HUT70197A - New benzamide derivatives, process for producing them and pharmaceutical compositions containing them - Google Patents
New benzamide derivatives, process for producing them and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- HUT70197A HUT70197A HU9401041A HU9401041A HUT70197A HU T70197 A HUT70197 A HU T70197A HU 9401041 A HU9401041 A HU 9401041A HU 9401041 A HU9401041 A HU 9401041A HU T70197 A HUT70197 A HU T70197A
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- HU
- Hungary
- Prior art keywords
- group
- formula
- compound
- lower alkyl
- alkyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 108
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 7
- 150000003936 benzamides Chemical class 0.000 title description 10
- -1 nitro, hydroxy Chemical group 0.000 claims abstract description 406
- 150000001875 compounds Chemical class 0.000 claims abstract description 276
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 228
- 150000003839 salts Chemical class 0.000 claims abstract description 195
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 75
- 239000001257 hydrogen Substances 0.000 claims abstract description 70
- 125000002252 acyl group Chemical group 0.000 claims abstract description 50
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 49
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 41
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 28
- 125000001424 substituent group Chemical group 0.000 claims abstract description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 19
- 150000002367 halogens Chemical class 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 162
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 98
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 86
- 238000002360 preparation method Methods 0.000 claims description 57
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 26
- 239000003638 chemical reducing agent Substances 0.000 claims description 22
- 238000006722 reduction reaction Methods 0.000 claims description 20
- 229910052727 yttrium Inorganic materials 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 230000002829 reductive effect Effects 0.000 claims description 12
- 229960003726 vasopressin Drugs 0.000 claims description 12
- 125000000676 alkoxyimino group Chemical group 0.000 claims description 11
- 150000001350 alkyl halides Chemical class 0.000 claims description 11
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 10
- 239000011591 potassium Substances 0.000 claims description 10
- 229910052700 potassium Inorganic materials 0.000 claims description 10
- 125000003277 amino group Chemical group 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 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 claims description 8
- 206010029897 Obsessive thoughts Diseases 0.000 claims description 8
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 claims description 8
- 108010004977 Vasopressins Proteins 0.000 claims description 8
- 102000002852 Vasopressins Human genes 0.000 claims description 8
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- 229910052708 sodium Inorganic materials 0.000 claims description 8
- 150000003973 alkyl amines Chemical class 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 230000002152 alkylating effect Effects 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 206010030113 Oedema Diseases 0.000 claims description 4
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 4
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 4
- 201000006370 kidney failure Diseases 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 230000002440 hepatic effect Effects 0.000 claims description 3
- 230000028327 secretion Effects 0.000 claims description 3
- 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 claims description 3
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 206010012735 Diarrhoea Diseases 0.000 claims 1
- 208000018522 Gastrointestinal disease Diseases 0.000 claims 1
- 125000004442 acylamino group Chemical group 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 208000019425 cirrhosis of liver Diseases 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 330
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 285
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 180
- 238000006243 chemical reaction Methods 0.000 description 171
- 239000000243 solution Substances 0.000 description 161
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
- 239000002904 solvent Substances 0.000 description 119
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000000203 mixture Substances 0.000 description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 63
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 52
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000002253 acid Substances 0.000 description 46
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 46
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 36
- 235000019341 magnesium sulphate Nutrition 0.000 description 36
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 32
- 229920006395 saturated elastomer Polymers 0.000 description 30
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 27
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
- XTDMZEZDXXJVMK-UHFFFAOYSA-N 1,2,3,5-tetrahydro-1,5-benzodiazepin-4-one Chemical compound N1C(=O)CCNC2=CC=CC=C21 XTDMZEZDXXJVMK-UHFFFAOYSA-N 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000003054 catalyst Substances 0.000 description 23
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
- 235000017557 sodium bicarbonate Nutrition 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 22
- 239000012267 brine Substances 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 235000011054 acetic acid Nutrition 0.000 description 21
- 239000003480 eluent Substances 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 238000001816 cooling Methods 0.000 description 18
- 238000010438 heat treatment Methods 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- 230000002411 adverse Effects 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- 229910052697 platinum Inorganic materials 0.000 description 14
- 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 13
- 239000000872 buffer Substances 0.000 description 13
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 12
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 10
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 10
- 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 10
- 229910052783 alkali metal Inorganic materials 0.000 description 10
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 9
- 238000010531 catalytic reduction reaction Methods 0.000 description 9
- 229910017052 cobalt Inorganic materials 0.000 description 9
- 239000010941 cobalt Substances 0.000 description 9
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 9
- 229910052802 copper Inorganic materials 0.000 description 9
- 239000010949 copper Substances 0.000 description 9
- 150000007524 organic acids Chemical class 0.000 description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 150000007522 mineralic acids Chemical class 0.000 description 8
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 235000019260 propionic acid Nutrition 0.000 description 8
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 239000002841 Lewis acid Substances 0.000 description 7
- 150000001340 alkali metals Chemical class 0.000 description 7
- 150000001342 alkaline earth metals Chemical class 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
- 150000007517 lewis acids Chemical class 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910052759 nickel Inorganic materials 0.000 description 7
- 235000005985 organic acids Nutrition 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 235000011121 sodium hydroxide Nutrition 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- 150000008065 acid anhydrides Chemical class 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
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- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
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- 150000001768 cations Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- XGRJZXREYAXTGV-UHFFFAOYSA-N chlorodiphenylphosphine Chemical compound C=1C=CC=CC=1P(Cl)C1=CC=CC=C1 XGRJZXREYAXTGV-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000007257 deesterification reaction Methods 0.000 description 1
- 125000004915 dibutylamino group Chemical group C(CCC)N(CCCC)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
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- 239000000839 emulsion Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- HBFXVTVOSLPOEY-UHFFFAOYSA-N ethoxyethane;2-propan-2-yloxypropane Chemical compound CCOCC.CC(C)OC(C)C HBFXVTVOSLPOEY-UHFFFAOYSA-N 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- DAAZNOILPHUOHD-UHFFFAOYSA-N ethyl 2-(1,2,3,4-tetrahydro-1,5-benzodiazepin-5-yl)acetate Chemical compound CCOC(=O)CN1CCCNC2=CC=CC=C12 DAAZNOILPHUOHD-UHFFFAOYSA-N 0.000 description 1
- KQTYQZRSXBRCFS-UHFFFAOYSA-N ethyl 2-(2-nitro-n-(4-nitrobenzoyl)anilino)acetate Chemical compound C=1C=CC=C([N+]([O-])=O)C=1N(CC(=O)OCC)C(=O)C1=CC=C([N+]([O-])=O)C=C1 KQTYQZRSXBRCFS-UHFFFAOYSA-N 0.000 description 1
- BTQMCWDXZITCMI-UHFFFAOYSA-N ethyl 2-(4-oxo-2,3-dihydro-1h-1,5-benzodiazepin-5-yl)acetate Chemical compound N1CCC(=O)N(CC(=O)OCC)C2=CC=CC=C21 BTQMCWDXZITCMI-UHFFFAOYSA-N 0.000 description 1
- ZYZRNZHXHROVRU-UHFFFAOYSA-N ethyl 2-(7-chloro-2,3,4,5-tetrahydro-1h-1-benzazepin-5-yl)acetate Chemical compound CCOC(=O)CC1CCCNC2=CC=C(Cl)C=C12 ZYZRNZHXHROVRU-UHFFFAOYSA-N 0.000 description 1
- KIHVXGGIUNEZCI-UHFFFAOYSA-N ethyl 2-[1-(4-amino-3-methoxybenzoyl)-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC=CC=C2N1C(=O)C1=CC=C(N)C(OC)=C1 KIHVXGGIUNEZCI-UHFFFAOYSA-N 0.000 description 1
- HDQNHDJLWARNJI-UHFFFAOYSA-N ethyl 2-[1-(4-amino-3-methoxybenzoyl)-7-chloro-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC(Cl)=CC=C2N1C(=O)C1=CC=C(N)C(OC)=C1 HDQNHDJLWARNJI-UHFFFAOYSA-N 0.000 description 1
- PBGMJUWXXAYBLT-UHFFFAOYSA-N ethyl 2-[1-(4-amino-3-methylbenzoyl)-7-chloro-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC(Cl)=CC=C2N1C(=O)C1=CC=C(N)C(C)=C1 PBGMJUWXXAYBLT-UHFFFAOYSA-N 0.000 description 1
- BDRZSUMQWKIUCS-UHFFFAOYSA-N ethyl 2-[1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1-benzazepin-5-yl]acetate Chemical compound C12=CC=CC=C2C(CC(=O)OCC)CCCN1C(=O)C1=CC=C(N)C=C1 BDRZSUMQWKIUCS-UHFFFAOYSA-N 0.000 description 1
- YPGZRAATDBJDPG-UHFFFAOYSA-N ethyl 2-[1-(4-aminobenzoyl)-7-methoxy-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(N)C=C1 YPGZRAATDBJDPG-UHFFFAOYSA-N 0.000 description 1
- BXSBNWMFMFVXTG-UHFFFAOYSA-N ethyl 2-[1-(4-aminobenzoyl)-7-methyl-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC(C)=CC=C2N1C(=O)C1=CC=C(N)C=C1 BXSBNWMFMFVXTG-UHFFFAOYSA-N 0.000 description 1
- MDFQWOCDPWMNFI-UHFFFAOYSA-N ethyl 2-[1-(4-nitrobenzoyl)-2,3-dihydro-1-benzazepin-5-yl]acetate Chemical compound C12=CC=CC=C2C(CC(=O)OCC)=CCCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 MDFQWOCDPWMNFI-UHFFFAOYSA-N 0.000 description 1
- GAIVHHKTYLEGFS-UHFFFAOYSA-N ethyl 2-[1-(4-nitrobenzoyl)-3,4-dihydro-2h-1-benzazepin-5-ylidene]acetate Chemical compound C12=CC=CC=C2C(=CC(=O)OCC)CCCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 GAIVHHKTYLEGFS-UHFFFAOYSA-N 0.000 description 1
- OPSPTERJPRNOFA-UHFFFAOYSA-N ethyl 2-[1-[3-methoxy-4-[[2-(2-methylphenyl)benzoyl]amino]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC=CC=C2N1C(=O)C(C=C1OC)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1C OPSPTERJPRNOFA-UHFFFAOYSA-N 0.000 description 1
- OQCPPSRLWMHJDX-UHFFFAOYSA-N ethyl 2-[1-[4-[[2-(2,4-dimethylphenyl)benzoyl]amino]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1C OQCPPSRLWMHJDX-UHFFFAOYSA-N 0.000 description 1
- HDNOOPCYPWZMLC-UHFFFAOYSA-N ethyl 2-[5-(4-nitrobenzoyl)-3,4-dihydro-2h-1,5-benzodiazepin-1-yl]acetate Chemical compound C12=CC=CC=C2N(CC(=O)OCC)CCCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 HDNOOPCYPWZMLC-UHFFFAOYSA-N 0.000 description 1
- HSAQZWGSESPXSJ-UHFFFAOYSA-N ethyl 2-[7-chloro-1-(4-methylphenyl)sulfonyl-2,3,4,5-tetrahydro-1-benzazepin-5-yl]acetate Chemical compound C12=CC=C(Cl)C=C2C(CC(=O)OCC)CCCN1S(=O)(=O)C1=CC=C(C)C=C1 HSAQZWGSESPXSJ-UHFFFAOYSA-N 0.000 description 1
- WQBIRAKGVOXFMY-UHFFFAOYSA-N ethyl 2-[7-chloro-1-[4-[[2-(4-methylphenyl)benzoyl]amino]benzoyl]-2,3,4,5-tetrahydro-1-benzazepin-5-yl]acetate Chemical compound C12=CC=C(Cl)C=C2C(CC(=O)OCC)CCCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 WQBIRAKGVOXFMY-UHFFFAOYSA-N 0.000 description 1
- YUZLMKJTZFAGOY-UHFFFAOYSA-N ethyl 2-[7-methoxy-1-(4-nitrobenzoyl)-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C([N+]([O-])=O)C=C1 YUZLMKJTZFAGOY-UHFFFAOYSA-N 0.000 description 1
- XKNKQRXCRLECCH-UHFFFAOYSA-N ethyl 2-[[1-(4-nitrobenzoyl)-3,4-dihydro-2h-1-benzazepin-5-ylidene]amino]oxyacetate Chemical compound C12=CC=CC=C2C(=NOCC(=O)OCC)CCCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 XKNKQRXCRLECCH-UHFFFAOYSA-N 0.000 description 1
- SEUMGBKCEFNDQO-UHFFFAOYSA-N ethyl 2-[[1-[4-[[2-(4-methylphenyl)benzoyl]amino]benzoyl]-3,4-dihydro-2h-1-benzazepin-5-ylidene]amino]oxyacetate Chemical compound C12=CC=CC=C2C(=NOCC(=O)OCC)CCCN1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 SEUMGBKCEFNDQO-UHFFFAOYSA-N 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- LSHRXVNXLCASHM-UHFFFAOYSA-N ethyl 3-(4-chloro-2-nitroanilino)propanoate Chemical compound CCOC(=O)CCNC1=CC=C(Cl)C=C1[N+]([O-])=O LSHRXVNXLCASHM-UHFFFAOYSA-N 0.000 description 1
- MTXVYUUXEXLBDN-UHFFFAOYSA-N ethyl 3-(4-methoxy-2-nitroanilino)propanoate Chemical compound CCOC(=O)CCNC1=CC=C(OC)C=C1[N+]([O-])=O MTXVYUUXEXLBDN-UHFFFAOYSA-N 0.000 description 1
- RHODJPYPNDZHMI-UHFFFAOYSA-N ethyl 3-(4-methyl-2-nitroanilino)propanoate Chemical compound CCOC(=O)CCNC1=CC=C(C)C=C1[N+]([O-])=O RHODJPYPNDZHMI-UHFFFAOYSA-N 0.000 description 1
- KOZQIGBHJBRSGS-UHFFFAOYSA-N ethyl 3-(4-methyl-3-nitroanilino)propanoate Chemical compound CCOC(=O)CCNC1=CC=C(C)C([N+]([O-])=O)=C1 KOZQIGBHJBRSGS-UHFFFAOYSA-N 0.000 description 1
- VUCFNXCCNLKDGT-UHFFFAOYSA-N ethyl 3-(5-methyl-2-nitroanilino)propanoate Chemical compound CCOC(=O)CCNC1=CC(C)=CC=C1[N+]([O-])=O VUCFNXCCNLKDGT-UHFFFAOYSA-N 0.000 description 1
- MPMOSLLADCJMCE-UHFFFAOYSA-N ethyl 3-[1-(4-aminobenzoyl)-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]propanoate Chemical compound C1CC(=O)N(CCC(=O)OCC)C2=CC=CC=C2N1C(=O)C1=CC=C(N)C=C1 MPMOSLLADCJMCE-UHFFFAOYSA-N 0.000 description 1
- XYGJQICMUNGDDJ-UHFFFAOYSA-N ethyl 3-chloro-4-[[2-(2-methylphenyl)benzoyl]amino]benzoate Chemical compound ClC1=CC(C(=O)OCC)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1C XYGJQICMUNGDDJ-UHFFFAOYSA-N 0.000 description 1
- PQENQTHQHUXCIP-UHFFFAOYSA-N ethyl 4-[[2-(2,4-dimethylphenyl)benzoyl]amino]-2-nitrobenzoate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OCC)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1C PQENQTHQHUXCIP-UHFFFAOYSA-N 0.000 description 1
- GLGYPNYEPGPUSP-UHFFFAOYSA-N ethyl 4-[[2-(2-methylphenyl)benzoyl]amino]-3-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC(C(=O)OCC)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=CC=C1C GLGYPNYEPGPUSP-UHFFFAOYSA-N 0.000 description 1
- MFDTVONVIRHHBR-UHFFFAOYSA-N ethyl 4-amino-3-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(N)C(Cl)=C1 MFDTVONVIRHHBR-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- LNOQURRKNJKKBU-UHFFFAOYSA-N ethyl piperazine-1-carboxylate Chemical compound CCOC(=O)N1CCNCC1 LNOQURRKNJKKBU-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
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- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
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- 125000002541 furyl group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 150000004050 homopiperazines Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YWOITFUKFOYODT-UHFFFAOYSA-N methanol;sodium Chemical compound [Na].OC YWOITFUKFOYODT-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- BSMLZAOJOWFIGN-UHFFFAOYSA-N methyl 2-[1-(4-aminobenzoyl)-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OC)C2=CC=CC=C2N1C(=O)C1=CC=C(N)C=C1 BSMLZAOJOWFIGN-UHFFFAOYSA-N 0.000 description 1
- NECAPBLWPZVSOU-UHFFFAOYSA-N methyl 2-[1-(4-nitrobenzoyl)-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OC)C2=CC=CC=C2N1C(=O)C1=CC=C([N+]([O-])=O)C=C1 NECAPBLWPZVSOU-UHFFFAOYSA-N 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- JACPDLJUQLKABC-UHFFFAOYSA-N methyl 6-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(N)N=C1 JACPDLJUQLKABC-UHFFFAOYSA-N 0.000 description 1
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- MLACQEBQGUBHKX-UHFFFAOYSA-N n,n-dimethylpiperidin-1-amine Chemical compound CN(C)N1CCCCC1 MLACQEBQGUBHKX-UHFFFAOYSA-N 0.000 description 1
- RGZNRLBUBNWNRK-UHFFFAOYSA-N n-[3-methoxy-4-[5-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-4-oxo-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]phenyl]-2-(4-methylphenyl)benzamide Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3N(CC(=O)N3CCN(C)CC3)C(=O)CC2)C(OC)=CC=1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 RGZNRLBUBNWNRK-UHFFFAOYSA-N 0.000 description 1
- OSIPDNDDJZCGHG-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-2-(2,4-dimethylphenyl)benzamide Chemical compound CC1=CC(C)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3CCC2)C=C1 OSIPDNDDJZCGHG-UHFFFAOYSA-N 0.000 description 1
- UIPCZINKCRHCGU-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-2-(4-methylphenyl)benzamide Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3CCC2)C=C1 UIPCZINKCRHCGU-UHFFFAOYSA-N 0.000 description 1
- VTIALBJAVFHIOA-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-2-[2-[(dimethylamino)methyl]phenyl]benzamide Chemical compound CN(C)CC1=CC=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3CCC2)C=C1 VTIALBJAVFHIOA-UHFFFAOYSA-N 0.000 description 1
- RKAVICHNPXSHLO-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-2-pyrrol-1-ylbenzamide Chemical compound C=1C=C(C(=O)N2C3=CC=CC=C3CCC2)C=CC=1NC(=O)C1=CC=CC=C1N1C=CC=C1 RKAVICHNPXSHLO-UHFFFAOYSA-N 0.000 description 1
- QUHCTUKKUDXQIF-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-4-hydroxy-2-(4-methylphenyl)benzamide Chemical compound C1=CC(C)=CC=C1C1=CC(O)=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3CCC2)C=C1 QUHCTUKKUDXQIF-UHFFFAOYSA-N 0.000 description 1
- BRDQNZDAQYYKHP-UHFFFAOYSA-N n-[4-(3,4-dihydro-2h-quinoline-1-carbonyl)phenyl]-4-methoxy-2-(4-methylphenyl)benzamide Chemical compound C=1C(OC)=CC=C(C(=O)NC=2C=CC(=CC=2)C(=O)N2C3=CC=CC=C3CCC2)C=1C1=CC=C(C)C=C1 BRDQNZDAQYYKHP-UHFFFAOYSA-N 0.000 description 1
- NUCZZIZRPWEQBN-UHFFFAOYSA-N n-[4-(5-hydroxy-2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl)phenyl]-2-(2-methylphenyl)benzamide Chemical compound CC1=CC=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3C(O)CCC2)C=C1 NUCZZIZRPWEQBN-UHFFFAOYSA-N 0.000 description 1
- QZEDKHQQHOFELJ-UHFFFAOYSA-N n-[4-[4-[3-(dimethylamino)propylsulfanyl]-2,3-dihydro-1,5-benzodiazepine-1-carbonyl]phenyl]-2-(4-methylphenyl)benzamide Chemical compound C1CC(SCCCN(C)C)=NC2=CC=CC=C2N1C(=O)C(C=C1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 QZEDKHQQHOFELJ-UHFFFAOYSA-N 0.000 description 1
- XBEAARRAHCFINQ-UHFFFAOYSA-N n-[5-[5-(dimethylamino)-2,3,4,5-tetrahydro-1-benzazepine-1-carbonyl]pyridin-2-yl]-2-(4-methylphenyl)benzamide Chemical compound C12=CC=CC=C2C(N(C)C)CCCN1C(=O)C(C=N1)=CC=C1NC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 XBEAARRAHCFINQ-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000003336 oxytocin antagonist Substances 0.000 description 1
- 229940121361 oxytocin antagonists Drugs 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000065 phosphene Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 150000003018 phosphorus compounds Chemical class 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- GZRKXKUVVPSREJ-UHFFFAOYSA-N pyridinylpiperazine Chemical compound C1CNCCN1C1=CC=CC=N1 GZRKXKUVVPSREJ-UHFFFAOYSA-N 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- VUDHCYGQSKFHQD-UHFFFAOYSA-N tert-butyl 2-[4-(4-nitrobenzoyl)-2-oxo-3h-quinoxalin-1-yl]acetate Chemical compound C12=CC=CC=C2N(CC(=O)OC(C)(C)C)C(=O)CN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 VUDHCYGQSKFHQD-UHFFFAOYSA-N 0.000 description 1
- AAFYMBXFCLGHFT-UHFFFAOYSA-N tert-butyl 4-[2-[1-[4-[[2-(4-methylphenyl)benzoyl]amino]benzoyl]-4-oxo-2,3-dihydro-1,5-benzodiazepin-5-yl]acetyl]piperazine-1-carboxylate Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1C(=O)NC1=CC=C(C(=O)N2C3=CC=CC=C3N(CC(=O)N3CCN(CC3)C(=O)OC(C)(C)C)C(=O)CC2)C=C1 AAFYMBXFCLGHFT-UHFFFAOYSA-N 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- SYQIIBRVOSBWME-UHFFFAOYSA-N trichloromethyl formate Chemical compound ClC(Cl)(Cl)OC=O SYQIIBRVOSBWME-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920001567 vinyl ester resin Polymers 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
- C07D215/08—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
-
- 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
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/04—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/12—1,5-Benzodiazepines; Hydrogenated 1,5-benzodiazepines
-
- 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
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Hematology (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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB939307527A GB9307527D0 (en) | 1993-04-13 | 1993-04-13 | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
Publications (2)
Publication Number | Publication Date |
---|---|
HU9401041D0 HU9401041D0 (en) | 1994-08-29 |
HUT70197A true HUT70197A (en) | 1995-09-28 |
Family
ID=10733683
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HU9401041A HUT70197A (en) | 1993-04-13 | 1994-04-12 | New benzamide derivatives, process for producing them and pharmaceutical compositions containing them |
Country Status (17)
Country | Link |
---|---|
US (1) | US5521170A (en, 2012) |
EP (1) | EP0620216B1 (en, 2012) |
JP (1) | JPH072800A (en, 2012) |
KR (1) | KR100290112B1 (en, 2012) |
CN (1) | CN1058710C (en, 2012) |
AT (1) | ATE230729T1 (en, 2012) |
AU (1) | AU679719B2 (en, 2012) |
CA (1) | CA2121112A1 (en, 2012) |
DE (1) | DE69431974T2 (en, 2012) |
DK (1) | DK0620216T3 (en, 2012) |
ES (1) | ES2185635T3 (en, 2012) |
GB (1) | GB9307527D0 (en, 2012) |
HU (1) | HUT70197A (en, 2012) |
IL (1) | IL109228A0 (en, 2012) |
PH (1) | PH30793A (en, 2012) |
TW (1) | TW260667B (en, 2012) |
ZA (1) | ZA942325B (en, 2012) |
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GB9508637D0 (en) * | 1995-04-28 | 1995-06-14 | Fujisawa Pharmaceutical Co | New use |
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US7326700B2 (en) | 2001-04-12 | 2008-02-05 | Wyeth | Cyclohexenyl phenyl carboxamides tocolytic oxytocin receptor antagonists |
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EP2532643A1 (en) | 2007-06-08 | 2012-12-12 | MannKind Corporation | IRE-1A Inhibitors |
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EP2217576B1 (en) | 2007-11-06 | 2016-05-11 | The Regents of the University of Michigan | Benzodiazepinone compounds useful in the treatment of skin conditions |
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ES2703752T3 (es) | 2009-11-17 | 2019-03-12 | Univ Michigan Regents | 1,4-Benzodiazepina-2,5-dionas y compuestos relacionados que presentan propiedades terapéuticas |
FR2969605A1 (fr) * | 2010-12-28 | 2012-06-29 | Univ Strasbourg | Derives de 2,3,4,5-tetrahydro-1h-benzo[b]azepine et leur utilisation |
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Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0450097T3 (da) * | 1989-10-20 | 1996-05-20 | Otsuka Pharma Co Ltd | Benzoheterocykliske forbindelser |
JP2905909B2 (ja) * | 1991-04-19 | 1999-06-14 | 大塚製薬株式会社 | バソプレシン拮抗剤 |
US5258510A (en) * | 1989-10-20 | 1993-11-02 | Otsuka Pharma Co Ltd | Benzoheterocyclic compounds |
CA2066104C (en) * | 1991-04-19 | 2003-05-27 | Hidenori Ogawa | Benzazepine derivatives as vasopressin antagonists |
JPH05320135A (ja) * | 1992-05-19 | 1993-12-03 | Yamanouchi Pharmaceut Co Ltd | テトラヒドロベンズアゼピン誘導体 |
AU657424B2 (en) * | 1992-07-02 | 1995-03-09 | Otsuka Pharmaceutical Co., Ltd. | Oxytocin antagonist |
JPH06157480A (ja) * | 1992-11-30 | 1994-06-03 | Yamanouchi Pharmaceut Co Ltd | 新規なベンズアニリド誘導体 |
WO1994020473A1 (en) * | 1993-03-11 | 1994-09-15 | Yamanouchi Pharmaceutical Co., Ltd. | Compound with vasopressin antagonism |
-
1993
- 1993-04-13 GB GB939307527A patent/GB9307527D0/en active Pending
-
1994
- 1994-03-31 US US08/220,695 patent/US5521170A/en not_active Expired - Fee Related
- 1994-04-05 IL IL10922894A patent/IL109228A0/xx unknown
- 1994-04-07 DE DE69431974T patent/DE69431974T2/de not_active Expired - Fee Related
- 1994-04-07 PH PH48055A patent/PH30793A/en unknown
- 1994-04-07 ES ES94105344T patent/ES2185635T3/es not_active Expired - Lifetime
- 1994-04-07 EP EP94105344A patent/EP0620216B1/en not_active Expired - Lifetime
- 1994-04-07 AT AT94105344T patent/ATE230729T1/de not_active IP Right Cessation
- 1994-04-07 TW TW083103003A patent/TW260667B/zh active
- 1994-04-07 DK DK94105344T patent/DK0620216T3/da active
- 1994-04-08 AU AU59322/94A patent/AU679719B2/en not_active Ceased
- 1994-04-11 KR KR1019940007553A patent/KR100290112B1/ko not_active Expired - Fee Related
- 1994-04-12 CN CN94103577A patent/CN1058710C/zh not_active Expired - Fee Related
- 1994-04-12 HU HU9401041A patent/HUT70197A/hu unknown
- 1994-04-12 JP JP6072997A patent/JPH072800A/ja active Pending
- 1994-04-12 CA CA002121112A patent/CA2121112A1/en not_active Abandoned
- 1994-10-31 ZA ZA942325A patent/ZA942325B/xx unknown
Also Published As
Publication number | Publication date |
---|---|
CN1098406A (zh) | 1995-02-08 |
AU5932294A (en) | 1994-10-20 |
JPH072800A (ja) | 1995-01-06 |
IL109228A0 (en) | 1994-07-31 |
EP0620216B1 (en) | 2003-01-08 |
ATE230729T1 (de) | 2003-01-15 |
PH30793A (en) | 1997-10-17 |
US5521170A (en) | 1996-05-28 |
TW260667B (en, 2012) | 1995-10-21 |
DK0620216T3 (da) | 2003-05-05 |
DE69431974D1 (de) | 2003-02-13 |
EP0620216A1 (en) | 1994-10-19 |
KR100290112B1 (ko) | 2001-05-15 |
ES2185635T3 (es) | 2003-05-01 |
GB9307527D0 (en) | 1993-06-02 |
HU9401041D0 (en) | 1994-08-29 |
ZA942325B (en) | 1995-02-16 |
CN1058710C (zh) | 2000-11-22 |
DE69431974T2 (de) | 2003-05-22 |
CA2121112A1 (en) | 1994-10-14 |
AU679719B2 (en) | 1997-07-10 |
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