ES2388297T3 - Inhibidores de 17-HSD1 y STS - Google Patents
Inhibidores de 17-HSD1 y STS Download PDFInfo
- Publication number
- ES2388297T3 ES2388297T3 ES06763273T ES06763273T ES2388297T3 ES 2388297 T3 ES2388297 T3 ES 2388297T3 ES 06763273 T ES06763273 T ES 06763273T ES 06763273 T ES06763273 T ES 06763273T ES 2388297 T3 ES2388297 T3 ES 2388297T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- group
- optionally substituted
- compound
- alkoxy
- 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.)
- Active
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- 239000003112 inhibitor Substances 0.000 title description 44
- 150000001875 compounds Chemical class 0.000 claims abstract description 320
- 125000001424 substituent group Chemical group 0.000 claims abstract description 181
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 121
- 150000002367 halogens Chemical group 0.000 claims abstract description 103
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 67
- 150000002825 nitriles Chemical group 0.000 claims abstract description 59
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 26
- -1 aryl (C1-C4) alkyl Chemical group 0.000 claims description 303
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 131
- 125000003118 aryl group Chemical group 0.000 claims description 127
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 124
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 105
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 84
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 74
- 125000004429 atom Chemical group 0.000 claims description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims description 66
- 108010070743 3(or 17)-beta-hydroxysteroid dehydrogenase Proteins 0.000 claims description 63
- 201000010099 disease Diseases 0.000 claims description 63
- 229910052760 oxygen Inorganic materials 0.000 claims description 62
- 208000035475 disorder Diseases 0.000 claims description 61
- 230000001419 dependent effect Effects 0.000 claims description 60
- 229910052717 sulfur Inorganic materials 0.000 claims description 57
- 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 claims description 54
- 125000004432 carbon atom Chemical group C* 0.000 claims description 51
- 229960005309 estradiol Drugs 0.000 claims description 48
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 47
- 125000005842 heteroatom Chemical group 0.000 claims description 42
- 102100037426 17-beta-hydroxysteroid dehydrogenase type 1 Human genes 0.000 claims description 41
- 125000004122 cyclic group Chemical group 0.000 claims description 40
- 229930182833 estradiol Natural products 0.000 claims description 38
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 37
- 239000003098 androgen Substances 0.000 claims description 35
- 229920006395 saturated elastomer Polymers 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000002252 acyl group Chemical group 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000004043 oxo group Chemical group O=* 0.000 claims description 26
- 210000001519 tissue Anatomy 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 229940124530 sulfonamide Drugs 0.000 claims description 25
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 24
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- 239000000262 estrogen Substances 0.000 claims description 24
- 150000003456 sulfonamides Chemical group 0.000 claims description 24
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 23
- 125000005110 aryl thio group Chemical group 0.000 claims description 23
- 125000004104 aryloxy group Chemical group 0.000 claims description 23
- 229940011871 estrogen Drugs 0.000 claims description 23
- 239000003270 steroid hormone Substances 0.000 claims description 23
- 125000003368 amide group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 22
- 201000009273 Endometriosis Diseases 0.000 claims description 21
- 125000004442 acylamino group Chemical group 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 21
- 201000010260 leiomyoma Diseases 0.000 claims description 21
- 206010046798 Uterine leiomyoma Diseases 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 230000009467 reduction Effects 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 15
- 208000026310 Breast neoplasm Diseases 0.000 claims description 15
- 125000003107 substituted aryl group Chemical group 0.000 claims description 15
- 206010006187 Breast cancer Diseases 0.000 claims description 14
- 241000282414 Homo sapiens Species 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
- 229940030486 androgens Drugs 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 11
- 206010000496 acne Diseases 0.000 claims description 11
- 150000001721 carbon Chemical group 0.000 claims description 11
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
- 201000004384 Alopecia Diseases 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 230000003211 malignant effect Effects 0.000 claims description 9
- 208000007106 menorrhagia Diseases 0.000 claims description 9
- 201000007954 uterine fibroid Diseases 0.000 claims description 9
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 8
- 206010020112 Hirsutism Diseases 0.000 claims description 8
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 8
- 230000004064 dysfunction Effects 0.000 claims description 8
- 230000002485 urinary effect Effects 0.000 claims description 8
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 208000005641 Adenomyosis Diseases 0.000 claims description 6
- 208000005171 Dysmenorrhea Diseases 0.000 claims description 6
- 206010013935 Dysmenorrhoea Diseases 0.000 claims description 6
- 206010014733 Endometrial cancer Diseases 0.000 claims description 6
- 206010027514 Metrorrhagia Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 201000002996 androgenic alopecia Diseases 0.000 claims description 6
- 201000009274 endometriosis of uterus Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 5
- 206010039792 Seborrhoea Diseases 0.000 claims description 5
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 201000006828 endometrial hyperplasia Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 208000008742 seborrheic dermatitis Diseases 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 206010046766 uterine cancer Diseases 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 208000002177 Cataract Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 206010012442 Dermatitis contact Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010039966 Senile dementia Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 206010047115 Vasculitis Diseases 0.000 claims description 4
- 206010052428 Wound Diseases 0.000 claims description 4
- 208000027418 Wounds and injury Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000010668 atopic eczema Diseases 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 208000010247 contact dermatitis Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 206010043778 thyroiditis Diseases 0.000 claims description 4
- 238000002054 transplantation Methods 0.000 claims description 4
- 210000001635 urinary tract Anatomy 0.000 claims description 4
- 230000037303 wrinkles Effects 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 2
- KGYJKPJMOXYPPL-MWQGOVGESA-N 4-[(8r,9s,13s,14s,15r)-2-ethyl-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-15-yl]-n-(5-methyl-1,3-thiazol-2-yl)butanamide Chemical compound C([C@H]1[C@@H]2[C@](C(C1)=O)(C)CC[C@@H]1C=3C=C(C(=CC=3CC[C@H]12)O)CC)CCC(=O)NC1=NC=C(C)S1 KGYJKPJMOXYPPL-MWQGOVGESA-N 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- SNASNVBLDFTPGU-XNEAZFQJSA-N OC1=CC=2CC[C@H]3[C@@H]4[C@@H](CC([C@@]4(C)CC[C@@H]3C2C=C1CCC)=O)CCCC(=O)N1CCOCC1.C(C)C=1C(=CC=2CC[C@H]3[C@@H]4[C@@H](CC([C@@]4(C)CC[C@@H]3C2C1)=O)CCCC(=O)N1CCOCC1)O Chemical compound OC1=CC=2CC[C@H]3[C@@H]4[C@@H](CC([C@@]4(C)CC[C@@H]3C2C=C1CCC)=O)CCCC(=O)N1CCOCC1.C(C)C=1C(=CC=2CC[C@H]3[C@@H]4[C@@H](CC([C@@]4(C)CC[C@@H]3C2C1)=O)CCCC(=O)N1CCOCC1)O SNASNVBLDFTPGU-XNEAZFQJSA-N 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- OCVQZQZCFBTRQD-BRTDTQBDSA-N n-benzyl-4-[(8r,9s,13s,14s,15r)-2-ethyl-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-15-yl]butanamide;n-benzyl-4-[(8r,9s,13s,14s,15r)-3-hydroxy-13-methyl-17-oxo-2-propyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta Chemical compound C([C@H]1[C@@H]2[C@](C(C1)=O)(C)CC[C@@H]1C=3C=C(C(=CC=3CC[C@H]12)O)CC)CCC(=O)NCC1=CC=CC=C1.C([C@H]1[C@@H]2[C@](C(C1)=O)(C)CC[C@@H]1C=3C=C(C(=CC=3CC[C@H]12)O)CCC)CCC(=O)NCC1=CC=CC=C1 OCVQZQZCFBTRQD-BRTDTQBDSA-N 0.000 claims description 2
- 206010040954 Skin wrinkling Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 293
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 136
- 239000000203 mixture Substances 0.000 description 82
- 230000015572 biosynthetic process Effects 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 75
- 238000003786 synthesis reaction Methods 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 67
- 239000000243 solution Substances 0.000 description 59
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 57
- 239000002253 acid Substances 0.000 description 55
- 239000000543 intermediate Substances 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
- 150000002167 estrones Chemical class 0.000 description 47
- 102000005262 Sulfatase Human genes 0.000 description 46
- 108060007951 sulfatase Proteins 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
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- 238000000034 method Methods 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- 150000001412 amines Chemical class 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 33
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- 239000007787 solid Substances 0.000 description 31
- 229910052740 iodine Inorganic materials 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 230000006870 function Effects 0.000 description 27
- 239000007832 Na2SO4 Substances 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- 239000000377 silicon dioxide Substances 0.000 description 26
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- 229910052681 coesite Inorganic materials 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 24
- 229910052906 cristobalite Inorganic materials 0.000 description 24
- 235000012239 silicon dioxide Nutrition 0.000 description 24
- 229910052682 stishovite Inorganic materials 0.000 description 24
- 229910052905 tridymite Inorganic materials 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 150000003431 steroids Chemical class 0.000 description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 22
- 230000000694 effects Effects 0.000 description 21
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- 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 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 229960003399 estrone Drugs 0.000 description 20
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 19
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- 239000012267 brine Substances 0.000 description 18
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- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- 125000006239 protecting group Chemical group 0.000 description 18
- 238000000746 purification Methods 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
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- 210000004940 nucleus Anatomy 0.000 description 17
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- 125000000468 ketone group Chemical group 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 15
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
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- 125000004076 pyridyl group Chemical group 0.000 description 14
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- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 9
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
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- 239000002585 base Substances 0.000 description 8
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 229940088597 hormone Drugs 0.000 description 8
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
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Classifications
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05104534 | 2005-05-26 | ||
| EP05104534 | 2005-05-26 | ||
| PCT/EP2006/062587 WO2006125800A1 (en) | 2005-05-26 | 2006-05-24 | 17β-HSD1 AND STS INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2388297T3 true ES2388297T3 (es) | 2012-10-11 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06763273T Active ES2388297T3 (es) | 2005-05-26 | 2006-05-24 | Inhibidores de 17-HSD1 y STS |
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| JP (1) | JP5268635B2 (cg-RX-API-DMAC7.html) |
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| ES (1) | ES2388297T3 (cg-RX-API-DMAC7.html) |
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| US8080540B2 (en) | 2006-09-19 | 2011-12-20 | Abbott Products Gmbh | Therapeutically active triazoles and their use |
| AU2007327653B2 (en) * | 2006-11-30 | 2013-04-18 | Solvay Pharmaceuticals Gmbh | Substituted estratrien derivatives as 17beta HSD inhibitors |
| US8288367B2 (en) | 2006-11-30 | 2012-10-16 | Solvay Pharmaceuticals Gmbh | Substituted estratriene derivatives as 17BETA HSD inhibitors |
| US11072632B2 (en) | 2011-03-25 | 2021-07-27 | UNIVERSITé LAVAL | Inhibitors of 17β-HSD1, 17β-HSD3 and 17β-HSD10 |
| SG195118A1 (en) | 2011-06-01 | 2013-12-30 | Estetra S A | Process for the production of estetrol intermediates |
| PT2714712T (pt) | 2011-06-01 | 2016-11-08 | Estetra Sprl | Processo para a produção de intermediários de estetrol |
| EP2383279A1 (en) | 2011-07-19 | 2011-11-02 | Pantarhei Bioscience B.V. | Process for the preparation of estetrol |
| WO2013078413A1 (en) * | 2011-11-22 | 2013-05-30 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Modulators of lipid storage |
| TW201512215A (zh) | 2013-06-25 | 2015-04-01 | Forendo Pharma Ltd | 治療活性雌三烯噻唑衍生物 |
| JP6456373B2 (ja) * | 2013-06-25 | 2019-01-23 | フォレンド ファーマ リミテッド | １７β−ヒドロキシステロイドデヒドロゲナーゼ タイプ１の阻害剤として治療活性のあるエストラトリエンチアゾール誘導体 |
| JP6556125B2 (ja) * | 2013-06-25 | 2019-08-07 | フォレンド ファーマ リミテッド | １７β−ヒドロキシステロイドデヒドロゲナーゼの阻害剤としての治療的に活性な１７−窒素置換エストラトリエンチアゾール誘導体 |
| JP6545266B2 (ja) | 2014-12-23 | 2019-07-17 | フォレンド ファーマ リミテッド | １７β‐ＨＳＤ１抑制剤のプロドラッグ |
| CN107207561B (zh) * | 2014-12-23 | 2020-03-31 | 佛恩多制药有限公司 | 17β-HSD1–抑制剂的前药 |
| LT3310346T (lt) | 2015-06-18 | 2021-06-10 | Estetra Sprl | Burnoje disperguojama tabletė, turinti estetrolio |
| LT3310345T (lt) | 2015-06-18 | 2021-06-25 | Estetra Sprl | Burnoje disperguojama tabletė, turinti estetrolio |
| DK3701944T3 (da) | 2015-06-18 | 2022-03-14 | Estetra Srl | Oro-dispergerbar doseringsenhed indeholdende en estetrolkomponent |
| CR20180042A (es) | 2015-06-18 | 2018-05-03 | Mithra Pharmaceuticals S A | Unidad de dosificación orodispersable que contiene un componente estetrol. |
| CN105963301B (zh) * | 2016-04-26 | 2018-12-28 | 兰州大学 | 以人fkbp51蛋白为靶点的先导化合物及筛选方法与应用 |
| CZ307437B6 (cs) | 2016-06-07 | 2018-08-22 | Ăšstav organickĂ© chemie a biochemie AV ÄŚR, v.v.i. | 15β-substituované deriváty estronu jako selektivní inhibitory 17β-hydroxysteoiddehydrogenáz |
| KR102712911B1 (ko) | 2016-08-05 | 2024-10-04 | 에스테트라, 소시에떼 아 레스폰서빌리떼 리미떼 | 월경통 및 생리통의 관리방법 |
| HRP20240679T1 (hr) * | 2017-06-08 | 2024-08-16 | Organon R&D Finland Ltd | 17-oksimi 15.beta.-[3-propanamido]-supstituiranih etera-1,3,5(10)-trien-17-ona za uporabu u inhibiciji 17.beta.-hidroksisteroid dehidrogenaza |
| TWI801561B (zh) | 2018-04-19 | 2023-05-11 | 比利時商依思特拉私人有限責任公司 | 化合物及其用於緩解絕經相關症狀的用途 |
| CN111989105B (zh) | 2018-04-19 | 2024-07-19 | 埃斯特拉私人有限责任公司 | 化合物以及它们在缓解绝经相关症状中的用途 |
| JP7417608B2 (ja) | 2018-12-05 | 2024-01-18 | フォレンド ファーマ リミテッド | １７－ｈｓｄ１阻害剤としての１６（１７）位でピラゾール環と縮合しているエストラ－１，３，５（１０）－トリエン化合物 |
| TWI893101B (zh) | 2020-04-16 | 2025-08-11 | 比利時商埃斯特拉有限責任公司 | 具有降低之副作用之避孕組成物 |
| US20240082208A1 (en) * | 2021-01-08 | 2024-03-14 | Industry-Academic Cooperation Foundation, Yonsei University | Antiviral pharmaceutical composition comprising steroid sulfatase inhibitor |
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|---|---|---|---|---|
| HU208150B (en) * | 1988-10-31 | 1993-08-30 | Endorecherche Inc | Process for producing new estrogen derivatives having steroid hormone inhibitor activity and pharmaceutical compositions comprising such derivatives |
| US7015211B2 (en) * | 2003-03-21 | 2006-03-21 | Yale University | 15α-substituted estradiol carboxylic acid esters as locally active estrogens |
| GB0306718D0 (en) * | 2003-03-24 | 2003-04-30 | Sterix Ltd | Compound |
| TWI331154B (en) * | 2003-11-12 | 2010-10-01 | Solvay Pharm Gmbh | Novel 17-hydroxysteroid dehydrogenase type i inhibitors |
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2006
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- 2006-05-24 CN CN2012103102224A patent/CN102796160A/zh active Pending
- 2006-05-24 BR BRPI0611623-0A patent/BRPI0611623A2/pt not_active IP Right Cessation
- 2006-05-24 ZA ZA200709854A patent/ZA200709854B/xx unknown
- 2006-05-24 UA UAA200714185A patent/UA92348C2/ru unknown
- 2006-05-24 RU RU2007147416/04A patent/RU2412196C2/ru not_active IP Right Cessation
- 2006-05-24 CA CA2609726A patent/CA2609726C/en not_active Expired - Fee Related
- 2006-05-24 KR KR1020077028969A patent/KR101364412B1/ko not_active Expired - Fee Related
- 2006-05-24 AU AU2006251154A patent/AU2006251154B2/en not_active Ceased
- 2006-05-24 EP EP06763273A patent/EP1888615B1/en active Active
- 2006-05-24 MX MX2007014736A patent/MX2007014736A/es active IP Right Grant
- 2006-05-24 ES ES06763273T patent/ES2388297T3/es active Active
- 2006-05-24 WO PCT/EP2006/062587 patent/WO2006125800A1/en not_active Ceased
- 2006-05-24 JP JP2008512837A patent/JP5268635B2/ja not_active Expired - Fee Related
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2007
- 2007-11-25 IL IL187620A patent/IL187620A/en not_active IP Right Cessation
- 2007-12-21 NO NO20076616A patent/NO20076616L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0611623A2 (pt) | 2010-09-21 |
| JP5268635B2 (ja) | 2013-08-21 |
| EP1888615B1 (en) | 2012-05-16 |
| ZA200709854B (en) | 2009-03-25 |
| CA2609726A1 (en) | 2006-11-30 |
| RU2007147416A (ru) | 2009-07-10 |
| KR20080012960A (ko) | 2008-02-12 |
| CA2609726C (en) | 2013-10-01 |
| AU2006251154A1 (en) | 2006-11-30 |
| IL187620A0 (en) | 2008-03-20 |
| AU2006251154B2 (en) | 2012-06-28 |
| IL187620A (en) | 2014-03-31 |
| MX2007014736A (es) | 2008-02-15 |
| CN102796160A (zh) | 2012-11-28 |
| HK1117538A1 (en) | 2009-01-16 |
| JP2008545678A (ja) | 2008-12-18 |
| CN101189251A (zh) | 2008-05-28 |
| WO2006125800A1 (en) | 2006-11-30 |
| RU2412196C2 (ru) | 2011-02-20 |
| KR101364412B1 (ko) | 2014-02-21 |
| NO20076616L (no) | 2008-02-01 |
| CN101189251B (zh) | 2012-09-12 |
| EP1888615A1 (en) | 2008-02-20 |
| UA92348C2 (en) | 2010-10-25 |
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