IL123898A - The history of compressed tropane, their preparation and the pharmaceutical preparations containing them - Google Patents
The history of compressed tropane, their preparation and the pharmaceutical preparations containing themInfo
- Publication number
- IL123898A IL123898A IL12389896A IL12389896A IL123898A IL 123898 A IL123898 A IL 123898A IL 12389896 A IL12389896 A IL 12389896A IL 12389896 A IL12389896 A IL 12389896A IL 123898 A IL123898 A IL 123898A
- Authority
- IL
- Israel
- Prior art keywords
- azatricyclo
- dichlorophenyl
- decan
- oxime
- alkyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 150000003813 tropane derivatives Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 87
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 53
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 208000035475 disorder Diseases 0.000 claims abstract description 32
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 20
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 18
- 230000005764 inhibitory process Effects 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 12
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 230000001561 neurotransmitter reuptake Effects 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 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 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
- JDPQWHLMBJZURR-UHFFFAOYSA-N decan-5-one Chemical compound CCCCCC(=O)CCCC JDPQWHLMBJZURR-UHFFFAOYSA-N 0.000 claims description 29
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 27
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- -1 decan-5-one oxime Chemical class 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- SZMNDOUFZGODBR-UHFFFAOYSA-N decan-5-ol Chemical compound CCCCCC(O)CCCC SZMNDOUFZGODBR-UHFFFAOYSA-N 0.000 claims description 12
- 208000026139 Memory disease Diseases 0.000 claims description 11
- 208000019901 Anxiety disease Diseases 0.000 claims description 10
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 10
- 208000026097 Factitious disease Diseases 0.000 claims description 10
- 208000008589 Obesity Diseases 0.000 claims description 10
- 230000036506 anxiety Effects 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- 208000019906 panic disease Diseases 0.000 claims description 10
- 230000000697 serotonin reuptake Effects 0.000 claims description 10
- 208000030814 Eating disease Diseases 0.000 claims description 9
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 8
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 5
- 206010052276 Pseudodementia Diseases 0.000 claims description 5
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- HEGYCCPHUPUFNT-JQHQGBHXSA-N C1([C@@H]2[C@]3([H])C(=NOCC)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 Chemical compound C1([C@@H]2[C@]3([H])C(=NOCC)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 HEGYCCPHUPUFNT-JQHQGBHXSA-N 0.000 claims description 3
- 238000007796 conventional method Methods 0.000 claims description 3
- 150000002923 oximes Chemical class 0.000 claims description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
- XLRPYZSEQKXZAA-OCAPTIKFSA-N tropane Chemical group C1CC[C@H]2CC[C@@H]1N2C XLRPYZSEQKXZAA-OCAPTIKFSA-N 0.000 claims description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims 2
- VSNVOPBKBFNSRJ-JLXZJAHCSA-N (1s,3s,4s,8r)-3-(4-chlorophenyl)-5-ethoxy-7-azatricyclo[5.3.0.04,8 ]decane Chemical compound C1([C@@H]2[C@]3([H])C(OCC)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C=C1 VSNVOPBKBFNSRJ-JLXZJAHCSA-N 0.000 claims 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 claims 1
- 125000003963 dichloro group Chemical group Cl* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 28
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 25
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229960003638 dopamine Drugs 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 230000002401 inhibitory effect Effects 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000001530 fumaric acid Substances 0.000 description 11
- 229960002748 norepinephrine Drugs 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000006260 foam Substances 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 239000002858 neurotransmitter agent Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 239000002775 capsule Substances 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 239000012458 free base Substances 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- FVGRGAHNDVYVJT-GYTBEQAESA-N (1s,3s,4s,8r)-3-(3,4-dichlorophenyl)-7-azatricyclo[5.3.0.04,8 ]decan-5-ol Chemical compound C1([C@@H]2[C@]3([H])C(O)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 FVGRGAHNDVYVJT-GYTBEQAESA-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
- 229910021529 ammonia Inorganic materials 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 229940076279 serotonin Drugs 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 230000001430 anti-depressive effect Effects 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 229960001779 pargyline Drugs 0.000 description 6
- 230000009870 specific binding Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- AXHNHGWBVFCLFB-CIGZNWKYSA-N (1S,2S,4S,7R)-2-(3,4-dichlorophenyl)-8-azatricyclo[5.4.0.04,8]undecan-11-one Chemical compound C1([C@@H]2[C@]3([H])C(=O)CCN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 AXHNHGWBVFCLFB-CIGZNWKYSA-N 0.000 description 5
- DHCMQYPZARIKNH-JQHQGBHXSA-N (1S,2S,4S,7R)-2-(3,4-dichlorophenyl)-N-methoxy-8-azatricyclo[5.4.0.04,8]undecan-11-imine Chemical compound C1([C@@H]2[C@]3([H])C(=NOC)CCN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 DHCMQYPZARIKNH-JQHQGBHXSA-N 0.000 description 5
- XPZBYZQTMUWPEF-VWFLFCASSA-N (1S,3S,4S,8R)-3-(3,4-dichlorophenyl)-7-azatricyclo[5.3.0.04,8]decan-5-one Chemical compound C1([C@@H]2[C@]3([H])C(=O)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 XPZBYZQTMUWPEF-VWFLFCASSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 5
- 239000002904 solvent Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- AXDGAGCMDRTNFA-UNNXFLIFSA-N (1s,3s,4s,8r)-3-(3,4-dichlorophenyl)-7-azatricyclo[5.3.0.04,8 ]decan-5-one oxime Chemical compound C1([C@@H]2[C@]3([H])C(=NO)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 AXDGAGCMDRTNFA-UNNXFLIFSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
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- 210000002569 neuron Anatomy 0.000 description 4
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
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- 210000003568 synaptosome Anatomy 0.000 description 4
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- MTCWULTWUZAUJI-NHIYQJMISA-N (1S,2S,4S,7R)-2-(4-chlorophenyl)-8-azatricyclo[5.4.0.04,8]undecan-11-one Chemical compound C1([C@@H]2[C@]3([H])C(=O)CCN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C=C1 MTCWULTWUZAUJI-NHIYQJMISA-N 0.000 description 3
- SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 description 3
- LWSUEBBSZINOJY-IRHXVLAXSA-N (1s,3s,4s,8r)-3-(3,4-dichlorophenyl)-7-azatricyclo[5.3.0.04,8 ]decan-5-one o-methyl-oxime Chemical compound C1([C@@H]2[C@]3([H])C(=NOC)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C(Cl)=C1 LWSUEBBSZINOJY-IRHXVLAXSA-N 0.000 description 3
- XFIYTAPFUDMMKE-AGQAROMHSA-N (1s,3s,4s,8r)-3-(4-chlorophenyl)-7-azatricyclo[5.3.0.04,8 ]decan-5-ol fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1([C@@H]2[C@]3([H])C(O)CN4[C@]3([H])CC[C@]4(C2)[H])=CC=C(Cl)C=C1 XFIYTAPFUDMMKE-AGQAROMHSA-N 0.000 description 3
- MGPYIZXQILGKLZ-YICICZCRSA-N (1s,3s,4s,8r)-5-allyloxy-3-(3,4-dichlorophenyl)-7-azatricyclo[5.3.0.04,8 ]decane fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1=C(Cl)C(Cl)=CC=C1[C@@H]1[C@H](C(CN23)OCC=C)[C@H]3CC[C@H]2C1 MGPYIZXQILGKLZ-YICICZCRSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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- 208000024827 Alzheimer disease Diseases 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 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 3
- 102000010909 Monoamine Oxidase Human genes 0.000 description 3
- 108010062431 Monoamine oxidase Proteins 0.000 description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
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- 238000003556 assay Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
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- 239000002270 dispersing agent Substances 0.000 description 3
- 230000028436 dopamine uptake Effects 0.000 description 3
- JEEZTCZXQWPJAS-QHDJUILOSA-N ethyl (1s,3s,4r,5r)-3-(3,4-dichlorophenyl)-8-(3-ethoxy-3-oxopropyl)-8-azabicyclo[3.2.1]octane-4-carboxylate Chemical compound C1([C@@H]2[C@H]([C@]3(CC[C@@](C2)(N3CCC(=O)OCC)[H])[H])C(=O)OCC)=CC=C(Cl)C(Cl)=C1 JEEZTCZXQWPJAS-QHDJUILOSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
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- 235000019322 gelatine Nutrition 0.000 description 3
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- 238000004519 manufacturing process Methods 0.000 description 3
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- 230000007246 mechanism Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- HNEGQIOMVPPMNR-UHFFFAOYSA-N methylfumaric acid Natural products OC(=O)C(C)=CC(O)=O HNEGQIOMVPPMNR-UHFFFAOYSA-N 0.000 description 3
- 230000012154 norepinephrine uptake Effects 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
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- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
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- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 229910021653 sulphate ion Inorganic materials 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
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- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Exhaust Gas After Treatment (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK122395 | 1995-11-02 | ||
| DK14696 | 1996-02-13 | ||
| PCT/EP1996/004793 WO1997016451A1 (en) | 1995-11-02 | 1996-11-04 | Fused tropane-derivatives as neurotransmitter reuptake inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL123898A0 IL123898A0 (en) | 1998-10-30 |
| IL123898A true IL123898A (en) | 2001-08-08 |
Family
ID=26063395
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12389896A IL123898A (en) | 1995-11-02 | 1996-11-04 | The history of compressed tropane, their preparation and the pharmaceutical preparations containing them |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US5998405A (cs) |
| EP (1) | EP0858461B1 (cs) |
| JP (1) | JP3157839B2 (cs) |
| KR (1) | KR100277482B1 (cs) |
| CN (1) | CN1060775C (cs) |
| AT (1) | ATE224392T1 (cs) |
| AU (1) | AU702720B2 (cs) |
| BR (1) | BR9611300A (cs) |
| CA (1) | CA2236707C (cs) |
| CZ (1) | CZ285571B6 (cs) |
| DE (1) | DE69623799T2 (cs) |
| DK (1) | DK0858461T3 (cs) |
| EE (1) | EE03566B1 (cs) |
| HU (1) | HUP9802534A3 (cs) |
| IL (1) | IL123898A (cs) |
| IS (1) | IS4708A (cs) |
| NO (1) | NO309569B1 (cs) |
| NZ (1) | NZ321970A (cs) |
| PL (1) | PL184843B1 (cs) |
| RU (1) | RU2162469C2 (cs) |
| SK (1) | SK282944B6 (cs) |
| TR (1) | TR199800780T2 (cs) |
| UA (1) | UA47442C2 (cs) |
| WO (1) | WO1997016451A1 (cs) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6329520B1 (en) * | 1990-08-09 | 2001-12-11 | Research Triangle Institute | Cocaine receptor binding ligands |
| US6706880B2 (en) | 1990-08-09 | 2004-03-16 | Research Triangle Institute | Cocaine receptor binding ligands |
| US6150376A (en) * | 1998-08-05 | 2000-11-21 | Georgetown University | Bi- and tri-cyclic aza compounds and their uses |
| NZ509762A (en) * | 1998-08-18 | 2002-12-20 | Ucb S | 5-Azatricyclo[3.3.1.1<3,7>]decane derivatives, pharmaceuticals thereof, and their use as cholinergic receptor agonists and antagonists |
| AU7723300A (en) | 1999-09-27 | 2001-04-30 | Georgetown University | Novel tropane analogs |
| US6479509B1 (en) | 2000-05-22 | 2002-11-12 | Research Triangle Institute | Method of promoting smoking cessation |
| AU2001265820A1 (en) * | 2000-07-04 | 2002-01-14 | Neurosearch A/S | Steric isomers of fused tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| CA2440196A1 (en) | 2001-04-09 | 2002-10-17 | Neurosearch A/S | Adenosine a2a receptor antagonists combined with neurotrophic activity compounds in the treatment of parkinson's disease |
| WO2002094827A1 (en) * | 2001-05-23 | 2002-11-28 | Neurosearch A/S | Fused tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| AR035898A1 (es) | 2001-05-25 | 2004-07-21 | Wyeth Corp | Aril-8-azabiciclo[3.2.1]octanos, un proceso para su preparacion, una formulacion y el uso de dichos compuestos para la manufactura de un medicamento para el tratamiento de la depresion |
| AU2002365288A1 (en) | 2001-11-30 | 2003-06-10 | Neurosearch A/S | Tropane derivatives having dopamine reuptake inhibitor activity for the treatment of ischemic diseases |
| NZ541249A (en) | 2003-02-12 | 2008-04-30 | Neurosearch As | Tropane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| NZ541248A (en) | 2003-02-12 | 2008-04-30 | Neurosearch As | Novel 8-aza-bicyclo[3.2.1]octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| CN100356940C (zh) * | 2004-12-01 | 2007-12-26 | 蒋毅 | 制备大叶蒟提取物的方法、提取物及其应用 |
| EP2272847A1 (en) | 2005-04-08 | 2011-01-12 | NeuroSearch A/S | Enantiomers and their use as monoamine neurotransmitter re-uptake inhibitors |
| US8093388B2 (en) | 2005-06-28 | 2012-01-10 | Neurosearch A/S | 3-aza spiro[5,5]undec-8-ene derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| WO2007000463A1 (en) * | 2005-06-28 | 2007-01-04 | Neurosearch A/S | Novel 3,9-diaza-spiro[5.5]undecane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| JP2009506988A (ja) * | 2005-08-19 | 2009-02-19 | エラン ファーマシューティカルズ，インコーポレイテッド | ガンマセクレターゼの架橋ｎ−環状スルホンアミド阻害剤 |
| TW200800980A (en) | 2006-02-17 | 2008-01-01 | Neurosearch As | Novel compounds |
| MX2011011904A (es) | 2009-05-15 | 2011-12-08 | Neurosearch As | Derivados de cromen-2-ona y su uso como inhibidores de la reabsorcion del neurotransmisor de monoamina. |
| KR20120044978A (ko) * | 2009-06-19 | 2012-05-08 | 아보트 러보러터리즈 | 디아자호모아다만탄 유도체 및 이들의 사용 방법 |
| WO2011032903A1 (en) | 2009-09-21 | 2011-03-24 | Neurosearch A/S | Piperazinyl-alkyl-benzoimidazol-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| WO2011092061A1 (en) | 2010-01-29 | 2011-08-04 | Neurosearch A/S | Chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| WO2011117289A1 (en) | 2010-03-25 | 2011-09-29 | Neurosearch A/S | Chromen-2-one derivatives and their use as monoamine neuro-transmitter re-uptake inhibitors |
| WO2012000881A1 (en) | 2010-07-02 | 2012-01-05 | Neurosearch A/S | Chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| JP6052524B1 (ja) * | 2015-07-30 | 2016-12-27 | 秋夫 湯田 | 持ち運び設置が容易な手提げハンドルの付いた薪ストーブ。 |
| AU2023303077A1 (en) | 2022-07-08 | 2025-02-06 | Initiator Pharma A/S | Compound for treatment of female sexual dysfunction |
| KR20250093316A (ko) | 2022-10-28 | 2025-06-24 | 이니시에이터 파마 에이/에스 | 통증 치료용 화합물 |
| TW202440106A (zh) | 2023-01-03 | 2024-10-16 | 丹麥商創始人製藥股份有限公司 | 用於治療勃起障礙之化合物 |
| WO2025051846A1 (en) | 2023-09-05 | 2025-03-13 | Initiator Pharma A/S | Compound for treatment of female sexual dysfunction |
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| AU672644B2 (en) * | 1992-12-23 | 1996-10-10 | Neurosearch A/S | Aryl substituted heterocyclic compounds |
| US5736556A (en) * | 1994-04-19 | 1998-04-07 | Neurosearch A/S | Tropane-2-aldoxime derivatives as nevro transmitter reuptake inhibitors |
-
1996
- 1996-11-04 DK DK96938064T patent/DK0858461T3/da active
- 1996-11-04 RU RU98110007/04A patent/RU2162469C2/ru not_active IP Right Cessation
- 1996-11-04 EE EE9800100A patent/EE03566B1/xx not_active IP Right Cessation
- 1996-11-04 HU HU9802534A patent/HUP9802534A3/hu unknown
- 1996-11-04 CA CA002236707A patent/CA2236707C/en not_active Expired - Fee Related
- 1996-11-04 AT AT96938064T patent/ATE224392T1/de not_active IP Right Cessation
- 1996-11-04 IL IL12389896A patent/IL123898A/en not_active IP Right Cessation
- 1996-11-04 DE DE69623799T patent/DE69623799T2/de not_active Expired - Lifetime
- 1996-11-04 NZ NZ321970A patent/NZ321970A/en unknown
- 1996-11-04 TR TR1998/00780T patent/TR199800780T2/xx unknown
- 1996-11-04 EP EP96938064A patent/EP0858461B1/en not_active Expired - Lifetime
- 1996-11-04 UA UA98041933A patent/UA47442C2/uk unknown
- 1996-11-04 PL PL96326448A patent/PL184843B1/pl unknown
- 1996-11-04 BR BR9611300A patent/BR9611300A/pt not_active Application Discontinuation
- 1996-11-04 JP JP51708397A patent/JP3157839B2/ja not_active Expired - Fee Related
- 1996-11-04 KR KR1019980702592A patent/KR100277482B1/ko not_active Expired - Fee Related
- 1996-11-04 SK SK422-98A patent/SK282944B6/sk unknown
- 1996-11-04 CN CN96198012A patent/CN1060775C/zh not_active Expired - Fee Related
- 1996-11-04 CZ CZ981138A patent/CZ285571B6/cs not_active IP Right Cessation
- 1996-11-04 US US09/051,107 patent/US5998405A/en not_active Expired - Lifetime
- 1996-11-04 WO PCT/EP1996/004793 patent/WO1997016451A1/en active IP Right Grant
- 1996-11-04 AU AU75631/96A patent/AU702720B2/en not_active Ceased
-
1998
- 1998-03-31 IS IS4708A patent/IS4708A/is unknown
- 1998-04-07 NO NO981609A patent/NO309569B1/no unknown
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