000000935 antidepressant agent Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 229940125797 compound 12 Drugs 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 239000002858 neurotransmitter agent Substances 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 6
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 6
- OFCNTYBPPAQCRE-UHFFFAOYSA-N 3-(2-aminoethyl)-3h-indol-5-ol Chemical compound C1=C(O)C=C2C(CCN)C=NC2=C1 OFCNTYBPPAQCRE-UHFFFAOYSA-N 0.000 description 5
- SFLSHLFXELFNJZ-CMIMLBRMSA-N 4-[(1r)-2-amino-1-hydroxy-1-tritioethyl]benzene-1,2-diol Chemical compound NC[C@@](O)([3H])C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-CMIMLBRMSA-N 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 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 5
- 241000282412 Homo Species 0.000 description 5
- 208000019695 Migraine disease Diseases 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000008186 active pharmaceutical agent Substances 0.000 description 5
- 229940005513 antidepressants Drugs 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 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 5
- 239000000969 carrier Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229940088679 drug related substance Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000012530 fluid Substances 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 125000004474 heteroalkylene group Chemical group 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 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 5
- 230000011987 methylation Effects 0.000 description 5
- 238000007069 methylation reaction Methods 0.000 description 5
- 206010027599 migraine Diseases 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000001242 postsynaptic effect Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000011369 resultant mixture Substances 0.000 description 5
- 230000013275 serotonin uptake Effects 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 description 4
- PVQFUJROYNQSCG-YOEHRIQHSA-N (1r,4s)-4-(3,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-1h-naphthalen-1-amine Chemical compound C1([C@@H]2CC([C@H](C3=CC=CC=C32)N)(C)C)=CC=C(Cl)C(Cl)=C1 PVQFUJROYNQSCG-YOEHRIQHSA-N 0.000 description 4
- JGMBHJNMQVKDMW-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1C2=CC=CC=C2C(=O)CC1 JGMBHJNMQVKDMW-UHFFFAOYSA-N 0.000 description 4
- KDERKEZKMQCRPQ-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C12=CC=CC=C2CC(NC)CC1C1=CC=C(Cl)C(Cl)=C1 KDERKEZKMQCRPQ-UHFFFAOYSA-N 0.000 description 4
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 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 4
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 239000010779 crude oil Substances 0.000 description 4
- 230000007812 deficiency Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- SXLUKHWQTXEIAP-UHFFFAOYSA-N ethyl 4-(3,4-dichlorophenyl)-1-oxo-3,4-dihydro-2h-naphthalene-2-carboxylate Chemical compound C12=CC=CC=C2C(=O)C(C(=O)OCC)CC1C1=CC=C(Cl)C(Cl)=C1 SXLUKHWQTXEIAP-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 230000000966 norepinephrine reuptake Effects 0.000 description 4
- 230000012154 norepinephrine uptake Effects 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 229960002296 paroxetine Drugs 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003141 primary amines Chemical class 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- QWHQHPHHXQYRCR-PKDNWHCCSA-N tert-butyl n-[1-[(4s)-4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-2-yl]ethyl]carbamate Chemical compound C1([C@H]2C3=CC=CC=C3C=C(C2)C(NC(=O)OC(C)(C)C)C)=CC=C(Cl)C(Cl)=C1 QWHQHPHHXQYRCR-PKDNWHCCSA-N 0.000 description 4
- 229960004688 venlafaxine Drugs 0.000 description 4
- CTWUNVCSQARVEA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene Chemical compound C1=C=C[C]2CCCCC2=C1 CTWUNVCSQARVEA-UHFFFAOYSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical class OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- SNDGNPRZZZPUAX-UHFFFAOYSA-N 2-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]ethanamine Chemical compound C12=CC=CC=C2CC(CCN)CC1C1=CC=C(Cl)C(Cl)=C1 SNDGNPRZZZPUAX-UHFFFAOYSA-N 0.000 description 3
- IQSIWRJLFWMEBD-UHFFFAOYSA-N 2-[4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-2-yl]acetonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1C1C2=CC=CC=C2C=C(CC#N)C1 IQSIWRJLFWMEBD-UHFFFAOYSA-N 0.000 description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
- DVCQRBZBVYAGNZ-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-n,n-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C12=CC=CC=C2CC(N(C)C)CC1C1=CC=C(Cl)C(Cl)=C1 DVCQRBZBVYAGNZ-UHFFFAOYSA-N 0.000 description 3
- BRCPWISABURVIH-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=C1C=CC=C2OC BRCPWISABURVIH-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 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 3
- 208000000044 Amnesia Diseases 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 3
- 206010021639 Incontinence Diseases 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 3
- 229920002732 Polyanhydride Polymers 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 235000010419 agar Nutrition 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 150000001414 amino alcohols Chemical class 0.000 description 3
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 230000000035 biogenic effect Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
- 239000007894 caplet Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000019771 cognition Effects 0.000 description 3
- 229940125898 compound 5 Drugs 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000028436 dopamine uptake Effects 0.000 description 3
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 3
- 229960004801 imipramine Drugs 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 208000024714 major depressive disease Diseases 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000036651 mood Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 3
- 230000000697 serotonin reuptake Effects 0.000 description 3
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 235000010487 tragacanth Nutrition 0.000 description 3
- 239000000196 tragacanth Substances 0.000 description 3
- 229940116362 tragacanth Drugs 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- AHNLEOCWKNTQQU-HONNSYHOSA-N (4s)-2-(1-aminoethyl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1([C@@H]2CC(C(C3=CC=CC=C32)O)C(N)C)=CC=C(Cl)C(Cl)=C1 AHNLEOCWKNTQQU-HONNSYHOSA-N 0.000 description 2
- MIXHVABNMHFQKA-AWEZNQCLSA-N (4s)-4-(3,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydronaphthalen-1-one Chemical compound C1([C@@H]2CC(C(C3=CC=CC=C32)=O)(C)C)=CC=C(Cl)C(Cl)=C1 MIXHVABNMHFQKA-AWEZNQCLSA-N 0.000 description 2
- VXOCXBGPTGPDFS-VZCZLHGCSA-N (4s)-4-(3,4-dichlorophenyl)-2-[1-(methylamino)ethyl]-1,2,3,4-tetrahydronaphthalen-1-ol Chemical compound C1([C@@H]2CC(C(C3=CC=CC=C32)O)C(C)NC)=CC=C(Cl)C(Cl)=C1 VXOCXBGPTGPDFS-VZCZLHGCSA-N 0.000 description 2
- YEQUIKPENPGXCX-SBNLOKMTSA-N (4s)-4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1([C@@H]2CC(C(C3=CC=CC=C32)=O)C)=CC=C(Cl)C(Cl)=C1 YEQUIKPENPGXCX-SBNLOKMTSA-N 0.000 description 2
- KNUWJXBVCOYOBW-ZZXKWVIFSA-N (e)-4-(3,4-dichlorophenyl)-1-(3,4-dimethoxyphenyl)but-3-en-2-one Chemical compound C1=C(OC)C(OC)=CC=C1CC(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 KNUWJXBVCOYOBW-ZZXKWVIFSA-N 0.000 description 2
- ZETUREABNNHYQG-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-n,n-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound CN(C)C1CCC2=CC=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 ZETUREABNNHYQG-UHFFFAOYSA-N 0.000 description 2
- YTBOYUYWXPLZQM-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound CNC1CCC2=CC=CC=C2C1C1=CC=C(Cl)C(Cl)=C1 YTBOYUYWXPLZQM-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
- JHLMMBQZPYQHRM-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-5-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C1=CC=C(OC)C2=C1CC(NC)CC2C1=CC=C(Cl)C(Cl)=C1 JHLMMBQZPYQHRM-UHFFFAOYSA-N 0.000 description 2
- LYRWQHWFGJIDMF-UHFFFAOYSA-N 4-(bromomethyl)-4-(3,4-dichlorophenyl)-2,3-dihydro-1H-naphthalene Chemical compound BrCC1(CCCC2=CC=CC=C12)C1=CC(=C(C=C1)Cl)Cl LYRWQHWFGJIDMF-UHFFFAOYSA-N 0.000 description 2
- GABLTKRIYDNDIN-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1CCC(=O)C2=CC(OC)=CC=C21 GABLTKRIYDNDIN-UHFFFAOYSA-N 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- 208000031091 Amnestic disease Diseases 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000001387 Causalgia Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 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
- 206010012289 Dementia Diseases 0.000 description 2
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 241000206672 Gelidium Species 0.000 description 2
- 208000004454 Hyperalgesia Diseases 0.000 description 2
- 208000035154 Hyperesthesia Diseases 0.000 description 2
- 241000546188 Hypericum Species 0.000 description 2
- 235000017309 Hypericum perforatum Nutrition 0.000 description 2
- 206010022998 Irritability Diseases 0.000 description 2
- 206010026749 Mania Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical group C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 2
- 208000019022 Mood disease Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 201000001880 Sexual dysfunction Diseases 0.000 description 2
- 206010066218 Stress Urinary Incontinence Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- AUOZLNRXVPELRP-UHFFFAOYSA-N [4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]methanamine Chemical compound C12=CC=CC=C2CC(CN)CC1C1=CC=C(Cl)C(Cl)=C1 AUOZLNRXVPELRP-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 229960000836 amitriptyline Drugs 0.000 description 2
- 230000001430 anti-depressive effect Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 150000001499 aryl bromides Chemical class 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 229960004424 carbon dioxide Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 239000003086 colorant Substances 0.000 description 2
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 229940125846 compound 25 Drugs 0.000 description 2
- 239000007891 compressed tablet Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000013078 crystal Substances 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
- 230000003111 delayed effect Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 229960003914 desipramine Drugs 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 230000002825 dopamine reuptake Effects 0.000 description 2
- BSMNRYCSBFHEMQ-UHFFFAOYSA-N dov-216,303 Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(CNC2)C2C1 BSMNRYCSBFHEMQ-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000000695 effect on serotonin Effects 0.000 description 2
- 229940098766 effexor Drugs 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 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 2
- 210000003016 hypothalamus Anatomy 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229960001344 methylphenidate Drugs 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 230000003982 neuronal uptake Effects 0.000 description 2
- 229950004211 nisoxetine Drugs 0.000 description 2
- ITJNARMNRKSWTA-UHFFFAOYSA-N nisoxetine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=CC=C1OC ITJNARMNRKSWTA-UHFFFAOYSA-N 0.000 description 2
- XXPANQJNYNUNES-UHFFFAOYSA-N nomifensine Chemical compound C12=CC=CC(N)=C2CN(C)CC1C1=CC=CC=C1 XXPANQJNYNUNES-UHFFFAOYSA-N 0.000 description 2
- 229960001073 nomifensine Drugs 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 239000012457 nonaqueous media Substances 0.000 description 2
- 230000001473 noxious effect Effects 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229920000728 polyester Polymers 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 229940035613 prozac Drugs 0.000 description 2
- 208000026961 psychosexual disease Diseases 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 230000000862 serotonergic effect Effects 0.000 description 2
- 229960002073 sertraline Drugs 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 231100000872 sexual dysfunction Toxicity 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 208000019116 sleep disease Diseases 0.000 description 2
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 239000003174 triple reuptake inhibitor Substances 0.000 description 2
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- CUAMEZDGVVKYAA-ZBEGNZNMSA-N (1s)-1-[(4s)-4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-2-yl]ethanamine Chemical compound C1([C@H]2C3=CC=CC=C3C=C(C2)[C@@H](N)C)=CC=C(Cl)C(Cl)=C1 CUAMEZDGVVKYAA-ZBEGNZNMSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- CSUUDNFYSFENAE-UHFFFAOYSA-N (2-methoxyphenyl)-phenylmethanone Chemical compound COC1=CC=CC=C1C(=O)C1=CC=CC=C1 CSUUDNFYSFENAE-UHFFFAOYSA-N 0.000 description 1
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- VUDZSIYXZUYWSC-DBRKOABJSA-N (4r)-1-[(2r,4r,5r)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-hydroxy-1,3-diazinan-2-one Chemical compound FC1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N[C@H](O)CC1 VUDZSIYXZUYWSC-DBRKOABJSA-N 0.000 description 1
- PVQFUJROYNQSCG-MBIQTGHCSA-N (4s)-4-(3,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-1h-naphthalen-1-amine Chemical compound C1([C@@H]2CC(C(C3=CC=CC=C32)N)(C)C)=CC=C(Cl)C(Cl)=C1 PVQFUJROYNQSCG-MBIQTGHCSA-N 0.000 description 1
- UXKLQDCALAWFIU-VKNDCNMPSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-tetradecoxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCCCC)C1=CC=CC=C1 UXKLQDCALAWFIU-VKNDCNMPSA-N 0.000 description 1
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RMMRRRLPDBJBQL-UHFFFAOYSA-N 1-(3-methoxyphenyl)propan-2-one Chemical compound COC1=CC=CC(CC(C)=O)=C1 RMMRRRLPDBJBQL-UHFFFAOYSA-N 0.000 description 1
- FJZNNKJZHQFMCK-LRDDRELGSA-N 1-[(3S,4R)-4-(2,6-difluoro-4-methoxyphenyl)-2-oxopyrrolidin-3-yl]-3-phenylurea Chemical compound C1(=CC(=CC(=C1[C@H]1[C@@H](C(=O)NC1)NC(=O)NC1=CC=CC=C1)F)OC)F FJZNNKJZHQFMCK-LRDDRELGSA-N 0.000 description 1
- RAQPOZGWANIDQT-UHFFFAOYSA-N 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine Chemical compound C=1C=CC=CC=1CCCN(CC1)CCN1CCOC(C=1C=CC=CC=1)C1=CC=CC=C1 RAQPOZGWANIDQT-UHFFFAOYSA-N 0.000 description 1
- WUSGTAILSJGBRD-UHFFFAOYSA-N 1-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-n,n-dimethylmethanamine Chemical compound C12=CC=CC=C2CC(CN(C)C)CC1C1=CC=C(Cl)C(Cl)=C1 WUSGTAILSJGBRD-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical class CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- YKYWUHHZZRBGMG-JWTNVVGKSA-N 1-methyl-2-[[(1r,5s)-6-[[5-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-3-azabicyclo[3.1.0]hexan-3-yl]methyl]benzimidazole Chemical compound C1([C@@H]2CN(C[C@@H]21)CC=1N(C2=CC=CC=C2N=1)C)COCC1=CC=C(C(F)(F)F)C=N1 YKYWUHHZZRBGMG-JWTNVVGKSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- SSZCFGZVVAHGRT-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-n-methyl-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1CC2=CC=CC=C2C(NC)C1C1=CC=C(Cl)C(Cl)=C1 SSZCFGZVVAHGRT-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- KWMBADTWRIGGGG-UHFFFAOYSA-N 2-diethoxyphosphorylacetonitrile Chemical compound CCOP(=O)(CC#N)OCC KWMBADTWRIGGGG-UHFFFAOYSA-N 0.000 description 1
- AJHRPRPRDUSREJ-UHFFFAOYSA-N 2-ethylidene-3,4-dihydronaphthalen-1-one Chemical compound C1=CC=C2C(=O)C(=CC)CCC2=C1 AJHRPRPRDUSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- AHRZQNGPODNKJV-UHFFFAOYSA-N 3-(azidomethyl)-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene Chemical compound C1=C(Cl)C(Cl)=CC=C1C1C2=CC=CC=C2CC(CN=[N+]=[N-])C1 AHRZQNGPODNKJV-UHFFFAOYSA-N 0.000 description 1
- NMJVGRBUSVDPHV-UHFFFAOYSA-N 3-(bromomethyl)-1-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene Chemical compound C1=C(Cl)C(Cl)=CC=C1C1C2=CC=CC=C2CC(CBr)C1 NMJVGRBUSVDPHV-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- REPNDUPMMXVULT-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-3,4-dihydro-1h-naphthalen-2-one Chemical compound C1=C(Cl)C(Cl)=CC=C1C1C2=CC=CC=C2CC(=O)C1 REPNDUPMMXVULT-UHFFFAOYSA-N 0.000 description 1
- CRHUWUWRXMLGTP-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-6-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C12=CC(OC)=CC=C2CC(NC)CC1C1=CC=C(Cl)C(Cl)=C1 CRHUWUWRXMLGTP-UHFFFAOYSA-N 0.000 description 1
- ITAOJOPCIOQJOR-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-7-methoxy-n-methyl-1,2,3,4-tetrahydronaphthalen-2-amine Chemical compound C12=CC=C(OC)C=C2CC(NC)CC1C1=CC=C(Cl)C(Cl)=C1 ITAOJOPCIOQJOR-UHFFFAOYSA-N 0.000 description 1
- JOFDSYLCZIHGGO-UHFFFAOYSA-N 4-[(4-cyclohexylphenyl)methyl-[2-[[5-(dimethylamino)naphthalen-1-yl]sulfonyl-methylamino]acetyl]amino]-2-hydroxybenzoic acid Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1S(=O)(=O)N(C)CC(=O)N(C=1C=C(O)C(C(O)=O)=CC=1)CC(C=C1)=CC=C1C1CCCCC1 JOFDSYLCZIHGGO-UHFFFAOYSA-N 0.000 description 1
- TXEBWPPWSVMYOA-UHFFFAOYSA-N 4-[3-[(1-amino-2-chloroethyl)amino]propyl]-1-[[3-(2-chlorophenyl)phenyl]methyl]-5-hydroxyimidazolidin-2-one Chemical compound NC(CCl)NCCCC1NC(=O)N(Cc2cccc(c2)-c2ccccc2Cl)C1O TXEBWPPWSVMYOA-UHFFFAOYSA-N 0.000 description 1
- WCDLCPLAAKUJNY-UHFFFAOYSA-N 4-[4-[3-(1h-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-6-yl]phenyl]morpholine Chemical compound C1COCCN1C1=CC=C(C2=CN3N=CC(=C3N=C2)C2=CNN=C2)C=C1 WCDLCPLAAKUJNY-UHFFFAOYSA-N 0.000 description 1
- HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
- CFPZDVAZISWERM-UHFFFAOYSA-N 4-bromo-1,2-dichlorobenzene Chemical compound ClC1=CC=C(Br)C=C1Cl CFPZDVAZISWERM-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 208000017194 Affective disease Diseases 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000007415 Anhedonia Diseases 0.000 description 1
- 235000003276 Apios tuberosa Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000010744 Arachis villosulicarpa Nutrition 0.000 description 1
- 208000036487 Arthropathies 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
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- QCMHGCDOZLWPOT-FMNCTDSISA-N COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 Chemical compound COC1=C(CC[C@@H]2CCC3=C(C2)C=CC(=C3)[C@H]2CC[C@](N)(CO)C2)C=CC=C1 QCMHGCDOZLWPOT-FMNCTDSISA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010058019 Cancer Pain Diseases 0.000 description 1
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102100038902 Caspase-7 Human genes 0.000 description 1
- 208000001573 Cataplexy Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010010071 Coma Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 208000013586 Complex regional pain syndrome type 1 Diseases 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
- 206010012374 Depressed mood Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 206010013886 Dysaesthesia Diseases 0.000 description 1
- 208000004483 Dyspareunia Diseases 0.000 description 1
- 241000283073 Equus caballus 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
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 101000741014 Homo sapiens Caspase-7 Proteins 0.000 description 1
- 101000639975 Homo sapiens Sodium-dependent noradrenaline transporter Proteins 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020651 Hyperkinesia Diseases 0.000 description 1
- 208000000269 Hyperkinesis Diseases 0.000 description 1
- 206010065952 Hyperpathia Diseases 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 201000006792 Lennox-Gastaut syndrome Diseases 0.000 description 1
- 208000030431 Male orgasmic disease Diseases 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 102000003939 Membrane transport proteins Human genes 0.000 description 1
- 108090000301 Membrane transport proteins Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- FSJZHRHTCUIWJP-UHFFFAOYSA-N N-[4-(3,4-dichlorophenyl)-2-methyl-3,4-dihydro-2H-naphthalen-1-ylidene]hydroxylamine Chemical compound C12=CC=CC=C2C(=NO)C(C)CC1C1=CC=C(Cl)C(Cl)=C1 FSJZHRHTCUIWJP-UHFFFAOYSA-N 0.000 description 1
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 208000001294 Nociceptive Pain Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 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
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 206010042458 Suicidal ideation Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 208000000921 Urge Urinary Incontinence Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010047791 Vulvovaginal dryness Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- UPKBWCCJYQLMRQ-UHFFFAOYSA-N [4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]methanol Chemical compound C12=CC=CC=C2CC(CO)CC1C1=CC=C(Cl)C(Cl)=C1 UPKBWCCJYQLMRQ-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 229940022663 acetate Drugs 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
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 206010053552 allodynia Diseases 0.000 description 1
- 102000030619 alpha-1 Adrenergic Receptor Human genes 0.000 description 1
- 108020004102 alpha-1 Adrenergic Receptor Proteins 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960002903 benzyl benzoate Drugs 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
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229920005556 chlorobutyl Polymers 0.000 description 1
- 150000008371 chromenes Chemical class 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940127206 compound 14d Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000001653 corpus striatum Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 229940097362 cyclodextrins Drugs 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 208000026725 cyclothymic disease Diseases 0.000 description 1
- 239000003405 delayed action preparation Substances 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
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 150000004656 dimethylamines Chemical class 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 230000010249 dopaminergic function Effects 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 229940011681 elavil Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZOCPUEIKQSMGLM-UHFFFAOYSA-N ethyl 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C12=CC=CC=C2CC(C(=O)OCC)CC1C1=CC=C(Cl)C(Cl)=C1 ZOCPUEIKQSMGLM-UHFFFAOYSA-N 0.000 description 1
- 229940093499 ethyl acetate Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 238000012048 forced swim test Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 230000003400 hallucinatory effect Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 102000055827 human SLC6A2 Human genes 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- JUMYIBMBTDDLNG-OJERSXHUSA-N hydron;methyl (2r)-2-phenyl-2-[(2r)-piperidin-2-yl]acetate;chloride Chemical compound Cl.C([C@@H]1[C@H](C(=O)OC)C=2C=CC=CC=2)CCCN1 JUMYIBMBTDDLNG-OJERSXHUSA-N 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 201000004197 inhibited female orgasm Diseases 0.000 description 1
- 201000000068 inhibited male orgasm Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000000185 intracerebroventricular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229940044173 iodine-125 Drugs 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000007794 irritation Effects 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 230000000155 isotopic effect 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
- 210000003734 kidney Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-M lactobionate Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-M 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000006166 lysate 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
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000015421 male orgasm disease Diseases 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 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
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- HBEDNENASUYMPO-LJQANCHMSA-N n-hydroxy-4-[[(2r)-3-oxo-2-(thiophen-2-ylmethyl)-2,4-dihydroquinoxalin-1-yl]methyl]benzamide Chemical compound C1=CC(C(=O)NO)=CC=C1CN1C2=CC=CC=C2NC(=O)[C@H]1CC1=CC=CS1 HBEDNENASUYMPO-LJQANCHMSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 201000003631 narcolepsy Diseases 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 206010029410 night sweats Diseases 0.000 description 1
- 230000036565 night sweats Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 208000024449 overflow incontinence Diseases 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 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
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 206010036596 premature ejaculation Diseases 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960002601 protriptyline Drugs 0.000 description 1
- BWPIARFWQZKAIA-UHFFFAOYSA-N protriptyline Chemical compound C1=CC2=CC=CC=C2C(CCCNC)C2=CC=CC=C21 BWPIARFWQZKAIA-UHFFFAOYSA-N 0.000 description 1
- 201000002274 psychologic vaginismus Diseases 0.000 description 1
- 238000000746 purification Methods 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
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000003340 retarding agent Substances 0.000 description 1
- 229940099204 ritalin Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000000698 schizophrenic effect Effects 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
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009155 sensory pathway Effects 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 201000009032 substance abuse Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- QWHQHPHHXQYRCR-LIRRHRJNSA-N tert-butyl n-[(1s)-1-[(4s)-4-(3,4-dichlorophenyl)-3,4-dihydronaphthalen-2-yl]ethyl]carbamate Chemical compound C1([C@H]2C3=CC=CC=C3C=C(C2)[C@@H](NC(=O)OC(C)(C)C)C)=CC=C(Cl)C(Cl)=C1 QWHQHPHHXQYRCR-LIRRHRJNSA-N 0.000 description 1
- GBIBLDGVHFGMSE-VNTLTUIWSA-N tert-butyl n-[1-[(2s,4s)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-2-yl]ethyl]carbamate Chemical compound C1([C@@H]2C[C@@H](CC3=CC=CC=C32)C(NC(=O)OC(C)(C)C)C)=CC=C(Cl)C(Cl)=C1 GBIBLDGVHFGMSE-VNTLTUIWSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetraline Natural products C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 206010046494 urge incontinence Diseases 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 230000001457 vasomotor Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 229940020965 zoloft Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/39—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton
- C07C211/40—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton containing only non-condensed rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
-
- 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
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P25/14—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
- A61P25/28—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
- A61P25/32—Alcohol-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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/16—Preparation of halogenated hydrocarbons by replacement by halogens of hydroxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/35—Preparation of halogenated hydrocarbons by reactions not affecting the number of carbon or of halogen atoms in the reaction
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/30—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the six-membered aromatic ring being part of a condensed ring system formed by two rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/39—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton
- C07C211/41—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton containing condensed ring systems
- C07C211/42—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of an unsaturated carbon skeleton containing condensed ring systems with six-membered aromatic rings being part of the condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/42—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/44—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton bound to carbon atoms of the same ring or condensed ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/38—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a primary hydroxyl group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
- C07C45/52—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition by dehydration and rearrangement involving two hydroxy groups in the same molecule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Addiction (AREA)
- Reproductive Health (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Gynecology & Obstetrics (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Pregnancy & Childbirth (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US75655506P | 2006-01-06 | 2006-01-06 | |
| US60/756,555 | 2006-01-06 | ||
| PCT/US2006/049069 WO2007081542A2 (en) | 2006-01-06 | 2006-12-21 | Tetralone-based monoamine reuptake inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2006335174A1 AU2006335174A1 (en) | 2007-07-19 |
| AU2006335174B2 true AU2006335174B2 (en) | 2012-09-06 |
Family
ID=38256799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2006335174A Ceased AU2006335174B2 (en) | 2006-01-06 | 2006-12-21 | Tetralone-based monoamine reuptake inhibitors |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8053603B2 (enExample) |
| EP (1) | EP1978961B1 (enExample) |
| JP (1) | JP5438975B2 (enExample) |
| KR (1) | KR101381768B1 (enExample) |
| CN (2) | CN104276955A (enExample) |
| AU (1) | AU2006335174B2 (enExample) |
| CA (1) | CA2636275C (enExample) |
| ES (1) | ES2566479T3 (enExample) |
| NZ (1) | NZ569608A (enExample) |
| WO (1) | WO2007081542A2 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004312530A1 (en) | 2003-12-29 | 2005-07-21 | Sepracor Inc. | Pyrrole and pyrazole DAAO inhibitors |
| WO2007006003A2 (en) | 2005-07-06 | 2007-01-11 | Sepracor Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
| KR101294014B1 (ko) | 2006-01-06 | 2013-08-09 | 선오비온 파마슈티컬스 인코포레이티드 | 모노아민 재흡수 저해제로서의 시클로알킬아민 |
| JP5438975B2 (ja) | 2006-01-06 | 2014-03-12 | サノビオン ファーマシューティカルズ インク | テトラロン系モノアミン再取り込み阻害剤 |
| CA2648121C (en) | 2006-03-31 | 2013-08-06 | Sepracor Inc. | Preparation of chiral amides and amines |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
| MX2009007410A (es) * | 2007-01-18 | 2009-09-09 | Sepracor Inc | Inhibidores de d-aminoacido oxidasa. |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| BRPI0811639A2 (pt) | 2007-05-31 | 2014-09-30 | Sepracor Inc | Cicloaquilaminas fenil substituídas como inibidores da recaptação de monoamina |
| US8586634B2 (en) | 2007-06-15 | 2013-11-19 | University Of Florida Research Foundation, Inc. | Therapeutic compounds |
| KR101653842B1 (ko) | 2008-01-04 | 2016-09-02 | 인텔리카인, 엘엘씨 | 특정 화학 물질, 조성물 및 방법 |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| WO2010017418A1 (en) * | 2008-08-07 | 2010-02-11 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| US9024071B2 (en) * | 2009-05-05 | 2015-05-05 | University Of Florida Research Foundation, Inc. | Therapeutic compounds |
| WO2011017634A2 (en) * | 2009-08-07 | 2011-02-10 | Sepracore Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| JP5951600B2 (ja) | 2010-05-21 | 2016-07-13 | インフィニティー ファーマシューティカルズ, インコーポレイテッド | キナーゼ調節のための、化合物、組成物および方法 |
| AR084824A1 (es) | 2011-01-10 | 2013-06-26 | Intellikine Inc | Procesos para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| MX2014000648A (es) | 2011-07-19 | 2014-09-25 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y sus usos. |
| US8785470B2 (en) | 2011-08-29 | 2014-07-22 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| WO2014071109A1 (en) | 2012-11-01 | 2014-05-08 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| KR101652080B1 (ko) | 2015-01-16 | 2016-08-29 | 김인호 | 축열식 냉난방시스템 |
| KR101737044B1 (ko) | 2015-06-26 | 2017-05-17 | 김인호 | 방(흡)열관, 태양열 집열관 축열탱크를 이용한 축열식 난방시스템 |
| RU2754507C2 (ru) | 2016-06-24 | 2021-09-02 | Инфинити Фармасьютикалз, Инк. | Комбинированная терапия |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3663608A (en) * | 1969-12-10 | 1972-05-16 | Bristol Myers Co | 1-phenyl-3-aminoalkyl-1,2,3,4-tetrahydronaphthalenes and the salts thereof |
| US5091429A (en) * | 1987-11-26 | 1992-02-25 | Laboratoires Lucien | Derivatives of 4-amino-1-trifluoromethyltetralines their preparation and their therapeutic application |
| WO2000007978A1 (en) * | 1998-07-31 | 2000-02-17 | Akzo Nobel N.V. | Aminomethylcarboxylic acid derivatives |
Family Cites Families (129)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE616646A (enExample) | ||||
| DE1124485B (de) | 1960-02-12 | 1962-03-01 | Hoechst Ag | Verfahren zur Herstellung von analeptisch wirksamen Phenylcycloalkylmethylaminen |
| JPS6033106B2 (ja) | 1977-10-07 | 1985-08-01 | 住友化学工業株式会社 | カルボン酸エステル、その製造法およびそれを有効成分とする殺虫、殺ダニ剤 |
| US4536518A (en) * | 1979-11-01 | 1985-08-20 | Pfizer Inc. | Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine |
| ZA817261B (en) * | 1980-10-23 | 1982-09-29 | Schering Corp | Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them |
| FR2496653A1 (fr) * | 1980-12-22 | 1982-06-25 | Delalande Sa | Nouveaux derives aminoalcoyl heterocycliques, leurs procedes de preparation et leur application en therapeutique |
| US4540690A (en) * | 1982-02-09 | 1985-09-10 | The Upjohn Company | 2-(Phenylmethylene)cycloalkylamines and -azetidines |
| JPS58177915A (ja) | 1982-04-12 | 1983-10-18 | Green Cross Corp:The | 抗血栓剤 |
| JPS61502818A (ja) | 1984-07-30 | 1986-12-04 | シェリング・コ−ポレ−ション | シス、エンド−オクタヒドロシクロペンタ〔b〕ピロ−ル−2−カルボキシレ−トの新規製造方法 |
| DE3431541A1 (de) * | 1984-08-28 | 1986-03-06 | Hoechst Ag, 6230 Frankfurt | Cis,endo-2-azabicycloalkan-3-carbonsaeure-derivate, verfahren zu deren herstellung, deren verwendung sowie zwischenprodukte bei deren herstellung |
| US4738709A (en) * | 1985-01-10 | 1988-04-19 | Ppg Industries, Inc. | Herbicidally active substituted benzisoxazoles |
| JPS6416786A (en) | 1987-07-09 | 1989-01-20 | Sumitomo Chemical Co | Thienopyrrolopyrroles and preparation thereof |
| US4751231A (en) * | 1987-09-16 | 1988-06-14 | Merck & Co., Inc. | Substituted thieno[2,3-b]pyrrole-5-sulfonamides as antiglaucoma agents |
| JPH01172388A (ja) | 1987-12-25 | 1989-07-07 | Sumitomo Chem Co Ltd | チエノ〔3,2−b〕ピロロ〔2,3−d〕ピロール類およびその製法 |
| DE3807922A1 (de) * | 1988-03-10 | 1989-09-21 | Boehringer Mannheim Gmbh | Substituierte heterocyclen, verfahren zu ihrer herstellung sowie arzneimittel, die diese verbindungen enthalten |
| DE69013672T2 (de) * | 1989-01-09 | 1995-03-30 | Upjohn Co | Halogensubstituierte aminotetraline. |
| US5225596A (en) * | 1989-01-09 | 1993-07-06 | The Upjohn Company | Halo substituted aminotetralins |
| US4981870A (en) * | 1989-03-07 | 1991-01-01 | Pfizer Inc. | Use of 4-phenyl-1,2,3,4-tetrahydro-1-naphthalenamine derivatives in the treatment of psychosis, inflammation and as immunosuppressants |
| JPH0347123A (ja) | 1989-05-05 | 1991-02-28 | G D Searle & Co | インドール―2―カルボキシレート化合物類を含有するcns疾患治療用組成物 |
| SE8901889D0 (sv) * | 1989-05-26 | 1989-05-26 | Astra Ab | Novel 8-substituted-2-aminotetralines |
| WO1992006967A1 (en) * | 1990-10-12 | 1992-04-30 | The Upjohn Company | Therapeutically useful 2-aminotetralin derivatives |
| CA2051399C (en) | 1989-05-31 | 2003-12-30 | Chiu-Hong Lin | Therapeutically useful 2-aminotetralin derivatives |
| DE3924365A1 (de) * | 1989-07-22 | 1991-01-24 | Boehringer Ingelheim Kg | 2-amino-7-carbamoyl-1,2,3,4- tetrahydronaphthaline, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| US5071875A (en) * | 1989-09-25 | 1991-12-10 | Northwestern University | Substituted 2-amidotetralins as melatonin agonists and antagonists |
| JPH0477476A (ja) | 1990-07-19 | 1992-03-11 | Sankyo Co Ltd | 抗潰瘍剤 |
| US5086054A (en) | 1990-07-31 | 1992-02-04 | Sri International | Novel arylcycloalkanepolyalkylamines |
| JPH0825973B2 (ja) * | 1991-04-12 | 1996-03-13 | シェリング・コーポレーション | アシル補酵素a:コレステロールアシルトランスフェラーゼの阻害剤としての二環式アミド |
| GB9208492D0 (en) * | 1992-04-16 | 1992-06-03 | Glaxo Spa | Heterocyclic compounds |
| WO1994010158A1 (fr) * | 1992-10-28 | 1994-05-11 | Toyama Chemical Co., Ltd. | Nouveaux derives de 1,2-benzisoxazole ou sel dudit derive, et agent de protection cerebrale contenant ce derive |
| GB9304500D0 (en) * | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| ES2081747B1 (es) | 1993-09-07 | 1997-01-16 | Esteve Labor Dr | Amidas derivadas de tienopirroles, su preparacion y su aplicacion como medicamentos. |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| WO1995011245A1 (en) * | 1993-10-20 | 1995-04-27 | Tokyo Tanabe Company Limited | Indole derivative |
| GB9326284D0 (en) | 1993-12-23 | 1994-02-23 | Erba Carlo Spa | Pyrrolydenemethyl-derivatives and process for their preparation |
| CN1047384C (zh) | 1994-07-28 | 1999-12-15 | 北京大学 | 雷米普利的合成方法 |
| DE69532039T2 (de) * | 1994-08-30 | 2004-07-08 | Sankyo Co., Ltd. | Isoxazole |
| DE4447305C2 (de) * | 1994-12-31 | 2003-04-17 | Knorr Bremse Systeme | Verfahren zum Entlüften von Bremszylindern in schlupfgeregelten Druckluft-Bremsanlagen |
| US5484763A (en) * | 1995-02-10 | 1996-01-16 | American Cyanamid Company | Substituted benzisoxazole and benzisothiazole herbicidal agents |
| US5620997A (en) * | 1995-05-31 | 1997-04-15 | Warner-Lambert Company | Isothiazolones |
| US5859042A (en) * | 1995-09-27 | 1999-01-12 | Ono Pharmaceutical Co., Ltd. | Five membered heterocyclic compounds |
| DE19711785A1 (de) | 1997-03-21 | 1998-09-24 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
| GB9717804D0 (en) | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| WO1999018065A1 (en) | 1997-10-03 | 1999-04-15 | Chirotech Technology Limited | Chiral amines |
| GB9803226D0 (en) | 1998-02-17 | 1998-04-08 | Zeneca Ltd | Chemical compounds |
| GB9803228D0 (en) | 1998-02-17 | 1998-04-08 | Zeneca Ltd | Chemical compounds |
| CA2325935A1 (en) | 1998-03-26 | 1999-09-30 | Sugen, Inc. | Heterocyclic families of compounds for the modulation of tyrosine protein kinase |
| AU4037699A (en) * | 1998-05-08 | 1999-11-29 | Akzo Nobel N.V. | Novel aryl-hydro naphthalenal kanamines |
| US6476078B2 (en) * | 1999-08-11 | 2002-11-05 | Sepracor, Inc. | Methods of using sibutramine metabolites in combination with a phosphodiesterase inhibitor to treat sexual dysfunction |
| US6632836B1 (en) | 1998-10-30 | 2003-10-14 | Merck & Co., Inc. | Carbocyclic potassium channel inhibitors |
| US6828460B2 (en) * | 1999-03-22 | 2004-12-07 | Pfizer Inc. | Resorcinol derivatives |
| FR2795733B1 (fr) | 1999-06-30 | 2001-09-07 | Aventis Pharma Sa | Derives de streptogramines, leur preparation et les compositions qui les contiennent |
| EP1088824B1 (en) * | 1999-09-30 | 2004-01-07 | Pfizer Products Inc. | Bicyclic pyrrolyl amides as glycogen phosphorylase inhibitors |
| EP1391460A1 (en) | 1999-09-30 | 2004-02-25 | Pfizer Products Inc. | Tricyclic pyrrolyl amides as glycogen phosphorylase inhibitors |
| DE60017180T2 (de) | 1999-10-08 | 2005-12-08 | Affinium Pharmaceuticals, Inc., Toronto | Fab i inhibitoren |
| DE19960917A1 (de) * | 1999-12-17 | 2001-06-21 | Bayer Ag | Neue 3-Oxo-2,1-benzisoxazol-1(3H)-carboxamide zur Behandlung von ZNS-Erkrankungen |
| US6632417B2 (en) * | 2000-03-07 | 2003-10-14 | Chevron U.S.A. Inc. | Process for preparing zeolites |
| JP2001247462A (ja) | 2000-03-07 | 2001-09-11 | Otsuka Pharmaceut Co Ltd | ウレアーゼ阻害剤 |
| EP1136071A3 (en) | 2000-03-22 | 2003-03-26 | Pfizer Products Inc. | Use of glycogen phosphorylase inhibitors |
| EP1188756B1 (en) | 2000-04-19 | 2004-06-23 | Kaneka Corporation | Novel azetidine derivative and process for preparation thereof |
| GB0012214D0 (en) | 2000-05-19 | 2000-07-12 | Merck Sharp & Dohme | Therapeutic agents |
| WO2002012249A2 (en) | 2000-08-04 | 2002-02-14 | Eli Lilly And Company | Substituted pyrrole compounds and their use as spla2 inhibitors |
| GB0021831D0 (en) | 2000-09-06 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
| EP1330515A4 (en) | 2000-10-06 | 2005-12-07 | Affinium Pharm Inc | METHOD FOR AGONIZATION AND ANTAGONIZATION OF FABK |
| TWI283575B (en) * | 2000-10-31 | 2007-07-11 | Eisai Co Ltd | Medicinal compositions for concomitant use as anticancer agent |
| DE10063992A1 (de) | 2000-12-21 | 2002-07-04 | Max Planck Gesellschaft | Tryptophan-Analoga in Proteinen, Peptiden und peptidischen Leitstrukturen |
| US6372919B1 (en) * | 2001-01-11 | 2002-04-16 | Dov Pharmaceutical, Inc. | (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane, compositions thereof, and uses as an anti-depressant agent |
| US20020123490A1 (en) * | 2001-03-01 | 2002-09-05 | Pfizer Inc. | Combination treatment for anxiety, depression, obsessive compulsive disorder and psychosis |
| US7365205B2 (en) * | 2001-06-20 | 2008-04-29 | Daiichi Sankyo Company, Limited | Diamine derivatives |
| US6603000B2 (en) * | 2001-07-11 | 2003-08-05 | Boehringer Ingelheim Pharmaceuticals, Inc. | Synthesis for heteroarylamine compounds |
| PL368402A1 (en) | 2001-08-09 | 2005-03-21 | Daiichi Pharmaceutical Co, Ltd. | Diamine derivatives |
| US7045543B2 (en) * | 2001-11-05 | 2006-05-16 | Enzrel Inc. | Covalent conjugates of biologically-active compounds with amino acids and amino acid derivatives for targeting to physiologically-protected sites |
| US20030162825A1 (en) | 2001-11-09 | 2003-08-28 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| US6780891B2 (en) * | 2001-11-30 | 2004-08-24 | Sepracor Inc. | Tramadol analogs and uses thereof |
| TW200307539A (en) | 2002-02-01 | 2003-12-16 | Bristol Myers Squibb Co | Cycloalkyl inhibitors of potassium channel function |
| GB0205165D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205170D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| US6995144B2 (en) * | 2002-03-14 | 2006-02-07 | Eisai Co., Ltd. | Nitrogen containing heterocyclic compounds and medicines containing the same |
| WO2003091213A1 (en) | 2002-04-25 | 2003-11-06 | Yamanouchi Pharmaceutical Co., Ltd. | Novel amide derivatives or salts thereof |
| AU2003236247A1 (en) | 2002-05-03 | 2003-11-17 | Warner-Lambert Company Llc | Bombesin antagonists |
| US7576204B2 (en) * | 2002-07-31 | 2009-08-18 | Mercian Corporation | Heterocyclic macrolide pharmaceutical agent, a method of producing the same and use of the same |
| PT1543011E (pt) * | 2002-09-06 | 2006-08-31 | Janssen Pharmaceutica Nv | Composto de tienopirrolilo e furanopirrolilo e sua utilizacao como ligandos do receptor h4 da histamina |
| PT1542961E (pt) * | 2002-09-16 | 2013-11-05 | Sunovion Pharmaceuticals Inc | Trans 4-(3,4-diclorofenil)-1,2,3,4-tetrahidro-1- naftalenamina para uso no tratamento de perturbações do sistema nervoso central |
| EP1545485A2 (en) | 2002-09-16 | 2005-06-29 | Sepracor Inc. | Treatment of cns disorders with trans-4- (3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine |
| AU2003284005B2 (en) * | 2002-10-03 | 2009-12-17 | Forest Laboratories Holdings Limited | Dosage escalation and divided daily dose of anti-depressants to treat neurological disorders |
| GB0222909D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| GB0222912D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| US20040097554A1 (en) | 2002-10-30 | 2004-05-20 | Pfizer Inc | Heteroaryl-hexanoic acid amide derivatives as immonomodulatory agents |
| BR0316099A (pt) | 2002-11-07 | 2005-09-27 | Pfizer Prod Inc | Agentes antidiabéticos |
| DK1595866T3 (en) * | 2003-01-31 | 2016-08-22 | Sanwa Kagaku Kenkyusho Co | Cyanopyrrolidines suitable for the treatment of inter alia metabolism syndrome |
| JP4629657B2 (ja) | 2003-04-11 | 2011-02-09 | ハイ・ポイント・ファーマスーティカルズ、エルエルシー | 11β−ヒドロキシステロイドデヒドロゲナーゼ1型化活性化合物 |
| GB0309440D0 (en) * | 2003-04-25 | 2003-06-04 | Lilly Co Eli | Quinolone derivatives |
| MXPA05011702A (es) * | 2003-04-30 | 2006-01-23 | Pfizer Prod Inc | Agentes antidiabeticos. |
| WO2004113345A1 (ja) | 2003-06-20 | 2004-12-29 | Japan Tobacco Inc. | 縮合ピロール化合物及びその医薬用途 |
| SI1362864T1 (sl) | 2003-06-30 | 2007-08-31 | Servier Lab | Nov postopek za sintezo perindoprila in njegovih farmacevtsko sprejemljivih soli |
| KR20060033780A (ko) * | 2003-07-07 | 2006-04-19 | 시바 스페셜티 케미칼스 홀딩 인크. | 푸로피롤의 제조방법 |
| WO2005046575A2 (en) | 2003-07-29 | 2005-05-26 | Signature R & D Holdings, Lcc | Amino acid prodrugs |
| GB0318463D0 (en) | 2003-08-07 | 2003-09-10 | Astrazeneca Ab | Chemical compounds |
| GB0319759D0 (en) | 2003-08-22 | 2003-09-24 | Astrazeneca Ab | Chemical compounds |
| WO2005020986A1 (en) | 2003-08-29 | 2005-03-10 | Astrazeneca Ab | Heterocyclic amide derivatives which posses glycogen phosphorylase inhibitory activity |
| GB0320422D0 (en) | 2003-08-30 | 2003-10-01 | Astrazeneca Ab | Chemical compounds |
| US7396940B2 (en) * | 2003-10-23 | 2008-07-08 | Hoffmann-La Roche Inc. | Combinatorial library of 3-aryl-1H-indole-2-carboxylic acid |
| ATE354586T1 (de) | 2003-11-19 | 2007-03-15 | Servier Lab | Verfahren für die synthese von perindopril und seiner pharmazeutischen annehmbaren salzen |
| AU2004312530A1 (en) | 2003-12-29 | 2005-07-21 | Sepracor Inc. | Pyrrole and pyrazole DAAO inhibitors |
| CN101798291A (zh) * | 2003-12-29 | 2010-08-11 | 塞普拉科公司 | 苯并[d]异噁唑-3-醇DAAO抑制剂 |
| WO2005089753A2 (en) | 2004-03-16 | 2005-09-29 | Janssen Pharmaceutica N.V. | Daao inhibiting bξnzisoxazoles and their use for the treatment of mental disorders |
| SI1747210T1 (sl) | 2004-05-07 | 2010-09-30 | Warner Lambert Co | ali monosubstituirani fenolin in tiofenolni derivati uporabni kot ligandi H |
| US20100234409A1 (en) | 2004-05-21 | 2010-09-16 | Lihu Yang | Amino cyclopentyl heterocyclic and carbocyclic modulators of chemokine receptor activity |
| US7667041B2 (en) | 2004-05-26 | 2010-02-23 | Eisai R&D Management Co., Ltd. | Cinnamide compound |
| WO2005123677A1 (en) | 2004-06-16 | 2005-12-29 | Actelion Pharmaceuticals Ltd | 4-carbonyl substituted 1,1,2-trimethyl-1a,4,5,5a-tetrahydro-1h-4-aza-cyclopropa'a!pentalene derivatives as agonists for the g-protein-coupled receptor s1p1/edg1 and immunosuppressive agents |
| DE102004030099A1 (de) * | 2004-06-22 | 2006-01-12 | Grünenthal GmbH | Gesättigte und ungesättigte 3-Pyridyl-benzocycloalkylmethyl-amine als Serotonin- und/oder Noradrenalin-Reuptake-Hemmer und/oder µ-Opioidrezeptor-Modulatoren |
| DK1775298T3 (da) | 2004-07-01 | 2013-05-21 | Daiichi Sankyo Co Ltd | Thienopyrazolderivat med PDE7-inhibitorisk aktivitet |
| US7276631B2 (en) * | 2004-07-20 | 2007-10-02 | Bristol-Myers Squibb Company | Cyclopentylamine and cyclohexylamine derivatives as NK-1/SSRI antagonists |
| JO2629B1 (en) | 2004-08-19 | 2012-06-24 | افينتيس فارما سوتيكالز انك | Branched carboxylic acid amides containing thienobirol, carboxylic acid amides containing pyrolithiazole, and the like as kinase inhibitors casein epsilon |
| WO2006077412A1 (en) | 2005-01-19 | 2006-07-27 | Biolipox Ab | Thienopyrroles useful in the treatment of inflammation |
| CN100391945C (zh) | 2005-05-31 | 2008-06-04 | 浙江大学 | 一种s-(-)-吲哚啉-2-羧酸的合成方法 |
| US20090306169A1 (en) | 2005-10-06 | 2009-12-10 | Brandish Philip E | Use of Fused Pyrrole Carboxylic Acids for the Treatment of Neurodegenerative and Psychiatric Diseases and D-Amino Acid Oxidase Inhibitors |
| UA95788C2 (en) | 2005-12-15 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Fused pyrrole derivatives |
| JP5438975B2 (ja) | 2006-01-06 | 2014-03-12 | サノビオン ファーマシューティカルズ インク | テトラロン系モノアミン再取り込み阻害剤 |
| KR101294014B1 (ko) | 2006-01-06 | 2013-08-09 | 선오비온 파마슈티컬스 인코포레이티드 | 모노아민 재흡수 저해제로서의 시클로알킬아민 |
| CA2648121C (en) | 2006-03-31 | 2013-08-06 | Sepracor Inc. | Preparation of chiral amides and amines |
| BRPI0713216A2 (pt) | 2006-06-30 | 2012-12-04 | Sepracor Inc | inibiadores heterocìclos fundidos da d-aminoácido oxidase |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US20080058395A1 (en) * | 2006-06-30 | 2008-03-06 | Sepracor Inc. | Fused heterocyclic inhibitors of D-amino acid oxidase |
| CN1962656A (zh) | 2006-11-29 | 2007-05-16 | 沈阳药科大学 | 吲哚美辛5-氟尿嘧啶甲酯药用化合物及其制剂和制备方法 |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| MX2009007410A (es) | 2007-01-18 | 2009-09-09 | Sepracor Inc | Inhibidores de d-aminoacido oxidasa. |
| BRPI0811639A2 (pt) | 2007-05-31 | 2014-09-30 | Sepracor Inc | Cicloaquilaminas fenil substituídas como inibidores da recaptação de monoamina |
| WO2010017418A1 (en) | 2008-08-07 | 2010-02-11 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
-
2006
- 2006-12-21 JP JP2008549498A patent/JP5438975B2/ja not_active Expired - Fee Related
- 2006-12-21 US US11/643,190 patent/US8053603B2/en active Active
- 2006-12-21 EP EP06848050.8A patent/EP1978961B1/en not_active Not-in-force
- 2006-12-21 KR KR1020087019188A patent/KR101381768B1/ko not_active Expired - Fee Related
- 2006-12-21 NZ NZ569608A patent/NZ569608A/en not_active IP Right Cessation
- 2006-12-21 ES ES06848050.8T patent/ES2566479T3/es active Active
- 2006-12-21 WO PCT/US2006/049069 patent/WO2007081542A2/en not_active Ceased
- 2006-12-21 CN CN201410377601.4A patent/CN104276955A/zh active Pending
- 2006-12-21 CA CA2636275A patent/CA2636275C/en active Active
- 2006-12-21 CN CNA2006800533762A patent/CN101426372A/zh active Pending
- 2006-12-21 AU AU2006335174A patent/AU2006335174B2/en not_active Ceased
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3663608A (en) * | 1969-12-10 | 1972-05-16 | Bristol Myers Co | 1-phenyl-3-aminoalkyl-1,2,3,4-tetrahydronaphthalenes and the salts thereof |
| US5091429A (en) * | 1987-11-26 | 1992-02-25 | Laboratoires Lucien | Derivatives of 4-amino-1-trifluoromethyltetralines their preparation and their therapeutic application |
| WO2000007978A1 (en) * | 1998-07-31 | 2000-02-17 | Akzo Nobel N.V. | Aminomethylcarboxylic acid derivatives |
Non-Patent Citations (3)
| Title |
|---|
| BERTOLINI, G. et al. Eur. J. Med. Chem. 1992, 27(7), 663-672 * |
| KOE, B. K. J. Pharmacol. Exp. Ther. 1976, 199(3), 649-661 * |
| WELCH, W. M. et al. J. Med. Chem. (1984), 27(11), 1508-1515 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104276955A (zh) | 2015-01-14 |
| WO2007081542A3 (en) | 2008-12-11 |
| KR101381768B1 (ko) | 2014-04-07 |
| EP1978961A2 (en) | 2008-10-15 |
| WO2007081542A9 (en) | 2008-10-09 |
| EP1978961A4 (en) | 2010-10-27 |
| CA2636275C (en) | 2013-02-12 |
| NZ569608A (en) | 2011-09-30 |
| CN101426372A (zh) | 2009-05-06 |
| AU2006335174A1 (en) | 2007-07-19 |
| JP2009527462A (ja) | 2009-07-30 |
| US8053603B2 (en) | 2011-11-08 |
| US20070197588A1 (en) | 2007-08-23 |
| ES2566479T3 (es) | 2016-04-13 |
| JP5438975B2 (ja) | 2014-03-12 |
| WO2007081542A2 (en) | 2007-07-19 |
| EP1978961B1 (en) | 2016-03-16 |
| KR20080085203A (ko) | 2008-09-23 |
| CA2636275A1 (en) | 2007-07-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2006335174B2 (en) | Tetralone-based monoamine reuptake inhibitors | |
| US9586888B2 (en) | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors | |
| US20100190861A1 (en) | Cycloalkylamines as monoamine reuptake inhibitors | |
| US9505716B2 (en) | Pyrrolidine triple reuptake inhibitors | |
| AU2015202379B2 (en) | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |