CA2624015A1 - Novel c18 modified retrosteroids as progesterone receptor modulator compounds - Google Patents

Info

Publication number

CA2624015A1

CA2624015A1 CA002624015A CA2624015A CA2624015A1 CA 2624015 A1 CA2624015 A1 CA 2624015A1 CA 002624015 A CA002624015 A CA 002624015A CA 2624015 A CA2624015 A CA 2624015A CA 2624015 A1 CA2624015 A1 CA 2624015A1

Authority

CA

Canada

Prior art keywords

pregna

ethyl

dione

group

phenyl

Prior art date

2005-09-30

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

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 295
• 239000002379 progesterone receptor modulator Substances 0.000 title abstract description 26
• 238000011282 treatment Methods 0.000 claims abstract description 41
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 36
• 201000009273 Endometriosis Diseases 0.000 claims abstract description 26
• 206010046798 Uterine leiomyoma Diseases 0.000 claims abstract description 24
• 201000010260 leiomyoma Diseases 0.000 claims abstract description 24
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 235000013350 formula milk Nutrition 0.000 claims description 131
• 102000003998 progesterone receptors Human genes 0.000 claims description 113
• 108090000468 progesterone receptors Proteins 0.000 claims description 113
• 125000003118 aryl group Chemical group 0.000 claims description 81
• 125000001424 substituent group Chemical group 0.000 claims description 64
• 229910052739 hydrogen Inorganic materials 0.000 claims description 57
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 54
• 125000001072 heteroaryl group Chemical group 0.000 claims description 53
• 125000004122 cyclic group Chemical group 0.000 claims description 51
• 239000001257 hydrogen Substances 0.000 claims description 44
• 238000000034 method Methods 0.000 claims description 42
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 40
• 150000003839 salts Chemical class 0.000 claims description 34
• 239000003814 drug Substances 0.000 claims description 31
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
• 125000005842 heteroatom Chemical group 0.000 claims description 25
• 206010027514 Metrorrhagia Diseases 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims description 23
• 239000000651 prodrug Substances 0.000 claims description 23
• 229940002612 prodrug Drugs 0.000 claims description 23
• 125000000623 heterocyclic group Chemical group 0.000 claims description 22
• 229920006395 saturated elastomer Polymers 0.000 claims description 22
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 20
• 208000035475 disorder Diseases 0.000 claims description 20
• 238000012360 testing method Methods 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 19
• 230000001419 dependent effect Effects 0.000 claims description 18
• 208000007106 menorrhagia Diseases 0.000 claims description 18
• 206010028980 Neoplasm Diseases 0.000 claims description 17
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
• 239000000284 extract Substances 0.000 claims description 16
• 102000005962 receptors Human genes 0.000 claims description 15
• 108020003175 receptors Proteins 0.000 claims description 15
• 206010013908 Dysfunctional uterine bleeding Diseases 0.000 claims description 14
• 229940088597 hormone Drugs 0.000 claims description 14
• 239000005556 hormone Substances 0.000 claims description 14
• 230000001404 mediated effect Effects 0.000 claims description 14
• 125000004434 sulfur atom Chemical group 0.000 claims description 14
• 239000000262 estrogen Substances 0.000 claims description 13
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 13
• 201000011510 cancer Diseases 0.000 claims description 12
• 208000026310 Breast neoplasm Diseases 0.000 claims description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 229940011871 estrogen Drugs 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 206010006187 Breast cancer Diseases 0.000 claims description 10
• 238000002657 hormone replacement therapy Methods 0.000 claims description 10
• 201000007954 uterine fibroid Diseases 0.000 claims description 10
• 206010013935 Dysmenorrhoea Diseases 0.000 claims description 9
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
• 239000004480 active ingredient Substances 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 239000000126 substance Substances 0.000 claims description 8
• 208000005171 Dysmenorrhea Diseases 0.000 claims description 7
• 208000001132 Osteoporosis Diseases 0.000 claims description 7
• 230000035558 fertility Effects 0.000 claims description 7
• 206010014733 Endometrial cancer Diseases 0.000 claims description 6
• 206010014759 Endometrial neoplasm Diseases 0.000 claims description 6
• 208000019022 Mood disease Diseases 0.000 claims description 6
• 208000022168 hypermenorrhea Diseases 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 206010060800 Hot flush Diseases 0.000 claims description 5
• 206010033128 Ovarian cancer Diseases 0.000 claims description 5
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
• 206010060862 Prostate cancer Diseases 0.000 claims description 5
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
• 230000004913 activation Effects 0.000 claims description 5
• 201000006828 endometrial hyperplasia Diseases 0.000 claims description 5
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 239000003163 gonadal steroid hormone Substances 0.000 claims description 5
• 206010027191 meningioma Diseases 0.000 claims description 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 4
• 208000014311 Cushing syndrome Diseases 0.000 claims description 4
• 208000016192 Demyelinating disease Diseases 0.000 claims description 4
• 230000004770 neurodegeneration Effects 0.000 claims description 4
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
• 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 4
• 208000024714 major depressive disease Diseases 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 2
• 238000002372 labelling Methods 0.000 claims description 2
• -1 and their production Substances 0.000 abstract description 44
• 229940095745 sex hormone and modulator of the genital system progesterone receptor modulator Drugs 0.000 abstract description 6
• 239000000825 pharmaceutical preparation Substances 0.000 abstract description 4
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 147
• 238000006243 chemical reaction Methods 0.000 description 95
• RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 94
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 78
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 76
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 70
• 239000000203 mixture Substances 0.000 description 69
• 239000002904 solvent Substances 0.000 description 66
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 60
• 230000000875 corresponding effect Effects 0.000 description 54
• 239000000186 progesterone Substances 0.000 description 52
• 239000000243 solution Substances 0.000 description 52
• 229960003387 progesterone Drugs 0.000 description 50
• 125000000217 alkyl group Chemical group 0.000 description 47
• 239000000047 product Substances 0.000 description 46
• 239000012071 phase Substances 0.000 description 41
• 235000019439 ethyl acetate Nutrition 0.000 description 38
• 238000003756 stirring Methods 0.000 description 37
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 238000004809 thin layer chromatography Methods 0.000 description 36
• 229910052786 argon Inorganic materials 0.000 description 35
• 238000007792 addition Methods 0.000 description 34
• 238000004458 analytical method Methods 0.000 description 34
• 238000005160 1H NMR spectroscopy Methods 0.000 description 33
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
• 239000011541 reaction mixture Substances 0.000 description 29
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
• 210000004027 cell Anatomy 0.000 description 25
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
• 239000000543 intermediate Substances 0.000 description 25
• 238000010626 work up procedure Methods 0.000 description 25
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 238000003556 assay Methods 0.000 description 24
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 24
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 22
• 239000003153 chemical reaction reagent Substances 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• 238000003786 synthesis reaction Methods 0.000 description 20
• 229940079593 drug Drugs 0.000 description 19
• JGMOKGBVKVMRFX-HQZYFCCVSA-N dydrogesterone Chemical compound C1=CC2=CC(=O)CC[C@@]2(C)[C@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 JGMOKGBVKVMRFX-HQZYFCCVSA-N 0.000 description 19
• 229960004913 dydrogesterone Drugs 0.000 description 19
• 239000012074 organic phase Substances 0.000 description 19
• 239000000741 silica gel Substances 0.000 description 18
• 229910002027 silica gel Inorganic materials 0.000 description 18
• 229960001866 silicon dioxide Drugs 0.000 description 18
• 210000004291 uterus Anatomy 0.000 description 18
• 239000000556 agonist Substances 0.000 description 17
• 239000006260 foam Substances 0.000 description 17
• LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 17
• 150000003431 steroids Chemical class 0.000 description 17
• HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• 230000001270 agonistic effect Effects 0.000 description 15
• 238000006356 dehydrogenation reaction Methods 0.000 description 15
• 201000010099 disease Diseases 0.000 description 15
• 125000006239 protecting group Chemical group 0.000 description 15
• 239000007787 solid Substances 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 14
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 14
• 239000005557 antagonist Substances 0.000 description 14
• 239000013078 crystal Substances 0.000 description 14
• 238000006567 deketalization reaction Methods 0.000 description 14
• 238000001212 derivatisation Methods 0.000 description 14
• 239000000583 progesterone congener Substances 0.000 description 13
• 235000017557 sodium bicarbonate Nutrition 0.000 description 13
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 230000003042 antagnostic effect Effects 0.000 description 12
• 238000004440 column chromatography Methods 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 230000003637 steroidlike Effects 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 11
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 11
• 210000004369 blood Anatomy 0.000 description 11
• 239000008280 blood Substances 0.000 description 11
• 241000283973 Oryctolagus cuniculus Species 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 230000006870 function Effects 0.000 description 10
• 239000007789 gas Substances 0.000 description 10
• 239000004615 ingredient Substances 0.000 description 10
• 238000007254 oxidation reaction Methods 0.000 description 10
• 125000004043 oxo group Chemical group O=* 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 238000005406 washing Methods 0.000 description 10
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 9
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
• PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• 125000004093 cyano group Chemical group *C#N 0.000 description 9
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• 239000000725 suspension Substances 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• 241000283690 Bos taurus Species 0.000 description 8
• 239000007832 Na2SO4 Substances 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 239000012300 argon atmosphere Substances 0.000 description 8
• 230000037396 body weight Effects 0.000 description 8
• 239000003054 catalyst Substances 0.000 description 8
• 238000001727 in vivo Methods 0.000 description 8
• 239000011630 iodine Substances 0.000 description 8
• 229910052740 iodine Inorganic materials 0.000 description 8
• ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 8
• 230000004048 modification Effects 0.000 description 8
• 238000012986 modification Methods 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• 238000006722 reduction reaction Methods 0.000 description 8
• 208000024891 symptom Diseases 0.000 description 8
• 101100515516 Arabidopsis thaliana XI-H gene Proteins 0.000 description 7
• 201000004458 Myoma Diseases 0.000 description 7
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
• 230000000708 anti-progestin effect Effects 0.000 description 7
• 239000003418 antiprogestin Substances 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 229960003248 mifepristone Drugs 0.000 description 7
• 239000007800 oxidant agent Substances 0.000 description 7
• 230000003647 oxidation Effects 0.000 description 7
• 238000000967 suction filtration Methods 0.000 description 7
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 6
• 208000002193 Pain Diseases 0.000 description 6
• 229930182558 Sterol Natural products 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 230000003054 hormonal effect Effects 0.000 description 6
• 238000011835 investigation Methods 0.000 description 6
• 239000012280 lithium aluminium hydride Substances 0.000 description 6
• 230000029860 luteolysis Effects 0.000 description 6
• 230000005906 menstruation Effects 0.000 description 6
• 239000000044 progesterone antagonist Substances 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• 102000005969 steroid hormone receptors Human genes 0.000 description 6
• 150000003432 sterols Chemical class 0.000 description 6
• 235000003702 sterols Nutrition 0.000 description 6
• 125000003107 substituted aryl group Chemical group 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 238000002560 therapeutic procedure Methods 0.000 description 6
• RJKFOVLPORLFTN-HQZYFCCVSA-N (8s,9r,10s,13s,14s,17s)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@]2(C)[C@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-HQZYFCCVSA-N 0.000 description 5
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
• 239000005909 Kieselgur Substances 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 238000005481 NMR spectroscopy Methods 0.000 description 5
• 108010029485 Protein Isoforms Proteins 0.000 description 5
• 102000001708 Protein Isoforms Human genes 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 150000001336 alkenes Chemical class 0.000 description 5
• GJMNAFGEUJBOCE-MEQIQULJSA-N asoprisnil Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@]([C@]3(C2)C)(COC)OC)=CC=C(\C=N\O)C=C1 GJMNAFGEUJBOCE-MEQIQULJSA-N 0.000 description 5
• 238000009835 boiling Methods 0.000 description 5
• 230000004069 differentiation Effects 0.000 description 5
• 230000000762 glandular Effects 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 239000007943 implant Substances 0.000 description 5
• 208000000509 infertility Diseases 0.000 description 5
• 230000036512 infertility Effects 0.000 description 5
• 231100000535 infertility Toxicity 0.000 description 5
• 239000012948 isocyanate Substances 0.000 description 5
• 150000002513 isocyanates Chemical class 0.000 description 5
• 230000007935 neutral effect Effects 0.000 description 5
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 5
• 230000016087 ovulation Effects 0.000 description 5
• 230000036961 partial effect Effects 0.000 description 5
• 230000035935 pregnancy Effects 0.000 description 5
• 230000000757 progestagenic effect Effects 0.000 description 5
• 230000001072 progestational effect Effects 0.000 description 5
• 230000002829 reductive effect Effects 0.000 description 5
• 230000001850 reproductive effect Effects 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
• ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 241000700198 Cavia Species 0.000 description 4
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
• 239000012190 activator Substances 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 239000003638 chemical reducing agent Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 231100000673 dose–response relationship Toxicity 0.000 description 4
• 238000001035 drying Methods 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 230000002357 endometrial effect Effects 0.000 description 4
• 210000004696 endometrium Anatomy 0.000 description 4
• 238000005886 esterification reaction Methods 0.000 description 4
• 229960005309 estradiol Drugs 0.000 description 4
• 102000015694 estrogen receptors Human genes 0.000 description 4
• 108010038795 estrogen receptors Proteins 0.000 description 4
• JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 4
• 238000005984 hydrogenation reaction Methods 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 125000000468 ketone group Chemical group 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• 238000002844 melting Methods 0.000 description 4
• 230000008018 melting Effects 0.000 description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• 239000012452 mother liquor Substances 0.000 description 4
• 210000000754 myometrium Anatomy 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 210000001672 ovary Anatomy 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• 239000004031 partial agonist Substances 0.000 description 4
• 239000000546 pharmaceutical excipient Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
• 230000036647 reaction Effects 0.000 description 4
• 210000002966 serum Anatomy 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 description 3
• 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 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• 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 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 102000003676 Glucocorticoid Receptors Human genes 0.000 description 3
• 108090000079 Glucocorticoid Receptors Proteins 0.000 description 3
• 208000032843 Hemorrhage Diseases 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 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 3
• 241000124008 Mammalia Species 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 102220497176 Small vasohibin-binding protein_T47D_mutation Human genes 0.000 description 3
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
• 108010085012 Steroid Receptors Proteins 0.000 description 3
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
• 239000008351 acetate buffer Substances 0.000 description 3
• 150000008065 acid anhydrides Chemical class 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• YLFIGGHWWPSIEG-UHFFFAOYSA-N aminoxyl Chemical compound [O]N YLFIGGHWWPSIEG-UHFFFAOYSA-N 0.000 description 3
• 102000001307 androgen receptors Human genes 0.000 description 3
• 108010080146 androgen receptors Proteins 0.000 description 3
• 230000001838 anti-progestagenic effect Effects 0.000 description 3
• 229950003620 asoprisnil Drugs 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 3
• 208000034158 bleeding Diseases 0.000 description 3
• 230000000740 bleeding effect Effects 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 150000001721 carbon Chemical group 0.000 description 3
• 235000011089 carbon dioxide Nutrition 0.000 description 3
• WIKQEUJFZPCFNJ-UHFFFAOYSA-N carbonic acid;silver Chemical compound [Ag].[Ag].OC(O)=O WIKQEUJFZPCFNJ-UHFFFAOYSA-N 0.000 description 3
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
• 150000001735 carboxylic acids Chemical class 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 230000009260 cross reactivity Effects 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 108010037444 diisopropylglutathione ester Proteins 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000003623 enhancer Substances 0.000 description 3
• 229930182833 estradiol Natural products 0.000 description 3
• 229940093476 ethylene glycol Drugs 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 235000021474 generally recognized As safe (food) Nutrition 0.000 description 3
• 235000021473 generally recognized as safe (food ingredients) Nutrition 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 150000002431 hydrogen Chemical group 0.000 description 3
• 238000005286 illumination Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 230000001939 inductive effect Effects 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 238000006317 isomerization reaction Methods 0.000 description 3
• 238000005907 ketalization reaction Methods 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 235000019198 oils Nutrition 0.000 description 3
• 229950011093 onapristone Drugs 0.000 description 3
• 239000012285 osmium tetroxide Substances 0.000 description 3
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 3
• 230000002611 ovarian Effects 0.000 description 3
• 238000007911 parenteral administration Methods 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 150000004714 phosphonium salts Chemical class 0.000 description 3
• 230000009257 reactivity Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 3
• KQTXIZHBFFWWFW-UHFFFAOYSA-L silver(I) carbonate Inorganic materials [Ag]OC(=O)O[Ag] KQTXIZHBFFWWFW-UHFFFAOYSA-L 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 238000005507 spraying Methods 0.000 description 3
• 108020003113 steroid hormone receptors Proteins 0.000 description 3
• 230000000638 stimulation Effects 0.000 description 3
• 238000007920 subcutaneous administration Methods 0.000 description 3
• 235000011149 sulphuric acid Nutrition 0.000 description 3
• 238000001356 surgical procedure Methods 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 3
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
• BSVHTRRLCAVQCZ-JDEXMCKMSA-N (2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrro Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 BSVHTRRLCAVQCZ-JDEXMCKMSA-N 0.000 description 2
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
• 208000037853 Abnormal uterine bleeding Diseases 0.000 description 2
• 208000005641 Adenomyosis Diseases 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 102000006771 Gonadotropins Human genes 0.000 description 2
• 108010086677 Gonadotropins Proteins 0.000 description 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
• 108010077495 Peptide oostatic hormone Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 230000002730 additional effect Effects 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 150000004705 aldimines Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 150000001350 alkyl halides Chemical class 0.000 description 2
• 239000004411 aluminium Substances 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 2
• 230000002521 anti-luteolytic effect Effects 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 229960002903 benzyl benzoate Drugs 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 238000004166 bioassay Methods 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 201000008275 breast carcinoma Diseases 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 235000011148 calcium chloride Nutrition 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000002837 carbocyclic group Chemical group 0.000 description 2
• 238000006473 carboxylation reaction Methods 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 239000004359 castor oil Substances 0.000 description 2
• 235000019438 castor oil Nutrition 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000013375 chromatographic separation Methods 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 2
• 230000002301 combined effect Effects 0.000 description 2
• 230000009850 completed effect Effects 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 230000000332 continued effect Effects 0.000 description 2
• 229920001577 copolymer Chemical group 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• 229940127089 cytotoxic agent Drugs 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 201000009274 endometriosis of uterus Diseases 0.000 description 2
• QTTMOCOWZLSYSV-QWAPEVOJSA-M equilin sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 QTTMOCOWZLSYSV-QWAPEVOJSA-M 0.000 description 2
• 230000032050 esterification Effects 0.000 description 2
• 150000002164 estratrienes Chemical class 0.000 description 2
• 239000002834 estrogen receptor modulator Substances 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 235000013373 food additive Nutrition 0.000 description 2
• 239000002778 food additive Substances 0.000 description 2
• 235000021472 generally recognized as safe Nutrition 0.000 description 2
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
• 239000002622 gonadotropin Substances 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 150000004820 halides Chemical class 0.000 description 2
• 238000001794 hormone therapy Methods 0.000 description 2
• 238000006197 hydroboration reaction Methods 0.000 description 2
• 150000002430 hydrocarbons Chemical class 0.000 description 2
• 229960000890 hydrocortisone Drugs 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 238000009802 hysterectomy Methods 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 229960004592 isopropanol Drugs 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 150000002632 lipids Chemical class 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 230000035800 maturation Effects 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
• 239000011859 microparticle Substances 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 210000004400 mucous membrane Anatomy 0.000 description 2
• 150000002825 nitriles Chemical class 0.000 description 2
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 230000027758 ovulation cycle Effects 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000035699 permeability Effects 0.000 description 2
• 230000002688 persistence Effects 0.000 description 2
• NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
• 230000037452 priming Effects 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 230000001737 promoting effect Effects 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 125000003226 pyrazolyl group Chemical group 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 238000001525 receptor binding assay Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
• MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 2
• 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 238000007070 tosylation reaction Methods 0.000 description 2
• 230000037317 transdermal delivery Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
• WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 description 1
• DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 1
• YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
• VUZNLSBZRVZGIK-UHFFFAOYSA-N 2,2,6,6-Tetramethyl-1-piperidinol Chemical compound CC1(C)CCCC(C)(C)N1O VUZNLSBZRVZGIK-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• OSJPPGNTCRNQQC-UHFFFAOYSA-N 3-phosphoglyceric acid Chemical compound OC(=O)C(O)COP(O)(O)=O OSJPPGNTCRNQQC-UHFFFAOYSA-N 0.000 description 1
• XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
• SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 201000005670 Anovulation Diseases 0.000 description 1
• 206010002659 Anovulatory cycle Diseases 0.000 description 1
• 206010003497 Asphyxia Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 101001011741 Bos taurus Insulin Proteins 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
• 206010053567 Coagulopathies Diseases 0.000 description 1
• XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 230000004568 DNA-binding Effects 0.000 description 1
• 206010012110 Defaecation urgency Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
• 208000004483 Dyspareunia Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
• 239000005977 Ethylene Substances 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• BJJXHLWLUDYTGC-ANULTFPQSA-N Gestrinone Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](CC)([C@](CC3)(O)C#C)C=C3)C3=C21 BJJXHLWLUDYTGC-ANULTFPQSA-N 0.000 description 1
• DHCLVCXQIBBOPH-UHFFFAOYSA-N Glycerol 2-phosphate Chemical compound OCC(CO)OP(O)(O)=O DHCLVCXQIBBOPH-UHFFFAOYSA-N 0.000 description 1
• NMJREATYWWNIKX-UHFFFAOYSA-N GnRH Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CC(C)C)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 NMJREATYWWNIKX-UHFFFAOYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101100435109 Homo sapiens PRNP gene Proteins 0.000 description 1
• 101000574060 Homo sapiens Progesterone receptor Proteins 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 102000014150 Interferons Human genes 0.000 description 1
• 108010050904 Interferons Proteins 0.000 description 1
• 102000015696 Interleukins Human genes 0.000 description 1
• 108010063738 Interleukins Proteins 0.000 description 1
• 239000003810 Jones reagent Substances 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000037093 Menstruation Disturbances Diseases 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 208000034424 Painful defaecation Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 208000000450 Pelvic Pain Diseases 0.000 description 1
• 208000010067 Pituitary ACTH Hypersecretion Diseases 0.000 description 1
• 208000020627 Pituitary-dependent Cushing syndrome Diseases 0.000 description 1
• 208000037062 Polyps Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 229940123788 Progesterone receptor antagonist Drugs 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 206010065951 Retrograde menstruation Diseases 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 239000005708 Sodium hypochlorite Substances 0.000 description 1
• 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 238000006859 Swern oxidation reaction Methods 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 206010046788 Uterine haemorrhage Diseases 0.000 description 1
• 238000007239 Wittig reaction Methods 0.000 description 1
• YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 1
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 239000004015 abortifacient agent Substances 0.000 description 1
• 231100000641 abortifacient agent Toxicity 0.000 description 1
• 206010000210 abortion Diseases 0.000 description 1
• 231100000176 abortion Toxicity 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 238000007259 addition reaction Methods 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001409 amidines Chemical class 0.000 description 1
• 150000001413 amino acids Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000001548 androgenic effect Effects 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 231100000552 anovulation Toxicity 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 230000000380 anti-gestagenic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 238000011861 anti-inflammatory therapy Methods 0.000 description 1
• 230000002513 anti-ovulatory effect Effects 0.000 description 1
• 230000001911 anti-progestational effect Effects 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000003849 aromatic solvent Substances 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 150000003939 benzylamines Chemical class 0.000 description 1
• 210000002459 blastocyst Anatomy 0.000 description 1
• 208000015294 blood coagulation disease Diseases 0.000 description 1
• 210000000746 body region Anatomy 0.000 description 1
• IXIBAKNTJSCKJM-BUBXBXGNSA-N bovine insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 IXIBAKNTJSCKJM-BUBXBXGNSA-N 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000004369 butenyl group Chemical group C(=CCC)* 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
• 238000004364 calculation method Methods 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 230000021523 carboxylation Effects 0.000 description 1
• 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 238000010531 catalytic reduction reaction Methods 0.000 description 1
• 230000001364 causal effect Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 1
• KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 238000010568 chiral column chromatography Methods 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 230000009852 coagulant defect Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 230000003931 cognitive performance Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000000052 comparative effect Effects 0.000 description 1
• 239000007859 condensation product Substances 0.000 description 1
• 230000001143 conditioned effect Effects 0.000 description 1
• 229940035811 conjugated estrogen Drugs 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 239000003433 contraceptive agent Substances 0.000 description 1
• 229940124558 contraceptive agent Drugs 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000002826 coolant Substances 0.000 description 1
• 239000000110 cooling liquid Substances 0.000 description 1
• 210000004246 corpus luteum Anatomy 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000003431 cross linking reagent Substances 0.000 description 1
• 239000012045 crude solution Substances 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 230000001351 cycling effect Effects 0.000 description 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 239000000824 cytostatic agent Substances 0.000 description 1
• 230000001085 cytostatic effect Effects 0.000 description 1
• 239000002254 cytotoxic agent Substances 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229960000766 danazol Drugs 0.000 description 1
• POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 229920006237 degradable polymer Polymers 0.000 description 1
• 238000010586 diagram Methods 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229960001342 dinoprost Drugs 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• VIYFPAMJCJLZKD-UHFFFAOYSA-L disodium;(4-nitrophenyl) phosphate Chemical compound [Na+].[Na+].[O-][N+](=O)C1=CC=C(OP([O-])([O-])=O)C=C1 VIYFPAMJCJLZKD-UHFFFAOYSA-L 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 210000003717 douglas' pouch Anatomy 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 230000004064 dysfunction Effects 0.000 description 1
• 206010013990 dysuria Diseases 0.000 description 1
• 201000003511 ectopic pregnancy Diseases 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 229920001971 elastomer Polymers 0.000 description 1
• 238000006056 electrooxidation reaction Methods 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 238000000921 elemental analysis Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 150000002081 enamines Chemical class 0.000 description 1
• 230000002124 endocrine Effects 0.000 description 1
• 201000003914 endometrial carcinoma Diseases 0.000 description 1
• 210000005168 endometrial cell Anatomy 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• 238000006266 etherification reaction Methods 0.000 description 1
• 229940093470 ethylene Drugs 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 229940124566 female contraceptive agent Drugs 0.000 description 1
• 239000003037 female contraceptive agent Substances 0.000 description 1
• 210000004996 female reproductive system Anatomy 0.000 description 1
• 230000004720 fertilization Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000010579 first pass effect Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003709 fluoroalkyl group Chemical group 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 239000003517 fume Substances 0.000 description 1
• 238000007306 functionalization reaction Methods 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 229960004761 gestrinone Drugs 0.000 description 1
• 210000004907 gland Anatomy 0.000 description 1
• 239000011491 glass wool Substances 0.000 description 1
• 229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000005337 ground glass Substances 0.000 description 1
• 239000000122 growth hormone Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 238000011554 guinea pig model Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 230000003284 homeostatic effect Effects 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 229960001330 hydroxycarbamide Drugs 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
• 238000003364 immunohistochemistry Methods 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 229940047122 interleukins Drugs 0.000 description 1
• 208000003243 intestinal obstruction Diseases 0.000 description 1
• 102000027411 intracellular receptors Human genes 0.000 description 1
• 108091008582 intracellular receptors Proteins 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 150000002497 iodine compounds Chemical class 0.000 description 1
• BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
• 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 230000006651 lactation Effects 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 238000002357 laparoscopic surgery Methods 0.000 description 1
• 229960004400 levonorgestrel Drugs 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• 230000009245 menopause Effects 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
• LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000005065 mining Methods 0.000 description 1
• 230000011278 mitosis Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-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
• 239000002105 nanoparticle Substances 0.000 description 1
• 239000006070 nanosuspension Substances 0.000 description 1
• 125000004998 naphthylethyl group Chemical group C1(=CC=CC2=CC=CC=C12)CC* 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229960003512 nicotinic acid Drugs 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 229940046835 other hormone for endocrine therapy in atc Drugs 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 210000003200 peritoneal cavity Anatomy 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• 150000003009 phosphonic acids Chemical class 0.000 description 1
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
• 238000006552 photochemical reaction Methods 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 150000004885 piperazines Chemical class 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 210000002826 placenta Anatomy 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 229940074439 potassium sodium tartrate Drugs 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000006259 progesterone secretion Effects 0.000 description 1
• 229940095055 progestogen systemic hormonal contraceptives Drugs 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• PXGPLTODNUVGFL-YNNPMVKQSA-N prostaglandin F2alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-YNNPMVKQSA-N 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000000541 pulsatile effect Effects 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 150000003235 pyrrolidines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 239000010453 quartz Substances 0.000 description 1
• 125000001453 quaternary ammonium group Chemical group 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 150000004671 saturated fatty acids Chemical class 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 229920002379 silicone rubber Polymers 0.000 description 1
• 239000004945 silicone rubber Substances 0.000 description 1
• QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical group [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• NYCVSSWORUBFET-UHFFFAOYSA-M sodium;bromite Chemical compound [Na+].[O-]Br=O NYCVSSWORUBFET-UHFFFAOYSA-M 0.000 description 1
• 239000007962 solid dispersion Substances 0.000 description 1
• 239000008137 solubility enhancer Substances 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000000995 spontaneous abortion Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 239000003270 steroid hormone Substances 0.000 description 1
• 230000002311 subsequent effect Effects 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 239000001117 sulphuric acid Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 150000003673 urethanes Chemical class 0.000 description 1
• 206010046459 urethral obstruction Diseases 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 208000013464 vaginal disease Diseases 0.000 description 1
• 239000006213 vaginal ring Substances 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 239000000341 volatile oil Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 230000005186 women's health Effects 0.000 description 1