JPS59172473A - 3−アミノ−1−ベンゾアゼピン−2−オン−1−アルカン酸 - Google Patents
3−アミノ−1−ベンゾアゼピン−2−オン−1−アルカン酸Info
- Publication number
 - JPS59172473A JPS59172473A JP59020905A JP2090584A JPS59172473A JP S59172473 A JPS59172473 A JP S59172473A JP 59020905 A JP59020905 A JP 59020905A JP 2090584 A JP2090584 A JP 2090584A JP S59172473 A JPS59172473 A JP S59172473A
 - Authority
 - JP
 - Japan
 - Prior art keywords
 - group
 - lower alkyl
 - alkyl group
 - hydrogen atom
 - formula
 - Prior art date
 - Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
 - Granted
 
Links
- 239000002253 acid Substances 0.000 title description 32
 - 125000000217 alkyl group Chemical group 0.000 claims description 173
 - 150000001875 compounds Chemical class 0.000 claims description 133
 - -1 sulfonyl- Chemical group 0.000 claims description 86
 - 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 81
 - 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 80
 - 125000003545 alkoxy group Chemical group 0.000 claims description 77
 - 150000003839 salts Chemical class 0.000 claims description 54
 - 125000003118 aryl group Chemical group 0.000 claims description 45
 - 238000000034 method Methods 0.000 claims description 45
 - 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
 - 125000004043 oxo group Chemical group O=* 0.000 claims description 30
 - 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
 - 125000003282 alkyl amino group Chemical group 0.000 claims description 26
 - 125000004423 acyloxy group Chemical group 0.000 claims description 22
 - 125000002837 carbocyclic group Chemical group 0.000 claims description 22
 - 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
 - 125000003277 amino group Chemical group 0.000 claims description 20
 - 150000002148 esters Chemical class 0.000 claims description 19
 - 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
 - 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
 - 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
 - 229910052757 nitrogen Inorganic materials 0.000 claims description 17
 - 150000001412 amines Chemical class 0.000 claims description 16
 - 125000004429 atom Chemical group 0.000 claims description 16
 - 239000000203 mixture Substances 0.000 claims description 16
 - 125000004442 acylamino group Chemical group 0.000 claims description 15
 - 125000004432 carbon atom Chemical group C* 0.000 claims description 15
 - 125000005843 halogen group Chemical group 0.000 claims description 15
 - 239000003638 chemical reducing agent Substances 0.000 claims description 14
 - 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
 - 238000005804 alkylation reaction Methods 0.000 claims description 13
 - 125000005530 alkylenedioxy group Chemical group 0.000 claims description 13
 - 229910052799 carbon Inorganic materials 0.000 claims description 13
 - 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
 - 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
 - 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
 - 230000008569 process Effects 0.000 claims description 11
 - 230000029936 alkylation Effects 0.000 claims description 10
 - 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
 - 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
 - 229910052801 chlorine Inorganic materials 0.000 claims description 8
 - 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
 - 125000004414 alkyl thio group Chemical group 0.000 claims description 6
 - 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
 - 238000009833 condensation Methods 0.000 claims description 6
 - 230000005494 condensation Effects 0.000 claims description 6
 - 230000003287 optical effect Effects 0.000 claims description 6
 - AYQMNFRCBKOMIA-UHFFFAOYSA-N 1-benzazepin-2-one Chemical compound O=C1C=CC=C2C=CC=CC2=N1 AYQMNFRCBKOMIA-UHFFFAOYSA-N 0.000 claims description 5
 - 241001465754 Metazoa Species 0.000 claims description 5
 - 125000001769 aryl amino group Chemical group 0.000 claims description 5
 - 125000004104 aryloxy group Chemical group 0.000 claims description 5
 - 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
 - 125000000524 functional group Chemical group 0.000 claims description 5
 - 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
 - 239000008194 pharmaceutical composition Substances 0.000 claims description 5
 - 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 5
 - 108010064733 Angiotensins Proteins 0.000 claims description 4
 - 102000015427 Angiotensins Human genes 0.000 claims description 4
 - 125000005110 aryl thio group Chemical group 0.000 claims description 4
 - 125000003963 dichloro group Chemical group Cl* 0.000 claims description 4
 - 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
 - 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
 - 239000002168 alkylating agent Substances 0.000 claims description 3
 - 229940100198 alkylating agent Drugs 0.000 claims description 3
 - 238000004519 manufacturing process Methods 0.000 claims description 3
 - 125000001424 substituent group Chemical group 0.000 claims description 3
 - YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 2
 - 239000003937 drug carrier Substances 0.000 claims description 2
 - 229940093817 Convertase inhibitor Drugs 0.000 claims 1
 - 241000252233 Cyprinus carpio Species 0.000 claims 1
 - ZFDLFHQAGYPRBY-UHFFFAOYSA-N chloro acetate Chemical group CC(=O)OCl ZFDLFHQAGYPRBY-UHFFFAOYSA-N 0.000 claims 1
 - 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
 - 239000000825 pharmaceutical preparation Substances 0.000 claims 1
 - 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
 - OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
 - VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
 - LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
 - 239000000243 solution Substances 0.000 description 41
 - RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
 - 239000007858 starting material Substances 0.000 description 34
 - QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
 - YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
 - XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
 - 235000019441 ethanol Nutrition 0.000 description 27
 - 239000002904 solvent Substances 0.000 description 27
 - 239000011541 reaction mixture Substances 0.000 description 25
 - WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
 - XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
 - 238000006243 chemical reaction Methods 0.000 description 20
 - 239000003054 catalyst Substances 0.000 description 19
 - 230000009467 reduction Effects 0.000 description 19
 - 238000006722 reduction reaction Methods 0.000 description 19
 - 230000002829 reductive effect Effects 0.000 description 19
 - ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
 - HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
 - 238000002844 melting Methods 0.000 description 18
 - 230000008018 melting Effects 0.000 description 18
 - IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
 - 239000002585 base Substances 0.000 description 16
 - ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
 - 125000006239 protecting group Chemical group 0.000 description 15
 - HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
 - 230000036772 blood pressure Effects 0.000 description 12
 - 238000003756 stirring Methods 0.000 description 12
 - YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
 - DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
 - 229960000583 acetic acid Drugs 0.000 description 11
 - 150000001408 amides Chemical class 0.000 description 11
 - QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
 - 230000007062 hydrolysis Effects 0.000 description 10
 - 238000006460 hydrolysis reaction Methods 0.000 description 10
 - BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 10
 - YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
 - 235000011054 acetic acid Nutrition 0.000 description 9
 - QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
 - 238000000354 decomposition reaction Methods 0.000 description 9
 - 239000000543 intermediate Substances 0.000 description 9
 - 239000000047 product Substances 0.000 description 9
 - 239000011734 sodium Substances 0.000 description 9
 - 150000007513 acids Chemical class 0.000 description 8
 - BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
 - 239000000376 reactant Substances 0.000 description 8
 - 239000007787 solid Substances 0.000 description 8
 - 238000012360 testing method Methods 0.000 description 8
 - 102400000344 Angiotensin-1 Human genes 0.000 description 7
 - 101800000734 Angiotensin-1 Proteins 0.000 description 7
 - 241000700159 Rattus Species 0.000 description 7
 - ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 7
 - 239000003795 chemical substances by application Substances 0.000 description 7
 - 230000000694 effects Effects 0.000 description 7
 - 230000005764 inhibitory process Effects 0.000 description 7
 - 229910052751 metal Inorganic materials 0.000 description 7
 - 239000002184 metal Substances 0.000 description 7
 - 150000007522 mineralic acids Chemical class 0.000 description 7
 - 239000003960 organic solvent Substances 0.000 description 7
 - 229910052708 sodium Inorganic materials 0.000 description 7
 - 235000011121 sodium hydroxide Nutrition 0.000 description 7
 - HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
 - WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
 - VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
 - KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
 - 230000009471 action Effects 0.000 description 6
 - 239000007864 aqueous solution Substances 0.000 description 6
 - 230000015572 biosynthetic process Effects 0.000 description 6
 - 150000001721 carbon Chemical group 0.000 description 6
 - GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 6
 - MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 6
 - 125000004185 ester group Chemical group 0.000 description 6
 - 239000001257 hydrogen Substances 0.000 description 6
 - 229910052739 hydrogen Inorganic materials 0.000 description 6
 - IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachlorophenol Chemical compound OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 6
 - UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 5
 - UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
 - 241000124008 Mammalia Species 0.000 description 5
 - 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 5
 - 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 5
 - NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
 - KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical class [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
 - DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
 - 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 5
 - 229910052783 alkali metal Inorganic materials 0.000 description 5
 - 229940024606 amino acid Drugs 0.000 description 5
 - 150000003863 ammonium salts Chemical class 0.000 description 5
 - 238000005984 hydrogenation reaction Methods 0.000 description 5
 - 238000007327 hydrogenolysis reaction Methods 0.000 description 5
 - 229910052697 platinum Inorganic materials 0.000 description 5
 - 238000000746 purification Methods 0.000 description 5
 - 238000005932 reductive alkylation reaction Methods 0.000 description 5
 - 230000004044 response Effects 0.000 description 5
 - UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
 - 239000000725 suspension Substances 0.000 description 5
 - 238000003786 synthesis reaction Methods 0.000 description 5
 - OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
 - OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
 - KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 4
 - 206010020772 Hypertension Diseases 0.000 description 4
 - CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
 - SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
 - VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
 - WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
 - 229920002472 Starch Polymers 0.000 description 4
 - HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
 - 239000004480 active ingredient Substances 0.000 description 4
 - 238000006136 alcoholysis reaction Methods 0.000 description 4
 - 125000005907 alkyl ester group Chemical group 0.000 description 4
 - 235000001014 amino acid Nutrition 0.000 description 4
 - 150000001413 amino acids Chemical class 0.000 description 4
 - 239000008346 aqueous phase Substances 0.000 description 4
 - 238000009835 boiling Methods 0.000 description 4
 - 238000007796 conventional method Methods 0.000 description 4
 - 239000003814 drug Substances 0.000 description 4
 - 235000019253 formic acid Nutrition 0.000 description 4
 - IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
 - 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
 - 238000001727 in vivo Methods 0.000 description 4
 - 239000012442 inert solvent Substances 0.000 description 4
 - HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
 - 229910052987 metal hydride Chemical class 0.000 description 4
 - 150000004681 metal hydrides Chemical class 0.000 description 4
 - 239000012071 phase Substances 0.000 description 4
 - 235000011007 phosphoric acid Nutrition 0.000 description 4
 - BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
 - 238000002360 preparation method Methods 0.000 description 4
 - 229910000104 sodium hydride Inorganic materials 0.000 description 4
 - 229910052938 sodium sulfate Inorganic materials 0.000 description 4
 - 235000011152 sodium sulphate Nutrition 0.000 description 4
 - 239000008107 starch Substances 0.000 description 4
 - 235000019698 starch Nutrition 0.000 description 4
 - 238000010189 synthetic method Methods 0.000 description 4
 - 239000011701 zinc Substances 0.000 description 4
 - 229910052725 zinc Inorganic materials 0.000 description 4
 - BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
 - NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
 - FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
 - CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
 - GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
 - 241000282472 Canis lupus familiaris Species 0.000 description 3
 - XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
 - LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
 - WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
 - GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
 - WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
 - AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
 - FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
 - MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
 - ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
 - 230000002378 acidificating effect Effects 0.000 description 3
 - 150000001298 alcohols Chemical class 0.000 description 3
 - 150000001335 aliphatic alkanes Chemical class 0.000 description 3
 - 125000001931 aliphatic group Chemical group 0.000 description 3
 - 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
 - 150000008046 alkali metal hydrides Chemical class 0.000 description 3
 - 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
 - 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
 - 230000003276 anti-hypertensive effect Effects 0.000 description 3
 - 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
 - 239000011230 binding agent Substances 0.000 description 3
 - 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
 - 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
 - 150000001735 carboxylic acids Chemical class 0.000 description 3
 - 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
 - 239000003153 chemical reaction reagent Substances 0.000 description 3
 - 238000004587 chromatography analysis Methods 0.000 description 3
 - KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
 - 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
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 - 229920000573 polyethylene Polymers 0.000 description 1
 - 229920001223 polyethylene glycol Polymers 0.000 description 1
 - 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
 - 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
 - 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
 - 235000015497 potassium bicarbonate Nutrition 0.000 description 1
 - 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
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 - 239000001103 potassium chloride Substances 0.000 description 1
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 - WCUXLLCKKVVCTQ-UHFFFAOYSA-M potassium chloride Inorganic materials [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 1
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 - 239000000741 silica gel Substances 0.000 description 1
 - 229910002027 silica gel Inorganic materials 0.000 description 1
 - 239000000377 silicon dioxide Substances 0.000 description 1
 - 125000003808 silyl group Chemical class [H][Si]([H])([H])[*] 0.000 description 1
 - CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
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 - 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
 - 159000000000 sodium salts Chemical class 0.000 description 1
 - 239000000600 sorbitol Substances 0.000 description 1
 - 241000894007 species Species 0.000 description 1
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 - 229940095064 tartrate Drugs 0.000 description 1
 - 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
 - IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
 - DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
 - 229940124597 therapeutic agent Drugs 0.000 description 1
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 - 150000003624 transition metals Chemical class 0.000 description 1
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Classifications
- 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07D—HETEROCYCLIC COMPOUNDS
 - C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
 - C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
 - C07D223/16—Benzazepines; Hydrogenated benzazepines
 
 - 
        
- A—HUMAN NECESSITIES
 - A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
 - A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
 - A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
 
 - 
        
- 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
 - A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
 
 - 
        
- 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
 - A61P9/12—Antihypertensives
 
 - 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07K—PEPTIDES
 - C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
 - C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
 - C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
 - C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
 
 - 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07K—PEPTIDES
 - C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
 - C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
 - C07K5/06—Dipeptides
 - C07K5/06008—Dipeptides with the first amino acid being neutral
 - C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
 - C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
 
 - 
        
- C—CHEMISTRY; METALLURGY
 - C07—ORGANIC CHEMISTRY
 - C07K—PEPTIDES
 - C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
 - C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
 - C07K5/06—Dipeptides
 - C07K5/06086—Dipeptides with the first amino acid being basic
 
 - 
        
- A—HUMAN NECESSITIES
 - A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
 - A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
 - A61K38/00—Medicinal preparations containing peptides
 
 - 
        
- 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)
 - Health & Medical Sciences (AREA)
 - Medicinal Chemistry (AREA)
 - General Health & Medical Sciences (AREA)
 - Life Sciences & Earth Sciences (AREA)
 - Biochemistry (AREA)
 - Proteomics, Peptides & Aminoacids (AREA)
 - Molecular Biology (AREA)
 - Genetics & Genomics (AREA)
 - Biophysics (AREA)
 - Bioinformatics & Cheminformatics (AREA)
 - Engineering & Computer Science (AREA)
 - Cardiology (AREA)
 - Chemical Kinetics & Catalysis (AREA)
 - Public Health (AREA)
 - Veterinary Medicine (AREA)
 - Animal Behavior & Ethology (AREA)
 - General Chemical & Material Sciences (AREA)
 - Pharmacology & Pharmacy (AREA)
 - Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
 - Heart & Thoracic Surgery (AREA)
 - Hospice & Palliative Care (AREA)
 - Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
 - Plural Heterocyclic Compounds (AREA)
 - Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
 - Peptides Or Proteins (AREA)
 
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title | 
|---|---|---|---|
| US465695 | 1983-02-10 | ||
| US06/465,695 US4473575A (en) | 1982-07-19 | 1983-02-10 | 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids | 
Publications (2)
| Publication Number | Publication Date | 
|---|---|
| JPS59172473A true JPS59172473A (ja) | 1984-09-29 | 
| JPH0460108B2 JPH0460108B2 (h) | 1992-09-25 | 
Family
ID=23848805
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date | 
|---|---|---|---|
| JP59020905A Granted JPS59172473A (ja) | 1983-02-09 | 1984-02-09 | 3−アミノ−1−ベンゾアゼピン−2−オン−1−アルカン酸 | 
| JP59022031A Granted JPS59172475A (ja) | 1983-02-10 | 1984-02-10 | 3−(5−アミノペンチル)−アミノ−1−ベンズアゼピン−2−オン−1−アルカン酸 | 
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date | 
|---|---|---|---|
| JP59022031A Granted JPS59172475A (ja) | 1983-02-10 | 1984-02-10 | 3−(5−アミノペンチル)−アミノ−1−ベンズアゼピン−2−オン−1−アルカン酸 | 
Country Status (24)
| Country | Link | 
|---|---|
| US (1) | US4473575A (h) | 
| EP (2) | EP0119955B1 (h) | 
| JP (2) | JPS59172473A (h) | 
| KR (1) | KR900009023B1 (h) | 
| AR (8) | AR242564A1 (h) | 
| AT (2) | ATE50989T1 (h) | 
| AU (1) | AU574061B2 (h) | 
| CA (2) | CA1218993A (h) | 
| CY (1) | CY1674A (h) | 
| DD (1) | DD218359A5 (h) | 
| DE (2) | DE3481612D1 (h) | 
| DK (2) | DK58184A (h) | 
| ES (10) | ES8707216A1 (h) | 
| FI (1) | FI77857C (h) | 
| GR (1) | GR79809B (h) | 
| HK (1) | HK97592A (h) | 
| HU (1) | HU192394B (h) | 
| IE (1) | IE56858B1 (h) | 
| IL (1) | IL70881A (h) | 
| NO (1) | NO166232C (h) | 
| NZ (1) | NZ207091A (h) | 
| PT (1) | PT78075B (h) | 
| SG (1) | SG94992G (h) | 
| ZA (1) | ZA84958B (h) | 
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title | 
|---|---|---|---|---|
| US4473575A (en) * | 1982-07-19 | 1984-09-25 | Ciba-Geigy Corporation | 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids | 
| US4575503A (en) * | 1983-02-10 | 1986-03-11 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids | 
| US4537885A (en) * | 1983-02-10 | 1985-08-27 | Ciba Geigy Corporation | Certain benzazocinone and benzazoninone derivatives | 
| US4600534A (en) * | 1984-02-06 | 1986-07-15 | Ciba-Geigy Corporation | Process and intermediates for manufacture of 3-(5-amino-1-carboxypentylamino)-tetrahydro-1-benzazepin-2-one-1-acetic acid | 
| EP0166354B1 (en) * | 1984-06-26 | 1992-08-05 | Merck & Co. Inc. | Benzofused lactam compounds and pharmaceutical compositions containing them | 
| EP0166357A3 (en) * | 1984-06-26 | 1988-10-26 | Merck & Co. Inc. | Benzofused lactams and pharmaceutical compositions containing them | 
| US4692522A (en) * | 1985-04-01 | 1987-09-08 | Merck & Co., Inc. | Benzofused lactams useful as cholecystokinin antagonists | 
| US4785089A (en) * | 1985-06-13 | 1988-11-15 | Ciba-Geigy Corporation | Novel sulfonic acid esters and their preparation | 
| EP0237267B1 (en) * | 1986-03-11 | 1991-01-23 | Barry Anthony Thompson | Feeding livestock with polymers | 
| US5028704A (en) * | 1986-05-28 | 1991-07-02 | Ciba-Geigy Corporation | (2,5-dihydro 5-phenyl-2-oxo-3-furanyl)amines, methods of manufacture, and use thereof in the production of angiotensin converting enzyme inhibitors | 
| FI88723C (fi) * | 1986-05-28 | 1993-06-28 | Ciba Geigy Ag | /2,5-dihydro-2-oxo-5-fenyl-3-furanyl/aminer samt deras anvaendning vid framstaellning av ACE-inhibitorer | 
| US4918187A (en) * | 1986-05-28 | 1990-04-17 | Ciba-Geigy Corporation | [2,5-Dihydro 5-phenyl-2-oxo-3-furanyl]amines | 
| AT399717B (de) * | 1986-05-28 | 1995-07-25 | Ciba Geigy Ag | Verfahren zur herstellung von (2,5-dihydro-2-oxo- 5-phenyl-3-furanyl)aminen | 
| US4962105A (en) | 1987-10-19 | 1990-10-09 | Ciba-Geigy Corporation | Potentiation of antihypertensive effect of ace inhibitors | 
| JPH07116224B2 (ja) * | 1987-12-29 | 1995-12-13 | 吉富製薬株式会社 | ベンゾラクタム化合物 | 
| GB9100028D0 (en) * | 1991-01-02 | 1991-02-20 | Ici Plc | Compounds | 
| US5428031A (en) * | 1991-12-03 | 1995-06-27 | Merck & Co., Inc. | Methods of treating cardiac arrhythmia | 
| US5552397A (en) * | 1992-05-18 | 1996-09-03 | E. R. Squibb & Sons, Inc. | Substituted azepinone dual inhibitors of angiotensin converting enzyme and neutral exdopeptidase | 
| US5646276A (en) * | 1992-05-13 | 1997-07-08 | Bristol-Myers Squibb Co. | Diazepine containing dual action inhibitors | 
| RU2124503C1 (ru) | 1992-05-18 | 1999-01-10 | И.Р.Сквибб энд Санз, Инк. | Гетероциклические азотсодержащие производные карбоновой кислоты, способ их получения и фармацевтическая композиция | 
| GB9212308D0 (en) * | 1992-06-10 | 1992-07-22 | Ici Plc | Therapeutic compositions | 
| GB9311948D0 (en) * | 1993-06-10 | 1993-07-28 | Zeneca Ltd | Substituted nitrogen heterocycles | 
| JPH09505597A (ja) * | 1993-11-22 | 1997-06-03 | メルク エンド カンパニー インコーポレーテッド | 3−アシルアミノベンゾアゼピン類 | 
| US5801168A (en) * | 1994-06-09 | 1998-09-01 | Zeneca Limited | Substituted nitrogen heterocycles | 
| CA2195974C (en) * | 1994-08-18 | 2000-12-05 | David A. Claremon | 2,3-dihydro-1-(2,2,2-trifluoroethyl)-2-oxo-5-phenyl-1h-1,4-benzodiazepines | 
| US5587375A (en) * | 1995-02-17 | 1996-12-24 | Bristol-Myers Squibb Company | Azepinone compounds useful in the inhibition of ACE and NEP | 
| US5877313A (en) | 1995-05-17 | 1999-03-02 | Bristol-Myers Squibb | Benzo-fused azepinone and piperidinone compounds useful in the inhibition of ACE and NEP | 
| US5700797A (en) * | 1995-06-07 | 1997-12-23 | Merck & Co, Inc. | N-(2,4-dioxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl)-3-amides | 
| US5691331A (en) * | 1995-06-07 | 1997-11-25 | Merck & Co., Inc. | N-(2,4-Dioxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3yl) -3- amides | 
| US5726171A (en) * | 1995-06-07 | 1998-03-10 | Merck & Co Inc | N-(1-alkyl-5-phenyl-2,3,4,5-tetrahydro-1H-benzo B! 1,4!diazepin-3yl)-acetamides | 
| US5650408A (en) * | 1995-06-07 | 1997-07-22 | Karanewsky; Donald S. | Thiazolo benzazepine containing dual action inhibitors | 
| US5635504A (en) * | 1995-06-07 | 1997-06-03 | Bristol-Myers Squibb Co. | Diazepine containing dual action inhibitors | 
| US5631251A (en) * | 1995-06-07 | 1997-05-20 | Merck & Co., Inc. | 5-cyclopropyl-1,4 benzodiazepine-2-ones | 
| EP0833819B1 (en) * | 1995-06-07 | 2003-03-26 | Merck & Co., Inc. | Novel n-(2-oxo-2,3,4,5-tetrahydro-1h-1,5-benzodiazepin-3yl)-3-amides | 
| US6211235B1 (en) | 1996-11-22 | 2001-04-03 | Elan Pharmaceuticals, Inc. | Compounds for inhibiting β-amyloid peptide release and/or its synthesis | 
| US6191166B1 (en) * | 1997-11-21 | 2001-02-20 | Elan Pharmaceuticals, Inc. | Methods and compounds for inhibiting β-amyloid peptide release and/or its synthesis | 
| US6635632B1 (en) | 1996-12-23 | 2003-10-21 | Athena Neurosciences, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| US6683075B1 (en) | 1996-12-23 | 2004-01-27 | Athena Neurosciences, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use | 
| JP2002241368A (ja) * | 1997-02-18 | 2002-08-28 | Shionogi & Co Ltd | 新規ベンゾラクタム誘導体およびそれを含有する医薬組成物 | 
| WO1998041510A1 (fr) * | 1997-03-14 | 1998-09-24 | Shionogi & Co., Ltd. | Nouveaux derives du benzolactame et compositions medicamenteuses les contenant | 
| US6569851B1 (en) * | 1998-06-22 | 2003-05-27 | Elan Pharmaceutials, Inc. | Cycloalkyl, lactam, lactone and related compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| US6552013B1 (en) | 1998-06-22 | 2003-04-22 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| US6528505B1 (en) | 1998-06-22 | 2003-03-04 | Elan Pharmaceuticals, Inc. | Cyclic amino acid compounds pharmaceutical compositions comprising same and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| US6774125B2 (en) * | 1998-06-22 | 2004-08-10 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| US6509331B1 (en) | 1998-06-22 | 2003-01-21 | Elan Pharmaceuticals, Inc. | Deoxyamino acid compounds, pharmaceutical compositions comprising same, and methods for inhibiting β-amyloid peptide release and/or its synthesis by use of such compounds | 
| CA2391498A1 (en) * | 1999-11-18 | 2001-05-25 | Antexpharma, Inc. | Substituted 1-benzazepines and derivatives thereof | 
| US7795468B2 (en) * | 2001-01-19 | 2010-09-14 | Chevron U.S.A. Inc. | Functionalized higher diamondoids | 
| AU2002348276A1 (en) * | 2001-11-16 | 2003-06-10 | Bristol-Myers Squibb Company | Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein | 
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| US3330823A (en) * | 1964-12-16 | 1967-07-11 | Squibb & Sons Inc | N-amino-loweralkylene-benzo-lactams | 
| US3395150A (en) * | 1965-02-26 | 1968-07-30 | Squibb & Sons Inc | Benzothiazepine carboxamides and derivatives thereof | 
| GB1305278A (h) * | 1970-03-12 | 1973-01-31 | ||
| JPS5129522B2 (h) * | 1972-07-13 | 1976-08-26 | ||
| JPS5520970B2 (h) * | 1972-07-15 | 1980-06-06 | ||
| FR2358151A1 (fr) * | 1976-03-31 | 1978-02-10 | Roussel Uclaf | Nouvelles benzazepines et leurs sels, procede de preparation et application a titre de medicaments | 
| IL58849A (en) * | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them | 
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| ZA825779B (en) * | 1981-08-11 | 1984-04-25 | Ciba Geigy Ag | Benzazepins-2-ones | 
| US4410520A (en) * | 1981-11-09 | 1983-10-18 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids | 
| US4473575A (en) * | 1982-07-19 | 1984-09-25 | Ciba-Geigy Corporation | 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids | 
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- 
        1983
        
- 1983-02-10 US US06/465,695 patent/US4473575A/en not_active Expired - Lifetime
 
 - 
        1984
        
- 1984-02-06 AT AT84810071T patent/ATE50989T1/de active
 - 1984-02-06 EP EP84810072A patent/EP0119955B1/de not_active Expired
 - 1984-02-06 DE DE8484810071T patent/DE3481612D1/de not_active Expired - Lifetime
 - 1984-02-06 EP EP84810071A patent/EP0119954B1/de not_active Expired - Lifetime
 - 1984-02-06 DE DE8484810072T patent/DE3480705D1/de not_active Expired - Lifetime
 - 1984-02-06 AT AT84810072T patent/ATE48598T1/de active
 - 1984-02-07 IL IL70881A patent/IL70881A/xx not_active IP Right Cessation
 - 1984-02-08 CA CA000446970A patent/CA1218993A/en not_active Expired
 - 1984-02-08 FI FI840513A patent/FI77857C/fi not_active IP Right Cessation
 - 1984-02-08 GR GR73754A patent/GR79809B/el unknown
 - 1984-02-08 CA CA000446971A patent/CA1225397A/en not_active Expired
 - 1984-02-08 PT PT78075A patent/PT78075B/pt not_active IP Right Cessation
 - 1984-02-09 NO NO840487A patent/NO166232C/no unknown
 - 1984-02-09 HU HU84523A patent/HU192394B/hu not_active IP Right Cessation
 - 1984-02-09 JP JP59020905A patent/JPS59172473A/ja active Granted
 - 1984-02-09 IE IE302/84A patent/IE56858B1/en not_active IP Right Cessation
 - 1984-02-09 ES ES529595A patent/ES8707216A1/es not_active Expired
 - 1984-02-09 ES ES529594A patent/ES8609261A1/es not_active Expired
 - 1984-02-09 ZA ZA84958A patent/ZA84958B/xx unknown
 - 1984-02-09 AU AU24430/84A patent/AU574061B2/en not_active Ceased
 - 1984-02-09 NZ NZ207091A patent/NZ207091A/en unknown
 - 1984-02-09 DK DK58184A patent/DK58184A/da not_active Application Discontinuation
 - 1984-02-09 DD DD84259979A patent/DD218359A5/de not_active IP Right Cessation
 - 1984-02-09 DK DK058284A patent/DK171257B1/da not_active IP Right Cessation
 - 1984-02-10 AR AR84295689A patent/AR242564A1/es active
 - 1984-02-10 JP JP59022031A patent/JPS59172475A/ja active Granted
 - 1984-02-10 KR KR1019840000630A patent/KR900009023B1/ko not_active Expired
 
 - 
        1985
        
- 1985-06-13 ES ES544127A patent/ES8702363A1/es not_active Expired
 - 1985-06-17 ES ES544257A patent/ES8609263A1/es not_active Expired
 - 1985-06-17 ES ES544259A patent/ES8700239A1/es not_active Expired
 - 1985-06-17 ES ES544254A patent/ES8703859A1/es not_active Expired
 - 1985-06-17 ES ES544255A patent/ES8609262A1/es not_active Expired
 - 1985-06-17 ES ES544260A patent/ES8609265A1/es not_active Expired
 - 1985-06-17 ES ES544258A patent/ES8609264A1/es not_active Expired
 - 1985-06-17 ES ES544256A patent/ES8705409A1/es not_active Expired
 
 - 
        1986
        
- 1986-08-15 AR AR86304925A patent/AR243162A1/es active
 - 1986-08-15 AR AR86304921A patent/AR242191A1/es active
 - 1986-08-15 AR AR86304922A patent/AR243165A1/es active
 - 1986-08-15 AR AR86304920A patent/AR242190A1/es active
 - 1986-08-15 AR AR86304923A patent/AR243164A1/es active
 - 1986-08-15 AR AR86304926A patent/AR243161A1/es active
 - 1986-08-15 AR AR86304924A patent/AR243163A1/es active
 
 - 
        1992
        
- 1992-09-21 SG SG949/92A patent/SG94992G/en unknown
 - 1992-12-03 HK HK975/92A patent/HK97592A/xx not_active IP Right Cessation
 
 - 
        1993
        
- 1993-10-10 CY CY1674A patent/CY1674A/xx unknown
 
 
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