IL135375A - History of dihydro and tetrahydroisoquinoline - Google Patents
History of dihydro and tetrahydroisoquinolineInfo
- Publication number
- IL135375A IL135375A IL13537596A IL13537596A IL135375A IL 135375 A IL135375 A IL 135375A IL 13537596 A IL13537596 A IL 13537596A IL 13537596 A IL13537596 A IL 13537596A IL 135375 A IL135375 A IL 135375A
- Authority
- IL
- Israel
- Prior art keywords
- biphenyl
- carboxylic acid
- trifluoromethyl
- amide
- tetrahydroisoquinolin
- Prior art date
Links
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 title description 3
- IOEPOEDBBPRAEI-UHFFFAOYSA-N 1,2-dihydroisoquinoline Chemical compound C1=CC=C2CNC=CC2=C1 IOEPOEDBBPRAEI-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 117
- -1 nitro, amino Chemical group 0.000 claims abstract description 81
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
- AKMALXRXYAFPLL-UHFFFAOYSA-N tert-butyl 6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AKMALXRXYAFPLL-UHFFFAOYSA-N 0.000 claims description 3
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- 239000002904 solvent Substances 0.000 description 52
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- 238000000034 method Methods 0.000 description 40
- 239000000243 solution Substances 0.000 description 40
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- IQOMYCGTGFGDFN-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C(F)(F)F)C=C1 IQOMYCGTGFGDFN-UHFFFAOYSA-N 0.000 description 36
- 239000002253 acid Substances 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 35
- 150000003254 radicals Chemical class 0.000 description 31
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 29
- 239000007787 solid Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 21
- 229910052799 carbon Inorganic materials 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 description 16
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 16
- 150000003839 salts Chemical class 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 230000028327 secretion Effects 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 10
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000002502 liposome Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 201000001320 Atherosclerosis Diseases 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 238000012546 transfer Methods 0.000 description 8
- 101150102415 Apob gene Proteins 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 208000008589 Obesity Diseases 0.000 description 7
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 7
- 229930006000 Sucrose Natural products 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000012131 assay buffer Substances 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 150000002009 diols Chemical class 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 235000020824 obesity Nutrition 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 229940086542 triethylamine Drugs 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 229940098773 bovine serum albumin Drugs 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 229940124530 sulfonamide Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 6
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- CKXXWBQEZGLFMV-UHFFFAOYSA-N 2-(carboxymethyl)-4-nitrobenzoic acid Chemical compound OC(=O)CC1=CC([N+]([O-])=O)=CC=C1C(O)=O CKXXWBQEZGLFMV-UHFFFAOYSA-N 0.000 description 5
- 102000018616 Apolipoproteins B Human genes 0.000 description 5
- 108010027006 Apolipoproteins B Proteins 0.000 description 5
- 206010033645 Pancreatitis Diseases 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 150000001540 azides Chemical class 0.000 description 5
- 125000002837 carbocyclic group Chemical group 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 5
- 125000000743 hydrocarbylene group Chemical group 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 150000003456 sulfonamides Chemical class 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- LPWHGVILSZJCQD-UHFFFAOYSA-N 2-(1,3-dimethoxy-1,3-dioxopropan-2-yl)-4-nitrobenzoic acid Chemical compound COC(=O)C(C(=O)OC)C1=CC([N+]([O-])=O)=CC=C1C(O)=O LPWHGVILSZJCQD-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 208000006575 hypertriglyceridemia Diseases 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- 125000005647 linker group Chemical group 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000003228 microsomal effect Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- XOYOWXXIKWPXFC-UHFFFAOYSA-N n-(1,2,3,4-tetrahydroisoquinolin-6-yl)-2-[4-(trifluoromethyl)phenyl]benzamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(CNCC2)C2=C1 XOYOWXXIKWPXFC-UHFFFAOYSA-N 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 229910052717 sulfur Chemical group 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 150000003585 thioureas Chemical class 0.000 description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 4
- 229920002554 vinyl polymer Polymers 0.000 description 4
- 125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 description 3
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 3
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000013877 carbamide Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000008282 halocarbons Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 3
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
- 229920000137 polyphosphoric acid Polymers 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- RVAPXPOTRYDTJS-UHFFFAOYSA-N tert-butyl 7-bromo-6-nitro-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound [O-][N+](=O)C1=C(Br)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 RVAPXPOTRYDTJS-UHFFFAOYSA-N 0.000 description 3
- 125000000335 thiazolyl group Chemical group 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 2
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 2
- IUWPMHYAMOUYKQ-UHFFFAOYSA-N 2-(4-bromophenyl)ethylazanium;bromide Chemical compound [Br-].[NH3+]CCC1=CC=C(Br)C=C1 IUWPMHYAMOUYKQ-UHFFFAOYSA-N 0.000 description 2
- SYBKBPXOVQYFFA-UHFFFAOYSA-N 2-[2-(hydroxymethyl)-5-nitrophenyl]ethanol Chemical compound OCCC1=CC([N+]([O-])=O)=CC=C1CO SYBKBPXOVQYFFA-UHFFFAOYSA-N 0.000 description 2
- UALJVGZBTOOZQQ-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]-n-[2-[(2,6,6-trimethylcyclohex-2-en-1-yl)methyl]-3,4-dihydro-1h-isoquinolin-6-yl]benzamide Chemical compound CC1=CCCC(C)(C)C1CN1CC2=CC=C(NC(=O)C=3C(=CC=CC=3)C=3C=CC(=CC=3)C(F)(F)F)C=C2CC1 UALJVGZBTOOZQQ-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 1
- 229940117972 triolein Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/06—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IB1995/000448 WO1996040640A1 (fr) | 1995-06-07 | 1995-06-07 | DERIVES DE BIPHENYL-2-ACIDE CARBOXYLIQUE-TETRAHYDRO-ISOQUINOLEINE-6-YL AMIDES, PREPARATION DE CES AMIDES ET UTILISATION EN TANT QU'INHIBITEURS DE LA PROTEINE DE TRANSFERT DE TRIGLYCERIDE MICROSOMAL ET/OU DE LA SECRETION D'APOLIPOPROTEINES B (Apo B) |
| IL11848496A IL118484A (en) | 1995-06-07 | 1996-05-30 | Trifluoromethyl-biphenyl carboxylic acid amides, uses thereof and pharmaceutical compositions containing them |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL135375A0 IL135375A0 (en) | 2001-05-20 |
| IL135375A true IL135375A (en) | 2001-07-24 |
Family
ID=11004342
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13537796A IL135377A (en) | 1995-06-07 | 1996-05-30 | Pharmaceutical preparations containing substances that lower fat content and MTP inhibitors |
| IL13537596A IL135375A (en) | 1995-06-07 | 1996-05-30 | History of dihydro and tetrahydroisoquinoline |
| IL13537696A IL135376A0 (en) | 1995-06-07 | 1996-05-30 | Hydroxyalkyl-phenyl derivatives |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13537796A IL135377A (en) | 1995-06-07 | 1996-05-30 | Pharmaceutical preparations containing substances that lower fat content and MTP inhibitors |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13537696A IL135376A0 (en) | 1995-06-07 | 1996-05-30 | Hydroxyalkyl-phenyl derivatives |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5919795A (fr) |
| KR (1) | KR100225713B1 (fr) |
| AR (1) | AR003424A1 (fr) |
| AT (1) | ATE233734T1 (fr) |
| AU (1) | AU703493B2 (fr) |
| BG (1) | BG62442B1 (fr) |
| CO (1) | CO4440626A1 (fr) |
| DE (1) | DE69529849T2 (fr) |
| DK (1) | DK0832069T3 (fr) |
| DZ (1) | DZ2045A1 (fr) |
| IL (3) | IL135377A (fr) |
| MA (1) | MA23895A1 (fr) |
| MX (1) | MX9709914A (fr) |
| OA (1) | OA10363A (fr) |
| RO (1) | RO116897B1 (fr) |
| RU (1) | RU2141478C1 (fr) |
| TN (1) | TNSN96085A1 (fr) |
| TR (1) | TR199600481A2 (fr) |
| TW (1) | TW476756B (fr) |
| YU (1) | YU35296A (fr) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1216988A (zh) * | 1996-04-30 | 1999-05-19 | 辉瑞大药厂 | 4'-三氟甲基联苯基-2-羧酸[2-(2h-[1,2,4]三唑-3-基甲基)-1,2,3,4-四氢-异喹啉-6-苯]酰胺的制备方法和用于制备它们的中间体 |
| JP2959765B2 (ja) | 1997-12-12 | 1999-10-06 | 日本たばこ産業株式会社 | 3−ピペリジル−4−オキソキナゾリン誘導体及びそれを含有してなる医薬組成物 |
| CA2325358C (fr) | 1999-11-10 | 2005-08-02 | Pfizer Products Inc. | Amides de l'acide 7-¬(4'-trifluoromethylbiphenyl-2-carbonyl)amino|-quinoleine-3-carboxylique et methodes pour inhiber la secretion d'apolipoproteine b |
| EP1259484B1 (fr) * | 2000-01-18 | 2005-05-18 | Novartis AG | Carboxamides utilises comme inhibiteurs de proteine de transfert triglyceridique microsomique et de la secretion d'apolipoproteine b |
| DE10023484A1 (de) * | 2000-05-09 | 2001-11-22 | Schering Ag | Anthranylamide und deren Verwendung als Arzneimittel |
| JO2654B1 (en) * | 2000-09-04 | 2012-06-17 | شركة جانسين فارماسوتيكا ان. في | Multiple aryl caroxa amides are useful as lipid - lowering agents |
| JO2409B1 (en) * | 2000-11-21 | 2007-06-17 | شركة جانسين فارماسوتيكا ان. في | Second-phenyl carboxy amides are useful as lipid-lowering agents |
| US6953671B2 (en) * | 2001-02-23 | 2005-10-11 | The Trustees Of Columbia University In The City Of New York | Plasma phospholipid transfer protein (PLTP) deficiency represents an anti-atherogenic state and PLTP inhibitor has anti-atherosclerosis action |
| RS50712B (sr) * | 2001-06-28 | 2010-06-30 | Pfizer Products Inc. | Triamid-supstituisani indoli, benzofurani i benzotiofeni kao inhibitori mikrozomalnog triglicerid transfer proteina (mtp) i/ili sekrecije apolipoproteina b (apo b) |
| US7012077B2 (en) * | 2001-12-20 | 2006-03-14 | Hoffmann-La Roche Inc. | Substituted cyclohexane derivatives |
| US7241774B2 (en) * | 2002-03-13 | 2007-07-10 | University Of Tennessee Research Foundation | Substituted tetrahydroisoquinoline compounds, methods of making, and their use |
| JP2007512359A (ja) | 2003-11-19 | 2007-05-17 | メタバシス・セラピューティクス・インコーポレイテッド | 新規なリン含有甲状腺ホルモン様物質 |
| WO2005051945A1 (fr) * | 2003-11-20 | 2005-06-09 | Eli Lilly And Company | Composes heterocycliques utilises comme modulateurs des recepteurs actives proliferateurs du peroxysome (ppar), utiles dans le traitement et/ou la prevention de troubles modules par un ppar |
| WO2005080373A1 (fr) * | 2004-02-04 | 2005-09-01 | Pfizer Products Inc. | Composes de quinoline substitues |
| US7262318B2 (en) * | 2004-03-10 | 2007-08-28 | Pfizer, Inc. | Substituted heteroaryl- and phenylsulfamoyl compounds |
| US20050288340A1 (en) * | 2004-06-29 | 2005-12-29 | Pfizer Inc | Substituted heteroaryl- and phenylsulfamoyl compounds |
| JP2006249022A (ja) | 2005-03-11 | 2006-09-21 | Sumitomo Chemical Co Ltd | 4−(2−メチルフェニル)ベンゾトリフルオライドの製造方法 |
| US8980915B2 (en) * | 2005-04-19 | 2015-03-17 | Surface Logix, Inc. | Inhibitors of microsomal triglyceride transfer protein and apo-B secretion |
| CA2609783A1 (fr) * | 2005-05-27 | 2006-12-07 | Pfizer Products Inc. | Polytherapie pour le traitement de l'obesite ou le maintien du poids apres une perte ponderale |
| ES2569558T3 (es) * | 2006-04-03 | 2016-05-11 | Roche Innovation Center Copenhagen A/S | Composición farmacéutica que comprende oligonucleótidos antisentido anti-ARNmi |
| MX2008012219A (es) | 2006-04-03 | 2008-10-02 | Santaris Pharma As | Composicion farmaceutica que comprende oligonucleotidos antisentido anti-miarn. |
| GB0619176D0 (en) * | 2006-09-29 | 2006-11-08 | Lectus Therapeutics Ltd | Ion channel modulators & uses thereof |
| CA2666191C (fr) * | 2006-10-09 | 2017-07-11 | Santaris Pharma A/S | Composes antagonistes de l'arn pour la modulation de pcsk9 |
| US20100210633A1 (en) * | 2006-10-12 | 2010-08-19 | Epix Delaware, Inc. | Carboxamide compounds and their use |
| WO2008113832A2 (fr) * | 2007-03-22 | 2008-09-25 | Santaris Pharma A/S | Composés arn antagonistes courts pour la modulation de l'arnm cible |
| US8470791B2 (en) * | 2007-03-22 | 2013-06-25 | Santaris Pharma A/S | RNA antagonist compounds for the inhibition of Apo-B100 expression |
| EP2198024A2 (fr) * | 2007-08-30 | 2010-06-23 | Santaris Pharma A/S | Composes antagonistes d'arn permettant la modulation de fabp4/ap2 |
| AU2008306327B2 (en) * | 2007-10-04 | 2014-05-15 | Roche Innovation Center Copenhagen A/S | Micromirs |
| US8569282B2 (en) | 2007-12-11 | 2013-10-29 | Cytopathfinder, Inc. | Carboxamide compounds and their use |
| US8404659B2 (en) * | 2008-03-07 | 2013-03-26 | Santaris Pharma A/S | Pharmaceutical compositions for treatment of MicroRNA related diseases |
| ES2541442T3 (es) | 2008-08-01 | 2015-07-20 | Roche Innovation Center Copenhagen A/S | Modulación mediada por microARN de factores estimulantes de colonias |
| CA2741153A1 (fr) * | 2008-10-29 | 2010-05-06 | F. Hoffmann-La Roche Ag | Nouveaux derives d'amides phenyliques ou d'amides pyridyliques et leur utilisation en tant agonistes de gpbar1 |
| WO2010093601A1 (fr) | 2009-02-10 | 2010-08-19 | Metabasis Therapeutics, Inc. | Nouveaux thyromimetiques contenant de l'acide sulfonique et methodes d'utilisation associees |
| WO2010122538A1 (fr) * | 2009-04-24 | 2010-10-28 | Santaris Pharma A/S | Compositions pharmaceutiques pour le traitement de patients souffrant du vhc ne réagissant pas aux interférons |
| WO2010127208A1 (fr) * | 2009-04-30 | 2010-11-04 | Forest Laboratories Holdings Limited | Inhibiteurs de l'acétyl-coa carboxylase |
| WO2010127212A1 (fr) * | 2009-04-30 | 2010-11-04 | Forest Laboratories Holdings Limited | Inhibiteurs de l'acétyl-coa carboxylase |
| EP2456870A1 (fr) | 2009-07-21 | 2012-05-30 | Santaris Pharma A/S | Oligomères anti-sens ciblant pcsk9 |
| CA2817093A1 (fr) * | 2010-11-15 | 2012-05-24 | Abbvie Inc. | Inhibiteurs de nampt |
| MX391977B (es) | 2013-06-27 | 2025-03-21 | Roche Innovation Ct Copenhagen As | Oligómeros antisentido y conjugados con diana en la proteína-convertasa subtilisina/kexina tipo 9(pcsk9). |
| US12453728B1 (en) | 2024-08-08 | 2025-10-28 | Redux Therapeutics, Llc | Compositions comprising inhibitors of microsomal triglyceride transfer protein and Apo-B secretion |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4022900A (en) * | 1970-09-09 | 1977-05-10 | Marion Laboratories, Inc. | Compositions containing 1,2,3,4-tetrahydroisoquinolines used as hypotensive agents |
| US3905982A (en) * | 1973-07-23 | 1975-09-16 | Searle & Co | 1-Aryl-n-dialkylaminoalkyl-3,4-dihydro-2(1H)-isoquinolinecarboxamides and related compounds |
| JPS5237048B2 (fr) * | 1973-08-18 | 1977-09-20 | ||
| HU174697B (hu) * | 1976-12-30 | 1980-03-28 | Chinoin Gyogyszer Es Vegyeszet | Sposob poluchenija novykh proizvodnykh 6,7-dimetoksi-1,2,3,4-tetragidro-1-izokinolin-acetamida |
| DE3377709D1 (en) * | 1982-09-10 | 1988-09-22 | Wellcome Found | Benzoic acid derivatives |
| DK8386A (da) * | 1986-01-15 | 1987-07-09 | Tpo Pharmachim | Nye n-substituerede 1-benzyl-2-carbamoyltetrahydroisoquinoliner og fremgangsmaade til fremstilling af samme |
| DE3734385A1 (de) * | 1987-10-10 | 1989-04-20 | Hoechst Ag | Verwendung der (alpha)-modifikation von cis-naphthoylen-bis-benzimidazol zum pigmentieren von polyolefinen |
| GB9127306D0 (en) * | 1991-12-23 | 1992-02-19 | Boots Co Plc | Therapeutic agents |
| US5595872A (en) * | 1992-03-06 | 1997-01-21 | Bristol-Myers Squibb Company | Nucleic acids encoding microsomal trigyceride transfer protein |
| US5246943A (en) * | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
| IL110172A (en) * | 1993-07-22 | 2001-10-31 | Lilly Co Eli | Bicyclic compounds and pharmaceutical compositions containing them |
| US5731324A (en) * | 1993-07-22 | 1998-03-24 | Eli Lilly And Company | Glycoprotein IIb/IIIa antagonists |
| EP0944602A1 (fr) * | 1996-11-27 | 1999-09-29 | Pfizer Inc. | Amides inhibant la secretion d'apo b et/ou la proteine mtp |
-
1995
- 1995-06-07 DK DK95918722T patent/DK0832069T3/da active
- 1995-06-07 AT AT95918722T patent/ATE233734T1/de not_active IP Right Cessation
- 1995-06-07 US US08/952,507 patent/US5919795A/en not_active Expired - Fee Related
- 1995-06-07 DE DE69529849T patent/DE69529849T2/de not_active Expired - Fee Related
- 1995-06-07 MX MX9709914A patent/MX9709914A/es not_active IP Right Cessation
-
1996
- 1996-04-19 TW TW085104696A patent/TW476756B/zh not_active IP Right Cessation
- 1996-05-30 IL IL13537796A patent/IL135377A/en not_active IP Right Cessation
- 1996-05-30 IL IL13537596A patent/IL135375A/en not_active IP Right Cessation
- 1996-05-30 IL IL13537696A patent/IL135376A0/xx not_active IP Right Cessation
- 1996-06-03 AR ARP960102871A patent/AR003424A1/es unknown
- 1996-06-05 DZ DZ960089A patent/DZ2045A1/fr active
- 1996-06-05 KR KR1019960020168A patent/KR100225713B1/ko not_active Expired - Fee Related
- 1996-06-05 BG BG100637A patent/BG62442B1/bg unknown
- 1996-06-06 RU RU96111018A patent/RU2141478C1/ru not_active IP Right Cessation
- 1996-06-06 AU AU54784/96A patent/AU703493B2/en not_active Ceased
- 1996-06-06 TN TNTNSN96085A patent/TNSN96085A1/fr unknown
- 1996-06-06 TR TR96/00481A patent/TR199600481A2/xx unknown
- 1996-06-06 MA MA24265A patent/MA23895A1/fr unknown
- 1996-06-06 YU YU35296A patent/YU35296A/sh unknown
- 1996-06-07 RO RO96-01181A patent/RO116897B1/ro unknown
- 1996-06-07 CO CO96029732A patent/CO4440626A1/es unknown
- 1996-06-07 OA OA60837A patent/OA10363A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TR199600481A2 (tr) | 1996-12-21 |
| OA10363A (en) | 2001-11-15 |
| DK0832069T3 (da) | 2003-04-22 |
| IL135375A0 (en) | 2001-05-20 |
| DZ2045A1 (fr) | 2002-07-21 |
| CO4440626A1 (es) | 1997-05-07 |
| KR100225713B1 (ko) | 1999-10-15 |
| TNSN96085A1 (fr) | 2005-03-15 |
| AU703493B2 (en) | 1999-03-25 |
| IL135377A0 (en) | 2001-05-20 |
| AU5478496A (en) | 1996-12-19 |
| RU2141478C1 (ru) | 1999-11-20 |
| IL135377A (en) | 2001-05-20 |
| ATE233734T1 (de) | 2003-03-15 |
| AR003424A1 (es) | 1998-08-05 |
| MX9709914A (es) | 1998-03-31 |
| TW476756B (en) | 2002-02-21 |
| MA23895A1 (fr) | 1996-12-31 |
| RO116897B1 (ro) | 2001-07-30 |
| KR970003589A (ko) | 1997-01-28 |
| YU35296A (sh) | 1999-06-15 |
| DE69529849T2 (de) | 2003-09-04 |
| DE69529849D1 (de) | 2003-04-10 |
| US5919795A (en) | 1999-07-06 |
| BG62442B1 (bg) | 1999-11-30 |
| IL135376A (en) | 2001-05-20 |
| IL135376A0 (en) | 2001-05-20 |
| BG100637A (bg) | 1997-03-31 |
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