HRP20100622T1 - Novi derivati cikloalkiliranog benzotiadizina, postupak njihove priprave i farmaceutski pripravci koji ih sadrže - Google Patents
Novi derivati cikloalkiliranog benzotiadizina, postupak njihove priprave i farmaceutski pripravci koji ih sadrže Download PDFInfo
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- HRP20100622T1 HRP20100622T1 HR20100622T HRP20100622T HRP20100622T1 HR P20100622 T1 HRP20100622 T1 HR P20100622T1 HR 20100622 T HR20100622 T HR 20100622T HR P20100622 T HRP20100622 T HR P20100622T HR P20100622 T1 HRP20100622 T1 HR P20100622T1
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- 238000000034 method Methods 0.000 title claims 3
- 150000007658 benzothiadiazines Chemical class 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 38
- 125000005843 halogen group Chemical group 0.000 claims abstract 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract 3
- 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims abstract 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract 2
- 125000006642 (C1-C6) cyanoalkyl group Chemical group 0.000 claims abstract 2
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract 2
- 125000004122 cyclic group Chemical group 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 2
- 239000001257 hydrogen Substances 0.000 claims abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
- 125000004149 thio group Chemical group *S* 0.000 claims abstract 2
- 238000006243 chemical reaction Methods 0.000 claims 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 5
- 201000011240 Frontotemporal dementia Diseases 0.000 claims 4
- 239000002253 acid Substances 0.000 claims 4
- 230000004770 neurodegeneration Effects 0.000 claims 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims 4
- 238000002360 preparation method Methods 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 238000000926 separation method Methods 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000006823 (C1-C6) acyl group Chemical group 0.000 claims 2
- 102000003678 AMPA Receptors Human genes 0.000 claims 2
- 108090000078 AMPA Receptors Proteins 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 208000019901 Anxiety disease Diseases 0.000 claims 2
- 206010012289 Dementia Diseases 0.000 claims 2
- 208000023105 Huntington disease Diseases 0.000 claims 2
- 208000006264 Korsakoff syndrome Diseases 0.000 claims 2
- 208000026139 Memory disease Diseases 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims 2
- 230000001154 acute effect Effects 0.000 claims 2
- 230000036506 anxiety Effects 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 208000010877 cognitive disease Diseases 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 206010015037 epilepsy Diseases 0.000 claims 2
- 208000028867 ischemia Diseases 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 230000000750 progressive effect Effects 0.000 claims 2
- 238000007363 ring formation reaction Methods 0.000 claims 2
- 201000000980 schizophrenia Diseases 0.000 claims 2
- 230000002739 subcortical effect Effects 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims 1
- XYVUVQQBGLMJTQ-UHFFFAOYSA-N 4-(cyclopropylmethyl)-7-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=CC(F)=CC=C2N1CC1CC1 XYVUVQQBGLMJTQ-UHFFFAOYSA-N 0.000 claims 1
- KJEKWUMGMVZKHK-UHFFFAOYSA-N 4-cyclopropyl-1,1-dioxo-2,3-dihydro-1$l^{6},2,4-benzothiadiazine-6-carbonitrile Chemical compound C12=CC(C#N)=CC=C2S(=O)(=O)NCN1C1CC1 KJEKWUMGMVZKHK-UHFFFAOYSA-N 0.000 claims 1
- OLRHCEUOAIOVHI-UHFFFAOYSA-N 4-cyclopropyl-1,1-dioxo-2,3-dihydro-1$l^{6},2,4-benzothiadiazine-6-carboxylic acid Chemical compound C=1C(C(=O)O)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 OLRHCEUOAIOVHI-UHFFFAOYSA-N 0.000 claims 1
- COOYEDFGKMWZFL-UHFFFAOYSA-N 4-cyclopropyl-5,6-difluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound FC=1C(F)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 COOYEDFGKMWZFL-UHFFFAOYSA-N 0.000 claims 1
- NPGUGDATFKXQOG-UHFFFAOYSA-N 4-cyclopropyl-5,7-difluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=CC(F)=CC(F)=C2N1C1CC1 NPGUGDATFKXQOG-UHFFFAOYSA-N 0.000 claims 1
- NOWSMZYQIDDGBM-UHFFFAOYSA-N 4-cyclopropyl-5-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound FC1=CC=CC(S(NC2)(=O)=O)=C1N2C1CC1 NOWSMZYQIDDGBM-UHFFFAOYSA-N 0.000 claims 1
- IAXWVEUMKCZZGU-UHFFFAOYSA-N 4-cyclopropyl-6,8-difluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(F)=CC(F)=C(S(NC2)(=O)=O)C=1N2C1CC1 IAXWVEUMKCZZGU-UHFFFAOYSA-N 0.000 claims 1
- KRUMFQJLFHMVAD-UHFFFAOYSA-N 4-cyclopropyl-6-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(F)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 KRUMFQJLFHMVAD-UHFFFAOYSA-N 0.000 claims 1
- LKNXTRUAJRLRKF-UHFFFAOYSA-N 4-cyclopropyl-6-iodo-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(I)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 LKNXTRUAJRLRKF-UHFFFAOYSA-N 0.000 claims 1
- BUBPQDIZCAGYTL-UHFFFAOYSA-N 4-cyclopropyl-6-methyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(C)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 BUBPQDIZCAGYTL-UHFFFAOYSA-N 0.000 claims 1
- IBGXCIXMVWDIIX-UHFFFAOYSA-N 4-cyclopropyl-7,8-difluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=C(F)C(F)=CC=C2N1C1CC1 IBGXCIXMVWDIIX-UHFFFAOYSA-N 0.000 claims 1
- APNFKOCXFKJXDY-UHFFFAOYSA-N 4-cyclopropyl-7-methyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=CC(C)=CC=C2N1C1CC1 APNFKOCXFKJXDY-UHFFFAOYSA-N 0.000 claims 1
- ZSLFNIAAFDLJLV-UHFFFAOYSA-N 4-cyclopropyl-8-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C=2C(F)=CC=CC=2N1C1CC1 ZSLFNIAAFDLJLV-UHFFFAOYSA-N 0.000 claims 1
- RQWQTTDKAIAANG-UHFFFAOYSA-N 6,7-dichloro-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C=2C=C(Cl)C(Cl)=CC=2N1C1CC1 RQWQTTDKAIAANG-UHFFFAOYSA-N 0.000 claims 1
- HMMYQIPUKHKTRZ-UHFFFAOYSA-N 6-bromo-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(Br)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 HMMYQIPUKHKTRZ-UHFFFAOYSA-N 0.000 claims 1
- QFHACNWTKRNDFM-UHFFFAOYSA-N 6-bromo-4-cyclopropyl-7-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1=C(Br)C(F)=CC(S(NC2)(=O)=O)=C1N2C1CC1 QFHACNWTKRNDFM-UHFFFAOYSA-N 0.000 claims 1
- WPXBSXUVOXOWKA-UHFFFAOYSA-N 6-chloro-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(Cl)=CC=C(S(NC2)(=O)=O)C=1N2C1CC1 WPXBSXUVOXOWKA-UHFFFAOYSA-N 0.000 claims 1
- HGEYPDAIHVMWBT-UHFFFAOYSA-N 7-bromo-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=CC(Br)=CC=C2N1C1CC1 HGEYPDAIHVMWBT-UHFFFAOYSA-N 0.000 claims 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- OHFNCFAKZOXHCS-UHFFFAOYSA-N 8-bromo-4-cyclopropyl-1,1-dioxo-2,3-dihydro-1$l^{6},2,4-benzothiadiazine-6-carbonitrile Chemical compound C1NS(=O)(=O)C=2C(Br)=CC(C#N)=CC=2N1C1CC1 OHFNCFAKZOXHCS-UHFFFAOYSA-N 0.000 claims 1
- QLZOYHGZHKEBAI-UHFFFAOYSA-N 8-bromo-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C=2C(Br)=CC=CC=2N1C1CC1 QLZOYHGZHKEBAI-UHFFFAOYSA-N 0.000 claims 1
- LZCQKMNKAGDDJC-UHFFFAOYSA-N 8-bromo-4-cyclopropyl-6-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(F)=CC(Br)=C(S(NC2)(=O)=O)C=1N2C1CC1 LZCQKMNKAGDDJC-UHFFFAOYSA-N 0.000 claims 1
- MPDFJDCIKJNDEM-UHFFFAOYSA-N 8-bromo-6-chloro-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(Cl)=CC(Br)=C(S(NC2)(=O)=O)C=1N2C1CC1 MPDFJDCIKJNDEM-UHFFFAOYSA-N 0.000 claims 1
- KVXHLEVTKKIVKC-UHFFFAOYSA-N 8-chloro-4-cyclopropyl-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C=2C(Cl)=CC=CC=2N1C1CC1 KVXHLEVTKKIVKC-UHFFFAOYSA-N 0.000 claims 1
- IPWNHCYRDIKBPV-UHFFFAOYSA-N 8-chloro-4-cyclopropyl-6-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C=1C(F)=CC(Cl)=C(S(NC2)(=O)=O)C=1N2C1CC1 IPWNHCYRDIKBPV-UHFFFAOYSA-N 0.000 claims 1
- KEXNTHGOUWUAJC-UHFFFAOYSA-N 8-chloro-4-cyclopropyl-7-fluoro-2,3-dihydro-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical compound C1NS(=O)(=O)C2=C(Cl)C(F)=CC=C2N1C1CC1 KEXNTHGOUWUAJC-UHFFFAOYSA-N 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 241001024304 Mino Species 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/15—Six-membered rings
- C07D285/16—Thiadiazines; Hydrogenated thiadiazines
- C07D285/18—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D285/20—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems
- C07D285/22—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D285/24—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom
- C07D285/26—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals
- C07D285/28—1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with oxygen atoms directly attached to the ring sulfur atom substituted in position 6 or 7 by sulfamoyl or substituted sulfamoyl radicals with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached in position 3
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—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
Abstract
Spojevi formule (I): naznačeni time, da: • RCy predstavlja: o (C3-C8)cikloalkilnu skupinu koja je nesupstituirana ili supstituirana s jednom ili više jednakih ili različitih skupina odabranih između ravnog ili razgrananog (C1-C6)alkila, koji je nesupstituiran ili supstituiran s jednim ili više atoma halogena; ravnog ili razgrananog (C1-C5)alkoksi; hidroksi; i amino, koji je nesupstituiran ili supstituiran s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil; o ili skupinu (C3-C8)cikloalkil-(C1-C6)alkil u kojoj je alkilna skupina ravna ili razgranana i koja je na cikličkoj skupini nesupstituirana ili supstituirana s jednom ili više jednakih ili različitih skupina odabranih između ravnog ili razgrananog (C1-C6)alkila, koji je nesupstituiran ili supstituiran s jednim ili više atoma halogena; ravnog ili razgrananog (C1-C6)alkoksi; hidroksi; i amino, koji je nesupstituiran ili supstituiran s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil; • R1, R2, R3 i R4, koji mogu biti jednaki ili različiti, a svaki predstavlja atom vodika ili halogena ili nitro skupinu; cijano skupinu; hidroksi skupinu; tio skupinu; skupinu ravni Mi razgranani (C1-C6)alkil, koja je nesupstituirana ili supstituirana s jednim ili više atoma halogena; skupinu ravni ili razgranani (C1-C6)cijanoalkil; skupinu ravni ili razgranani (C1-C6)hidroksialkil; skupinu ravni ili razgranani (C1-C6)alkoksi, koja je nesupstituirana ili supstituirana s jednim ili više atoma halogena; skupinu ravni ili razgranani (C1-C6)alkiltio; karboksi skupinu; skupinu ravni ili razgranani (C1-C6)-alkoksikarbonil; ariloksikarbonil skupinu; skupinu ravni ili razgranani
Claims (20)
1. Spojevi formule (I):
[image]
naznačeni time, da:
• RCy predstavlja:
o (C3-C8)cikloalkilnu skupinu koja je nesupstituirana ili supstituirana s jednom ili više jednakih ili različitih skupina odabranih između ravnog ili razgrananog (C1-C6)alkila, koji je nesupstituiran ili supstituiran s jednim ili više atoma halogena; ravnog ili razgrananog (C1-C5)alkoksi; hidroksi; i amino, koji je nesupstituiran ili supstituiran s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil;
o ili skupinu (C3-C8)cikloalkil-(C1-C6)alkil u kojoj je alkilna skupina ravna ili razgranana i koja je na cikličkoj skupini nesupstituirana ili supstituirana s jednom ili više jednakih ili različitih skupina odabranih između ravnog ili razgrananog (C1-C6)alkila, koji je nesupstituiran ili supstituiran s jednim ili više atoma halogena; ravnog ili razgrananog (C1-C6)alkoksi; hidroksi; i amino, koji je nesupstituiran ili supstituiran s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil;
• R1, R2, R3 i R4, koji mogu biti jednaki ili različiti, a svaki predstavlja atom vodika ili halogena ili nitro skupinu; cijano skupinu; hidroksi skupinu; tio skupinu; skupinu ravni Mi razgranani (C1-C6)alkil, koja je nesupstituirana ili supstituirana s jednim ili više atoma halogena; skupinu ravni ili razgranani (C1-C6)cijanoalkil; skupinu ravni ili razgranani (C1-C6)hidroksialkil; skupinu ravni ili razgranani (C1-C6)alkoksi, koja je nesupstituirana ili supstituirana s jednim ili više atoma halogena; skupinu ravni ili razgranani (C1-C6)alkiltio; karboksi skupinu; skupinu ravni ili razgranani (C1-C6)-alkoksikarbonil; ariloksikarbonil skupinu; skupinu ravni ili razgranani (C1-C6)-acil; a mino skupinu, koja je nesupstituirana ili supstituirana s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil ili skupinom ravni ili razgranani (C1-C6)acil; aminokarbonil skupinu, koja je nesupstituirana ili supstituirana s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil; arilaminokarbonil skupinu; ili skupinu ravni ili razgranani (C1-C6) alkilsulfonilamino;
njihove enantiomere i njihove dijastereoizomere kada postoje, kao i njihove adicijske soli s farmaceutski prihvatljivom kiselinom ili bazom, "arilom" se označava fenilna skupina koja je nesupstituirana ili supstituirana s jednom ili više jednakih ili različitih skupina odabranih između ravnog ili razgrananog (C1-C5)alkila, koji je nesupstituiran ili supstituiran s jednim ili više atoma halogena; ravnog ili razgrananog (C1-CeJalkoksi; hidroksi; i amino, koji je nesupstituiran ili supstituiran s jednom ili dvije skupine ravni ili razgranani (C1-C6)alkil.
2. Spojevi formule (I) u skladu s patentnim zahtjevom 1, naznačeni time, da RCy predstavlja skupinu (C3-C8)cikloalkil.
3. Spojevi formule (I) u skladu bilo s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačeni time, da RCy predstavlja ciklopropilnu skupinu.
4. Spojevi formule (I) u skladu s patentnim zahtjevom 1, naznačeni time, da RCy predstavlja skupinu (C3-C8)cikloalkil-(C1-C6)alkil u kojoj je alkilna skupina ravna ili razgranana.
5. Spojevi formule (I) u skladu bilo s patentnim zahtjevom 1 ili patentnim zahtjevom 4, naznačeni time, da RCy predstavlja ciklopropilmetilnu skupinu.
6. Spojevi formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačeni time, da R1 predstavlja atom vodika ili atom halogena.
7. Spojevi formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačeni time, da R2 predstavlja atom vodika, atom halogena, metilnu skupinu, cijano skupinu ili karboksi skupinu.
8. Spojevi formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačeni time, da R3 predstavlja atom vodika, atom halogena ili metilnu skupinu.
9. Spojevi formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačeni time, da R4 predstavlja atom vodika ili atom halogena.
10. Spojevi formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačeni time, da dvije od skupina R1, R2, R3 i R4 ne predstavljaju atom vodika.
11. Spojevi formule (I) u skladu s patentnim zahtjevom 1, naznačeni time, da dvije od skupina R1, R2, R3 i R4 predstavljaju atom halogena, a RCy predstavlja ciklopropilnu skupinu.
12. Spojevi formule (I) u skladu s patentnim zahtjevom 1, naznačeni time, da su to spojevi:
• 6,7-diklor-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-klor-4-ciklopropil-6-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-bromo-4-ciklopropil-6-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-cijano-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-bromo-6-klor-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-5-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-bromo-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-5,7-difluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-fluoro-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-klor-4-ciklopropil-7-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-3,4-dihidro-6-metil-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-8-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-klor-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-bromo-4-ciklopropil-7-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-bromo-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-6,8-difluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-5,6-difluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-3,4-dihidro-7-metil-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-klor-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-3,4-dihidro-6-jodo-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6,7-diklor-4-(1-metil)ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropilmetil-7-fluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 6-karboksi-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 4-ciklopropil-7,8-difluoro-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 8-bromo-6-cijano-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid;
• 7-bromo-4-ciklopropil-3,4-dihidro-2H-1,2,4-benzotiadiazin 1,1-dioksid, te njihove adicijske soli s farmaceutski prihvatljivom kiselinom ili bazom.
13. Postupak za pripravu spojeva formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se kao početna tvar koristi spoj formule (II):
[image]
kod kojeg su RCy, R1, R2, R3 i R4 definirani jednako kao u patentnom zahtjevu 1,
koji se podvrgava cikliranju u nazočnosti spoja formule (III):
H-C(OR5)3 (III),
kod kojeg R5 predstavlja skupinu ravni ili razgranani (C1-C5)alkil, čime se dobiva spoj formule (IV):
[image]
kod kojeg su RCy, R1, R2, R3 i R4 definirani jednako kao u gornjem tekstu, koji se izlaže reakciji s redukcijskim sredstvom, čime se dobiva spoj formule (I), inačica priprave spojeva formule (I) koja uključuje uporabu konvencionalnih kemijskih reakcija nakon provedbe redukcije na spoju formule (IV) kako bi se naknadno promijenili supstituenti na benzenskom prstenu, koji spoj formule (I) može se pročistiti konvencionalnom tehnikom separacije, prema potrebi se prevede u svoje adicijske soli s farmaceutski prihvatljivom kiselinom ili bazom, a po potrebi se razdvaja u svoje izomere, ako postoje, konvencionalnom tehnikom separacije.
14. Postupak za pripravu spojeva formule (I) u skladu s patentnim zahtjevom 1, naznačen time, da se kao početna tvar koristi spoj formule (V):
[image]
kod kojeg su R1, R2, R3 i R4 definirani jednako kao u patentnom zahtjevu 1, koji se podvrgava cikliranju u nazočnosti spoja formule (III):
H-C(OR5)3 (III),
kod kojeg R5 predstavlja skupinu ravni ili razgranani (C1-C6)alkil, čime se dobiva spoj formule (VI):
[image]
kod kojeg su R1, R2, R3 i R4 definirani jednako kao u prethodnom tekstu, koji se izlaže reakciji sa spojem formule (VII):
Y-RCy (VII),
kod kojeg je RCy definiran jednako kao u prethodnom tekstu, a Y predstavlja odlazeću skupinu odabranu između atoma joda i broma i tosilatne, mesilatne i triflatne skupine, čime se dobiva spoj formule (IV):
[image]
kod kojeg su RCy, R1, R2, R3 i R4 definirani jednako kao u gornjem tekstu, koji se izlaže reakciji s redukcijskim sredstvom, čime se dobiva spoj formule (I), inačica priprave spojeva formule (I) koja uključuje uporabu konvencionalnih kemijskih reakcija nakon provedbe redukcije na spoju formule (IV) kako bi se naknadno promijenili supstituenti na benzenskom prstenu, koji spoj formule (I) može se pročistiti konvencionalnom tehnikom separacije, prema potrebi se prevede u svoje adicijske soli s farmaceutski prihvatljivom kiselinom ili bazom, a po potrebi se razdvaja u svoje izomere, ako postoje, konvencionalnom tehnikom separacije.
15. Spojevi formule (IV) u skladu s patentnim zahtjevom 13 ili 14:
[image]
kod kojih su RCy, R1, R2, R3 i R4 definirani jednako kao u patentnom zahtjevu 1, naznačeni time, da se koriste kao međuspojevi u sintezi spojeva formule (I).
16. Farmaceutski pripravak, naznačen time, da kao djelatnu tvar sadrži spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 12 u kombinaciji s jednim ili više inertnih, netoksičnih, farmaceutski prihvatljivih nosača.
17. Farmaceutski pripravci u skladu s patentnim zahtjevom 16, naznačeni time, da se koriste kao modulatori AMPA receptora.
18. Farmaceutski pripravci u skladu s patentnim zahtjevom 16, naznačeni time, da se koriste u liječenju ili prevenciji poremećaja pamćenja i kognitivnih poremećaja koji su povezani s dobi, sindromima tjeskobe ili depresije, progresivnim neurodegenerativnim bolestima, Alzheimerovom bolešću, Parkinsonovom bolešću, Pickovom bolešću, Huntingtonovom korejom, Korsakoffljevom bolešću, shizofrenijom, sekvelama akutnih neurodegenerativnih bolesti, frontotemporalnom demencijom i subkortikalnom demencijom, sekvelama ishemije i sekvelama epilepsije.
19. Uporaba spojeva formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačena time, da se ta uporaba odnosi na proizvodnju lijekova koji se koriste kao modulatori AMPA receptora.
20. Uporaba spojeva formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 12, naznačena time, da se ta uporaba odnosi na proizvodnju lijekova za liječenje ili prevenciju poremećaja pamćenja i kognitivnih poremećaja koji su povezani s dobi, sindromima tjeskobe ili depresije, progresivnim neurodegenerativnim bolestima, Alzheimerovom bolešću, Parkinsonovom bolešću, Pickovom bolešću, Huntingtonovom korejom, Korsakoffljevom bolešću, shizofrenijom, sekvelama akutnih neurodegenerativnih bolesti, frontotemporalnom demencijom i subkortikalnom demencijom, sekvelama ishemije i sekvelama epilepsije.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0803898A FR2933698A1 (fr) | 2008-07-09 | 2008-07-09 | Nouveaux derives de benzothiadiazines cycloalkylees, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
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| Publication Number | Publication Date |
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| HRP20100622T1 true HRP20100622T1 (hr) | 2010-12-31 |
| HRP20100622T8 HRP20100622T8 (hr) | 2011-01-31 |
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| Country | Link |
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| US (1) | US7741320B2 (hr) |
| EP (1) | EP2147915B1 (hr) |
| AR (1) | AR072486A1 (hr) |
| AT (1) | ATE481393T1 (hr) |
| AU (1) | AU2009202704B2 (hr) |
| CA (1) | CA2671236C (hr) |
| CY (1) | CY1110944T1 (hr) |
| DE (1) | DE602009000183D1 (hr) |
| DK (1) | DK2147915T3 (hr) |
| ES (1) | ES2352873T3 (hr) |
| FR (1) | FR2933698A1 (hr) |
| HR (1) | HRP20100622T8 (hr) |
| PL (1) | PL2147915T3 (hr) |
| PT (1) | PT2147915E (hr) |
| RS (1) | RS51518B (hr) |
| SI (1) | SI2147915T1 (hr) |
| TW (1) | TW201006805A (hr) |
| WO (1) | WO2010004139A1 (hr) |
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| LT6064B (lt) | 2012-10-15 | 2014-08-25 | Vilniaus Universitetas | Fluorinti benzensulfonamidai kaip karboanhidrazės inhibitoriai |
| CN105175284B (zh) * | 2015-07-21 | 2017-06-16 | 中国药科大学 | 酰胺类化合物、制备方法及其医药用途 |
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| FR2722502B1 (fr) | 1994-07-12 | 1996-08-23 | Adir | Nouveau derive de benzothiadiazine, son procede depreparation et les compositions pharmaceutiques qui le contiennent |
| HUP0101280A3 (en) | 1998-02-18 | 2003-02-28 | Neurosearch As | Positive ampa receptor modulator compounds and their use |
| DE19854096A1 (de) * | 1998-11-24 | 2000-05-25 | Merck Patent Gmbh | Anschlußträger für plattenförmige Mikrokomponenten |
| EP1436270A1 (en) * | 2001-10-10 | 2004-07-14 | Neurosearch A/S | Novel benzothiazine derivatives, their preparation and use |
-
2008
- 2008-07-09 FR FR0803898A patent/FR2933698A1/fr active Pending
-
2009
- 2009-07-03 AU AU2009202704A patent/AU2009202704B2/en not_active Ceased
- 2009-07-03 CA CA2671236A patent/CA2671236C/fr not_active Expired - Fee Related
- 2009-07-07 WO PCT/FR2009/000841 patent/WO2010004139A1/fr active Application Filing
- 2009-07-08 ES ES09290547T patent/ES2352873T3/es active Active
- 2009-07-08 AT AT09290547T patent/ATE481393T1/de active
- 2009-07-08 SI SI200930008T patent/SI2147915T1/sl unknown
- 2009-07-08 DE DE602009000183T patent/DE602009000183D1/de active Active
- 2009-07-08 PL PL09290547T patent/PL2147915T3/pl unknown
- 2009-07-08 PT PT09290547T patent/PT2147915E/pt unknown
- 2009-07-08 RS RSP-2010/0540A patent/RS51518B/en unknown
- 2009-07-08 DK DK09290547.0T patent/DK2147915T3/da active
- 2009-07-08 EP EP09290547A patent/EP2147915B1/fr active Active
- 2009-07-08 TW TW098123134A patent/TW201006805A/zh unknown
- 2009-07-08 AR ARP090102578A patent/AR072486A1/es unknown
- 2009-07-09 US US12/459,844 patent/US7741320B2/en not_active Expired - Fee Related
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2010
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- 2010-11-29 CY CY20101101087T patent/CY1110944T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| RS51518B (en) | 2011-06-30 |
| ES2352873T3 (es) | 2011-02-23 |
| AR072486A1 (es) | 2010-09-01 |
| ATE481393T1 (de) | 2010-10-15 |
| US20100009974A1 (en) | 2010-01-14 |
| WO2010004139A1 (fr) | 2010-01-14 |
| CY1110944T1 (el) | 2015-06-10 |
| FR2933698A1 (fr) | 2010-01-15 |
| PL2147915T3 (pl) | 2011-03-31 |
| PT2147915E (pt) | 2010-10-13 |
| CA2671236A1 (fr) | 2010-01-09 |
| AU2009202704B2 (en) | 2013-01-17 |
| US7741320B2 (en) | 2010-06-22 |
| EP2147915B1 (fr) | 2010-09-15 |
| SI2147915T1 (sl) | 2010-11-30 |
| AU2009202704A1 (en) | 2010-01-28 |
| EP2147915A1 (fr) | 2010-01-27 |
| HRP20100622T8 (hr) | 2011-01-31 |
| DK2147915T3 (da) | 2010-12-20 |
| DE602009000183D1 (de) | 2010-10-28 |
| CA2671236C (fr) | 2012-06-19 |
| TW201006805A (en) | 2010-02-16 |
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