JPH11507360A - 視床下部作用を誘起する新規なノルプレグナン類 - Google Patents
視床下部作用を誘起する新規なノルプレグナン類Info
- Publication number
- JPH11507360A JPH11507360A JP9501937A JP50193797A JPH11507360A JP H11507360 A JPH11507360 A JP H11507360A JP 9501937 A JP9501937 A JP 9501937A JP 50193797 A JP50193797 A JP 50193797A JP H11507360 A JPH11507360 A JP H11507360A
- Authority
- JP
- Japan
- Prior art keywords
- norpregna
- hydrogen
- compound
- double bond
- methyl
- 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.)
- Pending
Links
- 230000002267 hypothalamic effect Effects 0.000 title claims abstract description 13
- 230000001939 inductive effect Effects 0.000 title description 3
- 150000003128 pregnanes Chemical class 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 50
- -1 19-norpregnane steroid Chemical class 0.000 claims abstract description 44
- 150000003431 steroids Chemical class 0.000 claims abstract description 37
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 239000003937 drug carrier Substances 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 101
- 239000000203 mixture Substances 0.000 claims description 72
- 150000001875 compounds Chemical class 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 210000001121 vomeronasal organ Anatomy 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- ALSXNTIVNJBNQE-ZWONNITHSA-N (8r,9r,10s,13r,14s,17s)-17-ethyl-13-methyl-1,2,3,4,5,6,7,8,9,10,11,12,14,15,16,17-hexadecahydrocyclopenta[a]phenanthrene Chemical class C1CC2CCCC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 ALSXNTIVNJBNQE-ZWONNITHSA-N 0.000 claims description 16
- 210000003016 hypothalamus Anatomy 0.000 claims description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 206010029216 Nervousness Diseases 0.000 claims description 13
- 230000002567 autonomic effect Effects 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 210000001519 tissue Anatomy 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 7
- 210000000461 neuroepithelial cell Anatomy 0.000 claims description 6
- 210000001706 olfactory mucosa Anatomy 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 239000000443 aerosol Substances 0.000 claims description 5
- 239000002674 ointment Substances 0.000 claims description 4
- 239000008297 liquid dosage form Substances 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 13
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 230000002152 alkylating effect Effects 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000003883 ointment base Substances 0.000 claims 1
- 150000003126 pregnane derivatives Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 150
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 78
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- 239000000706 filtrate Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 31
- 239000005909 Kieselgur Substances 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 238000004809 thin layer chromatography Methods 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000003016 pheromone Substances 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- 239000000284 extract Substances 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000012746 preparative thin layer chromatography Methods 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000003814 drug Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- 238000000537 electroencephalography Methods 0.000 description 9
- 230000009471 action Effects 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 230000008451 emotion Effects 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 230000035479 physiological effects, processes and functions Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000007858 starting material Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000006399 behavior Effects 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 108091008690 chemoreceptors Proteins 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 230000002996 emotional effect Effects 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- WKRLQDKEXYKHJB-UHFFFAOYSA-N Equilin Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3=CCC2=C1 WKRLQDKEXYKHJB-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
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000036760 body temperature Effects 0.000 description 6
- 230000000723 chemosensory effect Effects 0.000 description 6
- WKRLQDKEXYKHJB-HFTRVMKXSA-N equilin Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 WKRLQDKEXYKHJB-HFTRVMKXSA-N 0.000 description 6
- 239000003380 propellant Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 239000006188 syrup Substances 0.000 description 6
- 235000020357 syrup Nutrition 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 239000000356 contaminant Substances 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 230000036651 mood Effects 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- JYYNAJVZFGKDEQ-UHFFFAOYSA-N 2,4-Dimethylpyridine Chemical compound CC1=CC=NC(C)=C1 JYYNAJVZFGKDEQ-UHFFFAOYSA-N 0.000 description 4
- JWMFYGXQPXQEEM-NUNROCCHSA-N 5β-pregnane Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](CC)[C@@]2(C)CC1 JWMFYGXQPXQEEM-NUNROCCHSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- CWNKMHIETKEBCA-UHFFFAOYSA-N alpha-Ethylaminohexanophenone Chemical compound CCCCC(NCC)C(=O)C1=CC=CC=C1 CWNKMHIETKEBCA-UHFFFAOYSA-N 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000002254 contraceptive effect Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000010446 mirabilite Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000010539 reproductive behavior Effects 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- KRVXMNNRSSQZJP-PHFHYRSDSA-N 5alpha-androst-16-en-3alpha-ol Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CC[C@H]21 KRVXMNNRSSQZJP-PHFHYRSDSA-N 0.000 description 3
- QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 208000019901 Anxiety disease Diseases 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 210000003403 autonomic nervous system Anatomy 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- KRVXMNNRSSQZJP-UHFFFAOYSA-N beta-androstenol Natural products C1C(O)CCC2(C)C3CCC(C)(C=CC4)C4C3CCC21 KRVXMNNRSSQZJP-UHFFFAOYSA-N 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 230000001722 neurochemical effect Effects 0.000 description 3
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 3
- 210000001331 nose Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 230000036387 respiratory rate Effects 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 230000001953 sensory effect Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical compound CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 3
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 2
- CRMOMCHYBNOFIV-BDXSIMOUSA-N 16-estratetraen-3-ol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC2=C1 CRMOMCHYBNOFIV-BDXSIMOUSA-N 0.000 description 2
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- 150000000317 19-norpregnenes Chemical class 0.000 description 2
- WTRRIQCGCGCMQA-CBZIJGRNSA-N 3-Hydroxyestra-1,3,5(10),6-tetraen-17-one Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C=CC2=C1 WTRRIQCGCGCMQA-CBZIJGRNSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 2
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 2
- 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 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 239000003810 Jones reagent Substances 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 210000004727 amygdala Anatomy 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- NXQOQNROJJFYCJ-FZFXZXLVSA-N androst-16-ene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC21 NXQOQNROJJFYCJ-FZFXZXLVSA-N 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- QVQLCTNNEUAWMS-UHFFFAOYSA-N barium oxide Chemical compound [Ba]=O QVQLCTNNEUAWMS-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 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 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 229930182833 estradiol Natural products 0.000 description 2
- 229960005309 estradiol Drugs 0.000 description 2
- 229960003399 estrone Drugs 0.000 description 2
- 229960002568 ethinylestradiol Drugs 0.000 description 2
- BOUBUFOFBHNEAP-UHFFFAOYSA-N ethylborane Chemical compound BCC BOUBUFOFBHNEAP-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000000545 human pheromone Substances 0.000 description 2
- 235000003642 hunger Nutrition 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 230000007758 mating behavior Effects 0.000 description 2
- 102000006240 membrane receptors Human genes 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 210000000492 nasalseptum Anatomy 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical compound O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 2
- 210000003254 palate Anatomy 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 210000003370 receptor cell Anatomy 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 230000027272 reproductive process Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 210000001533 respiratory mucosa Anatomy 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000008786 sensory perception of smell Effects 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 230000036332 sexual response Effects 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- HTEOBMYSBPIKNK-YFRXESGTSA-N (8r,9r,10s,13s,14s)-17-iodo-13-methyl-1,2,3,4,5,6,7,8,9,10,11,12,14,15-tetradecahydrocyclopenta[a]phenanthrene Chemical class C1CCC[C@@H]2[C@H]3CC[C@](C)(C(=CC4)I)[C@@H]4[C@@H]3CCC21 HTEOBMYSBPIKNK-YFRXESGTSA-N 0.000 description 1
- GCJBPFVCQYMOKN-FCMAGTKHSA-N (8r,9s,10r,13s,14s)-17-ethyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC=C(CC)[C@@]1(C)CC2 GCJBPFVCQYMOKN-FCMAGTKHSA-N 0.000 description 1
- VZRAKVPDZIQRGT-WZBAXQLOSA-N (8r,9s,10s,13r,14s,17r)-17-ethenyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C=C)[C@@H]4[C@@H]3CCC21 VZRAKVPDZIQRGT-WZBAXQLOSA-N 0.000 description 1
- CSFSHOOQUIPHRO-NWSAAYAGSA-N (8s,9s,10r,13r,14s,17r)-17-ethenyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C=C)[C@@H]4[C@@H]3CCC2=C1 CSFSHOOQUIPHRO-NWSAAYAGSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- ICLYJLBTOGPLMC-KVVVOXFISA-N (z)-octadec-9-enoate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.CCCCCCCC\C=C/CCCCCCCC(O)=O ICLYJLBTOGPLMC-KVVVOXFISA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- CSFSHOOQUIPHRO-UHFFFAOYSA-N 17alpha-pregna-4,20-dien-3-one Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C=C)C4C3CCC2=C1 CSFSHOOQUIPHRO-UHFFFAOYSA-N 0.000 description 1
- CQAJPFMQZHVEQK-UHFFFAOYSA-N 19-norpregna-1,3,5(10),20-tetraen-3-ol Natural products OC1=CC=C2C3CCC(C)(C(CC4)C=C)C4C3CCC2=C1 CQAJPFMQZHVEQK-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 239000004169 Hydrogenated Poly-1-Decene Substances 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
- 241001072332 Monia Species 0.000 description 1
- 208000001705 Mouth breathing Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 108010002724 Pheromone Receptors Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 206010046788 Uterine haemorrhage Diseases 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 108091005722 Vomeronasal receptors Proteins 0.000 description 1
- 102100038344 Vomeronasal type-1 receptor 2 Human genes 0.000 description 1
- NWGKJDSIEKMTRX-BFWOXRRGSA-N [(2r)-2-[(3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)C1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-BFWOXRRGSA-N 0.000 description 1
- HPFVBGJFAYZEBE-XNBTXCQYSA-N [(8r,9s,10r,13s,14s)-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl] 3-cyclopentylpropanoate Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CCC(=O)C=C3CC2)C)CC[C@@]11C)CC1OC(=O)CCC1CCCC1 HPFVBGJFAYZEBE-XNBTXCQYSA-N 0.000 description 1
- MXVIGHXQQKNQDI-LBSXMSKVSA-N [Li]C=1[C@]2(C)[C@@H](CC1)[C@@H]1CCC3CCCC[C@@H]3[C@H]1CC2 Chemical compound [Li]C=1[C@]2(C)[C@@H](CC1)[C@@H]1CCC3CCCC[C@@H]3[C@H]1CC2 MXVIGHXQQKNQDI-LBSXMSKVSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical class O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- HNDHDMOSWUAEAW-VMXHOPILSA-N androstadienone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC2=C1 HNDHDMOSWUAEAW-VMXHOPILSA-N 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 230000009910 autonomic response Effects 0.000 description 1
- 239000013040 bath agent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000019383 crystalline wax Nutrition 0.000 description 1
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 210000002451 diencephalon Anatomy 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 210000000624 ear auricle Anatomy 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- GRXPVLPQNMUNNX-MHJRRCNVSA-N estrane Chemical compound C1CC2CCCC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 GRXPVLPQNMUNNX-MHJRRCNVSA-N 0.000 description 1
- VBAFPUVFQZWOJM-MHJRRCNVSA-N estrene group Chemical group C[C@@]12C=CC[C@H]1[C@@H]1CCC3CCCC[C@@H]3[C@H]1CC2 VBAFPUVFQZWOJM-MHJRRCNVSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 230000001158 estrous effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000008921 facial expression Effects 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- FIMAYKDZLLQUDW-UHFFFAOYSA-N fluoro(dioxido)borane;trimethyloxidanium Chemical compound C[O+](C)C.C[O+](C)C.[O-]B([O-])F FIMAYKDZLLQUDW-UHFFFAOYSA-N 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182480 glucuronide Natural products 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 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
- 230000003054 hormonal effect Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000001595 mastoid Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- MBXNQZHITVCSLJ-UHFFFAOYSA-N methyl fluorosulfonate Chemical compound COS(F)(=O)=O MBXNQZHITVCSLJ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 229960001566 methyltestosterone Drugs 0.000 description 1
- VDCLSGXZVUDARN-UHFFFAOYSA-N molecular bromine;pyridine;hydrobromide Chemical compound Br.BrBr.C1=CC=NC=C1 VDCLSGXZVUDARN-UHFFFAOYSA-N 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 230000003767 neural control Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000000929 nociceptor Anatomy 0.000 description 1
- 108091008700 nociceptors Proteins 0.000 description 1
- 229940053934 norethindrone Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical group CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000956 olfactory bulb Anatomy 0.000 description 1
- 210000000196 olfactory nerve Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 150000004686 pentahydrates Chemical class 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 239000002427 pheromone receptor Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 208000006155 precocious puberty Diseases 0.000 description 1
- 229960000249 pregnenolone Drugs 0.000 description 1
- ORNBQBCIOKFOEO-QGVNFLHTSA-N pregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 ORNBQBCIOKFOEO-QGVNFLHTSA-N 0.000 description 1
- 201000000484 premenstrual tension Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000004800 psychological effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000003620 semiochemical Substances 0.000 description 1
- 230000009329 sexual behaviour Effects 0.000 description 1
- 230000035941 sexual motivation Effects 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 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 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 230000037351 starvation Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004354 sulfur functional group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000001779 taste bud Anatomy 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000000211 third ventricle Anatomy 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 201000007954 uterine fibroid Diseases 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/007—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 17 (20)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.19−ノルプレグナンステロイド及び薬学的に許容しうる担体を含む、個体 において経鼻投与に適した医薬組成物であって、前記ステロイドが下記式を有す る組成物。 (式中、P1はオキソ、α−又はβ−ヒドロキシ、α−又はβ−アセトキシ、 α−又はβ−プロピオンオキシ、α−又はβ−低級アルコキシ、α−又はβ−低 級アシルオキシ又はα−又はβ−ベンジルオキシであり; “a”、“b”、“c”、“d”、“e”、“f”、“g”、“h”、“i” 、“j”、“m”及び“n”は任意の二重結合の選択位置であり、“k”は存在 しないか又は存在して“j”と共に三重結合を形成してもよく; P2はヒドロキシ、水素、炭素原子1〜6個の低級アルコキシであるか又は存 在せず; P3はオキソ、水素、ヒドロキシ、炭素原子1〜6個の低級アルコキシ又はハ ロであり; P4はメチル又はエチルであり; P5は水素、メチル又はハロであり; P6は水素又はメチルであり; R′及びR″は独立して水素又はハロであるか又は存在しない。 2.“a”、“e”及び“d”が二重結合である請求項1記載の組成物。 3.“h”が二重結合である請求項2記載の組成物。 4.“g”が二重結合である請求項2記載の組成物。 5.“n”が二重結合である請求項4記載の組成物。 6.“d”が二重結合である請求項1記載の組成物。 7.“b”が二重結合である請求項6記載の組成物。 8.“c”が二重結合である請求項1記載の組成物。 9.“f”が二重結合である請求項8記載の組成物。 10.前記ステロイドを前記担体に溶解させる請求項1〜9のいずれか1項に記載 の医薬組成物。 11.前記組成物が液体剤形である請求項1〜9のいずれか1項に記載の医薬組成 物。 12.前記組成物が薬学的に許容しうる軟膏基剤を更に含む請求項1〜9のいずれ か1項に記載の医薬組成物。 13.1種を超えない前記ステロイドを含む請求項1〜9のいずれか1項に記載の 医薬組成物。 14.1種を超える前記ステロイドを含む請求項1〜9のいずれか1項に記載の医 薬組成物。 15.個体の視床下部機能を変える方法であって、前記個体の嗅上皮以外の組織の 一部である鼻の神経上皮細胞の表面上の下記式 (式中、P1はオキソ、α−又はβ−ヒドロキシ、α−又はβ−アセトキシ、 α−又はβ−プロピオンオキシ、α−又はβ−低級アルコキシ、α−又はβ−低 級アシルオキシ又はα−又はβ−ベンジルオキシであり; “a”、“b”、“c”、“d”、“e”、“f”、“g”、“h”、“i” 、 “j”、“m”及び“n”は任意の二重結合の選択位置であり、“k”は存在し ないか又は存在して“j”と共に三重結合を形成してもよく; P2はヒドロキシ、水素、炭素原子1〜6個の低級アルコキシであるか又は存 在せず; P3はオキソ、水素、ヒドロキシ、炭素原子1〜6個の低級アルコキシ又はハ ロであり; P4はメチル又はエチルであり; P5は水素、メチル又はハロであり; P6は水素又はメチルであり; R′及びR″は独立して水素又はハロであるか又は存在しない。) を有する19−ノルプレグナンを供給する段階;及び 前記19−ノルプレグナン誘導体を前記個体の鼻道内に投与して前記19−ノ ルプレグナン誘導体が前記受容器に特異的に結合しかつ前記個体の視床下部機能 の変化をもたらす段階: を含む方法。 16.個体の自律神経機能を変える方法であって、前記個体の嗅上皮以外の組織の 一部である鼻の神経上皮細胞の表面上の下記式 (式中、P1はオキソ、α−又はβ−ヒドロキシ、α−又はβ−アセトキシ、 α−又はβ−プロピオンオキシ、α−又はβ−低級アルコキシ、α−又はβ−低 級アシルオキシ又はα−又はβ−ベンジルオキシであり; “a”、“b”、“c”、“d”、“e”、“f”、“g”、“h”、“i” 、 “j”、“m”及び“n”は任意の二重結合の選択位置であり、“k”は存在し ないか又は存在して“j”と共に三重結合を形成してもよく; P2はヒドロキシ、水素、炭素原子1〜6個の低級アルコキシであるか又は存 在せず; P3はオキソ、水素、ヒドロキシ、炭素原子1〜6個の低級アルコキシ又はハ ロであり; P4はメチル又はエチルであり; P5は水素、メチル又はハロであり; P6は水素又はメチルであり; R′及びR″は独立して水素又はハロであるか又は存在しない。) を有する19−ノルプレグナンを供給する段階;及び 前記19−ノルプレグナン誘導体を前記個体の鼻道内に投与して前記19−ノ ルプレグナン誘導体が前記受容器に特異的に結合しかつ前記個体の視床下部機能 の変化をもたらす段階: を含む方法。 17.前記神経上皮細胞が前記個体の鋤鼻器内に位置する請求項16記載の方法。 18.“a”、“e”及び“d”が二重結合である請求項17記載の方法。 19.“h”が二重結合である請求項18記載の方法。 20.“g”が二重結合である請求項18記載の方法。 21.“n”が二重結合である請求項20記載の方法。 22.“d”が二重結合である請求項17記載の方法。 23.“b”が二重結合である請求項22記載の方法。 24.“c”が二重結合である請求項12記載の方法。 25.“f”が二重結合である請求項24記載の方法。 26.前記19−ノルプレグナン誘導体の投与量が少なくとも約100ピコグラム であるが約100マイクログラムを超えない請求項15〜25のいずれか1項に記載 の方法。 27.前記19−ノルプレグナン誘導体の投与量が少なくとも約1ナノグラムであ るが約10マイクログラムを超えない請求項15記載の方法。 28.前記19−ノルプレグナン誘導体の投与量が少なくとも約10ナノグラムで あるが約1マイクログラムを超えない請求項27記載の方法。 29.薬学的に許容しうる担体に溶解した前記プレグナン誘導体の医薬組成物を調 製する段階を更に含む請求項15〜25のいずれか1項に記載の方法。 30.前記医薬組成物が軟膏である請求項29記載の方法。 31.前記医薬組成物が液体である請求項29記載の方法。 32.該投与がエアゾルによる請求項29記載の方法。 33.1種を超えるプレグナンステロイドが投与される請求項15〜25のいずれか1 項に記載の方法。 34.下記式を有する19−ノルプレグナン。 (式中、P1はオキソ、α−又はβ−ヒドロキシ、α−又はβ−アセトキシ、 α−又はβ−プロピオンオキシ、α−又はβ−低級アルコキシ、α−又はβ−低 級アシルオキシ又はα−又はβ−ベンジルオキシであり; “a”、“b”、“c”、“d”、“e”、“f”、“g”、“h”、“i” 、“j”、“m”及び“n”は任意の二重結合の選択位置であり、“k”は存在 しないか又は存在して“j”と共に三重結合を形成してもよく; P2はヒドロキシ、水素、炭素原子1〜6個の低級アルコキシであるか又は存 在せず; P3はオキソ、水素、ヒドロキシ、炭素原子1〜6個の低級アルコキシ又はハ ロであり; P4はメチル又はエチルであり; P5は水素、メチル又はハロであり; P6は水素又はメチルであり; R′及びR″は独立して水素又はハロであるか又は存在しない; 但し、P3及びP6が水素であり、“f”、“n”、“h”及び“g”が存在せ ず、P4がメチルであり、R′及びR″がハロでない場合、 i)P1がオキソであり、“c”が存在し、P2及びP5が水素である場合には 、“j”も“i”も単独で存在することができないか又は“m”と“j”は共に 存在することができないか又は“i”と“j”は共に存在することができないか 又は“m”、“j”と“k”は共に存在することができず、“i”、“j”、“ k”と“m”の少なくとも1つは存在しなければならない; ii)P1がOHであり、“a”、“d”及び“e”が存在し、P5が水素である 場合には、“j”、“i”又は“m”のいくつかは単独で存在することができな いか又は“j”と“k”は共に存在することができないか又は“i”と“j”は 共に存在することができないか又は“m”、“j”と“k”は共に存在すること ができず、“i”、“j”、“k”と“m”の少なくとも1つは存在しなければ ならない; iii)P1がβ−OHであり、“c”が存在し、P2とP5が水素である場合には 、“i”と“j”は共に存在することができないか又は“m”、“j”と“k” は共に存在することができない; iv)P1が−OMeであり、“d”と“b”が存在する場合には、“j”も“ i”も単独で存在することができない; v)P1がオキソであり、“d”が存在し、P5が水素である場合には、“i” は単独で存在することができないか又は“j”と“k”は共に存在することがで きない。) 35.17−ハロ−16−エンD環を有するステロイドをアルキル化する方法であ って、触媒量のPd(II)の存在下に前記ステロイドとトリアルキルボランと を接触させて17−アルキル−16−エンステロイド生成物を得る工程を含む方 法。 36.前記ステロイドが17−ヨード−16−エンD環を含む請求項35記載の方法 。 37.前記アルキル基が炭素原子1〜6個を含む請求項35記載の方法。 38.前記アルキル基がエチル基を含む請求項37記載の方法。 39.19−ノルプレグナ−4,20−ジエン−3β−オールである請求項34記載 の化合物。 40.19−ノルプレグナ−1,3,5(10),16,20−ペンタエン−3−オール である請求項34記載の化合物。 41.19−ノルプレグナ−5(10),20−ジエン−3−オンである請求項34 記載の化合物。 42.19−ノルプレグナ−5(10),20−ジエン−3−オールである請求項3 4記載の化合物。 43.19−ノルプレグナ−4,20−ジエン−10β−オール−3−オンである 請求項34記載の化合物。 44.19−ノルプレグナ−4,9(10),20−トリエン−3−オンである請求項 34記載の化合物。 45.19−ノルプレグナ−1,3,5(10),16−テトラエン−6−オン−20 −イン−3−イル酢酸塩である請求項34記載の化合物。 46.19−ノルプレグナ−1,3,5(10),16−テトラエン−3,6β−ジオー ル−20−インである請求項34記載の化合物。 47.19−ノルプレグナ−1,3,5(10),17−テトラエン−3−オールであ る請求項34記載の化合物。 48.19−ノルプレグナ−1,3,5(10),6,17−ペンタエン−3−オールで ある請求項34記載の化合物。 49.19−ノルプレグナ−1,3,5(10),6,8,17−ヘキサエン−3−オー ルである請求項34記載の化合物。 50.19−ノルプレグナ−1,3,5(10),7,16−ペンタエン−3−オールで ある請求項34記載の化合物。 51.19−ノルプレグナ−2,5(10),16−トリエン−3−イルメチルエーテ ルである請求項34記載の化合物。 52.19−ノルプレグナ−4,16−ジエン−3−オンである請求項34記載の化 合 物。 53.19−ノルプレグナ−5(10),16−ジエン−3−オンである請求項34記 載の化合物。 54.19−ノルプレグナ−4,16−ジエン−10β−オール−3−オンである 請求項34記載の化合物。 55.19−ノルプレグナ−2,5(10)−ジエン−3−イルメチルエーテルで ある請求項34記載の化合物。 56.19−ノルプレグナ−5(10)−エン−3−オンである請求項34記載の化 合物。 57.19−ノルプレグナ−4−エン−10β−オール−3−オンである請求項34 記載の化合物。 58.19−ノルプレグナ−4,17−ジエン−10β−オール−3−オンである 請求項34記載の化合物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/485,615 | 1995-06-07 | ||
US08/485,615 US5792757A (en) | 1994-08-04 | 1995-06-07 | 19-nor-pregnane steroids as neurochemical initiators of change in human hypothalamic function |
PCT/US1996/009665 WO1996040727A1 (en) | 1995-06-07 | 1996-06-07 | Novel nor-pregnanes for inducing hypothalamic effects |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH11507360A true JPH11507360A (ja) | 1999-06-29 |
Family
ID=23928825
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP9501937A Pending JPH11507360A (ja) | 1995-06-07 | 1996-06-07 | 視床下部作用を誘起する新規なノルプレグナン類 |
Country Status (17)
Country | Link |
---|---|
US (3) | US5792757A (ja) |
EP (1) | EP0830369B1 (ja) |
JP (1) | JPH11507360A (ja) |
KR (1) | KR19990022640A (ja) |
CN (1) | CN1191542A (ja) |
AT (1) | ATE240344T1 (ja) |
AU (1) | AU724787B2 (ja) |
BR (1) | BR9609012A (ja) |
CA (1) | CA2223397C (ja) |
CZ (1) | CZ391597A3 (ja) |
DE (1) | DE69628163T2 (ja) |
EA (1) | EA000965B1 (ja) |
ES (1) | ES2197949T3 (ja) |
HU (1) | HUP9900887A3 (ja) |
NO (1) | NO975709L (ja) |
NZ (1) | NZ312303A (ja) |
WO (1) | WO1996040727A1 (ja) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6117860A (en) * | 1994-08-04 | 2000-09-12 | Pherin Pharmaceuticals, Inc. | Steroids as neurochemical stimulators of the VNO to treat paroxistic tachycardia |
US6066627A (en) * | 1994-08-04 | 2000-05-23 | Pherin Corporation | Steroids as neurochemical initiators of change in human blood levels of LH |
US6057439A (en) * | 1994-08-04 | 2000-05-02 | Pherin Corporation | Steroids as neurochemical stimulators of the VNO to alleviate symptoms of PMS and anxiety |
US6331534B1 (en) | 1994-08-04 | 2001-12-18 | Pherin Pharmaceuticals, Inc. | Steroids as neurochemical stimulators of the VNO to alleviate pain |
US5922699A (en) * | 1996-06-07 | 1999-07-13 | Pherin Corporation | 19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function |
EP0914165B1 (en) * | 1996-07-23 | 2006-10-18 | Pherin Pharmaceuticals, Inc. | Steroids as neurochemical stimulators of the vno to alleviate symptoms of pms |
CA2330611A1 (en) | 1998-05-22 | 1999-12-02 | The Board Of Trustees Of The Leland Stanford Junior University | Bifunctional molecules and therapies based thereon |
EP2322182A1 (en) | 1999-09-30 | 2011-05-18 | Harbor BioSciences, Inc. | Androstenol derivatives as androgen receptor modulator |
AUPQ342599A0 (en) * | 1999-10-14 | 1999-11-04 | University Of Melbourne, The | Conjugates and uses thereof |
US6555531B1 (en) * | 1999-12-30 | 2003-04-29 | Pherin Pharmaceuticals, Inc. | Weight promoting composition, method, and product |
US6413951B2 (en) * | 2000-06-27 | 2002-07-02 | Aventis Pharmaceuticals, Inc. | 20-fluoro-17(20)-vinyl steroids |
AU2002244247B2 (en) | 2001-03-01 | 2007-12-13 | Harbor Biosciences, Inc. | Use of certain steroids for treatment of blood cell deficiencies |
ATE445838T1 (de) | 2001-07-25 | 2009-10-15 | Raptor Pharmaceutical Inc | Zusammensetzungen und verfahren zur modulation des transports durch die blut-hirn-schranke |
AU2003278744B2 (en) | 2002-08-28 | 2010-07-29 | Harbor Biosciences, Inc. | Therapeutic treatment methods |
CA2582231A1 (en) | 2004-09-29 | 2006-10-19 | Hollis-Eden Pharmaceuticals, Inc. | Steroid analogs and uses |
EP2671508B1 (en) | 2005-04-28 | 2020-09-16 | Proteus Digital Health, Inc. | Pharma-informatics system |
JP2009508494A (ja) | 2005-09-16 | 2009-03-05 | ラプトール ファーマシューティカル インコーポレイテッド | Crを含むタンパク質に対して特異的な受容体−結合タンパク質(rap)変異体を含む組成物およびその使用 |
WO2009039103A2 (en) * | 2007-09-17 | 2009-03-26 | Human Pheromone Sciences, Inc. | Fragrance compositions and other compositions which contain naturally occurring substances found in corals |
MX2010011063A (es) | 2008-04-09 | 2010-11-22 | Pherin Pharm Inc | Tratamiento esteroidal para sofocos. |
HUE059078T2 (hu) | 2009-02-20 | 2022-10-28 | Enhanx Biopharm Inc | Glutation-alapú hatóanyagszállító rendszer |
JP2012526144A (ja) | 2009-05-06 | 2012-10-25 | ラボラトリー スキン ケア インコーポレイテッド | 活性物質−リン酸カルシウム粒子複合体を含む経皮送達組成物およびその使用方法 |
KR102396328B1 (ko) * | 2013-04-17 | 2022-05-10 | 세이지 테라퓨틱스, 인크. | 19-노르 c3,3-이치환된 c21-n-피라졸릴 스테로이드 및 그의 사용 방법 |
CN107108689A (zh) * | 2014-09-17 | 2017-08-29 | 普瑞维卡斯有限公司 | C‑20类固醇化合物、其组合物和用于治疗包括震荡的创伤性脑损伤(tbi)的用途 |
DE102020204506A1 (de) | 2020-04-07 | 2021-10-07 | Henkel Ag & Co. Kgaa | Weichspüler mit Pheromonen |
DE102020204505A1 (de) | 2020-04-07 | 2021-10-07 | Henkel Ag & Co. Kgaa | Wasch-/Pflegeartikel umfassend Pheromone |
DE102020204509A1 (de) | 2020-04-07 | 2021-10-07 | Henkel Ag & Co. Kgaa | Waschmittel mit Pheromonen |
DE102020204507A1 (de) | 2020-04-07 | 2021-10-07 | Henkel Ag & Co. Kgaa | Weichspüler mit aphrodisierend wirkenden Duftstoffen |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL287863A (ja) | ||||
US2840582A (en) * | 1953-08-31 | 1958-06-24 | Searle & Co | Derivatives of 13-methyl-17-hydroxy-1, 2, 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17-tetradecahydro-15h-cyclopenta[a]phenanthren-3-ones |
DE1297603B (de) | 1964-08-08 | 1969-06-19 | Schering Ag | Verfahren zur Herstellung von 3-Keto-delta 17(20)-pregnenen |
ES319318A1 (es) | 1964-11-13 | 1966-10-16 | American Cyanamid Co | Procedimiento para la preparaciën de una composiciën anticonceptiva |
US3385849A (en) * | 1965-07-01 | 1968-05-28 | Hoffmann La Roche | Process for the preparation of 17beta-pregnanes from 17-oxo-steroids |
US3492318A (en) * | 1968-01-22 | 1970-01-27 | Syntex Corp | Cyclopropenyl androstanes |
US3682983A (en) * | 1969-11-12 | 1972-08-08 | Klaus Prezewowsky | Preparation of {66 {11 {11 -17 ethinyl steroids |
FR2097045A1 (en) | 1970-07-30 | 1972-03-03 | Roussel Uclaf | 17-ethynylgon-4-en-3-ones - with progestomimetic activity useful as contraceptives and for gynaecological disorders |
US3681410A (en) * | 1970-08-07 | 1972-08-01 | Syntex Corp | Process for preparing 17{60 -hydroxy-20-keto and 17{60 ,21-dihydroxy-20-keto pregnanes and derivatives and intermediates thereof |
US3946052A (en) * | 1975-06-16 | 1976-03-23 | Stanford Research Institute | 19-Norpregna- 1,3,5(10)-trien-3-ol and loweralkyl homologs thereof having postcoital antifertility activity |
US5155045A (en) | 1985-01-25 | 1992-10-13 | Trustees Of The University Of Penn. | Use of male essence to alter female endocrine response |
US5108995A (en) | 1987-09-24 | 1992-04-28 | Jencap Research Ltd. | Hormone preparation and method |
JP2578369B2 (ja) * | 1989-05-09 | 1997-02-05 | ポーラ化成工業株式会社 | 芳香組成物 |
GB8912043D0 (en) * | 1989-05-25 | 1989-07-12 | Beecham Group Plc | Novel compounds |
US5272134A (en) * | 1992-03-24 | 1993-12-21 | Erox Corporation | Fragrance compositions and other compositions which contain human pheromones |
US5278141A (en) * | 1992-03-24 | 1994-01-11 | Erox Corporation | Fragrance compositions containing human pheromones |
-
1995
- 1995-06-07 US US08/485,615 patent/US5792757A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 US US08/660,297 patent/US5962443A/en not_active Expired - Lifetime
- 1996-06-07 HU HU9900887A patent/HUP9900887A3/hu unknown
- 1996-06-07 EA EA199800052A patent/EA000965B1/ru not_active IP Right Cessation
- 1996-06-07 NZ NZ312303A patent/NZ312303A/xx unknown
- 1996-06-07 WO PCT/US1996/009665 patent/WO1996040727A1/en not_active Application Discontinuation
- 1996-06-07 CZ CZ973915A patent/CZ391597A3/cs unknown
- 1996-06-07 JP JP9501937A patent/JPH11507360A/ja active Pending
- 1996-06-07 CN CN96195782A patent/CN1191542A/zh active Pending
- 1996-06-07 EP EP96923241A patent/EP0830369B1/en not_active Expired - Lifetime
- 1996-06-07 KR KR1019970709215A patent/KR19990022640A/ko not_active Application Discontinuation
- 1996-06-07 BR BR9609012-0A patent/BR9609012A/pt unknown
- 1996-06-07 CA CA002223397A patent/CA2223397C/en not_active Expired - Fee Related
- 1996-06-07 ES ES96923241T patent/ES2197949T3/es not_active Expired - Lifetime
- 1996-06-07 AU AU63807/96A patent/AU724787B2/en not_active Ceased
- 1996-06-07 AT AT96923241T patent/ATE240344T1/de not_active IP Right Cessation
- 1996-06-07 DE DE69628163T patent/DE69628163T2/de not_active Expired - Lifetime
-
1997
- 1997-12-05 NO NO975709A patent/NO975709L/no not_active Application Discontinuation
-
1998
- 1998-08-11 US US09/131,998 patent/US6242619B1/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CA2223397A1 (en) | 1996-12-19 |
WO1996040727A1 (en) | 1996-12-19 |
CZ391597A3 (cs) | 1998-06-17 |
EP0830369A4 (en) | 1999-06-09 |
EA000965B1 (ru) | 2000-08-28 |
ATE240344T1 (de) | 2003-05-15 |
CN1191542A (zh) | 1998-08-26 |
EP0830369A1 (en) | 1998-03-25 |
NZ312303A (en) | 2000-01-28 |
US6242619B1 (en) | 2001-06-05 |
EP0830369B1 (en) | 2003-05-14 |
EA199800052A1 (ru) | 1998-08-27 |
KR19990022640A (ko) | 1999-03-25 |
AU6380796A (en) | 1996-12-30 |
NO975709D0 (no) | 1997-12-05 |
HUP9900887A2 (hu) | 1999-08-30 |
NO975709L (no) | 1998-02-05 |
BR9609012A (pt) | 1999-12-14 |
ES2197949T3 (es) | 2004-01-16 |
DE69628163D1 (de) | 2003-06-18 |
AU724787B2 (en) | 2000-09-28 |
CA2223397C (en) | 2007-07-31 |
US5962443A (en) | 1999-10-05 |
US5792757A (en) | 1998-08-11 |
HUP9900887A3 (en) | 1999-11-29 |
MX9709693A (es) | 1998-10-31 |
DE69628163T2 (de) | 2004-04-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH11507360A (ja) | 視床下部作用を誘起する新規なノルプレグナン類 | |
JP3834060B2 (ja) | 視床下部機能の変化の神経化学的イニシエーターとしてのプレグナン及びコラン | |
WO1996040727A9 (en) | Novel nor-pregnanes for inducing hypothalamic effects | |
US5883087A (en) | Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods | |
CA2165325A1 (en) | Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods | |
CA2250309C (en) | Steroids as neurochemical initiators of change in human blood levels of lh or fsh | |
US6331534B1 (en) | Steroids as neurochemical stimulators of the VNO to alleviate pain | |
US6437156B1 (en) | 19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function | |
JP4450435B2 (ja) | Pmsおよび不安の症状を緩和する、vnoにおける神経化学刺激物質としてのステロイド | |
RU2160740C2 (ru) | Андростаны | |
WO1997036596A9 (en) | Steroids as neurochemical initiators of change in human blood levels of lh or fsh | |
WO1997046574A9 (en) | 19-nor-cholane steroids as neurochemical initiators of change in human hypothalamic function | |
JPH10509423A (ja) | 視床下部作用を誘起する新規なエストレン類 | |
US6352980B1 (en) | Estrenes for inducting hypothalamic effects | |
EP0775154A1 (en) | Pregnanes and cholanes as neurochemical initiators of change in hypothalamic function | |
US20020103391A1 (en) | Novel androstanes for inducing hypothalamic effects | |
US20020143001A1 (en) | Androstane steroids as neurochemical initiators of change in human hypothalamic function and related pharmaceutical compositions and methods | |
MXPA99000885A (en) | Steroids as neurochemical stimulants of the vomeronasal organ for mitigating symptoms of the pre-menstrual syndrome and ansie | |
MXPA98007951A (en) | Steroids as neurochemical initiators of change in the levels in human blood of luteinizing hormone or stimulating hormone of folicu | |
MXPA97009693A (en) | Novedosos nor-pregnanos, to induce hipotalami effects |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R370 | Written measure of declining of transfer procedure |
Free format text: JAPANESE INTERMEDIATE CODE: R370 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070116 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20061221 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20070416 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20070611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070713 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20080807 Year of fee payment: 10 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20070911 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20090807 Year of fee payment: 11 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20100807 Year of fee payment: 12 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110807 Year of fee payment: 13 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20110807 Year of fee payment: 13 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120807 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120807 Year of fee payment: 14 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130807 Year of fee payment: 15 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |