JP2016534148A - 前立腺癌を治療するための化合物 - Google Patents
前立腺癌を治療するための化合物 Download PDFInfo
- Publication number
- JP2016534148A JP2016534148A JP2016543991A JP2016543991A JP2016534148A JP 2016534148 A JP2016534148 A JP 2016534148A JP 2016543991 A JP2016543991 A JP 2016543991A JP 2016543991 A JP2016543991 A JP 2016543991A JP 2016534148 A JP2016534148 A JP 2016534148A
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- JP
- Japan
- Prior art keywords
- substituted
- compound according
- alkanediyl
- phenyl
- containing group
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims description 127
- 206010060862 Prostate cancer Diseases 0.000 title claims description 25
- 208000000236 Prostatic Neoplasms Diseases 0.000 title claims description 25
- -1 amino, thio Chemical group 0.000 claims abstract description 112
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 55
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 125000003118 aryl group Chemical group 0.000 claims abstract description 39
- 150000002148 esters Chemical class 0.000 claims abstract description 32
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 28
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 24
- 150000004820 halides Chemical class 0.000 claims abstract description 15
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 15
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 13
- 125000000707 boryl group Chemical group B* 0.000 claims abstract description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 13
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims abstract description 13
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 13
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 239000003795 chemical substances by application Substances 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 37
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000003386 piperidinyl group Chemical group 0.000 claims description 20
- 125000002541 furyl group Chemical group 0.000 claims description 19
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 229940079593 drug Drugs 0.000 claims description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
- 125000002883 imidazolyl group Chemical group 0.000 claims description 13
- 125000001041 indolyl group Chemical group 0.000 claims description 13
- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 6
- 125000005438 isoindazolyl group Chemical class 0.000 claims description 6
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- 238000009167 androgen deprivation therapy Methods 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
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- 239000000203 mixture Substances 0.000 description 50
- 235000002639 sodium chloride Nutrition 0.000 description 39
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
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- 239000003981 vehicle Substances 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 16
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- 239000002585 base Substances 0.000 description 13
- 239000011734 sodium Substances 0.000 description 12
- 238000012384 transportation and delivery Methods 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- 229910004298 SiO 2 Inorganic materials 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
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- 238000006467 substitution reaction Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
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- 125000003710 aryl alkyl group Chemical group 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000005089 Luciferase Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 231100000252 nontoxic Toxicity 0.000 description 8
- 230000003000 nontoxic effect Effects 0.000 description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 7
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
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- 238000003670 luciferase enzyme activity assay Methods 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
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- 125000000547 substituted alkyl group Chemical group 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- UFJHCGXCDQLCMZ-UHFFFAOYSA-N 2-[(3,5-dimethyl-1,2-oxazol-4-yl)methylsulfanyl]acetic acid Chemical compound CC1=NOC(C)=C1CSCC(O)=O UFJHCGXCDQLCMZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000004103 aminoalkyl group Chemical group 0.000 description 6
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- 239000000047 product Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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Abstract
Description
本発明は、国立衛生研究所(National Institutes of Health)により拠出された政府支援の助成金第GM067082号によりなされたものである。政府は本発明に一定の権利を有する。
R20−(Z)b−(Y)c−(R21)a−X−R22−R23
{式中、
R20は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Zは、アルカンジイル、置換アルカンジイル、シクロアルカンジイルまたは置換シクロアルカンジイルであり、
Yは、S、OまたはNR10(式中R10はHまたはアルキルである)であり、
R21は、アルカンジイル、置換アルカンジイル、シクロアルカンジイル、置換シクロアルカンジイル、アルカジエニル、置換アルカジエニル、アルカトリエニル、置換アルカトリエニルであり、
Xは、−C(=O)−または−S(=O)(=O)−であり、
R22は、少なくとも1つの二価アミノラジカルを含む部分であり、
R23は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
aは0または1であり、
bは0または1であり、ならびに
cは0または1であり、
Xが−C(=O)−であることを条件に、その場合にYはSではない}
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステルが開示される。
さらに、本明細書において式II:
R30−(Z’)b−(Y’)−(R31)a−X’−R32−R33
(式中、
R30は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Z’は、アルカンジイルまたは置換アルカンジイルであり、
Y’は、Sであり、
R31は、アルカンジイルまたは置換アルカンジイルであり、
Xは、−C(=O)−であり、
R32は、少なくとも1つの二価アミノラジカルを含む部分であり、
R33は、少なくとも1つのハロゲンまたはシアノで置換されたフェニルであり、
aは0または1であり、ならびに
bは0または1である)
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステルが開示される。
また、対象において前立腺癌を処置する方法であって、治療有効量の薬剤を対象に投与するステップを含み、該薬剤が式Iの化合物またはこれらの医薬として許容され得る塩もしくはエステルである方法が本明細書において開示される。
概要
薬剤
R20−(Z)b−(Y)c−(R21)a−X−R22−R23
{式中、
R20は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Zは、アルカンジイル、置換アルカンジイル、シクロアルカンジイルまたは置換シクロアルカンジイルであり、
YはS、OまたはNR10(式中、R10はHまたはアルキル(好ましくはメチル)である)、
R21はアルカンジイル、置換アルカンジイル、シクロアルカンジイル、置換シクロアルカンジイル、アルカジエニル、置換アルカジエニル、アルカトリエニルまたは置換アルカトリエニルであり、
Xは、−C(=O)−または−S(=O)(=O)−であり、
R22は、少なくとも1つの二価アミノラジカルを含む部分であり、
R23は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
aは0または1であり、
bは0または1であり、ならびに
cは0または1であり、
Xが−C(=O)−であることを条件として、その場合にYはSではない}
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステルである。
ある実施形態において、R20はフェニルまたは置換イソオキサゾリルであり、bは0であり、cは1であり、aは1であり、R21は−CH2−であり、YはSであり、Xは−S(=O)(=O)−であり、R22は:
ある実施形態において、bは0であり、cは0であり、aは1であり、Xは−C(=O)−であり、R21はアルカンジイル(特に−CH2CH2−)または
R22は
R20はフェニルまたは置換イソオキサゾリルであり、ならびにR23は置換フェニルである。
さらなる実施形態において、薬剤は式II:
R30−(Z’)b−(Y’)−(R31)a−X’−R32−R33
(式中、R30は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Z’はアルカンジイルまたは置換アルカンジイルであり、
Y’はSであり、
R31は、アルカンジイルまたは置換アルカンジイルであり、
Xは−C(=O)−であり、
R32は、少なくとも1つの二価アミノラジカルを含む部分であり、
R33は、少なくとも1つのハロゲンまたはシアノで置換されたフェニルであり、
aは0または1であり、ならびに
bは0または1である)
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステルである。
ある実施形態を、下記の番号で箇条書きにより以下に記載する。
R20−(Z)b−(Y)c−(R21)a−X−R22−R23
{式中、
R20は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Zは、アルカンジイルまたは置換アルカンジイルであり、
Yは、S、OまたはNR10(式中、R10はHまたはアルキルである)であり、
R21は、アルカンジイル、置換アルカンジイル、アルカジエニル、置換アルカジエニル、アルカトリエニル、置換アルカトリエニルであり、
Xは−C(=O)−または−S(=O)(=O)−であり、
R22は、少なくとも1つの二価アミノラジカルを含む部分であり、
R23は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
aは0または1であり、
bは0または1であり、ならびに
cは0または1であり、
Xが−C(=O)−であることを条件として、その場合にYはSではない}
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステル。
5.R22が:
R30−(Z’)b−(Y’)−(R31)a−X’−R32−R33
(式中、
R30は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Z’はアルカンジイルまたは置換アルカンジイルであり、
Y’はSであり、
R31はアルカンジイルまたは置換アルカンジイルであり、
X’は−C(=O)−であり、
R32は、少なくとも1つの二価アミノラジカルを含む部分であり、
R33は、少なくとも1つのハロゲンまたはシアノにより置換されたフェニルであり、
aは0または1であり、ならびに
bは0または1である)
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステル。
を有する置換フェニルである、第11項から第16項のいずれか一項に記載の化合物。
例示的化合物を図1に示す。
ある実施形態において、本明細書に開示の薬剤は、1またはそれを超える下記の特性を有し得る:
さらなる化合物を以下に示す:
本明細書に開示の薬剤は、前立腺癌、特に去勢抵抗性前立腺癌の処置のために対象に投与することができる。ある実施形態において、対象は、本明細書に開示の薬剤に応答性であり得る去勢抵抗性前立腺癌を有することが特定される。例えば、前立腺癌に対処するために、アビラテロンまたはMDV3100による処置を含む任意の形態のアンドロゲン除去療法または抗アンドロゲン療法を提供された患者が、本明細書に開示の薬剤による処置の候補となる。
Claims (33)
- 式I:
R20−(Z)b−(Y)c−(R21)a−X−R22−R23
{式中、
R20は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Zは、アルカンジイル、置換アルカンジイル、シクロアルカンジイルまたは置換シクロアルカンジイルであり、
Yは、S、OまたはNR10(式中、R10はHまたはアルキルである)であり、
R21は、アルカンジイル、置換アルカンジイル、シクロアルカンジイル、置換シクロアルカンジイル、アルカジエニル、置換アルカジエニル、アルカトリエニルまたは置換アルカトリエニルであり、
Xは−C(=O)−または−S(=O)(=O)−であり、
R22は、少なくとも1つの二価アミノラジカルを含む部分であり、
R23は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
aは0または1であり、
bは0または1であり、ならびに
cは0または1であり、
Xが−C(=O)−であることを条件として、その場合にYはSではない}
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステル。 - R20が、イソオキサゾリル、置換イソオキサゾリル、オキサゾリル、置換オキサゾリル、シクロヘキシル、置換シクロヘキシル、ピペリジニル、置換ピペリジニル、オキサシクロペンチル、置換オキサシクロペンチル、オキサシクロヘキサニル、置換オキサシクロペンチル、チオフェニル、置換チオフェニル、フェニル、置換フェニル、ピリジニル、置換ピリジニル、インドリル、置換インドリル、フラニル、置換フラニル、イミダゾリルまたは置換イミダゾリルから選択される、請求項1に記載の化合物。
- R20が置換イソオキサゾリルまたはフェニルである、請求項2に記載の化合物。
- R21が、C1−C3アルカンジイルまたは置換C1−C3アルカンジイルから選択される、請求項1から3のいずれか一項に記載の化合物。
- R23が、フェニル、置換フェニル、ピペリジニル、置換ピペリジニル、フラニル、置換フラニル、ピリジニル、置換ピリジニル、ピリミジニル、置換ピリミジニル、ナフテニル、置換ナフテニル、チアゾール、置換チアゾール、イソインダゾリル、置換イソインダゾリル、トリアゾリルまたは置換トリアゾリルから選択される、請求項1から6のいずれか一項に記載の化合物。
- ZがC1−C3アルカンジイルから選択される、請求項1から8のいずれか一項に記載の化合物。
- R21が−CH2−であり、YがSであり、ならびにXが−S(=O)(=O)−である、請求項1に記載の化合物。
- R22が、N−複素環基の二価のラジカルである、請求項1から5、7または8のいずれか一項に記載の化合物。
- bが0であり、cが0であり、aが1であり、ならびにXが−C(=O)−である、請求項1に記載の化合物
- R20が、フェニルまたは置換イソオキサゾリルであり、ならびにR23が置換フェニルである、請求項14から16のいずれか一項に記載の化合物。
- 式II:
R30−(Z’)b−(Y’)−(R31)a−X’−R32−R33
(式中、
R30は、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アルコキシ、アリールオキシ、シリル含有基、ボリル含有基、ホスフィン含有基、アミノ、チオ含有基、セレノ含有基、ハロゲン化物またはニトロ含有基であり、
Z’はアルカンジイルまたは置換アルカンジイルであり、
Y’はSであり、
R31はアルカンジイルまたは置換アルカンジイルであり、
X’は−C(=O)−であり、
R32は、少なくとも1つの二価アミノラジカルを含む部分であり、
R33は、少なくとも1つのハロゲンまたはシアノにより置換されたフェニルであり、
aは0または1であり、ならびに
bは0または1である)
を有する化合物またはこれらの医薬として許容され得る塩もしくはエステル。 - R30が、イソオキサゾリル、置換イソオキサゾリル、オキサゾリル、置換オキサゾリル、シクロヘキシル、置換シクロヘキシル、ピペリジニル、置換ピペリジニル、オキサシクロペンチル、置換オキサシクロペンチル、オキサシクロヘキサニル、置換オキサシクロペンチル、チオフェニル、置換チオフェニル、フェニル、置換フェニル、ピリジニル、置換ピリジニル、インドリル、置換インドリル、フラニル、置換フラニル、イミダゾリルまたは置換イミダゾリルから選択される、請求項18に記載の化合物。
- R30が置換イソオキサゾリルである、請求項18に記載の化合物。
- Z’が−CH2−である、請求項18から20のいずれか一項に記載の化合物。
- R31が、C1−C3アルカンジイルまたは置換C1−C3アルカンジイルから選択される、請求項18から21のいずれか一項に記載の化合物。
- R1が、アルキル、ハロゲンまたはシアノである、請求項24の記載の化合物。
- 少なくとも1つの医薬として許容され得る添加剤および請求項1から26のいずれか一項に記載の化合物を含む医薬組成物。
- 治療有効量の、請求項1から26のいずれか一項に記載の化合物を対象に投与するステップを含む、対象において前立腺癌を処置する方法。
- 前記前立腺癌が去勢抵抗性前立腺癌である、請求項28に記載の方法。
- 前記化合物が経口投与される、請求項28または29に記載の方法。
- 前記方法が、アンドロゲン除去療法と組み合わせて使用される、請求項28から30のいずれか一項に記載の方法。
- 前記薬剤がアビラテロンと同時投与される、請求項28から31のいずれか一項に記載の方法。
- 前記方法が、前記薬剤による処置を必要とする対象を特定するステップをさらに含む、請求項28から32のいずれか一項に記載の方法。
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