PH27098A - 4-substituted 17beta-(cyclopropylamino)anddrost-5-EN-3beta-OL and related compounds useful as C17-20lyase inhibitors - Google Patents

4-substituted 17beta-(cyclopropylamino)anddrost-5-EN-3beta-OL and related compounds useful as C17-20lyase inhibitors Download PDF

Info

Publication number: PH27098A
Authority: PH; Philippines
Prior art keywords: hydrogen; alkanoyl; substituted; methyl; compound
Prior art date: 1989-08-15

Application number

PH41034A

Other languages

English (en)

Inventor

Michael R Angelastro

Thomas R Blohm

Original Assignee

Merrell Dow Pharma

Priority date (The priority date 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 date listed.)

1989-08-15

Filing date

1990-08-15

Publication date

1993-02-26

1990-08-15 Application filed by Merrell Dow Pharma filed Critical Merrell Dow Pharma

1993-02-26 Publication of PH27098A publication Critical patent/PH27098A/en

Links

150000001875 compounds Chemical class 0.000 title claims description 42
239000003112 inhibitor Substances 0.000 title description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
238000000034 method Methods 0.000 claims description 14
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
125000001589 carboacyl group Chemical group 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 9
-1 C.-C Chemical group 0.000 claims description 8
239000003098 androgen Substances 0.000 claims description 8
230000001419 dependent effect Effects 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims 4
229910052799 carbon Inorganic materials 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
239000000203 mixture Substances 0.000 description 11
238000011282 treatment Methods 0.000 description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000012279 sodium borohydride Substances 0.000 description 6
229910000033 sodium borohydride Inorganic materials 0.000 description 6
239000002904 solvent Substances 0.000 description 6
150000003431 steroids Chemical class 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
102000004317 Lyases Human genes 0.000 description 5
108090000856 Lyases Proteins 0.000 description 5
239000002253 acid Substances 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
150000003839 salts Chemical class 0.000 description 4
239000007858 starting material Substances 0.000 description 4
229960003604 testosterone Drugs 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
206010060862 Prostate cancer Diseases 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
239000012346 acetyl chloride Substances 0.000 description 3
229940030486 androgens Drugs 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
238000013459 approach Methods 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
150000002466 imines Chemical class 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
229940083608 sodium hydroxide Drugs 0.000 description 3
235000011121 sodium hydroxide Nutrition 0.000 description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
AFGDPPHTYUQKOF-QAGGRKNESA-N (8r,9s,10r,13s,14s)-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 AFGDPPHTYUQKOF-QAGGRKNESA-N 0.000 description 2
SBNLPRGISFUZQE-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1C=C2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 SBNLPRGISFUZQE-VMXHOPILSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
238000006036 Oppenauer oxidation reaction Methods 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 2
AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 2
229960005471 androstenedione Drugs 0.000 description 2
230000037396 body weight Effects 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
150000002081 enamines Chemical class 0.000 description 2
229940011871 estrogen Drugs 0.000 description 2
239000000262 estrogen Substances 0.000 description 2
239000000284 extract Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229960004279 formaldehyde Drugs 0.000 description 2
235000019256 formaldehyde Nutrition 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000002243 precursor Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000010992 reflux Methods 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
238000012360 testing method Methods 0.000 description 2
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
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 1
125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
201000004384 Alopecia Diseases 0.000 description 1
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
FMGSKLZLMKYGDP-UHFFFAOYSA-N Dehydroepiandrosterone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CC=C21 FMGSKLZLMKYGDP-UHFFFAOYSA-N 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
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 1
206010020112 Hirsutism Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 1
208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
241000812633 Varicus Species 0.000 description 1
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 1
206010068168 androgenetic alopecia Diseases 0.000 description 1
150000001430 androst-3-enes Chemical class 0.000 description 1
229960003473 androstanolone Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000006317 cyclopropyl amino group Chemical group 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000007423 decrease Effects 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
229960000452 diethylstilbestrol Drugs 0.000 description 1
201000010099 disease Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
229960005309 estradiol Drugs 0.000 description 1
229930182833 estradiol Natural products 0.000 description 1
229960003399 estrone Drugs 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 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
150000002440 hydroxy compounds Chemical class 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
239000007943 implant Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
239000002697 lyase inhibitor Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
230000003228 microsomal effect Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
JKWKFBUUNGGYBP-UHFFFAOYSA-N n-cyclopropylcyclopropanamine Chemical compound C1CC1NC1CC1 JKWKFBUUNGGYBP-UHFFFAOYSA-N 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000011474 orchiectomy Methods 0.000 description 1
125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229960002847 prasterone Drugs 0.000 description 1
ORNBQBCIOKFOEO-QGVNFLHTSA-N pregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 ORNBQBCIOKFOEO-QGVNFLHTSA-N 0.000 description 1
229960000249 pregnenolone Drugs 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
230000001235 sensitizing effect Effects 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000003826 tablet Substances 0.000 description 1
210000001550 testis Anatomy 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000009901 transfer hydrogenation reaction Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

PH41034A 1989-08-15 1990-08-15 4-substituted 17beta-(cyclopropylamino)anddrost-5-EN-3beta-OL and related compounds useful as C17-20lyase inhibitors PH27098A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/394,025 US4966898A (en)	1989-08-15	1989-08-15	4-substituted 17β-(cyclopropylamino)androst-5-en-3β-ol and related compounds useful as C17-20 lyase inhibitors

Publications (1)

Publication Number	Publication Date
PH27098A true PH27098A (en)	1993-02-26

Family

ID=23557240

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH41034A PH27098A (en)	1989-08-15	1990-08-15	4-substituted 17beta-(cyclopropylamino)anddrost-5-EN-3beta-OL and related compounds useful as C17-20lyase inhibitors

Country Status (20)

Country	Link
US (1)	US4966898A (de)
EP (1)	EP0413270B1 (de)
JP (1)	JP2879703B2 (de)
KR (1)	KR910004649A (de)
CN (1)	CN1050196A (de)
AT (1)	ATE137761T1 (de)
AU (1)	AU628209B2 (de)
CA (1)	CA2023012C (de)
DD (1)	DD299650A5 (de)
DE (1)	DE69026881T2 (de)
ES (1)	ES2088928T3 (de)
FI (1)	FI95804C (de)
HU (1)	HUT55029A (de)
IE (1)	IE72516B1 (de)
IL (1)	IL95358A (de)
NO (1)	NO903564L (de)
NZ (1)	NZ234856A (de)
PH (1)	PH27098A (de)
PT (1)	PT94993B (de)
ZA (1)	ZA906308B (de)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4966897A (en) *	1989-08-15	1990-10-30	Merrell Dow Pharmaceuticals Inc.	4-substituted 17β-(cyclopropyloxy)androst-5-en-3β-ol and related compounds useful as C17-20 lyase inhibitors
US5604213A (en) *	1992-03-31	1997-02-18	British Technology Group Limited	17-substituted steroids useful in cancer treatment
CZ287434B6 (en) *	1992-03-31	2000-11-15	British Tech Group	Use of steroids, substituted in position 17, steroids functioning as carcinostatics and pharmaceutical preparation containing thereof
TW369521B (en) *	1993-09-17	1999-09-11	Smithkline Beecham Corp	Androstenone derivative
US5541322A (en) *	1994-10-14	1996-07-30	Glaxo Wellcome Inc.	Synthesis of 6-azaandrostenones
US6365597B1 (en)	1996-02-14	2002-04-02	Aventis Pharmaceuticals Inc.	4-aza steroids
RU2291863C2 (ru) *	2000-06-09	2007-01-20	Байер Кропсайенс С.А.	Способ получения пестицидных соединений
JP3753971B2 (ja)	2000-11-17	2006-03-08	武田薬品工業株式会社	新規イミダゾール誘導体、その製造法および用途
DE60144246D1 (de)	2000-11-20	2011-04-28	Takeda Pharmaceutical	Imidazolderivate, verfahren zu deren herstellung und deren verwendung
AU2002221080A1 (en)	2000-12-08	2002-06-18	Masami Kusaka	Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparingthe same and use thereof
US20080051380A1 (en)	2006-08-25	2008-02-28	Auerbach Alan H	Methods and compositions for treating cancer
UY32730A (es)	2009-06-26	2011-01-31	Novartis Ag	Inhibidores de cyp17
JP2011098893A (ja) *	2009-11-04	2011-05-19	Sumitomo Chemical Co Ltd	テストステロンの生合成を抑制するための化合物の使用およびその化合物
KR101926320B1 (ko)	2010-08-04	2018-12-06	펠피큐어 파마슈티걸즈 아이엔씨	전립선 암종의 치료를 위한 병용 요법
EP2627648A1 (de)	2010-09-16	2013-08-21	Novartis AG	17a-HYDROXYLASE-C17, 20-LYASE-INHIBITOREN
MX359399B (es)	2011-04-28	2018-09-27	Novartis Ag	Inhibidores de 17alfa-hidroxilasa/c17-20-liasa.
WO2014158875A1 (en)	2013-03-14	2014-10-02	Pellficure Pharmaceuticals Inc.	Novel therapy for prostate carcinoma
CA2960750A1 (en)	2014-09-12	2016-03-17	Pellficure Pharmaceuticals, Inc.	Compositions and methods for treatment of prostate carcinoma
MX2019001224A (es)	2016-07-29	2019-06-03	Janssen Pharmaceutica Nv	Metodos para tratar el cancer de prostata.
WO2018080933A1 (en)	2016-10-24	2018-05-03	Pellficure Pharmaceuticals Inc.	Pharmaceutical compositions of 5-hydroxy-2-methylnaphthalene-1, 4-dione

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3107254A (en) *	1960-10-05	1963-10-15	Upjohn Co	17beta-dialkylamino-17-cyanosteroids and their 17alpha-alkyl, alkylene and alkyne derivatives
US3097200A (en) *	1962-01-03	1963-07-09	Syntex Corp	17-aminoandrostanes
NL302932A (de) *	1962-12-31
ZA882717B (en) *	1987-04-22	1988-10-17	Merrell Dow Pharmaceuticals Inc.	17beta-(cyclopropylamino)-androst-5-eb-3beta-ol and related compounds useful as c17-20 lyase inhibitors
US4966897A (en) *	1989-08-15	1990-10-30	Merrell Dow Pharmaceuticals Inc.	4-substituted 17β-(cyclopropyloxy)androst-5-en-3β-ol and related compounds useful as C17-20 lyase inhibitors

1989
- 1989-08-15 US US07/394,025 patent/US4966898A/en not_active Expired - Fee Related
1990
- 1990-08-09 JP JP2209389A patent/JP2879703B2/ja not_active Expired - Fee Related
- 1990-08-09 ZA ZA906308A patent/ZA906308B/xx unknown
- 1990-08-09 AU AU60877/90A patent/AU628209B2/en not_active Ceased
- 1990-08-09 CA CA002023012A patent/CA2023012C/en not_active Expired - Fee Related
- 1990-08-10 DE DE69026881T patent/DE69026881T2/de not_active Expired - Fee Related
- 1990-08-10 NZ NZ234856A patent/NZ234856A/en unknown
- 1990-08-10 ES ES90115391T patent/ES2088928T3/es not_active Expired - Lifetime
- 1990-08-10 AT AT90115391T patent/ATE137761T1/de not_active IP Right Cessation
- 1990-08-10 EP EP90115391A patent/EP0413270B1/de not_active Expired - Lifetime
- 1990-08-13 IL IL9535890A patent/IL95358A/en not_active IP Right Cessation
- 1990-08-14 HU HU905004A patent/HUT55029A/hu unknown
- 1990-08-14 IE IE294290A patent/IE72516B1/en not_active IP Right Cessation
- 1990-08-14 KR KR1019900012533A patent/KR910004649A/ko not_active Ceased
- 1990-08-14 PT PT94993A patent/PT94993B/pt not_active IP Right Cessation
- 1990-08-14 NO NO90903564A patent/NO903564L/no unknown
- 1990-08-15 FI FI904035A patent/FI95804C/fi not_active IP Right Cessation
- 1990-08-15 DD DD90343476A patent/DD299650A5/de unknown
- 1990-08-15 PH PH41034A patent/PH27098A/en unknown
- 1990-08-15 CN CN90107580A patent/CN1050196A/zh active Pending

Also Published As

Publication number	Publication date
NO903564D0 (no)	1990-08-14
EP0413270A2 (de)	1991-02-20
KR910004649A (ko)	1991-03-29
JP2879703B2 (ja)	1999-04-05
JPH0383998A (ja)	1991-04-09
CA2023012C (en)	2001-07-03
FI95804B (fi)	1995-12-15
IE902942A1 (en)	1991-02-27
PT94993B (pt)	1997-07-31
AU6087790A (en)	1991-02-21
DE69026881T2 (de)	1996-09-12
ZA906308B (en)	1991-06-26
HUT55029A (en)	1991-04-29
FI95804C (fi)	1996-03-25
DE69026881D1 (de)	1996-06-13
CA2023012A1 (en)	1991-02-16
EP0413270B1 (de)	1996-05-08
ATE137761T1 (de)	1996-05-15
DD299650A5 (de)	1992-04-30
NO903564L (no)	1991-02-18
AU628209B2 (en)	1992-09-10
CN1050196A (zh)	1991-03-27
EP0413270A3 (en)	1992-05-20
HU905004D0 (en)	1991-01-28
IE72516B1 (en)	1997-04-23
NZ234856A (en)	1992-08-26
IL95358A0 (en)	1991-06-30
IL95358A (en)	1995-03-30
ES2088928T3 (es)	1996-10-01
FI904035A0 (fi)	1990-08-15
PT94993A (pt)	1991-04-18
US4966898A (en)	1990-10-30

Publication	Publication Date	Title
PH27098A (en)	1993-02-26	4-substituted 17beta-(cyclopropylamino)anddrost-5-EN-3beta-OL and related compounds useful as C17-20lyase inhibitors
SU1574178A3 (ru)	1990-06-23	Способ получени производных 4-замещенного андростендиона, или их фармацевтически приемлемых солей
JP2711672B2 (ja)	1998-02-10	Ｃ１７−２０リアーゼ阻害剤として有用な１７β‐（シクロプロピルアミノ）アンドロスト‐５‐エン‐３β‐オール及び関連化合物
EP0413269B1 (de)	1996-06-05	4-Substitutiertes 17-beta-(Cyclopropyloxy)androst-5-en-3-beta-ol und seine Derivate, verwendbar als Inhibitoren der C17-20-Lyase
SK137994A3 (en)	1995-04-12	7-beta-substituted-4-aza-5-alpha-cholestan-ons their using for production of pharmaceutical agent and pharmaceutical agent containing them
AU692614B2 (en)	1998-06-11	7-substituted 4-aza cholanic acid derivatives and their use
GB1569135A (en)	1980-06-11	Steroids
US5264427A (en)	1993-11-23	20-substituted pregnene derivatives and their use as androgen synthesis inhibitors
JPH08510733A (ja)	1996-11-12	４−アミノ−１７β−（シクロプロピロキシ）アンドロスト−４−エン−３−オン、４−アミノ−１７β−（シクロプロピルアミノ）アンドロスト−４−エン−３−オン及びＣ▲下１７−２０▼リアーゼ及び５α−レダクターゼ阻害剤としての関連する化合物類
JP2000505444A (ja)	2000-05-09	テストステロン５α―レダクターゼおよびＣ▲下１７―２０▼リアーゼの活性阻害剤としての１７β―シクロプロピル（アミノ／オキシ）４―アザステロイド
US3398140A (en)	1968-08-20	Steroido [17. 16-c] pyrozoles and preparation thereof
WO1992017489A1 (fr)	1992-10-15	Nouveau derive oxa- ou azasteroide
EP1409512A1 (de)	2004-04-21	20-fluoro-17(20)-vinyl steroide - inhibitoren von c17-20-lyase und 5-alpha reductase
US3661940A (en)	1972-05-09	Derivatives of 21-methyl-19-norpregnanes
US3812165A (en)	1974-05-21	18-methyl-5alpha-h-androstane derivatives and process of making the same
US3840568A (en)	1974-10-08	Estratriene derivatives
NO763545L (de)	1977-05-12