NO844423L - 11-substituerte 5h,11h-pyrrolo(2,1-c)(1,4)benzoksazepin, fremgangsmaate til dets fremstilling samt anvendelse som legemiddel - Google Patents

11-substituerte 5h,11h-pyrrolo(2,1-c)(1,4)benzoksazepin, fremgangsmaate til dets fremstilling samt anvendelse som legemiddel

Info

Publication number: NO844423L
Authority: NO; Norway
Prior art keywords: compound; formula; give; pyrrolo; piperidin
Prior art date: 1983-11-07

Application number

NO844423A

Other languages

English (en)

Norwegian (no)

Inventor

Richard C Effland

Larry Davis

Kevin J Kapples

Original Assignee

Hoechst Roussel Pharma

Priority date (The priority date 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 date listed.)

1983-11-07

Filing date

1984-11-06

Publication date

1985-05-08

1984-11-06 Application filed by Hoechst Roussel Pharma filed Critical Hoechst Roussel Pharma

1985-05-08 Publication of NO844423L publication Critical patent/NO844423L/no

Links

238000002360 preparation method Methods 0.000 title claims description 12
238000000034 method Methods 0.000 title claims description 8
150000001875 compounds Chemical class 0.000 claims description 120
239000007787 solid Substances 0.000 claims description 119
ZCXLTWVZYXBHJS-UHFFFAOYSA-N 1,2-benzoxazepine Chemical compound O1N=CC=CC2=CC=CC=C12 ZCXLTWVZYXBHJS-UHFFFAOYSA-N 0.000 claims description 39
-1 cyano, hydroxy, cyclohexyl Chemical group 0.000 claims description 37
238000006243 chemical reaction Methods 0.000 claims description 34
125000000217 alkyl group Chemical group 0.000 claims description 29
239000000460 chlorine Substances 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
238000007327 hydrogenolysis reaction Methods 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000001544 thienyl group Chemical group 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 4
239000003849 aromatic solvent Substances 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000002798 polar solvent Substances 0.000 claims description 4
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
WMJMABVHDMRMJA-UHFFFAOYSA-M [Cl-].[Mg+]C1CCCCC1 Chemical compound [Cl-].[Mg+]C1CCCCC1 WMJMABVHDMRMJA-UHFFFAOYSA-M 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
239000011230 binding agent Substances 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
239000007788 liquid Substances 0.000 claims description 3
229910052751 metal Inorganic materials 0.000 claims description 3
239000002184 metal Substances 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
150000003751 zinc Chemical class 0.000 claims description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 15
239000004480 active ingredient Substances 0.000 claims 2
238000006798 ring closing metathesis reaction Methods 0.000 claims 2
150000001266 acyl halides Chemical class 0.000 claims 1
150000001350 alkyl halides Chemical class 0.000 claims 1
239000012752 auxiliary agent Substances 0.000 claims 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
229940126601 medicinal product Drugs 0.000 claims 1
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 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 261
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 178
239000000243 solution Substances 0.000 description 175
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 159
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 92
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
235000019439 ethyl acetate Nutrition 0.000 description 91
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 76
239000003921 oil Substances 0.000 description 76
239000000203 mixture Substances 0.000 description 72
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 63
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
239000002904 solvent Substances 0.000 description 45
238000003756 stirring Methods 0.000 description 43
239000011541 reaction mixture Substances 0.000 description 40
238000004128 high performance liquid chromatography Methods 0.000 description 37
239000000463 material Substances 0.000 description 32
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 30
150000001412 amines Chemical class 0.000 description 30
238000001914 filtration Methods 0.000 description 30
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 25
239000002244 precipitate Substances 0.000 description 25
238000000354 decomposition reaction Methods 0.000 description 23
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
235000006408 oxalic acid Nutrition 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 16
150000001408 amides Chemical class 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 13
239000012280 lithium aluminium hydride Substances 0.000 description 11
238000010992 reflux Methods 0.000 description 11
239000000725 suspension Substances 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 10
239000011734 sodium Substances 0.000 description 10
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
239000005457 ice water Substances 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
239000013078 crystal Substances 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
239000000126 substance Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
150000004795 grignard reagents Chemical class 0.000 description 7
229910000104 sodium hydride Inorganic materials 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
239000007818 Grignard reagent Substances 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 6
229960004046 apomorphine Drugs 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
150000003891 oxalate salts Chemical class 0.000 description 6
239000000047 product Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
230000009194 climbing Effects 0.000 description 5
235000011087 fumaric acid Nutrition 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
238000000746 purification Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 4
BARLPBPUTCZWPM-WLHGVMLRSA-N 1,2-benzoxazepine;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.O1N=CC=CC2=CC=CC=C12 BARLPBPUTCZWPM-WLHGVMLRSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000001530 fumaric acid Substances 0.000 description 4
239000011521 glass Substances 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 3
MYGXGCCFTPKWIH-UHFFFAOYSA-N 4-chloro-1-methylpiperidine Chemical compound CN1CCC(Cl)CC1 MYGXGCCFTPKWIH-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
230000000202 analgesic effect Effects 0.000 description 3
230000000561 anti-psychotic effect Effects 0.000 description 3
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
238000001665 trituration Methods 0.000 description 3
KDGZMBSTLZUZPE-UHFFFAOYSA-N 1,2-benzoxazepine;oxalic acid Chemical compound OC(=O)C(O)=O.O1N=CC=CC2=CC=CC=C12 KDGZMBSTLZUZPE-UHFFFAOYSA-N 0.000 description 2
UWXIKAZQXAYFPT-UHFFFAOYSA-N 1,4-benzoxazepine Chemical compound O1C=CN=CC2=CC=CC=C12 UWXIKAZQXAYFPT-UHFFFAOYSA-N 0.000 description 2
WFMSAHWKWXBPRA-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]pyrrole-2-carbaldehyde Chemical compound FC1=CC=CC=C1CN1C(C=O)=CC=C1 WFMSAHWKWXBPRA-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
238000003747 Grignard reaction Methods 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
150000008038 benzoazepines Chemical class 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000008298 dragée Substances 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
230000007017 scission Effects 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000008174 sterile solution Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000003826 tablet Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
NTURQZFFJDCTMZ-UHFFFAOYSA-N 1-(2-bromoethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CCBr)C=C1 NTURQZFFJDCTMZ-UHFFFAOYSA-N 0.000 description 1
MOHHYRNERKYTEA-UHFFFAOYSA-N 1-(2-chloroethyl)-2,3-dimethoxybenzene Chemical compound COC1=CC=CC(CCCl)=C1OC MOHHYRNERKYTEA-UHFFFAOYSA-N 0.000 description 1
DVVUYHHYCOHCNH-UHFFFAOYSA-N 1-(2-chloroethyl)-4-ethoxybenzene Chemical compound CCOC1=CC=C(CCCl)C=C1 DVVUYHHYCOHCNH-UHFFFAOYSA-N 0.000 description 1
LPUURRVXQCVXCX-UHFFFAOYSA-N 1-(2-chloroethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCCl)C=C1 LPUURRVXQCVXCX-UHFFFAOYSA-N 0.000 description 1
QIJNVLLXIIPXQT-UHFFFAOYSA-N 1-(4-fluorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=C(F)C=C1 QIJNVLLXIIPXQT-UHFFFAOYSA-N 0.000 description 1
MOBRMRJUKNQBMY-UHFFFAOYSA-N 1-(chloromethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCl MOBRMRJUKNQBMY-UHFFFAOYSA-N 0.000 description 1
XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 1
WJKYPEYVAMJLQL-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]-5-methylpyrrole-2-carbaldehyde Chemical compound CC1=CC=C(C=O)N1CC1=CC=CC=C1F WJKYPEYVAMJLQL-UHFFFAOYSA-N 0.000 description 1
PAMPHILDHRTJLG-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carbaldehyde Chemical compound C1C(C=O)CCN1CC1=CC=CC=C1 PAMPHILDHRTJLG-UHFFFAOYSA-N 0.000 description 1
LECYCYNAEJDSIL-UHFFFAOYSA-N 1-bromo-2-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC=C1Br LECYCYNAEJDSIL-UHFFFAOYSA-N 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
CNCVUPUJXVURKY-UHFFFAOYSA-N 2-(3,4,5-trimethoxyphenyl)ethyl methanesulfonate Chemical compound COC1=CC(CCOS(C)(=O)=O)=CC(OC)=C1OC CNCVUPUJXVURKY-UHFFFAOYSA-N 0.000 description 1
QDZAWVLWIMOXJT-UHFFFAOYSA-N 2-(4-methylphenyl)acetyl chloride Chemical compound CC1=CC=C(CC(Cl)=O)C=C1 QDZAWVLWIMOXJT-UHFFFAOYSA-N 0.000 description 1
UNRGEIXQCZHICP-UHFFFAOYSA-N 2-(chloromethyl)-1,3,5-trimethylbenzene Chemical compound CC1=CC(C)=C(CCl)C(C)=C1 UNRGEIXQCZHICP-UHFFFAOYSA-N 0.000 description 1
SKUSNIXIBFEGSU-UHFFFAOYSA-N 2-[4-(trifluoromethyl)phenyl]ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=CC=C(C(F)(F)F)C=C1 SKUSNIXIBFEGSU-UHFFFAOYSA-N 0.000 description 1
SAQAERNKMHATDZ-UHFFFAOYSA-N 2-bromo-1h-pyrrole Chemical compound BrC1=CC=CN1 SAQAERNKMHATDZ-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
OFTKFKYVSBNYEC-UHFFFAOYSA-N 2-furoyl chloride Chemical compound ClC(=O)C1=CC=CO1 OFTKFKYVSBNYEC-UHFFFAOYSA-N 0.000 description 1
PKUPAJQAJXVUEK-UHFFFAOYSA-N 2-phenoxyacetyl chloride Chemical compound ClC(=O)COC1=CC=CC=C1 PKUPAJQAJXVUEK-UHFFFAOYSA-N 0.000 description 1
RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 1
VTXNOVCTHUBABW-UHFFFAOYSA-N 3,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1 VTXNOVCTHUBABW-UHFFFAOYSA-N 0.000 description 1
XONBKLFCLPGIPC-UHFFFAOYSA-N 3-(3-chloropropyl)-6-fluoro-1,2-benzoxazole Chemical compound FC1=CC=C2C(CCCCl)=NOC2=C1 XONBKLFCLPGIPC-UHFFFAOYSA-N 0.000 description 1
NIDWUZTTXGJFNN-UHFFFAOYSA-N 3-bromopropoxybenzene Chemical compound BrCCCOC1=CC=CC=C1 NIDWUZTTXGJFNN-UHFFFAOYSA-N 0.000 description 1
AAHQPLJUSLMHHR-UHFFFAOYSA-N 3-chloro-1-(4-fluorophenyl)propan-1-one Chemical compound FC1=CC=C(C(=O)CCCl)C=C1 AAHQPLJUSLMHHR-UHFFFAOYSA-N 0.000 description 1
XZBXAYCCBFTQHH-UHFFFAOYSA-N 3-chloropropylbenzene Chemical compound ClCCCC1=CC=CC=C1 XZBXAYCCBFTQHH-UHFFFAOYSA-N 0.000 description 1
NNLAGIHHJWDWIQ-UHFFFAOYSA-N 4-(2-chloroethyl)-2-methoxyphenol Chemical compound COC1=CC(CCCl)=CC=C1O NNLAGIHHJWDWIQ-UHFFFAOYSA-N 0.000 description 1
JAJYJABMCMDWHA-UHFFFAOYSA-N 4-(2-chloroethyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(CCCl)C=C1 JAJYJABMCMDWHA-UHFFFAOYSA-N 0.000 description 1
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
IGYSFJHVFHNOEI-UHFFFAOYSA-N 4-bromo-2,2-diphenylbutanenitrile Chemical compound C=1C=CC=CC=1C(C#N)(CCBr)C1=CC=CC=C1 IGYSFJHVFHNOEI-UHFFFAOYSA-N 0.000 description 1
YTEUQGXRCFYPSA-UHFFFAOYSA-N 4-chloro-1-(4-fluorophenyl)butan-1-ol Chemical compound ClCCCC(O)C1=CC=C(F)C=C1 YTEUQGXRCFYPSA-UHFFFAOYSA-N 0.000 description 1
RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
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 1
240000008415 Lactuca sativa Species 0.000 description 1
229910010082 LiAlH Inorganic materials 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
XFZWZCZNZVMAIK-UHFFFAOYSA-N OS(=O)(=O)CCCC1=CC=CC=C1F Chemical compound OS(=O)(=O)CCCC1=CC=CC=C1F XFZWZCZNZVMAIK-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
244000018633 Prunus armeniaca Species 0.000 description 1
235000009827 Prunus armeniaca Nutrition 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
UCTLHLZWKJIXJI-LXIBVNSESA-N [(3s,8r,9s,10r,13s,14s)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1h-cyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(Cl)=C(C=O)C[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 UCTLHLZWKJIXJI-LXIBVNSESA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
150000001243 acetic acids Chemical class 0.000 description 1
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic anhydride Substances CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 1
WFDIJRYMOXRFFG-XPULMUKRSA-N acetyl acetate Chemical compound [14CH3]C(=O)OC([14CH3])=O WFDIJRYMOXRFFG-XPULMUKRSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001263 acyl chlorides Chemical class 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001348 alkyl chlorides Chemical class 0.000 description 1
230000036592 analgesia Effects 0.000 description 1
MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
229940005529 antipsychotics Drugs 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000000872 buffer Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
YKWNUSJLICDQEO-UHFFFAOYSA-N ethoxyethane;propan-2-ol Chemical compound CC(C)O.CCOCC YKWNUSJLICDQEO-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
150000002238 fumaric acids Chemical class 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical group CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
150000002689 maleic acids Chemical class 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
235000019392 nitrosyl chloride Nutrition 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002913 oxalic acids Chemical class 0.000 description 1
230000036407 pain Effects 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000010791 quenching Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
235000012045 salad Nutrition 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
150000003444 succinic acids Chemical class 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
238000007039 two-step reaction Methods 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurosurgery (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Neurology (AREA)
Public Health (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO844423A 1983-11-07 1984-11-06 11-substituerte 5h,11h-pyrrolo(2,1-c)(1,4)benzoksazepin, fremgangsmaate til dets fremstilling samt anvendelse som legemiddel NO844423L (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US06/549,098 US4608374A (en)	1983-11-07	1983-11-07	11-substituted 5H,11H-pyrrolo[2,1-c][1,4]benzoxazepines as antipsychotic and analgesic agents

Publications (1)

Publication Number	Publication Date
NO844423L true NO844423L (no)	1985-05-08

Family

ID=24191656

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO844423A NO844423L (no)	1983-11-07	1984-11-06	11-substituerte 5h,11h-pyrrolo(2,1-c)(1,4)benzoksazepin, fremgangsmaate til dets fremstilling samt anvendelse som legemiddel

Country Status (19)

Country	Link
US (1)	US4608374A (de)
EP (2)	EP0144729B1 (de)
JP (1)	JPS60115590A (de)
KR (1)	KR850003893A (de)
AT (1)	ATE47856T1 (de)
AU (2)	AU582553B2 (de)
CA (1)	CA1267893A (de)
DE (1)	DE3480399D1 (de)
DK (1)	DK527984A (de)
ES (4)	ES8608524A1 (de)
FI (1)	FI78103C (de)
GR (1)	GR80839B (de)
HU (1)	HU193233B (de)
IL (1)	IL73434A0 (de)
NO (1)	NO844423L (de)
NZ (1)	NZ210100A (de)
PH (1)	PH21257A (de)
PT (1)	PT79457B (de)
ZA (1)	ZA848655B (de)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4758559A (en) *	1986-01-21	1988-07-19	Ciba-Geigy Corporation	Pyrrolo[1,2-a] [4,1]benzoxazepine derivatives useful as calmodulin and histamine inhibitors
US4794110A (en) *	1987-07-20	1988-12-27	Hoechst-Roussel Pharmaceuticals, Inc.	5-Aryl-11-substituted-5H,11H-pyrrolo[2,1-c][1,4]benzoxazepined as analgesic and hypotensive agents
US4865764A (en) *	1987-07-20	1989-09-12	Hoechst-Roussel Pharmaceuticals, Inc.	5-aryl-11-substituted-5H,11H-pyrrolo[2,1-][1,4]benzoxazepines as hypotensive agents
US4812450A (en) *	1987-07-30	1989-03-14	Hoechst-Roussel Pharmaceuticals Inc.	Spiro((piperidine-pyrrolidine- or hexahydroazepinyl substituted) pyrrolo(2,1-C) (1,4)benzoxazepines)
US5015637A (en) *	1990-05-25	1991-05-14	Hoechst-Roussel Pharmaceutical Inc.	Pyrido[3,4-b]pyrrolo[1,2-e][1,4,5]oxadiazepines
GB9418326D0 (en) *	1994-09-12	1994-11-02	Lilly Industries Ltd	Pharmaceutical compounds
GB2308362A (en) *	1995-12-19	1997-06-25	Lilly Industries Ltd	Pharmaceutical indole derivatives
AU2002322720B2 (en)	2001-07-25	2008-11-13	Raptor Pharmaceutical Inc.	Compositions and methods for modulating blood-brain barrier transport
JP4400441B2 (ja)	2004-12-14	2010-01-20	三菱電機株式会社	半導体装置
CN102379684B (zh)	2005-04-28	2014-11-19	普罗透斯数字保健公司	药物信息系统
KR20090071598A (ko)	2006-09-18	2009-07-01	랩터 파마슈티컬 인코포레이티드	수용체 결합 단백질(ｒａｐ)-접합체 투여에 의한 간 질환의 치료
GB0711776D0 (en) *	2007-06-18	2007-07-25	Syngenta Participations Ag	Substituted aromatic heterocyclic compounds as fungicides
EP2398500B1 (de)	2009-02-20	2019-03-13	2-BBB Medicines B.V.	Arzneiabgabesystem auf glutathion-basis
ES2942923T3 (es)	2009-05-06	2023-06-07	Laboratory Skin Care Inc	Composiciones de administración dérmica que comprenden complejos de agente activo-partículas de fosfato de calcio y métodos de uso de las mismas
US20120077778A1 (en)	2010-09-29	2012-03-29	Andrea Bourdelais	Ladder-Frame Polyether Conjugates

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4029672A (en) *	1976-02-26	1977-06-14	American Hoechst Corporation	Aminoalkylpyrrolobenzoxazalkanes
US4053599A (en) *	1976-02-26	1977-10-11	American Hoechst Corporation	Piperazionalkylpyrrolobenzoxazalkanes
US4045448A (en) *	1976-02-26	1977-08-30	American Hoechst Corporation	Pyrrolo[2,1-c][1,4]benzoxazepine and benzoxazocine derivatives
US4169095A (en) *	1977-01-19	1979-09-25	American Hoechst Corporation	Process for preparing aminoalkylpyrrolobenzoxazalkanes
US4169094A (en) *	1977-01-19	1979-09-25	American Hoechst Corporation	Process for preparing aminoalkylpyrrolobenzoxazalkanes
US4263438A (en) *	1977-09-13	1981-04-21	Pfizer Inc.	3-[2,4-(Disubstituted)-phenyl]azacycloalkanones as analgesics
US4208417A (en) *	1978-06-29	1980-06-17	Pharmindustrie	Indole derivatives and their use as anxiolytics
GR73560B (de) *	1979-02-24	1984-03-15	Pfizer
CA1211437A (en) *	1981-08-12	1986-09-16	Rene Borer	Benzazepines

1983
- 1983-11-07 US US06/549,098 patent/US4608374A/en not_active Expired - Fee Related
1984
- 1984-10-31 HU HU844037A patent/HU193233B/hu not_active IP Right Cessation
- 1984-11-02 DE DE8484113181T patent/DE3480399D1/de not_active Expired
- 1984-11-02 EP EP84113181A patent/EP0144729B1/de not_active Expired
- 1984-11-02 AT AT84113181T patent/ATE47856T1/de not_active IP Right Cessation
- 1984-11-02 EP EP87110724A patent/EP0258612A1/de not_active Withdrawn
- 1984-11-05 GR GR80839A patent/GR80839B/el unknown
- 1984-11-05 NZ NZ210100A patent/NZ210100A/xx unknown
- 1984-11-05 AU AU35104/84A patent/AU582553B2/en not_active Ceased
- 1984-11-05 PH PH31405A patent/PH21257A/en unknown
- 1984-11-05 IL IL73434A patent/IL73434A0/xx unknown
- 1984-11-05 FI FI844333A patent/FI78103C/fi not_active IP Right Cessation
- 1984-11-05 ES ES537369A patent/ES8608524A1/es not_active Expired
- 1984-11-06 CA CA000467151A patent/CA1267893A/en not_active Expired - Lifetime
- 1984-11-06 NO NO844423A patent/NO844423L/no unknown
- 1984-11-06 DK DK527984A patent/DK527984A/da not_active Application Discontinuation
- 1984-11-06 ZA ZA848655A patent/ZA848655B/xx unknown
- 1984-11-06 JP JP59232553A patent/JPS60115590A/ja active Pending
- 1984-11-06 PT PT79457A patent/PT79457B/pt unknown
- 1984-11-07 KR KR1019840006971A patent/KR850003893A/ko not_active Ceased
1985
- 1985-07-30 ES ES545728A patent/ES8707538A1/es not_active Expired
1986
- 1986-01-31 ES ES551522A patent/ES8704950A1/es not_active Expired
- 1986-03-01 ES ES552578A patent/ES8707953A1/es not_active Expired
1989
- 1989-01-18 AU AU28565/89A patent/AU2856589A/en not_active Abandoned

Also Published As

Publication number	Publication date
DK527984D0 (da)	1984-11-06
FI78103C (fi)	1989-06-12
AU2856589A (en)	1989-07-13
ES8704950A1 (es)	1987-04-16
DE3480399D1 (en)	1989-12-14
DK527984A (da)	1985-05-08
PH21257A (en)	1987-08-31
ES8707538A1 (es)	1987-08-01
FI844333A0 (fi)	1984-11-05
KR850003893A (ko)	1985-06-29
FI844333L (fi)	1985-05-08
JPS60115590A (ja)	1985-06-22
PT79457B (en)	1986-11-14
GR80839B (en)	1985-02-26
ES8608524A1 (es)	1986-06-16
ATE47856T1 (de)	1989-11-15
EP0144729B1 (de)	1989-11-08
ES552578A0 (es)	1987-09-16
HUT36127A (en)	1985-08-28
ES545728A0 (es)	1987-08-01
PT79457A (en)	1984-12-01
EP0144729A1 (de)	1985-06-19
ES8707953A1 (es)	1987-09-16
ES551522A0 (es)	1987-04-16
EP0258612A1 (de)	1988-03-09
HU193233B (en)	1987-08-28
AU582553B2 (en)	1989-04-06
CA1267893A (en)	1990-04-17
ES537369A0 (es)	1986-06-16
FI78103B (fi)	1989-02-28
IL73434A0 (en)	1985-02-28
NZ210100A (en)	1988-06-30
ZA848655B (en)	1985-06-26
AU3510484A (en)	1985-05-16
US4608374A (en)	1986-08-26

Publication	Publication Date	Title
FI82242B (fi)	1990-10-31	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 3-(piperidinyl)-1h-indazolderivat.
KR100815772B1 (ko)	2008-03-20	신규 고리상 아미드 유도체
US6380238B1 (en)	2002-04-30	Indoline derivatives as 5-HT2B and or 5-HTC receptor ligands
US6727264B1 (en)	2004-04-27	Substituted anilinic piperidines as MCH selective antagonists
US4670447A (en)	1987-06-02	Antipsychotic 3-(piperidinyl)- and 3-(pyrrolidinyl)-1H-indazoles
TW200811141A (en)	2008-03-01	Cyclohexylpyrazole-lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
EP0144729B1 (de)	1989-11-08	11-Substituierte 5H,11H-Pyrrolo[2,1-c][1,4]benzoxazepine, ein Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
CA2454613A1 (en)	2003-01-16	Substituted anilinic piperidines as mch selective antagonists
NO176143B (no)	1994-10-31	Analogifremgangsmåte for fremstilling av terapeutisk aktive 3-[4(1-substituert 4-piperazinyl)butylÅ-4-tiazlidinoner
US5864039A (en)	1999-01-26	Benzoic acid compounds and use thereof as medicaments
JPWO2001064670A1 (ja)	2003-07-02	新規環状アミド誘導体
DK155327B (da)	1989-03-28	Analogifremgangsmaade til fremstilling af 5h-2,3-benzodiazepinderivater eller et farmaceutisk acceptabelt syreadditionssalt deraf
WO2000066551A1 (en)	2000-11-09	Cyclic amide compounds, process for the preparation of the same and uses thereof
MX2011003500A (es)	2011-05-02	Derivado de 7-piperidinoalquil-3,4-dihidroquinolona.
IL99264A (en)	1996-01-19	6,7-dihydro-3-phenyl-1,2-benzisoxazol-4(5h)-ones and ols a process for their preparation and their use as medicaments
NZ239038A (en)	1994-04-27	1-(pyridinylamino)-1h-indoylcarbamate ester derivative, preparation and pharmaceutical compositions thereof
US4458075A (en)	1984-07-03	6-Fluoro-3-[3-(1-heterocyclo)propyl]-1,2-benzisoxazoles
US4681879A (en)	1987-07-21	11-substituted 5H,11H-pyrrolo[2,1-c][1,4]benzoxazepines as antipsychotic and analgesic agents
US4667039A (en)	1987-05-19	11-substituted 5H,11H-pyrrolo(2,1-C) (1,4)benzoxazepines as antipsychotic and analgesic agents
RU2038355C1 (ru)	1995-06-27	Способ получения 3-(1-тиазолидинилбутил-4-пиперазинил)-1н-индазолов
AU718719B2 (en)	2000-04-20	4-{(thien-2-yl)methyl}imidazole derivatives having alpha2-adrenoceptor agonistic activity
US8912179B2 (en)	2014-12-16	Heterocyclyl compounds as histamine H3 receptor ligands
NO151387B (no)	1984-12-17	Innstillingsinnretning for en elektronisk digitalindikator
WO1997011054A1 (fr)	1997-03-27	Composes d'acide benzoique et leur emploi medical
DE60019619T2 (de)	2006-03-02	Dihydrobenzofuranderivate, verfahren zu ihrer herstellung und mittel