ZA200103976B - Use of N-substituted azabicycloalkane derivatives for treating diseases of the central nervous system. - Google Patents
Use of N-substituted azabicycloalkane derivatives for treating diseases of the central nervous system. Download PDFInfo
- Publication number
- ZA200103976B ZA200103976B ZA200103976A ZA200103976A ZA200103976B ZA 200103976 B ZA200103976 B ZA 200103976B ZA 200103976 A ZA200103976 A ZA 200103976A ZA 200103976 A ZA200103976 A ZA 200103976A ZA 200103976 B ZA200103976 B ZA 200103976B
- Authority
- ZA
- South Africa
- Prior art keywords
- azabicyclo
- exo
- heptan
- fluorophenyl
- group
- Prior art date
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 12
- 210000003169 central nervous system Anatomy 0.000 title claims description 6
- 201000010099 disease Diseases 0.000 title 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- -1 Cj-s-alkyl Chemical group 0.000 claims description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 239000011737 fluorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 230000001955 cumulated effect Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000005561 phenanthryl group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 3
- 208000022497 Cocaine-Related disease Diseases 0.000 claims 1
- 201000006145 cocaine dependence Diseases 0.000 claims 1
- 206010013663 drug dependence Diseases 0.000 claims 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 10
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 6
- UEZROEGYRDHMRV-UHFFFAOYSA-N [1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound O=C1C=CN=C2SC=CN12 UEZROEGYRDHMRV-UHFFFAOYSA-N 0.000 description 5
- 239000001273 butane Substances 0.000 description 5
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 5
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 4
- IOHCGRJBQIIEOU-UHFFFAOYSA-N thiazin-6-one Chemical compound O=C1C=CC=NS1 IOHCGRJBQIIEOU-UHFFFAOYSA-N 0.000 description 3
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 2
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 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
- 238000005516 engineering process Methods 0.000 description 2
- XBCXJKGHPABGSD-UHFFFAOYSA-N methyluracil Natural products CN1C=CC(=O)NC1=O XBCXJKGHPABGSD-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- CVIBKISSHDMEKJ-UHFFFAOYSA-N 1-ethylquinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(CC)C2=C1 CVIBKISSHDMEKJ-UHFFFAOYSA-N 0.000 description 1
- ZBZFHKRVXVKBOU-UHFFFAOYSA-N 2-amino-3-ethyl-6-methylpyrimidin-4-one Chemical compound CCN1C(N)=NC(C)=CC1=O ZBZFHKRVXVKBOU-UHFFFAOYSA-N 0.000 description 1
- QHCCOYAKYCWDOJ-UHFFFAOYSA-N 2-ethyl-1h-benzimidazole Chemical compound C1=CC=C2NC(CC)=NC2=C1 QHCCOYAKYCWDOJ-UHFFFAOYSA-N 0.000 description 1
- BWNBLGQCCSCCHF-UHFFFAOYSA-N 2-ethyl-1h-indole Chemical compound C1=CC=C2NC(CC)=CC2=C1 BWNBLGQCCSCCHF-UHFFFAOYSA-N 0.000 description 1
- HGSJSGJZOMBIAB-UHFFFAOYSA-N 2h-pyrimido[2,1-b][1,3]thiazin-6-one Chemical compound S1CC=CN2C(=O)C=CN=C21 HGSJSGJZOMBIAB-UHFFFAOYSA-N 0.000 description 1
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 3H-quinazolinyl-4-one Natural products C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 description 1
- SLUYEZHWAHGANQ-UHFFFAOYSA-N 3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound O=C1C=CN=C2N=CCN12 SLUYEZHWAHGANQ-UHFFFAOYSA-N 0.000 description 1
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N Butanol Natural products CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 208000001613 Gambling Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 125000005236 alkanoylamino group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
J 0050/49558 ~~ py { - ‘
Use of N-substituted azabicycloalkane derivatives for treating disorders of the central nervous system
N-substituted azabicycloalkane derivatives are already known as neuroleptics (WO 95/13279, WO 95/15327, WO 96/04272, US 5.475.105, US 5.521.209, US 5.616.705, US 5.753.690). It has now been found that these substances are also suitable for controlling addictive disorders and other disorders of the central nervous system.
The present invention provides the use of N-substituted 3-azabicycloalkane derivatives of the formula I
Rl
IOS CHz ) n—R? I, in which
B is a 4-, 5- or 6-membered ring, which may contain a double bond,
R! is a phenyl, naphthyl, phenanthryl or thienyl group, in each case unsubstituted or mono- or disubstituted by halogen atoms, Cj;-s-alkyl, trifluoromethyl, hydroxyl, C;_g-alkoxy, amino, monomethylamino, dimethylamino, cyano or nitro groups, n is the number 0, 1, 2, 3 or 4 and
R2 is a naphthyl group which is unsubstituted or substituted by one or two halogen atoms, or is one of the following radicals: 40
0050/49558 “4 2 i i y i r+ — NR6—C—R7 ——t 14 4
R i RS i RS R8 et ed 8 RS
R — n° — —N ’
SOC fo) 14
RS
0
I= 0 rR — yd a ~N R10 —N 0] [4
R8 r NC ’ (Cre
RS
A 0 _ \ CHj3 R11
N N ’ nN R ~~
Io DES ’ X~ ~-Y \Qy H3C N N z '
RS
0] RS 058 ox —x—(O) ——~O) in which 40
R3 is a hydrogen atom, a hydroxyl group or a phenyl radical which is unsubstituted or substituted by a fluorine, chlorine or bromine atom, 45 R4 is a hydrogen atom or
0050/49558 ba - x - R3 and R% together are an oxygen atom,
R35 is a phenyl, naphthyl or thienyl group, each of which is unsubstituted or mono- or disubstituted by fluorine, chlorine or bromine atoms or by hydroxyl, nitro, amino,
Ci-s~alkanoylamino, Cj;_g-alkylamino, Cj_g-alkyl or methoxy groups,
Ré¢ is a hydrogen atom or a methyl group,
R? is a phenyl, naphthyl, benzofuryl, benzothienyl, thienyl, indolyl, N-methylindolyl or indenyl group, in each case unsubstituted or mono- or disubstituted by fluorine, chlorine or bromine atoms or by Cj_s~alkyl, hydroxyl, methoxy, nitro, cyano, trifluoromethyl, amino or di-Cj;_g-alkylamino groups, or is a Cj3.7-cycloalkyl group,
R8 is a hydrogen atom or a fluorine or chlorine atom or a
Ci-4-alkyl, methoxy or amino group,
R? is a hydrogen atom or a methyl group and
R10 is a hydrogen atom or a methyl group or
RY and R10 together with the ring carbon atom are a spirocyclopropane ring,
R!! is a hydrogen atom, a hydroxyl, C;-Cs-alkyl or C;-Cg-alkoxy group, or together with the adjacent carbon atom is a C=0- or
C=8 group,
X and Y are carbon atoms, CH, CH, NH or C;-C4-alkyl-N groups or nitrogen atoms, 2 is a direct bond, a CO group, CS group or a CH or CH; group in which a hydrogen atom may be replaced by a hydroxyl, amino or
C1-C4-alkoxy group or by a halogen atom, and
A is a hydrogen atom, a hydroxyl, amino, mercapto, 40 C1-Cg-alkylamino, di-C;-Cyq-alkylamino, Ci-Cs-alkylthio or
C;-Cs-alkoxy group or together with the adjacent carbon atom is a C=0 group or
A is a Y-bonded C3-Cs-alkylene group which may contain one or 45 two non-cumulated double bonds and in which one CH or CH, group may be replaced by a nitrogen or sulfur atom or an NH or N-CH; group and where the ring is either monosubstituted
0050/49558 ha - 1
E by a fluorine or chlorine atom or a methyl, methoxy, nitro or amino group or, in the case of a benzene ring, this may be mono-, di- or trisubstituted by fluorine or chlorine atoms or methyl, trifluoromethyl, nitro, hydroxyl, methoxy, amino, monomethyl or dimethylamino groups, and in which the X-, Y- and Z-containing ring at the nitrogen atom No. 1 may carry a C;-Cs-alkyl, allyl or benzyl group and may contain 1 to 3 non-cumulated double bonds, and their salts with physiologically acceptable acids for preparing medicaments for controlling addiction, for treating concentration disorders (attention deficit disorders), hyperactivity in children (attention deficit hyperactivity disorders), learning and memory weaknesses (impaired cognitive function).
The use according to the invention relates to all addictive disorders, whether they are caused by abuse of substances or other addictive disorders such as, for example, addiction to gambling. Habit-forming substances can be: opioids such as, for example, morphine or heroin, nicotine, alcohol, substances which interact with the benzodiazepine receptor complex, sedatives or tranquilizers, such as, for example, the benzodiazepines.
Possible habit-forming substances according to the invention are, in particular, cocaine or amphetamine and amphetamine-like substances.
The compounds of the formula I can be employed both in the form of their racemates and their optical isomers.
For the novel indication, the compounds can be administered in a customary manner orally or parenterally, intravenously or intramuscularly. 40
The dosage depends on the age, condition and weight of the patient and on the type of administration. In general, the daily dose of active compound is between about 1 and 100 mg/kg of bodyweight in the case of oral administration and between 0.1 and 45 10 mg/kg of bodyweight in the case of parenteral administration.
0050/49558 ;- . : The compounds can be employed in customary pharmaceutical administration forms, in solid or liquid form, for example as tablets, film-coated tablets, capsules, powders, granules, sugar-coated tablets, suppositories, solutions, ointments, creams or sprays. These are prepared in a customary manner. For this purpose, the active compounds can be processed with the customary pharmaceutical auxiliaries such as tablet binders, fillers, preservatives, tablet disintegrants, flow regulators, plasticizers, wetting agents, dispersants, emulsifiers, solvents, release-delaying agents, antioxidants and/or propellants (cf. H.
Sucker et al.: Pharmazeutische Technologie [Pharmaceutical
Technology}, Thieme-~Verlag, Stuttgart, 1978). The resulting administration forms usually comprise the active compound in an amount of from 1 to 99% by weight.
The following substances may be mentioned as examples of compounds of the formula I: 1. 1-(4-fluorophenyl)-4-[exo-6-phenyl-3-azabicyclo[3.2.0]- heptan-3-yl]butan-1l-one 2. 1-phenyl-4-[exo-6-phenyl-3-azabicyclo[3.2.0}heptan-3-yl]- butan-1-one 3. 1-(4-fluorophenyl)-4-[exo-6,7-diphenyl-~3-azabicyclo- [3.2.0]heptan-3-yl]butan-1-one 4. 1-(4-fluorophenyl)-4-[exo-6-phenyl~3-azabicyclo[3.2.0]- heptan-3-yl]butane 5. l-phenyl-2-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethan-1-one 6. 1-(4-fluorophenyl)-4-[exo-6-p-fluorophenyl-3-azabicyclo- [3.2.0)heptan-3-yl]butane 7. 1l-(4-fluorophenyl)-4-[exo-6-m-fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yljbutan-1-one 40 8. 1-(4-fluorophenyl)-4-[exo-6-o-fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-1l-one 9. 1-(4-fluorophenyl)-4-[exo-6-p-chlorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-l-one
0050/49558
T- ! : 10. 1-(4-fluorophenyl)-4-[exo-6-m-chlorophenyl-3-azabicyclo- [3.2.0}heptan-3-yl]butan-1-one 11. 1-(4-fluorophenyl)-4-[exo-6-p-methoxyphenyl-3-azabicyclo- [3.2.0}heptan-3-yllbutan-1-one 12. 1-(4-fluorophenyl)-4-[exo-6-m,p-dichlorophenyl-3-azabicyclo- [3.2.0)heptan-3-yl]butan-1l-one 13. 1-(4-fluorophenyl)-4-[exo-6-m,p-dimethoxyphenyl-3-aza- bicyclo[3.2.0]heptan-3-yl]butan-l-one 14. 1-(4-fluorophenyl)-4-[exo-6-p-fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-l1-one 15. l-phenyl-4-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]- heptan-3-yljbutan-1l-one 16. 1-(4-fluorophenyl)-4-[exo-6-p-fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butane 17. 1-(4-fluorophenyl)-4-[exo-6-p-nitrophenyl-3-azabicyclo- [3.2.0]heptan-3-yl}butan-1-one 18. 1-(4-fluorophenyl)-4-[exo-6-m-nitrophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-1-one 19. 1-(4-fluorophenyl)-4-[exo-6-p-trifluoromethylphenyl-3- azabicyclo[3.2.0]heptan-3-yl]butan-1l-one 20. 1l-(4-fluorophenyl)-4-[exo-6-p-cyanophenyl-3-azabicyclo- [3.2.0)heptan-3-yljbutan-1-one 21. 1-(4-fluorophenyl)-4-[exo-6-thien-3-yl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-1-one 22. 1-(4-fluorophenyl)-4-[exo-6-pyrid-3-yl-3-azabicyclo- [3.2.0)heptan-3-yl]butan-1-one 40 23. 1l-(4-fluorophenyl)-3-[exo-6-p-fluorophenyl-3-azabicyclo- [3.2.0}heptan-3-yl])propan-1l-one 24. l1l-(bis-4-fluorophenyl)-4-[exo-6-~p~fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butane
0050/49558 1 a *
) 25, 1-(bis-4-fluorophenyl)-4-[exo-6-phenyl-3-azabicyclo- [3.2.0]heptan~3-yl]butane 26. 1-(4-fluorophenyl)-4-[exo-6-phenyl-3-azabicyclo[3.2.0]~ heptan-3-yl]butan-1-0l 27. 1-(4-fluorophenyl)-4-[exo-6-p-fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]jbutan-1-0l 28. 1-(4-fluorophenyl)-4-[exo-6,7-diphenyl-3-azabicyclo[3.2.0]- heptan-3-yl}]butan-~1-ol 29. l-phenyl-4-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl}- butan-1-ol
30. l-phenyl-4-[exo-6-~-p-fluorophenyl-3-azabicyclo[3.2.0]- heptan-3-yl]butan-1-0l 31. 1-(4-fluorophenyl)-4-[exo-6-0~fluorophenyl-3-azabicyclo- [3.2.0]heptan-3-yl]butan-1-0l 32. 1-(4-fluorophenyl)-4-[exo-6-m-chlorophenyl-3-azabicyclo-~ [3.2.0)heptan-3-yl]butan-1-0l 33. 1-(4-fluorophenyl)-4-[exo-6-p-trifluoromethylphenyl-3- azabicyclo{3.2.0)heptan-3-yl]lbutan-1-01 34. 1-(4-fluorophenyl)-4-{exo-6-p-aminophenyl-3-azabicyclo~ [3.2.0]heptan-3-yl]butan-1-one
35. N-(3-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]propyl)-4- fluorobenzamide 36. N-(3-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- propyl)benzamide 37. N-(2-[exo-6-phenyl-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl)-4-fluorobenzamide 40 38. N-(2-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl )benzamide 39. N-(2-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl)-N-methyl-4-fluorobenzamide
0050/49558 i ‘
: 40. N-(2-[exo-6-phenyl-3-azabicyclo[3.2.0]lheptan-3-yl]- ethyl)-N-methylbenzamide 41. N-(2-[exo-6-phenyl-3-azabicyclo[3.2.0])heptan-3-yl]- ethyl)-N-methyl-4-isopropylbenzamide 42. N~(3-[exo-6-phenyl-3-azabicyclo[3.2.0]lheptan-3-yl]- propyl)-4-chlorobenzamide 43. N-(2-[exo-6-p-trifluoromethylphenyl-3-azabicyclo[3.2.0]- heptan-3-ylJ]ethyl)-4-chlorobenzamide 44. N-(3-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- propyl)-3-methoxybenzamide
45. N-(3-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]- propyl)-3-nitrobenzamide 46. N-(3-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl}propyl)-4-fluorobenzamide 47. N-(3-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl])propyl)benzamide 48. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl)-4-fluorobenzamide 49. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl]lethyl)benzamide
50. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0])heptan- 3-yl]ethyl)-N-methyl-4-fluorobenzamide 51. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl)-N-methylbenzamide 52. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl)-N-methyl-4-isopropylbenzamide 40 53. N-(3-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl]lpropyl)-4-chlorobenzamide 54. N-(3-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan- 3-yl]propyl)-3-methoxybenzamide
0050/49558 y - « p 9 : 55. N-(3-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-~ 3-yl]propyl)-3-nitrobenzamide 56. N-(2-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0}heptan- 3-yljethyl)-4-chlorobenzamide 57. N-(2-[exo-6-o-fluorophenyl-3-azabicyclo[3.2.0]heptan~ 3-yljethyl)-4-chlorobenzamide 58. N-(2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl]ethyl)-2-hydroxybenzamide 59. N-(2-[exo-6-m-hydroxyphenyl-3-azabicyclo[3.2.0)heptan-3-yl]- ethyl)-4-chlorobenzamide
60. exo-3-n-butyl-6-phenyl-3-azabicyclo[3.2.0]heptane 61. exo-3-methyl-6-phenyl-3-azabicyclo[3.2.0]}heptane 62. exo-3-methyl-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptane 63. exo-3-n-propyl-6-p-fluorophenyl-3-azabicyclo[3.2.0]- heptane 64. exo-3-methyl-6,7-diphenyl-3-azabicyclo[3.2.0]heptane 65. exo-3-n-propyl-6-m-hydroxyphenyl-3-azabicyclo[3.2.0]- heptane 66. exo-3-allyl-6-m-methoxyphenyl-3-azabicyclo[3.2.0]- heptane 67. exo-3-(3,4-dimethoxy)phenethyl-6-phenyl-3-azabicyclo- [3.2.0]heptane
68. exo-3-(3,4~-dimethoxy)phenethyl-6-p-fluorophenyl-3- azabicyclo[3.2.0]heptane 69. exo-3-(3,4-dihydroxy)phenethyl-3-azabicyclo[3.2.0]- 40 heptane 70. exo-3-phenethyl-6-p-fluorophenyl-3-azabicyclo{3.2.0]- heptane 45 71. 6-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-ylj- ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
0050/49558 1 - t j 10 : 72. (+)-6-B-[{exo-6-p-fluorophenyl-3-azabicyclo{3.2.0]heptan- 3-yllethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 73. (-)-6-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 74. 6-B-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yljethyl-7- methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 75. 6-B-[{ex0o-6,7-diphenyl-3-azabicyclo[3.2.0]heptan-3~yljethyl- 7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 76. 6-B-[exo-6,7-bis-(p~fluorophenyl)-3-azabicyclo[3.2.0}lheptan~- 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
77. 6-B-[exo-6-m-chlorophenyl-3-azabicyclo{3.2.0]heptan-3-ylj- ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 78. 6-B-(exo-6-m-methoxyphenyl-3-azabicyclo[3.2.0]}heptan-3-yl]- ethyl-7-methyl-5H-thiazolo[3,2-a]}pyrimidin-5-one 79. 6-B-[(exo-6-m-hydroxyphenyl-3-azabicyclo(3.2.0]heptan~ 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 80. 6-B-(2-[exo-6-p-aminophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 81. 6-B~-[exo-6-p-chlorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin~5-one
82. 6-B-[exo-6-p-methoxyphenyl-3-azabicyclo[3.2.0]heptan- 3-yl}ethyl-7-methyl-5H~thiazolo[3,2-a]pyrimidin-5-one 83. 6-B-{exo-6-p-nitrophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 84. 6-B-[exo-6-m~fluorophenyl-3-azabicyclo(3.2.0]heptan- 3-yllethyl-7-methyl-5H~thiazolo[3,2-a]pyrimidin-5-one 40 85. 6-B-[exo-6-p-hydroxyphenyl-3-azabicyclo[3.2.0]heptan- 3-yl]ethyl-7-methyl-5H~thiazolo[3,2-a]pyrimidin-5-one 86. 6-B-[exo-6-p~trifluoromethylphenyl-3-azabicyclo{3.2.0]- heptan-3-ylJ]ethyl-7-methyl-5H-thiazolo[3,2~-a]pyrimidin- 45 5-one
0050/49558 p - 1
. 87. 6-B-[exo-6-(p-t-butylphenyl)-3-azabicyclo[3.2.0]heptan~ 3-yl]ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 88. 6-B-[endo-6-(p-t-butylphenyl)-3-azabicyclo{3.2.0}heptan~ 3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 89. 6-B-[ex0-6-(3,4-dichlorophenyl)-3-azabicyclo[3.2.0]heptan- 3-yljethyl-7-methyl-5H-thiazolo[3,2~-a]pyrimidin-5-one 90. 6-B-[exo0-6-(3,4-dimethoxyphenyl)-3-azabicyclo{3.2.0]- heptan-3-yl]ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin- 5-one 91. 6-B-[exo-6-p-cyanophenyl-3-azabicyclo{3.2.0]heptan- 3-yljethyl-7-methyl-5H-thiazolo[3,2-a)pyrimidin-5-one 92. 6-B-[exo0-6-(3,4-dihydroxyphenyl)-3-azabicyclo(3.2.0]- heptan-~3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin- 5-one
93. 6-B-[exo0-6-(o-fluorophenyl)-3-azabicyclo[3.2.0]heptan- 3~yllethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 94. 6-B-[exo-6-thien-3-yl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 95. 6-B-[exo-6-(5-chlorothien-2-yl)-3-azabicyclo[3.2.0]}heptan- 3-yljlethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 96. 6-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-methyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin- 5-one 97. 6-8-[exo-6-m~-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-methyl-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin- 5-one 98. 6-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,3,7-trimethyl~5H-thiazolo[3,2-a]pyrimidin-5-one 40 99. 6-B-[exo-6-p-fluorophenyl-3-azabicyclo(3.2.0]heptan-3-yl}- ethyl-5H-thiazolo[3,2~a]pyrimidin-5-one 100. 6-B-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]ethyl-5H- 45 thiazolo[3,2-a}pyrimidin-5-one
0050/49558
: 101. 7-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-8-methyl-2H,6H~-pyrimido[2,1-b][1l,3]thiazin-6-one 102. 7-B-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]ethyl- 8-methyl-2H,6H-pyrimido{2,1-b][(1,3]thiazin-6-one 103. 7-B-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-8-methyl-2H,6H~pyrimido[2,1-b][1,3]thiazin-6-0one 104. 7-B-[exo-6~p-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-8-methyl-2H,6H~pyrimido[2,1-b][1,3]thiazin-6-one 105. 7-B-[exo-6-p-methoxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-8-methyl-2H,6H-pyrimido[2,1-b][1.3]thiazin-6-one
106. 7-B-[exo-6-m~-hydroxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-8-methyl-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-one 107. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 108. (+)-3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan~ 3-yljlethyl-2,4-(1H,3H)quinazolinedione 109. (-)-3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl)ethyl-2,4-(1H,3H)quinazolinedione 110. 3-B-[exo-6-phenyl-3-azabicyclo{3.2.0]heptan-3-yl]ethyl-2,4- (1H, 3H)quinazolinedione
111, 3-B-[ex0o-6-m-fluorophenyl-3-~-azabicyclo[3.2.0]heptan-3-yl}- ethyl-2,4-(1H,3H)quinazolinedione 112. 3-B-[exo-6-p-cyanophenyl-3-azabicyclo([3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 113. 3-B-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 40 114. 3-B-[exo-6-p-hydroxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-~(1H,3H)quinazolinedione 115. 3-B-[exo~-6-p-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-2,4-(1H,3H)quinazolinedione
0050/49558
Tl. 116. 3-B-{exo-6-m-methoxyphenyl-3-azabicyclo[3.2.0]lheptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 117. 3-B-[exo-6-p-nitrophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 118. 3-B-[endo-6-p-nitrophenyl-3-azabicyclo[3.2.0]heptan~-3-yl}]- ethyl-2,4-~(1H,3H)quinazolinedione 119. 3-B-[ex0o-6-m-hydroxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 120. 3-B-[exo-6-p-aminophenyl-3-azabicyclo[3.2.0}heptan-3-yl)- ethyl-2,4~(1H,3H)quinazolinedione 121. 3-B-[exo-6-p-iodophenyl-3-azabicyclo[3.2.0]heptan-3-yl)- ethyl-2,4-(1H,3H)quinazolinedione 122. 3-B-[exo-6-p-trifluoromethylphenyl-3-azabicyclo[3.2.0]- heptan-3-yl]lethyl-2,4-(1H,3H)quinazolinedione 123. 3-B-[exo-6-(3,4-dichlorophenyl)-3-azabicyclo[3.2.0])- heptan-3-yl]ethyl-2,4-(1H,3H)guinazolinedione 124. 3-B-[ex0-6-(3,4-dihydroxyphenyl)~-3-azabicyclo[3.2.0]- heptan-3-yllethyl-2,4-(1H,3H)guinazolinedione 125. 3-B-[ex0o-6-(3,5~dichlorophenyl)-3-azabicyclo{3.2.0]heptan- 3-yllethyl-2,4-(1H,3H)quinazolinedione 126. 3-B-[exo-6-0-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4~(1H,3H)quinazolinedione 127. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0}heptan-3-yl]- ethyl-8-methyl-2,4-(1H,3H)guinazolinedione 128. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan-3-yl}- ethyl-7-chloro-2,4-(1H,3H)quinazolinedione 40 129. 3-B-[exo0-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-fluoro-2,4-(1H,3H)quinazolinedione 130. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]lheptan-3-yl]- ethyl-5-chloro-2,4-(1H,3H)quinazolinedione
0050/49558 “4. 4
. 131. 3-B-[exo-6-p~fluorophenyl-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl-6-fluoro-2,4~(1H,3H)quinazolinedione 132. 3-B-[ex0o-6-p~-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6-methyl-2,4~(1H,3H)quinazolinedione 133. 3-B~-[exo-6-p~fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-8-methoxy-2,4-(1H,3H)quinazolinedione 134. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0)heptan-3-yl}- ethyl-6-trifluoromethyl-2,4-(1H,3H)quinazolinedione 135. 3-B~-[{exo-6-p~fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-nitro-2,4-(1H,3H)guinazolinedione
136. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-ylj}- ethyl-6-nitro-2,4-(1H,3H)quinazolinedione 137. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-7-amino-2,4-(1H,3H)quinazolinedione 138. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-6-amino-2,4-(1H,3H)quinazolinedione 139. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6-hydroxy-2,4-(1H,3H)guinazolinedione 140. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-5-chloro-2,4-(1H,3H)quinazolinedione
141. 3-B~[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6,7-dimethoxy-2,4-(1H,3H)quinazolinedione 142. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6,8-dichloro-2,4-(1H,3H)quinazolinedione 143. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl-6,7,8-trimethoxy-2,4-(1H,3H)quinazolinedione 40 144. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-ylj- ethyl-1-methyl-2,4-(1H,3H)quinazolinedione 145. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-l-ethyl-2,4-(1H,3H)quinazolinedione
0050/49558
Lr . he 146. 3-B-{exo-6-p~fluorophenyl-3-azabicyclo[3.2.0)heptan-3-yl]~ ethyl-1-allyl-2,4-(1H,3H)quinazolinedione 147. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0)heptan-3-yl]- ethyl-1-benzyl-2,4-(1H,3H)quinazolinedione 148. 3-y-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- propyl-2,4-(1H,3H)quinazolinedione 149. 3-06-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0)heptan-3-yl]- butyl-2,4-(1H,3H)quinazolinedione 150. 3-B-[exo-6-(2-thienyl)-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 151. 3-B-[exo-6-(5-chloro-2-thienyl)-3-azabicyclo[3.2.0]heptan- 3-yllethyl-2,4-(1H,3H)quinazolinedione 152. 3-B-[ex0o-6-(3-thienyl)-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 153. 3-B-[{exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-1H-thieno[3,2~-d]pyrimidine-2,4-dione 154. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-1H-thieno[2,3-d]pyrimidine-2,4-dione 155. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-1H-thieno[3,4-d]pyrimidine-2,4-dione 156. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]=- ethyl-l-methyl-1H,3H-pyrido[2,3-d]pyrimidine-2,4-dione 157. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan-3-yl}- ethyl-2-methyl-3H-quinazolin-4-one 158. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methoxy-3H-quinazolin-4-one 40 159. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methyl-4H-pyrido[l,2-a]pyrimidin~-4-one dihydrochloride 160. 3-B-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]ethyl- 45 2-methyl-4H-pyrido[1l,2-a]lpyrimidin-4-one
0050/49558 oo 161. 3-B-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one 162. 3-B-[exo-6~-m-methoxyphenyl-3-azabicyclo[3.2.0]heptan~ 3-yllethyl-2-methyl-4H-pyrido[1l,2-a]pyrimidin-4-one 163. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yl)ethyl-2,6-dimethyl-4H-pyrido[l,2-a]pyrimidin-4-one 164. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0Jheptan- 3-yljethyl-2,7-dimethyl-4H-pyrido[1l,2-a}pyrimidin-4-one 165. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0)heptan- 3-yllethyl-2,8-dimethyl-4H-pyrido[1l,2-a]pyrimidin-4-one
166. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-2,9-dimethyl-4H-pyrido[1l,2-a]pyrimidin-4-one 167. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan- 3-yllethyl-2,6,8-trimethyl-4H-pyrido{l,2-a]pyrimidin-4~one 168. 3-B-[exo-6-m~chlorophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl-2,7-dimethyl-4H-pyrido[1l,2-a]pyrimidin-4-one 169. 3-B-[ex0-6-0-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-2,7-dimethyl-4H-pyrido[1l,2-a]pyrimidin-4-one 170. 3-B-[exo-6-phenyl-3~-azabicyclo[{3.2.0]heptan-3-yl]jethyl- 2,8-dimethyl-4H-pyrido[1l,2-a]pyrimidin-4-one
171. 3-B-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-2,9-dimethyl-4H-pyrido{1l,2-a]pyrimidin-4-one 172. 3-B-[ex0-6~(5-chlorothien-2-yl)-3-azabicyclo{3.2.0]heptan- 3-yljethyl-2-methyl-4H-pyrido[1,2~-a]pyrimidin-4-one 173. 3-B-[exo-~-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyridofl,2-a]pyrimidin- 4-one 40 174. 3-B-[exo-6-p-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1l,2-alpyrimidin- 4-one
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: 175. 3-B-[exo-6-p-methoxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin- 4-one 176. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methyl-4H-pyrimido[1,2-a]pyrimidin-4-one 177. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methyl-7-chloro-4H-pyrimido[1,2-a]pyrimidin-4-one
178. 6-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]~- ethyl-7-methyl-1H,5H~imidazo[1,2-a]pyrimidin-5-one 179. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methyl-7,8-dihydro-4H, 6H-pyrrolo[1,2-a]lpyrimidin- 4-one 180. 2-[exo~6-p-fluorophenyl-3-azabicyclo{3.2.0]heptan-3-yl]- methylbenzimidazole
181. 1-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]~ ethylbenzimidazole 182. 1-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2,3-dihydrobenzimidazol-2-one 183. 2-[exo-6-m-methoxyphenyl-3-azabicyclo[3.2.0]heptan-3-yl]- methylbenzimidazole 184. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethylindole, m.p. 193-195°C (hydrochloride) 185. 3-B-(2-[exo-6-m-chlorophenyl-3-azabicyclo[3.2.0]heptan-3- yl}ethylindole
186. 3-B-[exo-6-phenyl-3-azabicyclo{3.2.0]heptan-3-yljethyl- indole, m.p. 104-105°C (hydrochloride) 187. 3-B-[exo-6-m-methoxyphenyl-3-azabicyclo{3.2.0]heptan-3-yl]- 40 ethylindole 188. 2-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0]heptan-3-yl}- methyl-3,4-dihydroquinazolin-4-one 45 189. 2-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- methyl-3, 4-dihydroquinazoline-4-thione
0050/49558 hE 190. 2-[exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]methyl- 3,4-dihydroquinazolin-4-one 191. 2-[exo~6-m-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- methyl-3,4-dihydroquinazolin-4-one 192. 2-[exo-6-0~-methoxyphenyl-3-azabicyclo{3.2.0}heptan-3-yl]- methyl-3,4-dihydroquinazolin-4-one 193. 2-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0]heptan-3-ylj}- methyl-4-hydroxy-6-methylpyrimidine 194. 6-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- methyl-2-methyl-4-hydroxypyrimidine
195. 6~[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- methyluracil 196. 6-{exo-6-phenyl-3-azabicyclo[3.2.0]heptan-3-yl]methyl- uracil 197. 6-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0lheptan-3-yl]- 1,2,3,4-tetrahydro-1,3-dimethyl-2,4-dioxopyrimidine 198. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-1,2,3,4-tetrahydro-6-methyl-2,4-dioxopyrimidine 199. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0]heptan-3-yl]- ethyl-1,2,3,4-tetrahydro-1,6-dimethyl-2,4-dioxopyrimidine
200. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-1,2,3,4-tetrahydro-3,6-dimethyl-2,4-dioxopyrimidine 201. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo{3.2.0]}heptan-3-yl]- ethyl-1,2,3,4~-tetrahydro-3, 6-dimethyl-2,4-dithiopyrimidine 202. 5-B-[exo-6-p~fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-1,2,3,4-tetrahydro-1,3,6-trimethyl-2,4-dioxopyrimidine 40 203. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan-3-yl]- ethyl-1,2,3,4-tetrahydro-6-amino-1-methyl-2, 4-dioxo- pyrimidine 204. 5-B-[exo-6~p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}-~ 45 ethyl-2-amino-6-methyl-4(3H)pyrimidinone
0050/49558
. 205. 5-B~[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]}- ethyl-2-amino-3,6-dimethyl-4(3H)pyrimidinone 206. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methylamino-3,6-dimethyl-4 (3H)pyrimidinone 207. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methylamino-3-ethyl-6-methyl-4(3H)pyrimidinone 208. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-amino-3-ethyl-6-methyl-4(3H)pyrimidinone 209. 5-B-[{exo-6-p-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl}- ethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone
210. 5-B-[exo-6~-m-chlorophenyl-3-azabicyclo[3.2.0]heptan-3-yl]- ethyl-2-methylamino-3,6-dimethyl-4 (3H)pyrimidinone 211. 5-B-[{exo-6-0-fluorophenyl-3-azabicyclo[3.2.0])heptan-3-yl]- ethyl-2-methylamino-3,6~-dimethyl-4(3H)pyrimidinone 212. 5-B-(exo-6-p-trifluoromethylphenyl-3-azabicyclo[3.2.0]- heptan-3-yl)ethyl-2-methylamino-3, 6-dimethyl-4(3H)~ pyrimidinone
213. 5-B-[ex0o-6-p-cyanophenyl-3-azabicyclo[3.2.0]heptan- 3-yllethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone 214. 5-B-[exo-6-m-fluorophenyl-3-azabicyclo[3.2.0]heptan- 3-yljethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone 215. 5-B-[exo-6-p-fluorophenyl-3-azabicyclo[3.2.0}heptan- 3-yl}ethyl-2-methylamino-4-methoxy-6-methylpyrimidine 216. 3-f-[exo-6-phenyl-7-methyl-1,5-cis-3,7~-diazabicyclo[3.3.0]- octan-3-yljethyl-2,4-(1H,3H)quinazolinedione 217. 3-B-[endo-6-phenyl-7-methyl-1,5-cis-3,7-diazabicyclo[3.3.0]- octan-3-yl]ethyl-2,4-(1H,3H)quinazolinedione 40 218. 3-f-[exo-6~-p-fluorophenyl-7-methyl-1,5-cis-3,7~diazabicyclo- [3.3.0])Joctan-3-yl]ethyl-2,4~(1H,3H)quinazolinedione 219. 3-p-[exo-6-p-trifluoromethylphenyl-7-methyl-1,5-cis-3,7~ 45 diazabicyclo[3.3.0]octan-3-yl]jethyl-6-fluoro-2,4-(1H,3H)- quinazolinedione
0050/49558
: 220. 3-B-[exo~-6-m-chlorophenyl-7-methyl-1,5-cis-3,7~diazabicyclo- [3.3.0]octan-3-yl]ethyl-2,4-(1H,3H)quinazolinedione 221. 3-f-[exo-6-p-methoxyphenyl-7-methyl-1,5-cis-3,7-diazabicyclo- {3.3.0]octan-3-yl]ethyl-6-methyl-2,4-(1H,3H)quinazolinedione 222. 5-pf-[exo-6-phenyl-7-methyl-1,5-cis-3,7-diazabicyclo{3.3.0]- octan-3-yl}ethyl-2-methylamino-3,6-dimethyl-4(3H)- pyrimidinone
223. 5-p-[exo-6-p-fluorophenyl-7-methyl-1,5-cis~3,7-diazabicyclo- [3.3.0)Joctan-3-yl]ethyl-2-methylamino-3,6-dimethyl- 4 (3H)pyrimidinone 224. 1-B-[exo-6-p-fluorophenyl-7-methyl-1,5-cis-3,7-diazabicyclo- [3.3.0]octan-3-yl)lethyl-2(3H)benzimidazolone 225. 5-f-[exo-6-p-nitrophenyl-7-methyl-1,5-cis-3,7-diazabicyclo~ [3.3.0)octan-3-yl]ethyl-2-methylamino-3,6-dimethyl- 4 (3H)pyrimidinone 226. 5-p-[exo-6-phenyl-7-methyl-1,5-cis-3,7-diazabicyclo[3.3.0]~ octan-3-yl]ethyl-2-methylamino-3,6-dimethyl-4(3H)- pyrimidinone
227. 5-B~[endo-6-phenyl-7-methyl-1,5-cis~3,7~-diazabicyclo[3.3.0}- octan-3-yl]ethyl-2-methylamino-3,6-dimethyl-4(3H)- pyrimidinone 228. 3-f-[exo-6-p-fluorophenyl-7-methyl-1,5-cis-3,7~-diazabicyclo- [3.3.0]octan-3-yl]ethyl-2-methyl-4H~pyridofl.2-a]- pyrimidin-4-one 229. 1-B-[exo-6-p-fluorophenyl-7-methyl-1,5-cis-3,7-diazabicyclo~ [3.3.0]octan-3-yl]lethylindolin-2-one 230. 6-B-~[exo-6-p-fluorophenyl-7-methyl-1,5-cis-3,7-diazabicyclo- [3.3.0]octan-3-yl]ethyl-7-methyl-5H~thiazolo[3.2-a]- pyrimidin-5-one 40 231. 1-B~[exo-6-p-fluorophenyl-7-methyl-1,5-cis-3,7-diazabicyclo- [3.3.0]octan-3-yl]jethyl-2(1H)gquinolone 232. 3-B-[7-phenyl-1,5-cis-3,7-diazabicyclo[3.3.0]octan-3-yl]- 45 ethyl-2,4-(1H,3H)quinazolinedione
0050/49558
. 233. 3-f-[{7-p-fluorophenyl-1,5-cis-3,7-diazabicyclo{3.3.0]- octan-3-yl)ethyl-2,4-(1H,3H)quinazolinedione 234. 5~-f~[ 7-p-fluorophenyl-1,5-cis-3, 7-diazabicyclo[3.3.0]- octan-3-yl)ethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone 235. 3-B-[exo-6-p-fluorophenyl-3-azabicyclo{3.1.0]hexan-3-yl]- ethyl-2,4-(1H,3H)quinazolinedione 236. 3-f-[exo-6-phenyl~3-azabicyclo[3.1.0]hexan-3~yl]ethyl-2,4~ (1H,3H)quinazolinedione 237.3-B-[6,6-diphenyl-3-azabicyclo{3.1.0)hexan-3~yl]ethyl-2,4~ (1H, 3H)quinazolinedione
238. 5-p-[exo-6~p-fluorophenyl-3~azabicyclo[3.1.0]hexan-3-yl]- ethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone 239. 6-f-[exo-6~-m-chlorophenyl-3-azabicyclo[3.1.0]hexan-3-yl]- ethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one 240. 3-pf~[6-p-fluorophenyl-1,5-cis-3-~azabicyclo{3.3.0]oct-6- en-3-yl]ethyl-2,4-(1H,3H)quinazolinedione 241, 5-B-[6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0]oct-6- en-3-yl)ethyl-2-methylamino-3,6~dimethyl-4(3H)pyrimidinone 242. 6-pB-[6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0]Joct-6~ en-3-yljethyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one
243. 1-B-[6-phenyl-1,5-cis-3-azabicyclo[3.3.0)oct~-6-en-3-yl]- ethyl-2(3H)benzimidazolone } 244. 1-pB-{6-p-fluorophenyl-1,5-cis-3-~azabicyclo[3.3.0]oct-6- en-3-yljethylindolin-2-one 245. 1-p-[6-p-fluorophenyl-1,5-cis-3~azabicyclo{3.3.0]Joct-6- en-3-yllethyl-2(1H)quinolone 40 246. 3-p-[exo-6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0])octan- 3-yllethyl-2,4~(1H,3H)quinazolinedione 247. 5-p-[exo-6-p-fluorophenyl-1,5-cis-3~azabicyclo[3.3.0]octan~ 3-yllethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone
0050/49558
: 248. 6-p-[exo-6-phenyl-1,5-cis-3-azabicyclo[3.3.0]octan-3-yl}- ethyl-7-methyl-5H-thiazolo[3.2-a]pyrimidin-5-one 249. 1-pf-[exo-6-p-fluorophenyl-1,5~cis-3-azabicyclo[3.3.0]octan- 3-yljethylindolin~2-one 250. 1-B-[exo-6-p-fluorophenyl-1,5-~cis-3~azabicyclo[3.3.0]octan- 3-yl]ethyl-2(1H)quinolone 251. 3-B-[endo-6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0]octan- 3-yljethyl-2,4-(1H,3H)quinazolinedione 252. 5-pB-[endo-6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0]octan- 3-yl]ethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone
253. 6-B-[endophenyl-1,5-cis~3~-azabicyclo[{3.3.0]octan-3-yl]- ethyl-7-methyl-5H-thiazolo[3.2-a]pyrimidin-5-one 254. 1-B-[endo-6-p-fluorophenyl-1,5-~cis-3-azabicyclo[3.3.0]octan~ 3-yllethylindolin-2-one 255. 1-pf-[endo-6-p-fluorophenyl-1,5-cis-3-azabicyclo[3.3.0]octan~- 3-yl)ethyl-2(1H)quinolone 256. 3-p-[exo-7-p-fluorophenyl-1l,5-cis-3~azabicyclo[3.3.0})octan~ 3-yljethyl-2,4-(1H,3H)quinazolinedione 257. 5-p-[exo-7-p-fluorophenyl-1,5~cis-3~azabicyclo[3.3.0]octan- 3-yljethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone
258. 6-B-[exo-7-phenyl-1,5-cis-3-azabicyclo[3.3.0]octan-3-yl]- ethyl-7-methyl-5H-thiazolo[3.2-a]lpyrimidin-5-0one 259. 1-f-[exo-7-p-fluorophenyl-1,5-cis-3~-azabicyclo[3.3.0]octan- 3-yllethylindolin-2-one 260. 1-pf-[exo-7-p-fluorophenyl-1,5-cis-3~azabicyclo{3.3.0]octan- 3-yljethyl-2(1H)gquinolone 40 261. 3-B-[endo-6-p-fluorophenyl-1,5-cis-3-azabicyclo[4.3.0]non- 3-yljethyl-2,4-(1H,3H)quinazolinedione 262. 5-p-[endo-6-p-fluorophenyl-1,5-cis~-3-azabicyclo[4.3.0]non- 3-yl]ethyl-2-methylamino-3,6-dimethyl-4(3H)pyrimidinone
Claims (1)
- 0050/49558 wr We claim:1. The use of N-substituted 3-azabicycloalkane derivatives of the formula I Rl OG CHy) n—R? 1, in which B is a 4-, 5- or 6-membered ring, which may contain a double bond, Rl is a phenyl, naphthyl, phenanthryl or thienyl group, in each case unsubstituted or mono- or disubstituted by halogen atoms, Cj-s-alkyl, trifluoromethyl, hydroxyl, C1-s4—-alkoxy, amino, monomethylamino, dimethylamino, cyano or nitro groups, n is the number 0, 1, 2, 3 or 4 and R?2 is a naphthyl group which is unsubstituted or substituted by one or two halogen atoms, or is one of the following radicals: il 1 RS —C—R5 + — NR6—C —R’ r — NR6— or {Tf [4 L i RS I RS RS 40 8 RS R —N 0 — a JR [e] ’ 0 7 [4 45 RS0050/49558 > 42 N= o RO Q J \_/ a N 8 R10 —N 0] ’ ; “TNS.Gh R NEA RS ha i _ CH; R11 = | ZI oF : \Q Hc” NN ’ XS ’ RS 0 RS8 or —5—O) —3—O)})in whichR3 is a hydrogen atom, a hydroxyl group or a phenyl radical which is unsubstituted or substituted by a fluorine, chlorine or bromine atom,R4 is a hydrogen atom orR3 and R? together are an oxygen atom,R53 is a phenyl, naphthyl or thienyl group, each of which is unsubstituted or mono- or disubstituted by fluorine, chlorine or bromine atoms or by hydroxyl, nitro, amino,Cj-s4—-alkanoylamino, Cj;_g-alkylamino, Cj;_s-alkyl or methoxy groups,R® is a hydrogen atom or a methyl group,40R7 is a phenyl, naphthyl, benzofuryl, benzothienyl, thienyl, indolyl, N-methylindolyl or indenyl group, in each case unsubstituted or mono- or disubstituted by fluorine, chlorine or bromine atoms or by Cj;_g-alkyl, hydroxyl,45 methoxy, nitro, cyano, trifluoromethyl, amino or di-C;.4-alkylamino groups, or is a Ci_y-cycloalkyl group,0050/49558 > 43 ha R8 is a hydrogen atom or a fluorine or chlorine atom or a Ci-g-alkyl, methoxy or amino group, R% is a hydrogen atom or a methyl group andR10 is a hydrogen atom or a methyl group orR? and R!0 together with the ring carbon atom are a spirocyclopropane ring,R11 is a hydrogen atom, a hydroxyl, C;-C4-alkyl or C;-Cs-alkoxy group, or together with the adjacent carbon atom is a C=0-~ or C=S group,X and Y¥ are carbon atoms, CH, CH;, NH or C;-Cy-alkyl-N groups or nitrogen atoms,Z is a direct bond, a CO group, CS group or a CH or CH; group in which a hydrogen atom may be replaced by a hydroxyl, amino or C;-C4-alkoxy group or by a halogen atom, andA is a hydrogen atom, a hydroxyl, amino, mercapto, C;-C4-alkylamino, di-C;-Cg-alkylamino, C;-Cy-alkylthio or C1-Cs-alkoxy group or together with the adjacent carbon atom is a C=0 group orA is a Y-bonded C3-Cy-alkylene group which may contain one or two non-cumulated double bonds and in which one CH or CH, group may be replaced by a nitrogen or sulfur atom or an NH or N-CH; group and where the ring is either monosubstituted by a fluorine or chlorine atom or a methyl, methoxy, nitro or amino group or, in the case of a benzene ring, this may be mono-, di- or trisubstituted by fluorine or chlorine atoms or methyl, trifluoromethyl, nitro, hydroxyl, methoxy, amino, monomethyl or dimethylamino groups,40 and in which the X-, Y- and Z-containing ring at the nitrogen atom No. 1 may carry a C;-Cy-alkyl, allyl or benzyl group and may contain 1 to 3 non-cumulated double bonds,0050/49558 CL and their salts with physiologically acceptable acids for preparing medicaments for treating disorders of the central nervous system. So Lo5 .2. The use as claimed in claim 1 for the production of drugs for treating addictive disorders. ’3. The use as claimed in claim 1 or 2 for the production of drugs for treating cocaine addiction. oo94. The use as claimed in claim 1 or 2 for the production of drugs for controlling addiction for amphetamines and amphetamine-like substances.5. The use as claimed in any one of claims 1 to 4, substantially as hereinbefore described or exemplified.6. The use of the compound of formula I including any new and inventive integer or combination of integers, substantially as herein described. : : - a0 | a 45 AMENDED SHEET“to 0050/49558 a 4 o£ 2 Use of N-substituted azabicycloalkane derivatives for treating disorders of the central nervous systemAbstract The use of N-substituted 3-azabicycloalkane derivatives of the formula IR1 JOG SEI I, in which B, Rl, R2 and n are as defined in the description for controlling addictive disorders and other disorders of the central nervous system is described.40
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19854147A DE19854147A1 (en) | 1998-11-24 | 1998-11-24 | Control of cocaine addiction comprises administration of N-substituted azabicycloalkane derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200103976B true ZA200103976B (en) | 2002-05-16 |
Family
ID=7888824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200103976A ZA200103976B (en) | 1998-11-24 | 2001-05-16 | Use of N-substituted azabicycloalkane derivatives for treating diseases of the central nervous system. |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP1133293A1 (en) |
| JP (1) | JP2002530333A (en) |
| KR (1) | KR20010080535A (en) |
| CN (1) | CN1328455A (en) |
| AR (1) | AR021502A1 (en) |
| AU (1) | AU1775300A (en) |
| BG (1) | BG105549A (en) |
| BR (1) | BR9915589A (en) |
| CA (1) | CA2352526A1 (en) |
| CZ (1) | CZ20011796A3 (en) |
| DE (1) | DE19854147A1 (en) |
| HK (1) | HK1040933A1 (en) |
| HR (1) | HRP20010472A2 (en) |
| HU (1) | HUP0104416A3 (en) |
| IL (1) | IL143181A0 (en) |
| NO (1) | NO20012538L (en) |
| PL (1) | PL348758A1 (en) |
| SK (1) | SK7112001A3 (en) |
| TR (1) | TR200101476T2 (en) |
| WO (1) | WO2000030639A1 (en) |
| ZA (1) | ZA200103976B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2589363A1 (en) | 2004-12-13 | 2006-06-22 | Eli Lilly And Company | Spiro derivatives as lipoxygenase inhibitors |
| GB0812310D0 (en) | 2008-07-03 | 2008-08-13 | Syngenta Ltd | Novel herbicides |
| JP2016508159A (en) * | 2013-01-15 | 2016-03-17 | ノバルティス アーゲー | Use of alpha 7 nicotinic acetylcholine receptor agonists |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989004311A1 (en) * | 1987-11-12 | 1989-05-18 | American Home Products Corporation | Polycyclicamines with psychotropic activity |
| DE4427648A1 (en) * | 1994-08-04 | 1996-02-08 | Basf Ag | N-Stubstituted 3-azabicyclo [3,2,0,] heptane derivatives, their preparation and use |
| DE4341403A1 (en) * | 1993-12-04 | 1995-06-08 | Basf Ag | N-substituted 3-azabicycloalkane derivatives, their preparation and use |
| DE4427647A1 (en) * | 1994-08-04 | 1996-02-08 | Basf Ag | N-substituted azabicycloheptane derivatives, their preparation and use |
-
1998
- 1998-11-24 DE DE19854147A patent/DE19854147A1/en not_active Withdrawn
-
1999
- 1999-11-12 EP EP99960974A patent/EP1133293A1/en not_active Withdrawn
- 1999-11-12 HK HK02102768.4A patent/HK1040933A1/en unknown
- 1999-11-12 CZ CZ20011796A patent/CZ20011796A3/en unknown
- 1999-11-12 CN CN99813559A patent/CN1328455A/en active Pending
- 1999-11-12 IL IL14318199A patent/IL143181A0/en unknown
- 1999-11-12 CA CA002352526A patent/CA2352526A1/en not_active Abandoned
- 1999-11-12 HR HR20010472A patent/HRP20010472A2/en not_active Application Discontinuation
- 1999-11-12 AU AU17753/00A patent/AU1775300A/en not_active Abandoned
- 1999-11-12 SK SK711-2001A patent/SK7112001A3/en unknown
- 1999-11-12 TR TR2001/01476T patent/TR200101476T2/en unknown
- 1999-11-12 KR KR1020017006445A patent/KR20010080535A/en not_active Ceased
- 1999-11-12 BR BR9915589-3A patent/BR9915589A/en not_active IP Right Cessation
- 1999-11-12 HU HU0104416A patent/HUP0104416A3/en unknown
- 1999-11-12 JP JP2000583522A patent/JP2002530333A/en active Pending
- 1999-11-12 PL PL99348758A patent/PL348758A1/en not_active Application Discontinuation
- 1999-11-12 WO PCT/EP1999/008734 patent/WO2000030639A1/en not_active Ceased
- 1999-11-24 AR ARP990105979A patent/AR021502A1/en unknown
-
2001
- 2001-05-16 ZA ZA200103976A patent/ZA200103976B/en unknown
- 2001-05-23 NO NO20012538A patent/NO20012538L/en not_active Application Discontinuation
- 2001-05-30 BG BG105549A patent/BG105549A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL348758A1 (en) | 2002-06-03 |
| CA2352526A1 (en) | 2000-06-02 |
| AR021502A1 (en) | 2002-07-24 |
| SK7112001A3 (en) | 2001-12-03 |
| BG105549A (en) | 2001-12-29 |
| EP1133293A1 (en) | 2001-09-19 |
| CN1328455A (en) | 2001-12-26 |
| NO20012538L (en) | 2001-07-04 |
| JP2002530333A (en) | 2002-09-17 |
| IL143181A0 (en) | 2002-04-21 |
| HRP20010472A2 (en) | 2003-04-30 |
| CZ20011796A3 (en) | 2002-05-15 |
| DE19854147A1 (en) | 2000-05-25 |
| HUP0104416A2 (en) | 2002-04-29 |
| HK1040933A1 (en) | 2002-06-28 |
| TR200101476T2 (en) | 2001-10-22 |
| NO20012538D0 (en) | 2001-05-23 |
| HUP0104416A3 (en) | 2002-11-28 |
| AU1775300A (en) | 2000-06-13 |
| WO2000030639A1 (en) | 2000-06-02 |
| KR20010080535A (en) | 2001-08-22 |
| BR9915589A (en) | 2001-08-07 |
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