CA2861045A1 - Novel compounds, their manufacture and uses (ii) - Google Patents
Novel compounds, their manufacture and uses (ii) Download PDFInfo
- Publication number
- CA2861045A1 CA2861045A1 CA2861045A CA2861045A CA2861045A1 CA 2861045 A1 CA2861045 A1 CA 2861045A1 CA 2861045 A CA2861045 A CA 2861045A CA 2861045 A CA2861045 A CA 2861045A CA 2861045 A1 CA2861045 A1 CA 2861045A1
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- CA
- Canada
- Prior art keywords
- preferred
- compound
- hydrogen
- methyl
- reagent
- 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.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 587
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- 238000000034 method Methods 0.000 claims abstract description 314
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 76
- 230000016571 aggressive behavior Effects 0.000 claims abstract description 50
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 47
- 230000002708 enhancing effect Effects 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 27
- 230000001939 inductive effect Effects 0.000 claims abstract description 21
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 9
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 9
- 230000004071 biological effect Effects 0.000 claims abstract description 7
- -1 isobutyryl Chemical group 0.000 claims description 467
- 230000008569 process Effects 0.000 claims description 242
- 239000003153 chemical reaction reagent Substances 0.000 claims description 174
- 229910052739 hydrogen Inorganic materials 0.000 claims description 167
- 239000001257 hydrogen Substances 0.000 claims description 165
- 150000001408 amides Chemical class 0.000 claims description 103
- 150000002431 hydrogen Chemical class 0.000 claims description 103
- 125000004429 atom Chemical group 0.000 claims description 101
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 93
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 87
- 239000000203 mixture Substances 0.000 claims description 77
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 71
- 229910052799 carbon Inorganic materials 0.000 claims description 71
- 125000001424 substituent group Chemical group 0.000 claims description 60
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 55
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 46
- 150000002630 limonoids Chemical class 0.000 claims description 43
- 238000001275 scanning Auger electron spectroscopy Methods 0.000 claims description 43
- 230000003024 amidolytic effect Effects 0.000 claims description 41
- 238000007254 oxidation reaction Methods 0.000 claims description 41
- 150000002596 lactones Chemical class 0.000 claims description 40
- 230000003647 oxidation Effects 0.000 claims description 40
- 239000007858 starting material Substances 0.000 claims description 39
- 239000000654 additive Substances 0.000 claims description 38
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 claims description 38
- 241001156380 Chukrasia tabularis Species 0.000 claims description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
- 230000000996 additive effect Effects 0.000 claims description 36
- 125000004043 oxo group Chemical group O=* 0.000 claims description 36
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 34
- 230000010933 acylation Effects 0.000 claims description 32
- 238000005917 acylation reaction Methods 0.000 claims description 32
- 241000196324 Embryophyta Species 0.000 claims description 30
- 125000006239 protecting group Chemical group 0.000 claims description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 29
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 27
- 230000000694 effects Effects 0.000 claims description 26
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 26
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 24
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 claims description 22
- 230000001681 protective effect Effects 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 230000001590 oxidative effect Effects 0.000 claims description 21
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 20
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 20
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 238000009833 condensation Methods 0.000 claims description 20
- 230000005494 condensation Effects 0.000 claims description 20
- 239000003921 oil Substances 0.000 claims description 19
- 235000019198 oils Nutrition 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 230000001568 sexual effect Effects 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 17
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 17
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 16
- 230000007062 hydrolysis Effects 0.000 claims description 16
- 238000006460 hydrolysis reaction Methods 0.000 claims description 16
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 15
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 241000158728 Meliaceae Species 0.000 claims description 13
- 235000019197 fats Nutrition 0.000 claims description 13
- 239000004006 olive oil Substances 0.000 claims description 13
- 235000008390 olive oil Nutrition 0.000 claims description 13
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 12
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 claims description 12
- 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 claims description 12
- 230000004048 modification Effects 0.000 claims description 12
- 238000012986 modification Methods 0.000 claims description 12
- 230000035484 reaction time Effects 0.000 claims description 12
- 239000003826 tablet Substances 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 229940126208 compound 22 Drugs 0.000 claims description 11
- 125000004122 cyclic group Chemical group 0.000 claims description 11
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 238000007792 addition Methods 0.000 claims description 10
- 230000002152 alkylating effect Effects 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 10
- 239000011347 resin Substances 0.000 claims description 10
- 229920005989 resin Polymers 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 9
- 230000029936 alkylation Effects 0.000 claims description 9
- 238000005804 alkylation reaction Methods 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000000839 emulsion Substances 0.000 claims description 9
- 239000003925 fat Substances 0.000 claims description 9
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 229930182901 bussein Natural products 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 230000009467 reduction Effects 0.000 claims description 8
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 229910015900 BF3 Inorganic materials 0.000 claims description 7
- 241000009821 Entandrophragma Species 0.000 claims description 7
- 239000002841 Lewis acid Substances 0.000 claims description 7
- 239000002202 Polyethylene glycol Substances 0.000 claims description 7
- 150000008064 anhydrides Chemical class 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Substances FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 7
- 150000001718 carbodiimides Chemical class 0.000 claims description 7
- 230000006240 deamidation Effects 0.000 claims description 7
- 230000006870 function Effects 0.000 claims description 7
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 7
- 150000007517 lewis acids Chemical class 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- 230000002285 radioactive effect Effects 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 claims description 6
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 229940125833 compound 23 Drugs 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 238000005859 coupling reaction Methods 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000001212 derivatisation Methods 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 201000001881 impotence Diseases 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 6
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 6
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims description 6
- 239000011777 magnesium Substances 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 6
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 6
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 5
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 5
- 239000007821 HATU Substances 0.000 claims description 5
- 206010024419 Libido decreased Diseases 0.000 claims description 5
- IERDPZTZIONHSM-UHFFFAOYSA-N O=C1OCCN1[ClH]P(=O)[ClH]N1C(OCC1)=O Chemical compound O=C1OCCN1[ClH]P(=O)[ClH]N1C(OCC1)=O IERDPZTZIONHSM-UHFFFAOYSA-N 0.000 claims description 5
- 235000019483 Peanut oil Nutrition 0.000 claims description 5
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- KCUHVQNGKXNNCX-UHFFFAOYSA-N ac1l8suo Chemical compound O1C23C(OC(=O)CC)C4(O)C(OC(=O)C(C)C)C(C(C56C)CC(=O)OC)(C)CC45OC1(C)OC36CCC1(C)C2CC(=O)OC1C=1C=COC=1 KCUHVQNGKXNNCX-UHFFFAOYSA-N 0.000 claims description 5
- MBTCJFPZNOOGKO-UHFFFAOYSA-N ac1l8sur Chemical compound CC12C(CC(=O)OC)C(C(C3(O)C(OC(=O)C(C)C)C45O6)OC(=O)C(C)C)(C)CC32OC6(C)OC41CCC1(C)C5CC(=O)OC1C=1C=COC=1 MBTCJFPZNOOGKO-UHFFFAOYSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 238000005842 biochemical reaction Methods 0.000 claims description 5
- 238000006555 catalytic reaction Methods 0.000 claims description 5
- 235000019868 cocoa butter Nutrition 0.000 claims description 5
- 229940110456 cocoa butter Drugs 0.000 claims description 5
- 238000000354 decomposition reaction Methods 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 230000008030 elimination Effects 0.000 claims description 5
- 238000003379 elimination reaction Methods 0.000 claims description 5
- 230000002140 halogenating effect Effects 0.000 claims description 5
- 230000026030 halogenation Effects 0.000 claims description 5
- 238000005658 halogenation reaction Methods 0.000 claims description 5
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 5
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- 208000017020 hypoactive sexual desire disease Diseases 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 239000000312 peanut oil Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 230000008707 rearrangement Effects 0.000 claims description 5
- 238000006722 reduction reaction Methods 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- 229920000742 Cotton Polymers 0.000 claims description 4
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 4
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 claims description 4
- 230000002378 acidificating effect Effects 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 125000005336 allyloxy group Chemical group 0.000 claims description 4
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 4
- 239000003599 detergent Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 claims description 4
- 229940093471 ethyl oleate Drugs 0.000 claims description 4
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 4
- 239000001087 glyceryl triacetate Substances 0.000 claims description 4
- 239000012051 hydrophobic carrier Substances 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 229920000136 polysorbate Polymers 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- 229930189310 tabulalide Natural products 0.000 claims description 4
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229960002622 triacetin Drugs 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- OEAILFQKPDJEPG-UHFFFAOYSA-N xylocarpin Natural products O=C1C2(C)C(CC(=O)OC)C(C)(C)C(OC(C)=O)C1C1OC11C2CCC2(C)C1CC(=O)OC2C=1C=COC=1 OEAILFQKPDJEPG-UHFFFAOYSA-N 0.000 claims description 4
- OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims 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 claims description 3
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 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 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 229930012601 Swietenitin Natural products 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/18—Bridged systems
-
- 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
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Gynecology & Obstetrics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
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| SE1200678-9 | 2012-11-06 | ||
| SE1300011-2 | 2013-01-04 | ||
| SE1300011 | 2013-01-04 | ||
| PCT/EP2013/051413 WO2013110744A2 (en) | 2012-01-25 | 2013-01-25 | Novel compounds, their manufacture and uses (ii) |
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| DK (1) | DK2807170T3 (enExample) |
| ES (1) | ES2723248T3 (enExample) |
| IN (1) | IN2014DN05615A (enExample) |
| NZ (1) | NZ626736A (enExample) |
| PL (1) | PL2807170T3 (enExample) |
| WO (1) | WO2013110744A2 (enExample) |
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| CN109394732A (zh) * | 2017-08-16 | 2019-03-01 | 安徽中医药大学 | 盐酸青藤碱肠溶定位渗透泵控释胶囊及其制备方法 |
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| CN104628692B (zh) * | 2015-02-09 | 2016-02-10 | 庄爱华 | 柠檬苦素类化合物，其药物组合物及其制备方法和用途 |
| CN208336488U (zh) * | 2015-07-31 | 2019-01-04 | 株式会社村田制作所 | 线圈天线以及天线装置 |
| CN110903912B (zh) * | 2019-11-29 | 2022-01-28 | 华东理工大学 | 一种芳基油脂及其制备方法与应用 |
| CN111755072B (zh) * | 2020-08-04 | 2021-02-02 | 深圳吉因加医学检验实验室 | 一种同时检测甲基化水平、基因组变异和插入片段的方法及装置 |
| CN112898263B (zh) * | 2021-01-28 | 2022-03-08 | 江西中医药大学 | 一种从佛手中分离的香豆素骈木脂素化合物及其保肝用途 |
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| WO2025040810A1 (en) | 2023-08-23 | 2025-02-27 | Dicot Pharma Ab | Therapeutic compounds, a method of manufacturing thereof as well as uses thereof |
| WO2025141142A1 (en) * | 2023-12-29 | 2025-07-03 | Dicot Pharma Ab | A novel method for recovering limonoid compounds |
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| EP1318825A2 (de) | 2000-07-26 | 2003-06-18 | Vitaplant AG | Piper methysticum pflanzenextrakt |
| CN1226298C (zh) * | 2003-08-07 | 2005-11-09 | 中国科学院南海海洋研究所 | 柠檬苦素化合物－木果楝内酯及其用途 |
| JP2005213202A (ja) | 2004-01-29 | 2005-08-11 | Maruzen Pharmaceut Co Ltd | 抗酸化剤、抗老化剤及び抗炎症剤、並びに、皮膚化粧料 |
| CA2623831A1 (en) | 2005-09-12 | 2007-03-22 | Council Of Scientific And Industrial Research | An extract from xylocarpus useful for the treatment of diabetes and dyslipidemia |
| AU2008256521B2 (en) | 2007-05-29 | 2014-09-04 | Dicot Ab | Novel compounds and pharmaceutical preparations from Neobeguea spec |
| GB0710230D0 (en) | 2007-05-30 | 2007-07-11 | Reckitt Benckiser Nv | Detergent dosing device |
| US7786171B2 (en) | 2008-04-04 | 2010-08-31 | Abbott Laboratories | Amide derivatives as positive allosteric modulators and methods of use thereof |
-
2013
- 2013-01-25 AU AU2013213580A patent/AU2013213580B2/en not_active Ceased
- 2013-01-25 NZ NZ626736A patent/NZ626736A/en not_active IP Right Cessation
- 2013-01-25 WO PCT/EP2013/051413 patent/WO2013110744A2/en not_active Ceased
- 2013-01-25 EP EP13702766.0A patent/EP2807170B1/en active Active
- 2013-01-25 IN IN5615DEN2014 patent/IN2014DN05615A/en unknown
- 2013-01-25 DK DK13702766.0T patent/DK2807170T3/da active
- 2013-01-25 ES ES13702766T patent/ES2723248T3/es active Active
- 2013-01-25 CA CA2861045A patent/CA2861045A1/en not_active Abandoned
- 2013-01-25 CN CN201380006854.4A patent/CN104254537B/zh not_active Expired - Fee Related
- 2013-01-25 PL PL13702766T patent/PL2807170T3/pl unknown
- 2013-01-25 US US14/374,356 patent/US9403841B2/en active Active
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109394732A (zh) * | 2017-08-16 | 2019-03-01 | 安徽中医药大学 | 盐酸青藤碱肠溶定位渗透泵控释胶囊及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013213580B2 (en) | 2017-06-15 |
| EP2807170A2 (en) | 2014-12-03 |
| NZ626736A (en) | 2016-11-25 |
| DK2807170T3 (da) | 2019-05-27 |
| AU2013213580A1 (en) | 2014-07-24 |
| EP2807170B1 (en) | 2019-03-13 |
| US20150011616A1 (en) | 2015-01-08 |
| ES2723248T3 (es) | 2019-08-22 |
| IN2014DN05615A (enExample) | 2015-04-03 |
| PL2807170T3 (pl) | 2019-09-30 |
| CN104254537A (zh) | 2014-12-31 |
| WO2013110744A2 (en) | 2013-08-01 |
| CN104254537B (zh) | 2017-06-30 |
| HK1204325A1 (en) | 2015-11-13 |
| WO2013110744A3 (en) | 2013-10-31 |
| US9403841B2 (en) | 2016-08-02 |
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| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20180112 |
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| FZDE | Discontinued |
Effective date: 20210831 |
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| FZDE | Discontinued |
Effective date: 20210831 |