CA1058610A - 17a, 21-diesters of the pregnane series - Google Patents
17a, 21-diesters of the pregnane seriesInfo
- Publication number
- CA1058610A CA1058610A CA232,579A CA232579A CA1058610A CA 1058610 A CA1058610 A CA 1058610A CA 232579 A CA232579 A CA 232579A CA 1058610 A CA1058610 A CA 1058610A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- group
- beta
- compound
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 150000003128 pregnanes Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 239000002253 acid Substances 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000005864 Sulphur Substances 0.000 claims abstract description 4
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
- 239000011737 fluorine Substances 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
- 125000000468 ketone group Chemical group 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- -1 sulphonyloxy group Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 150000004820 halides Chemical class 0.000 claims description 5
- 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 5
- QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- VIWZVFVJPXTXPA-UHFFFAOYSA-N N-(2-Carboxymethyl)-morpholine Chemical compound OC(=O)CN1CCOCC1 VIWZVFVJPXTXPA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 8
- 230000009885 systemic effect Effects 0.000 abstract description 7
- 230000000699 topical effect Effects 0.000 abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 229910001868 water Inorganic materials 0.000 description 35
- 239000000203 mixture Substances 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 15
- 239000007787 solid Substances 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
- ITYMTTQVNYAJAA-XGQKBEPLSA-N [(8s,9r,10s,11s,13s,14s,16s,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(OC(=O)CC)[C@@]1(C)C[C@@H]2O ITYMTTQVNYAJAA-XGQKBEPLSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 150000003431 steroids Chemical class 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 239000006260 foam Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229940089960 chloroacetate Drugs 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 3
- 229960002537 betamethasone Drugs 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 150000004682 monohydrates Chemical class 0.000 description 3
- PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 2
- UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 239000004677 Nylon Substances 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 230000001506 immunosuppresive effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 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
- 229960004927 neomycin Drugs 0.000 description 2
- 229920001778 nylon Polymers 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000007614 solvation Methods 0.000 description 2
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- 239000000829 suppository Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
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- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
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- 241000786363 Rhampholeon spectrum Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- GGISZLOBBISXOZ-UHFFFAOYSA-N acetic acid;chloroform Chemical compound CC(O)=O.ClC(Cl)Cl GGISZLOBBISXOZ-UHFFFAOYSA-N 0.000 description 1
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- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
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- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- 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 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
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- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
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- 238000002329 infrared spectrum Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- ZBJWWKFMHOAPNS-UHFFFAOYSA-N loretin Chemical compound C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 ZBJWWKFMHOAPNS-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 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 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical class OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0088—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing unsubstituted amino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB33786/74A GB1516095A (en) | 1974-07-31 | 1974-07-31 | 17,21-diesters of 17alpha,21-dihydroxy-steroids of the pregnane series |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1058610A true CA1058610A (en) | 1979-07-17 |
Family
ID=10357423
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA232,579A Expired CA1058610A (en) | 1974-07-31 | 1975-07-30 | 17a, 21-diesters of the pregnane series |
Country Status (13)
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4456602A (en) * | 1982-08-23 | 1984-06-26 | The Upjohn Company | Amine containing ester prodrugs of corticosteroids |
| US4443440A (en) * | 1982-08-30 | 1984-04-17 | The Upjohn Company | Amine containing ester prodrugs of corticosteroids |
| FR2600653B1 (fr) * | 1986-06-24 | 1988-12-16 | Pasteur Strasbourg Universite | Composes de synthese associative d'acides amines soufres ou non soufres avec des derives du d-4 pregnene 3,20-dione ou avec des derives du d-1,4 pregnadiene 3,20-dione aux proprietes glucocorticoides et anti-inflammatoires, procedes d'obtention, compositions pharmaceutiques les contenant. proprietes pharmacologiques et applications |
| DE4333920A1 (de) | 1993-10-05 | 1995-04-13 | Hoechst Ag | Corticoid-17,21-dicarbonsäureester sowie Corticosteroid-17-carbonsäureester-21-kohlensäureester, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1044212B (it) * | 1971-03-17 | 1980-03-20 | Sigma Tau Ind Farmaceuti | Esteri del besametazone e betametazone |
| GB1440063A (en) * | 1972-08-11 | 1976-06-23 | Glaxo Lab Ltd | 17alpha-esters of 17alpha,21-dihydroxy-20-oxo-steroids |
-
1974
- 1974-07-31 GB GB33786/74A patent/GB1516095A/en not_active Expired
-
1975
- 1975-07-30 CH CH996575A patent/CH615442A5/de not_active IP Right Cessation
- 1975-07-30 ES ES439852A patent/ES439852A1/es not_active Expired
- 1975-07-30 ZA ZA00754907A patent/ZA754907B/xx unknown
- 1975-07-30 DK DK346975AA patent/DK139303B/da unknown
- 1975-07-30 NL NL7509075A patent/NL7509075A/xx not_active Application Discontinuation
- 1975-07-30 SE SE7508654A patent/SE7508654L/xx unknown
- 1975-07-30 IE IE1708/75A patent/IE42124B1/en unknown
- 1975-07-30 JP JP50092137A patent/JPS51125059A/ja active Pending
- 1975-07-30 CA CA232,579A patent/CA1058610A/en not_active Expired
- 1975-07-30 DE DE19752534051 patent/DE2534051A1/de not_active Withdrawn
- 1975-07-30 BE BE158780A patent/BE831931A/xx unknown
- 1975-07-30 FR FR7523787A patent/FR2280383A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| CH615442A5 (en) | 1980-01-31 |
| NL7509075A (nl) | 1976-02-03 |
| FR2280383B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1978-10-06 |
| JPS51125059A (en) | 1976-11-01 |
| IE42124B1 (en) | 1980-06-04 |
| ZA754907B (en) | 1976-07-28 |
| DK139303B (da) | 1979-01-29 |
| BE831931A (fr) | 1976-01-30 |
| SE7508654L (sv) | 1976-02-02 |
| AU8353175A (en) | 1977-02-03 |
| DE2534051A1 (de) | 1976-02-19 |
| DK139303C (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1979-08-06 |
| FR2280383A1 (fr) | 1976-02-27 |
| IE42124L (en) | 1976-01-31 |
| DK346975A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1976-02-01 |
| ES439852A1 (es) | 1977-03-01 |
| GB1516095A (en) | 1978-06-28 |
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