HRP20120182T1 - Postupak za pripremu benzotiazepina iz gama-aminoalkilbenzena - Google Patents
Postupak za pripremu benzotiazepina iz gama-aminoalkilbenzena Download PDFInfo
- Publication number
- HRP20120182T1 HRP20120182T1 HR20120182T HRP20120182T HRP20120182T1 HR P20120182 T1 HRP20120182 T1 HR P20120182T1 HR 20120182 T HR20120182 T HR 20120182T HR P20120182 T HRP20120182 T HR P20120182T HR P20120182 T1 HRP20120182 T1 HR P20120182T1
- Authority
- HR
- Croatia
- Prior art keywords
- alkyl
- aryl
- formula
- heteroaryl
- cycloalkyl
- Prior art date
Links
- 150000007657 benzothiazepines Chemical class 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 32
- 238000000034 method Methods 0.000 claims abstract 32
- 125000003118 aryl group Chemical group 0.000 claims abstract 28
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract 26
- 229910052736 halogen Inorganic materials 0.000 claims abstract 25
- 150000002367 halogens Chemical class 0.000 claims abstract 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 24
- -1 oxo-substituted nitrogen Chemical class 0.000 claims abstract 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 16
- 125000000217 alkyl group Chemical group 0.000 claims abstract 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 14
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract 14
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 14
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 13
- 238000006243 chemical reaction Methods 0.000 claims abstract 13
- 229930195733 hydrocarbon Natural products 0.000 claims abstract 13
- 150000002430 hydrocarbons Chemical class 0.000 claims abstract 13
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims abstract 12
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract 12
- 239000002253 acid Substances 0.000 claims abstract 11
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract 11
- 125000001424 substituent group Chemical group 0.000 claims abstract 11
- 125000002252 acyl group Chemical group 0.000 claims abstract 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract 9
- SUBDEKBXSIKCSA-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1,4-benzothiazepine Chemical compound C1NCCSC2=CC=CC=C21 SUBDEKBXSIKCSA-UHFFFAOYSA-N 0.000 claims abstract 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 7
- 125000005075 adamantyloxy group Chemical group C12(CC3CC(CC(C1)C3)C2)O* 0.000 claims abstract 6
- 125000005336 allyloxy group Chemical group 0.000 claims abstract 6
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract 6
- 125000004104 aryloxy group Chemical group 0.000 claims abstract 2
- 125000002619 bicyclic group Chemical group 0.000 claims abstract 2
- 125000002950 monocyclic group Chemical group 0.000 claims abstract 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims 20
- 239000002585 base Substances 0.000 claims 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 8
- 229910052783 alkali metal Inorganic materials 0.000 claims 8
- 150000001340 alkali metals Chemical class 0.000 claims 8
- 150000002148 esters Chemical class 0.000 claims 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 5
- 230000010933 acylation Effects 0.000 claims 5
- 238000005917 acylation reaction Methods 0.000 claims 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 5
- 239000001257 hydrogen Substances 0.000 claims 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 5
- 125000005270 trialkylamine group Chemical group 0.000 claims 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 4
- 238000003776 cleavage reaction Methods 0.000 claims 4
- 150000004678 hydrides Chemical class 0.000 claims 4
- 229910052757 nitrogen Inorganic materials 0.000 claims 4
- 230000007017 scission Effects 0.000 claims 4
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims 4
- FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 238000010931 ester hydrolysis Methods 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 230000007062 hydrolysis Effects 0.000 claims 3
- 238000006460 hydrolysis reaction Methods 0.000 claims 3
- 230000020477 pH reduction Effects 0.000 claims 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 claims 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 2
- JUSXLWAFYVKNLT-UHFFFAOYSA-N 2-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1Br JUSXLWAFYVKNLT-UHFFFAOYSA-N 0.000 claims 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims 2
- VXSSDKLUAZVADY-UHFFFAOYSA-N 7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine Chemical compound S1CCNCC2=CC(OC)=CC=C21 VXSSDKLUAZVADY-UHFFFAOYSA-N 0.000 claims 2
- HWTDMFJYBAURQR-UHFFFAOYSA-N 80-82-0 Chemical compound OS(=O)(=O)C1=CC=CC=C1[N+]([O-])=O HWTDMFJYBAURQR-UHFFFAOYSA-N 0.000 claims 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 239000002841 Lewis acid Substances 0.000 claims 2
- 229930040373 Paraformaldehyde Natural products 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- 150000008065 acid anhydrides Chemical group 0.000 claims 2
- 125000004423 acyloxy group Chemical group 0.000 claims 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims 2
- 229940077388 benzenesulfonate Drugs 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims 2
- 150000001768 cations Chemical class 0.000 claims 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims 2
- 150000007517 lewis acids Chemical class 0.000 claims 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims 2
- 229920002866 paraformaldehyde Polymers 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 150000003573 thiols Chemical class 0.000 claims 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims 1
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 claims 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 claims 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims 1
- 150000008046 alkali metal hydrides Chemical class 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 229910000024 caesium carbonate Inorganic materials 0.000 claims 1
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 claims 1
- NXXGJRZWYCYPCB-HBWRTXEVSA-N dihydroresveratrol-3-O-beta-D-glucuronide Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC1=CC(O)=CC(CCC=2C=CC(O)=CC=2)=C1 NXXGJRZWYCYPCB-HBWRTXEVSA-N 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical group O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- 230000000269 nucleophilic effect Effects 0.000 claims 1
- 125000003431 oxalo group Chemical group 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 235000015320 potassium carbonate Nutrition 0.000 claims 1
- 235000011118 potassium hydroxide Nutrition 0.000 claims 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 claims 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- 229910000104 sodium hydride Inorganic materials 0.000 claims 1
- 235000011121 sodium hydroxide Nutrition 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims 1
- 125000005425 toluyl group Chemical group 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims 1
- 239000011592 zinc chloride Substances 0.000 claims 1
- 235000005074 zinc chloride Nutrition 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Postupak za pripremu 2,3,4,5-tetrahidro[1,4]benzotiazepina formule: koji uključuje reakciju [2-(acilaminoetil)tio]arena formules aldehidom formule R4CHO ili njegovim multimerom, te s kiselinom, naznačen time, da: Ar je monociklički, biciklički ili triciklički arilni ili heteroarilni prstenski sustav; R1, R2 i R4 svaki za sebe predstavlja H, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1-C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; R3 je (C1-C10)acil; P(O)R8R9, C(=O)-R10, C(=S)-R11, S(=O)2R12, (CH2)mR13, zaštitna skupina za dušik, OH, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil- cikloalkil, (C1-C6)alkilheterociklil ili (C1-C6)alkilheteroaril, a svaka od sljedećih skupina aril, cikloalkil, heterociklil i heteroaril po izboru supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; ili, zajedno, R2 i R3 tvore okso-supstituirani heterocikl koji sadrži dušik; R5 je u svakom od svojih pojavljivana neovisno odabran između sljedećeg: H, (C1-C20) ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil- cikloalkil, (C1-C6)alkil-heterociklil, (C1-C6)alkil-heteroaril, halogen, acil, SO3, -OR6, -SR6, - NR6aR6b, -N(R6)C(=O)OR7, N(R6)C(=O)R7, -C(=O)NR6aR6b, -C(=O) OR6, -C(=O)R6, -OC(=O)R6, - NO2, -CN, -(C1-C6)haloalkil, -O-(C1-C6)haloalkil, -N3 ili -P(O)R8R9, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; R10 i R11 svaki za sebe predstavlja H, -OR14, -NR6aR6b, NHNHR15, NHOH, CONH2NHR15, CO2R15, CONR15, halogen, alkoksi, ariloksi, aliloksi, benziloksi, supstituirani benziloksi, fluoroenilmetoksi, adamantiloksi, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkilheterociklil ili (C1-C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; R6, R6a, R6b, R7, R8, R9, R12, R14, R15, R16 i R17 svaki za sebe predstavlja u svakom od svojih pojavljivanja H, -OR15, -NR15R16, NHNHR16, NHOH, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1- C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je sup
Claims (28)
1. Postupak za pripremu 2,3,4,5-tetrahidro[1,4]benzotiazepina formule:
[image]
koji uključuje reakciju [2-(acilaminoetil)tio]arena formule
[image]
s aldehidom formule R4CHO ili njegovim multimerom, te s kiselinom, naznačen time, da:
Ar je monociklički, biciklički ili triciklički arilni ili heteroarilni prstenski sustav;
R1, R2 i R4 svaki za sebe predstavlja H, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1-C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil;
R3 je (C1-C10)acil; P(O)R8R9, C(=O)-R10, C(=S)-R11, S(=O)2R12, (CH2)mR13, zaštitna skupina za dušik, OH, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil- cikloalkil, (C1-C6)alkilheterociklil ili (C1-C6)alkilheteroaril, a svaka od sljedećih skupina aril, cikloalkil, heterociklil i heteroaril po izboru supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; ili, zajedno, R2 i R3 tvore okso-supstituirani heterocikl koji sadrži dušik;
R5 je u svakom od svojih pojavljivana neovisno odabran između sljedećeg: H, (C1-C20) ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil- cikloalkil, (C1-C6)alkil-heterociklil, (C1-C6)alkil-heteroaril, halogen, acil, SO3, -OR6, -SR6, - NR6aR6b, -N(R6)C(=O)OR7, N(R6)C(=O)R7, -C(=O)NR6aR6b, -C(=O) OR6, -C(=O)R6, -OC(=O)R6, - NO2, -CN, -(C1-C6)haloalkil, -O-(C1-C6)haloalkil, -N3 ili -P(O)R8R9, a svaka od sljedećih skupina:
aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil;
R10 i R11 svaki za sebe predstavlja H, -OR14, -NR6aR6b, NHNHR15, NHOH, CONH2NHR15, CO2R15, CONR15, halogen, alkoksi, ariloksi, aliloksi, benziloksi, supstituirani benziloksi, fluoroenilmetoksi, adamantiloksi, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkilheterociklil ili (C1-C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil;
R6, R6a, R6b, R7, R8, R9, R12, R14, R15, R16 i R17 svaki za sebe predstavlja u svakom od svojih pojavljivanja H, -OR15, -NR15R16, NHNHR16, NHOH, (C1-C20)ugljikovodik, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1- C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil, ili R6a i R6b, zajedno s dušikom na koji su spojeni, predstavljaju 5, 6, ili 7-eročlani prstenasti heterocikl koji sadrži dušik;
R13 je NH2, OH, -SO2R16, -NHSO2R16, C(=O)R17 NH(C=O)R17, -O(C=O)R17, ili -P(O)R8R9; m je cijeli broj u rasponu 1 - 10; a q je nula ili cijeli broj u rasponu 1 - 4, pod uvjetom da kada R5 je - C(=O)R6, R5 nije u orto položaju u odnosu na sumporni bočni lanac.
2. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da prvo [2-(acilaminoetil)tio]aren reagira s aldehidom ili njegovim multimerom i bazom, čime se dobiva [N- hidroksimetil-2-[acilaminoetil) tio]aren formule
[image]
zatim se [N-hidroksimetil-2-(acilaminoetil)tio]aren obrađuje s kiselinom, čime se dobiva 2,3,4,5-tetrahidro[1,4]benzotiazepin.
3. Postupak u skladu s patentnim zahtjevom 1 ili 2, naznačen time, da je baza hidrid, hidroksid ili karbonat alkalijskog metala, piridina ili trialkilamin.
4. Postupak u skladu s patentnim zahtjevom 1, 2 ili 3, naznačen time, da je kiselina sulfonska kiselina ili Lewisova kiselina, pri čemu je sulfonska kiselina odabrana iz skupine koju čine: toluensulfonska kiselina, benzensulfonska kiselina, metansulfonska kiselina, piridinij p-toluensulfonat i trifluormetansulfonska kiselina, a Lewisova kiselina odabrana je iz skupine koju čine: bor trifluorid eterat, titanijev tetraklorid, aluminijev klorid i cinkov klorid.
5. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time, da je aldehid ili njegov multimer formaldehid, paraformaldehid ili 1,3,5-trioksan.
6. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time, da:
R3 je acetil, benzoil, toluoil, benziloksikarbonil, t-butoksikarbonil, akriloil, oksalil ili -C(=O)N(R19)2, pri čemu je svaki od R19 vodik, alkil, aril, heterociklil, heteroaril, alkilaril, alkilheterociklil ili alkilheteroaril, ili zajedno, N(R19)2 predstavlja 5, 6, ili 7-eročlani prstenasti heterocikl koji sadrži dušik; ili
R5 je (C1-C4)ugljikovodik, halogen, -OR6, -SR6, -NO2, -CN, -(C1-C4)haloalkil ili -O-(C1-C4) haloalkil; i R6 je H ili (C1-C6)ugljikovodik; ili Ar je fenil; ili
zajedno, R2 i R3 tvore pirolidon, oksazolidinon ili piperidinon; ili R1, R2 i R4 su vodik.
7. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time, da q je 0 ili 1; R1, R2 i R4 su vodik;
R3 je (C1-C10)acil formule -C(=O)-R18, ili zaštitna skupina za dušik, pri čemu R18 je H, (C1-C6) alkil, (C1-C6)alkoksi, aliloksi, benziloksi, supstituirani benziloksi, fluorenilmetoksi ili adamantiloksi;
R5 je H, (C1-C4)ugljikovodik, halogen, -OR6, -SR6, -NO2, -CN, -(C1-C4)haloalkil ili -O-(C1-C4) haloalkil,
R6 je H ili (C1-C6)ugljikovodik; postupak dodatno uključuje konvertiranje spoja formule
[image]
u oksalatni spoj formule
[image]
u kojem M je H, amonij, alkalijski metal ili zemnoalkalijski metal.
8. Postupak u skladu s patentnim zahtjevom 7, naznačen time, da korak konverzije uključuje cijepanje skupine R3, čime se dobiva 2,3,4,5-tetrahidrobenzo[f][1,4]tiazepin formule:
[image]
acilaciju 2,3,4,5-tetrahidrobenzo[f][1,4]tiazepina s oksalatnim esterom; te hidrolizu estera.
9. Postupak u skladu s patentnim zahtjevom 8, naznačen time, da korak hidrolize uključuje obradu estera bazom hidrida, hidroksida ili karbonata alkalnog metala, piridina ili trialkilamin te, po izboru, kada M je H, zakiseljavanjem.
10. Postupak u skladu s patentnim zahtjevom 8 ili 9, naznačen time, da dodatno, kada M je H, uključuje konverziju oksalatnog spoja u njegovu sol, pri čemu je M kation poput Na+, Mg++, Ca++ ili amonij.
11. Postupak u skladu s patentnim zahtjevom 8, 9 ili 10, naznačen time, da q je 1 i R5 je OCH3 na položaju 7 benzotiazepinskog prstena, a spoj ima formulu
[image]
pri čemu M je vodik, amonij, alkalijski metal ili zemnoalkalijski metal.
12. Postupak u skladu s patentnim zahtjevom 11, naznačen time, da je posebno namijenjen pripremi spoja formule
[image]
u kojem [2-(acilaminoetil)tio]aren ima formulu
[image]
aldehid je paraformaldehid, a kiselina je toluensulfonska kiselina ili klorovodična kiselina, a reakcijom se dobiva CBZ-zaštićen benzotiazepin formule
[image]
a postupak dodatno obuhvaća:
cijepanje karbobenziloksi skupine kiselinom, čime se dobiva 7-metoksi-2,3,4,5- tetrahidrobenzo[f][1,4]tiazepin;
aciliranje 7-metoksi-2,3,4,5-tetrahidrobenzo[f][1,4]tiazepina metil klor-oksalatom; hidrolizu metil estera vodenom otopinom baze; zakiseljavanje kako bi se dobio kiselinski spoj; i po izboru, konvertiranje kiselinskog spoja u spoj formule
[image]
u kojem M je amonij, alkalijski metal ili zemnoalkalijski metal.
13. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da R3 je R3a, a 2,3,4,5- tetrahidro[1,4]benzotiazepin se priprema obradom [2-(acilaminoetil)tio]arena formule
[image]
s aldehidom formule R4CHO ili njegovim multimerom i kiselinom, čime se dobiva spoj formule
[image]
u kojem R3a je (C1-C10)acil formule -C(=O)-R18 ili zaštitna skupina za dušik, u kojoj R18 je H, (C1-C6) alkil, (C1-C6)alkoksi, aliloksi, benziloksi, supstituirani benziloksi, fluorenilmetoksi ili adamantiloksi.
14. Postupak u skladu s patentnim zahtjevom 13, naznačen time, da dodatno uključuje cijepanje R3a, čime se dobiva 4-nesupstituirani-2,3,4,5-tetrahidrobenzo[f][1,4]tiazepin formule
[image]
15. Postupak u skladu s patentnim zahtjevom 13 ili 14, naznačen time, da dodatno uključuje aciliranje 4-nesupstituirani-2,3,4,5-tetrahidrobenzo[f][1,4]tiazepina s R3X, čime se dobiva spoj formule
[image]
kod kojeg
R3 je (C1-C10)acil; P(O)R8R9, C(=O)-R10, C(=S)-R11, S(=O)2R12, (CH2)mR13, zaštitna skupina za dušik, OH, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1-C6)alkil-heteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; ili, zajedno, R2 i R3 tvore okso-supstituirani heterocikl koji sadrži dušik; i X je halogen, (C1-C10)aciloksi ili aktivirani ostatak estera.
16. Postupak u skladu s patentnim zahtjevom 15, naznačen time, da R3a je t-butoksikarbonil, benziloksikarbonil, supstituirani benziloksikarbonil ili fluorenilmetoksikarbonil; ili kada je R3X kiselinski klorid, kiselinski anhidrid, aktivirani ester, kloroformat ili karbamin-klorid.
17. Postupak u skladu s patentnim zahtjevom 13, naznačen time, da taj postupak dodatno uključuje obradu spoja formule
[image]
u kojem R3a je -C(=O)-R18, pri čemu R18 je (C1-C4)alkoksi, aliloksi, benziloksi, supstituirani benziloksi, fluorenilmetoksi ili adamantiloksi, s aminom formule HN(R19)2, pri čemu je svaki R19 vodik, alkil, aril, heterociklil, heteroaril, alkilaril, alkilheterociklil ili alkilheteroaril, ili zajedno, N(R19)2 predstavlja 5, 6, ili 7-eročlani prstenasti heterocikl koji sadrži dušik, čime se dobiva spoj formule:
[image]
18. Postupak u skladu s patentnim zahtjevom 13, naznačen time, da [2-(acilaminoetil) tio]arenski spoj ima formulu
[image]
i izlaže se reakciji s
(i) formaldehidom i kiselinom, čime se dobiva zaštićeni benzotiazepin formule:
[image]
(ii) formaldehidom i bazom, čime se dobiva [N-hidroksimetil-2-(acilaminoetil)tio]benzen formule:
[image]
i
[N-hidroksimetil-2-(acilaminoetil)tio]benzen dodatno reagira s kiselinom, čime se dobiva zaštićeni benzotiazepin formule
[image]
u kojem:
R3a je (C1-C10)acil formule -C(=O)-R18 ili zaštitna skupina za dušik;
R5a je H, (C1-C4)ugljikovodik, halogen, -OR6, -SR6, -NO2, -CN, -(C1-C4haloalkil ili -O-(C1-C4)haloalkil;
R6 je H ili (C1-C6)ugljikovodik; i
R18 je H, (C1-C6)alkil, (C1-C4)alkoksi, aliloksi, benziloksi, supstituirani benziloksi, fluorenilmetoksi ili adamantiloksi.
19. Postupak u skladu s patentnim zahtjevom 18, naznačen time, da dodatno uključuje korak cijepanja skupine R3a, čime se dobiva spoj formule
[image]
20. Postupak u skladu s patentnim zahtjevom 19, naznačen time, da dodatno uključuje korak aciliranja 4-nesupstituirani 2,3,4,5-tetrahidrobenzo[f][1,4]benzotiazeina s R3X, čime se dobiva spoj formule
[image]
u kojem
R3 je (C1-C10)acil; P(O)R8R9, C(=O)-R10, C(=S)-R11, S(=O)2R12, (CH2)mR13, zaštitna skupina za dušik, OH, (C1-C6)alkil, cikloalkil, aril, heterociklil, heteroaril, (C1-C6)alkil-aril, (C1-C6)alkil-cikloalkil, (C1-C6)alkil-heterociklil ili (C1-C6)alkilheteroaril, a svaka od sljedećih skupina: aril, cikloalkil, heterociklil i heteroaril po izboru je supstituirana s jednim do tri supstituenta neovisno odabranih iz skupine koju čine: halogen, alkil, alkoksil, nitro, cijano i haloalkil; i X je halogen, (C1-C10)aciloksi ili aktivirani ostatak estera.
21. Postupak u skladu s patentnim zahtjevom 18, naznačen time, da dodatno uključuje reakciju 4-nesupstituirani-2,3,4,5-tetrahidrobenzo[f][1,4]tiazepina sa spojem formule X-CH2-COOR’, u kojem je X halogen i R’ je alkil, čime se dobiva esterni spoj formule:
[image]
te hidrolizu estera, čime se dobiva spoj formule:
[image]
22. Postupak u skladu s patentnim zahtjevom 18, naznačen time, da dodatno uključuje konverziju
[image]
u
[image]
u kojem M je H, amonij, alkalijski metal ili zemnoalkalijski metal.
23. Postupak u skladu s patentnim zahtjevom 22, naznačen time, da:
konverzija se obavlja cijepanjem skupine R3a, čime se dobiva 2,3,4,5-tetrahidrobenzo [f][1,4]tiazepin, aciliranjem 2,3,4,5-tetrahidrobenzo[f][1,4]tiazepina oksalatnim esterom i hidrolizom estera; i/ili korak hidrolize uključuje obradu estera bazom i, po izboru, kada M je H, zakiseljavanje, pri čemu je baza hidrid, hidroksid ili karbonat alkalijskog metala, piridina ili trialkilamin, te po izboru konverziju dobivenog proizvoda, kada M je H, u njegovu sol, pri čemu M je kation.
24. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da dodatno uključuje pripravu [2-(acilaminoetil)tio]arena reakcijom spoja formule
[image]
sa spojem formule
[image]
čime se dobiva spoj formule
[image]
po izboru u prisutnosti baze, nakon čega slijedi reakcija sa spojem formule R3X, pri čemu LG je odlazeća skupina u nukleofilnoj supstituciji tiolom, a X je odlazeća skupina u nukleofilnoj supstituciji aminom.
25. Postupak u skladu s patentnim zahtjevom 24, naznačen time, da LG je halogen ili sulfonat, baza je hidrid, hidroksid ili karbonat alkalijskog metala, piridina ili trialkilamin, a R3X je kiselinski klorid, kiselinski anhidrid, aktivirani ester, kloroformat ili karbamin-klorid; pri čemu je sulfonat odabran iz skupine koju čine: metansulfonat, toluensulfonat, benzensulfonat, trifluormetansulfonat, nitrofenilsulfonat i bromofenilsulfonat, a halogen je odabran iz skupine koju čine: kloro, jodo i bromo.
26. Postupak u skladu s patentnim zahtjevom 1, naznačen time, da se [2-(acilaminoetil)tio]aren priprema:
reakcijom spoja formule
[image]
sa spojem formule
[image]
po izboru u prisutnosti baze, pri čemu je LG odlazeća skupina u nukleofilnoj supstituciji tiolom.
27. Postupak u skladu s patentnim zahtjevom 26, naznačen time, da LG je halogen ili sulfonat, a baza je hidrid, hidroksid ili karbonat alkalijskog metala, piridina ili trialkilamin, pri čemu je sulfonat odabran iz skupine koju čine: metansulfonat, toluensulfonat, benzensulfonat, trifluormetansulfonat, nitrofenilsulfonat i bromofenilsulfonat, a halogen je odabran iz skupine koju čine: kloro, jodo i bromo.
28. Postupak u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time, da je baza NaH, NaOH, KOH, Na2CO3, K2CO3, Cs2CO3, Et3N ili (iPr)2NEt.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3319708P | 2008-03-03 | 2008-03-03 | |
| PCT/US2009/035863 WO2009111463A1 (en) | 2008-03-03 | 2009-03-03 | Process for preparing benzothiazepines from gamma-aminoalkylbenzenes |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20120182T1 true HRP20120182T1 (hr) | 2012-03-31 |
Family
ID=40585577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20120182T HRP20120182T1 (hr) | 2008-03-03 | 2012-02-24 | Postupak za pripremu benzotiazepina iz gama-aminoalkilbenzena |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US8618282B2 (hr) |
| EP (1) | EP2250159B1 (hr) |
| JP (1) | JP5458025B2 (hr) |
| KR (1) | KR101260859B1 (hr) |
| CN (1) | CN101977902B (hr) |
| AR (1) | AR071282A1 (hr) |
| AT (1) | ATE536348T1 (hr) |
| AU (1) | AU2009221969B2 (hr) |
| BR (1) | BRPI0908570A2 (hr) |
| CA (1) | CA2717523C (hr) |
| CY (1) | CY1112538T1 (hr) |
| DK (1) | DK2250159T3 (hr) |
| EA (2) | EA020602B9 (hr) |
| ES (1) | ES2378871T3 (hr) |
| HK (1) | HK1154006A1 (hr) |
| HR (1) | HRP20120182T1 (hr) |
| IL (1) | IL207651A (hr) |
| ME (1) | ME01989B (hr) |
| MX (1) | MX2010009608A (hr) |
| NZ (1) | NZ587767A (hr) |
| PL (1) | PL2250159T3 (hr) |
| PT (1) | PT2250159E (hr) |
| RS (1) | RS52172B (hr) |
| SI (1) | SI2250159T1 (hr) |
| WO (1) | WO2009111463A1 (hr) |
| ZA (1) | ZA201005956B (hr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8710045B2 (en) * | 2004-01-22 | 2014-04-29 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the ryanodine receptors |
| EP2708535A1 (en) | 2012-05-11 | 2014-03-19 | Les Laboratoires Servier | Agents for treating disorders involving modulation of ryanodine receptors |
| CN108530385B (zh) * | 2018-07-16 | 2019-10-01 | 青岛科技大学 | 一种1,3-苯并硫氮杂*类化合物的制备方法 |
| US11504383B2 (en) | 2021-01-08 | 2022-11-22 | Armgo Pharma, Inc. | Crystalline forms of a Ryanodine receptor modulator and uses thereof |
| US11717526B2 (en) | 2021-05-20 | 2023-08-08 | Armgo Pharma, Inc. | Pharmaceutical compositions comprising a ryanodine receptor modulator and uses thereof |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2703408B2 (ja) * | 1990-12-28 | 1998-01-26 | 麒麟麦酒株式会社 | １，４‐ベンゾチアゼピン誘導体 |
| ATE163927T1 (de) | 1992-11-09 | 1998-03-15 | Knoll Ag | 1,4-benzothiazepine verwendbar als neurologische mittel |
| IL108634A0 (en) * | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions containing them |
| GB9616279D0 (en) * | 1996-08-02 | 1996-09-11 | Knoll Ag | Chemical process |
| US20040229781A1 (en) * | 2000-05-10 | 2004-11-18 | Marks Andrew Robert | Compounds and methods for treating and preventing exercise-induced cardiac arrhythmias |
| US7718644B2 (en) * | 2004-01-22 | 2010-05-18 | The Trustees Of Columbia University In The City Of New York | Anti-arrhythmic and heart failure drugs that target the leak in the ryanodine receptor (RyR2) and uses thereof |
| US7879840B2 (en) * | 2005-08-25 | 2011-02-01 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US8022058B2 (en) | 2000-05-10 | 2011-09-20 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| US7704990B2 (en) | 2005-08-25 | 2010-04-27 | The Trustees Of Columbia University In The City Of New York | Agents for preventing and treating disorders involving modulation of the RyR receptors |
-
2009
- 2009-03-03 ES ES09718412T patent/ES2378871T3/es active Active
- 2009-03-03 AU AU2009221969A patent/AU2009221969B2/en active Active
- 2009-03-03 AT AT09718412T patent/ATE536348T1/de active
- 2009-03-03 WO PCT/US2009/035863 patent/WO2009111463A1/en active Application Filing
- 2009-03-03 DK DK09718412.1T patent/DK2250159T3/da active
- 2009-03-03 CN CN2009801079022A patent/CN101977902B/zh active Active
- 2009-03-03 US US12/397,212 patent/US8618282B2/en active Active
- 2009-03-03 SI SI200930194T patent/SI2250159T1/sl unknown
- 2009-03-03 PT PT09718412T patent/PT2250159E/pt unknown
- 2009-03-03 JP JP2010549813A patent/JP5458025B2/ja active Active
- 2009-03-03 BR BRPI0908570-0A patent/BRPI0908570A2/pt not_active Application Discontinuation
- 2009-03-03 EP EP09718412A patent/EP2250159B1/en active Active
- 2009-03-03 NZ NZ587767A patent/NZ587767A/en unknown
- 2009-03-03 KR KR1020107022040A patent/KR101260859B1/ko active IP Right Grant
- 2009-03-03 EA EA201001406A patent/EA020602B9/ru not_active IP Right Cessation
- 2009-03-03 RS RS20120066A patent/RS52172B/en unknown
- 2009-03-03 ME MEP-2012-160A patent/ME01989B/me unknown
- 2009-03-03 CA CA2717523A patent/CA2717523C/en active Active
- 2009-03-03 EA EA201400570A patent/EA028108B1/ru not_active IP Right Cessation
- 2009-03-03 PL PL09718412T patent/PL2250159T3/pl unknown
- 2009-03-03 MX MX2010009608A patent/MX2010009608A/es active IP Right Grant
- 2009-03-04 AR ARP090100751A patent/AR071282A1/es active IP Right Grant
-
2010
- 2010-08-17 IL IL207651A patent/IL207651A/en active IP Right Grant
- 2010-08-20 ZA ZA2010/05956A patent/ZA201005956B/en unknown
-
2011
- 2011-08-09 HK HK11108313.0A patent/HK1154006A1/xx not_active IP Right Cessation
-
2012
- 2012-02-21 CY CY20121100178T patent/CY1112538T1/el unknown
- 2012-02-24 HR HR20120182T patent/HRP20120182T1/hr unknown
-
2013
- 2013-12-23 US US14/138,893 patent/US9573914B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20120182T1 (hr) | Postupak za pripremu benzotiazepina iz gama-aminoalkilbenzena | |
| KR900003496B1 (ko) | 티에닐 축합 피라졸 유도체의 제조방법 | |
| AU2009303335A1 (en) | Activators of human pyruvate kinase | |
| CA2636992A1 (en) | Thiophenyl and pyrrolyl azepines as serotonin 5-ht2c receptor ligands and uses thereof | |
| WO1998008850A1 (en) | Spirocyclic metalloprotease inhibitors | |
| TW201904975A (zh) | 1,3-苯并二氧雜環戊烯雜環化合物之製備方法 | |
| CN105555781A (zh) | 喹唑啉衍生物和其作为dna甲基转移酶抑制剂的用途 | |
| ES2445024T3 (es) | Un procedimiento de tionación y un agente de tionación | |
| ES2361330T3 (es) | Procedimiento para la preparación de tolterodina. | |
| ES2294652T3 (es) | Procedimiento de sintesis de derivados de 1,3-dihidro-2h-3-benzacepin-2-ona y su aplicacion en la sintesis de ivabradina y de sus sales de adicion de un acido farmaceuticamente aceptable. | |
| KR101564401B1 (ko) | 브린졸아마이드의 제조방법 | |
| JP6594351B2 (ja) | 新規中間体を含むアルキル化アリールピペラジン及びアルキル化アリールピペリジン化合物の製造方法 | |
| US3249603A (en) | Novel pyrimidine sulfanilamides and processes for their preparation | |
| KR860001338B1 (ko) | 4-아로일이미다졸-2-온의 제조방법 | |
| HRP20090514T1 (hr) | Novi postupak dobivanja kvaternih kiselih i amonijevih soli | |
| FR2864079B1 (fr) | Nouveaux intermediaires de syntheses de la (r)-tamsulosine et de ses sels pharmaceutiquement acceptables et procede pour leur preparation | |
| RU2550694C2 (ru) | Синтез замещенных производных пиразолин карбоксамидина | |
| NO742586L (hr) | ||
| ITMI20111135A1 (it) | Procedimento per la preparazione di apixaban |