JP2000515550A - サイクリン依存キナーゼ2およびIκB―αのプリン阻害剤 - Google Patents
サイクリン依存キナーゼ2およびIκB―αのプリン阻害剤Info
- Publication number
- JP2000515550A JP2000515550A JP10508039A JP50803998A JP2000515550A JP 2000515550 A JP2000515550 A JP 2000515550A JP 10508039 A JP10508039 A JP 10508039A JP 50803998 A JP50803998 A JP 50803998A JP 2000515550 A JP2000515550 A JP 2000515550A
- Authority
- JP
- Japan
- Prior art keywords
- substituted
- lower alkyl
- composition
- aryl
- 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.)
- Ceased
Links
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
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- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
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- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- APVPOHHVBBYQAV-UHFFFAOYSA-N n-(4-aminophenyl)sulfonyloctadecanamide Chemical group CCCCCCCCCCCCCCCCCC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 APVPOHHVBBYQAV-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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000003499 redwood Nutrition 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000005477 standard model Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000003954 umbilical cord Anatomy 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
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- A61P31/10—Antimycotics
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 次式: [式中、R1はハロゲンまたはR’1−Xであり、そしてXはアミノ、オキソ、チ オ、またはスルホン基であり、 R’1は低級アルキル、置換された低級アルキル、シクロアルキル、置換され たシクロアルキル、シクロヘテロアルキル、置換されたシクロヘテロアルキル、 アリール、置換されたアリール、複素環、ヘテロアリール、置換されたヘテロア リール、アリールアルキル、ヘテロアリールアルキル、ヘテロアルキル、アルキ ルアルケニル、アルキルアルキニル、アルキルシクロアルキルまたはアルキルシ クロヘテロアルキルであって、それぞれ1ないし20個の炭素原子を有し; R2は水素、または低級アルキル、置換された低級アルキル、シクロアルキル 、置換されたシクロアルキル、アリール、置換されたアリール、複素環、ヘテロ アリール、置換されたヘテロアリール、アリールアルキル、ヘテロアリールアル キル、ヘテロアルキル、アルキルアルケニル、アルキルアルキニル、アルキルシ クロアルキルもし くはアルキルシクロヘテロアルキルの群から選択される炭化水素化合物であり、 そしてそれらにおいて、各炭化水素化合物は1ないし20個の炭素原子を有し; R3はハロゲン、ヒドロキシル、チオ、アルコキシ、アルキルチオ、低級アル キル、−NR4R5または次の式で表される部分構造であって、 式中、m=1−3、n=1−3、o=1−3、Y=カルボニル、−NR4R5、 ヒドロキシル、チオ、アルコキシ、アルキルチオであり、そしてR4およびR5は 、それぞれ独立に、水素、または低級アルキル、置換された低級アルキル、アル コキシ、アミノ、アミド、カルボキシル、シクロアルキル、置換されたシクロア ルキル、複素環、シクロヘテロアルキル、置換されたシクロヘテロアルキル、ア シル、アリール、置換されたアリール、アリールオキシ、ヘテロアリール、置換 されたヘテロアリール、アリールアルキル、ヘテロアリールアルキル、アルキル アルケニル、アルキルアルキニル、アルキルシクロアルキル、アルキルシクロヘ テロアルキルもしくはシアノを含む群から選択される炭化水素であり、そしてそ れらにおいて、各炭化水素は1ないし20個の炭素原子を 有し、そしてYがカルボニルの時は、R’4は組成物中に存在せず、R4"および R5"はただ1つの酸素でもよく、R4”’およびR5”’はただ1つの酸素原子で もよく、そしてまた、R3が2−ヒドロキシエチルアミノおよびR2がメチルの時 は、R1’−Xはアミノ、3−メチル−2−ブテニルアミノ、ベンジルアミノま たはm−ヒドロキシベンジル−アミノではなく、そして、R3が2−ヒドロキシ エチルアミノ、R2がイソプロピルの時は、R1’−Xはベンジルアミノ、m−ヒ ドロキシベンジルアミノまたは3−メチルブチルアミノではなく、そして、R3 が2−ヒドロキシエチルアミノ、R2が2−ヒドロキシエチルの時は、R1’−X はベンジルアミノではなく、そしてR3が2−プロパノール−2−メチルアミノ および2−ジメチルアミノエチルアミノからなる群から選択され、R2がメチル である時はR1’−Xはベンジルアミノではない。] で表される2,6,9−トリ置換プリン組成物。 2. Xがアミノである請求項1に記載の2,6,9−トリ置換プリン組成物。 3. R3が次式で表される部分構造である請求項1に記載の2,6,9−トリ 置換プリン組成物。 [式中、m=1−3、n=1−3、o=1−3、Y=カルボニル、−NR4R5、 ヒドロキシル、チオ、アルコキシ、アルキルチオであり、そしてそれらにおいて 、R4およびR5は、それぞれ、水素、低級アルキル、置換された低級アルキル、 アルコキシ、アミノ、アミド、カルボキシル、シクロアルキル、置換されたシク ロアルキル、複素環、シクロヘテロアルキル、置換されたシクロヘテロアルキル 、アシル、アリール、置換アリール、アリールオキシ、ヘテロアリール、置換さ れたヘテロアリール、アリールアルキル、ヘテロアリールアルキル、アルキルア ルケニル、アルキルアルキニル、アルキルシクロアルキル、アルキルシクロヘテ ロアルキルまたはシアノを含む群から選択され、そしてそれらにおいて、Yがカ ルボニルの時は、R’4は組成物中に存在せず、R4”およびR5”はただ1つの 酸素でもよく、R4”’およびR5”’はただ1つの酸素原子であってもよい。] 4. R1’がアリールアルキルおよびヘテロアリールアルキルからなる群から 選択される請求項3に記載の2,6,9−トリ置換プリン組成物。 5. R1’がアリールアルキル、置換されていないピリ ジルアルキルおよび置換されたピリジルアルキルからなる群から選択され、そし てR2が低級アルキル、置換された低級アルキルおよびアルキルシクロアルキル からなる群から選択される請求項4に記載の2,6,9−トリ置換プリン組成物 。 6. R1’がアリール、複素環、ヘテロアリール、置換されたヘテロアリール および置換されたアリールからなる群から選択される請求項3に記載の2,6, 9−トリ置換プリン組成物。 7. R1’がアリール、置換されていないピリジル、置換されたピリジルおよ び置換されたアリールからなる群から選択され、そしてR2は低級アルキル、置 換された低級アルキルおよびアルキルシクロアルキルからなる群から選択される 請求項3に記載の2,6,9−トリ置換プリン組成物。 8. R3が−NR4R5であり、そしてそのR4およびR5はそれぞれ、水素、低 級アルキル、置換された低級アルキル、アルコキシ、アミノ、アミド、カルボキ シル、シクロアルキル、置換されたシクロアルキル、複素環、シクロヘテロアル キル、置換されたシクロヘテロアルキル、アシル、アリール、置換されたアリー ル、アリールオキシ、ヘテロアリール、置換されたヘテロアリール、アリールア ルキル、ヘテロアリールアルキル、アルキルアルケニル、アルキルアルキニル、 アルキルシクロアルキル、アルキルシクロヘテロアルキルまたはシアノを含む群 か ら選択される請求項2に記載の2,6,9−トリ置換プリン組成物。 9. R1’がアリールアルキル、置換されたピリジルアルキルおよび置換され ていないピリジルアルキルからなる群から選択され、R2は低級アルキル、置換 された低級アルキル、シクロアルキルおよび置換されたシクロアルキルからなる 群から選択され、R4は2ないし6個の炭素原子を有する置換された低級アルキ ルで、そしてR5は水素、低級アルキル、置換された低級アルキル、アリール、 置換されたアリール、シクロアルキル、アリールシクロアルキル、複素環、置換 された複素環、ヘテロアリール、置換されたヘテロアリール、ヘテロアルキル、 ヘテロアリールアルキルおよび置換されたシクロアルキルからなる群から選択さ れる請求項8に記載の2,6,9−トリ置換プリン組成物。 10. R1’がアリール、置換されたアリール、ピリジルおよび置換されたピ リジルからなる群から選択され、R2は低級アルキル、置換された低級アルキル 、シクロアルキル、アルキルシクロアルキルおよび置換されたアルキルシクロア ルキルからなる群から選択され、R4は2ないし6個の炭素原予を有する置換さ れた低級アルキルで、そしてR5は水素、低級アルキル、置換された低級アルキ ル、アリール、置換されたアリール、シクロアルキル、アリールシクロアルキル 、複素環、置換された複素環、ヘテロアリール、置換されたヘテロアリール、ヘ テロア ルキル、ヘテロアリールアルキルおよび置換されたシクロアルキルからなる群か ら選択される請求項8に記載の2,6,9−トリ置換プリン組成物。 11. R1’がアリールアルキル、ピリジルアルキルおよび置換されたピリジ ルアルキルからなる群から選択され、R2は低級アルキル、置換された低級アル キルおよびアルキルシクロアルキルからなる群から選択され、そしてR4および R5は、それぞれ2ないし6個の炭素原子を有する置換された低級アルキルであ る請求項8に記載の2,6,9−トリ置換プリン組成物。 12. R1’がCH2−ArまたはCH2−置換アリールであり、R2は低級アル キルまたは置換された低級アルキルであり、そしてR4およびR5は、それぞれ、 −CH2CH2OH、−CHR’CH2OHまたは−CH2CHR’OHであって、 ここでR’は水素または1ないし6個の炭素原子を有するアルキルである請求項 8に記載の2,6,9−トリ置換プリン組成物。 13. R2がイソピルである請求項12に記載の2,6,9−トリ置換プリン 組成物。 14. R1’がアリール、置換されたアリール、ピリジルおよび置換されたピ リジルからなる群から選択され、R2は低級アルキル、置換された低級アルキル およびアルキルシクロアルキルからなる群から選択され、そしてR4およびR5は それぞれ2ないし6個の炭素原子を有する置換された低級アルキルである請求項 8に記載の2,6, 9−トリ置換プリン組成物。 15. R1’がアリールまたは置換されたアリールであり、R2は低級アルキル または置換された低級アルキルであり、そしてR4およびR5は、それぞれ、−C H2CH2OH、−CHR'CH2OHまたはCH2CHR’OHであって、ここで R’は水素または1ないし6個の炭素原子を有するアルキルである請求項8に記 載の2,6,9−トリ置換プリン組成物。 16. R2がイソピルである請求項15に記載の2,6,9−トリ置換プリン 組成物。 17. R1’がハロゲン、アルコキシ、フェニル、ピリジルまたはニトロ基で 置換されているベンジルで、R2はイソプロピルで、そしてR4およびR5はそれ ぞれ−CH2CH2OHである請求項8に記載の2,6,9−トリ置換プリン組成 物。 18. R1’がハロゲン、アルコキシ、フェニル、ピリジルまたはニトロ基で 置換されているフェニルで、R2はイソプロピルで、そしてR4およびR5はそれ ぞれ−CH2CH2OHである請求項8に記載の2,6,9−トリ置換プリン組成 物。 19. R1’がビフェニルであり、R2はイソプロピル、そしてR4およびR5は それぞれ−CH2CH2OHである請求項8に記載の2,6,9−トリ置換プリン 組成物。 20. R1’が3−チオメトキシフェニル、4−チオメトキシフェニル、4− ブロモフェニル、4−フェニルベ ンジル、4−メトキシベンジル、4−ビフェニル、3−メトキシベンジル、4− (2−チエニル)ベンジル、4−(4−メチル)フェニルベンジル、4−(4− トリフルオロメチル)フェニルベンジル、4−(4−ニトリロ)フェニルベンジ ル、4−(2−ピリジニル)ベンジル、ピペロニル、3−メトキシベンジル、4 −クロロベンジルおよび4−ニトロベンジルからなる群から選択され、R2はイ ソプロピルで、そしてR4およびR5は共に−CH2CH2OHである請求項8に記 載の2,6,9−トリ置換プリン組成物。 21. R1’が4−メトキシベンジルである請求項20に記載の2,6,9− トリ置換プリン組成物。 22. R1’が4−フェニルベンジルである請求項20に記載の2,6,9− トリ置換プリン組成物。 23. R1は4−メトキシベンジルである請求項20に記載の2,6,9−ト リ置換プリン組成物。 24. R’1が4−ビフェニルである請求項20に記載の2,6,9−トリ置 換プリン組成物。 25. R’1が3−メトキシベンジルである請求項20に記載の2,6,9− トリ置換プリン組成物。 26. R’1が4−(2−チエニル)ベンジルである請求項20に記載の2, 6,9−トリ置換プリン組成物。 27. R’1が4−(4−メチル)フェニルベンジルである請求項20に記載 の2,6,9−トリ置換プリン組成物。 28. R’1が4−(4−トリフルオロメチル)フェニルベンジルである請求 項20に記載の2,6,9−トリ置換プリン組成物。 29. R’1が4−(4−ニトリロ)フェニルベンジルである請求項20に記 載の2,6,9−トリ置換プリン組成物。 30. R’1が4−(2−ピリジニル)ベンジルである請求項20に記載の2 ,6,9−トリ置換プリン組成物。 31. R’1がピペロニルである請求項20に記載の2,6,9−トリ置換プ リン組成物。 32. R’1が3−チオメトキシフェニルである請求項20に記載の2,6, 9−トリ置換プリン組成物。 33. R’1が4−チオメトキシフェニルである請求項20に記載の2,6, 9−トリ置換プリン組成物。 34. R’1が4−ブロモフェニルである請求項20に記載の2,6,9−ト リ置換プリン組成物。 35. 請求項1に記載の組成物のカチオン塩。 36. 請求項1に記載の組成物の酸付加塩。 37. 請求項1に記載の組成物の製薬的に効果的な量を哺乳動物に投与するこ とを備える哺乳動物における細胞増殖を阻害する方法。 38. 製薬的に効果的な量が哺乳動物の体重1kg当たり約0.001mgな いし約100mgである請求項37に記載の方法。 39. 組成物が、リューマチ様関節炎、狼瘡、I型糖 尿病、多発性硬化症、癌、再狭窄などの心臓病、宿主移植片疾患および通風から なる群から選択される細胞増殖異常の疾患を有する哺乳動物に投与される請求項 37に記載の方法。 40. 細胞増殖異常の疾患は再狭窄である請求項39に記載の方法。 41. 細胞増殖異常の疾患は癌である請求項39に記載の方法。 42. 細胞増殖異常の疾患は多嚢胞性腎疾患である請求項39に記載の方法。 43. 哺乳動物がヒトである請求項39に記載の方法。 44. 請求項1に記載の組成物および1種類以上の製薬上の賦形剤を含む製薬 組成物。 45. 製薬的組成物が溶液の形をなしている請求項43に記載の物質の製薬的 組成物。 46. 製薬組成物が錠剤の形をなしている請求項43に記載の物質の製薬的組 成物。 47. ヒトおよび動物における真菌感染症を治療するために有用な、請求項1 に記載の組成物を含む抗真菌剤。
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JP2006056879A (ja) * | 2004-07-21 | 2006-03-02 | Kobe Univ | インスリン抵抗性の改善剤、及びそのスクリーニング方法 |
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JP2010539146A (ja) * | 2007-09-12 | 2010-12-16 | セントレ・ナショナル・デ・ラ・レシェルシェ・サイエンティフィーク | 医薬品の製造のためにプリン誘導体を使用する方法 |
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US10981903B2 (en) | 2011-11-17 | 2021-04-20 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-Jun-N-terminal kinase (JNK) |
US10906889B2 (en) | 2013-10-18 | 2021-02-02 | Dana-Farber Cancer Institute, Inc. | Polycyclic inhibitors of cyclin-dependent kinase 7 (CDK7) |
US10870651B2 (en) | 2014-12-23 | 2020-12-22 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
JP2021107396A (ja) * | 2015-03-27 | 2021-07-29 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
US11325910B2 (en) | 2015-03-27 | 2022-05-10 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinases |
JP7200282B2 (ja) | 2015-03-27 | 2023-01-06 | ダナ-ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
JP2018515434A (ja) * | 2015-03-27 | 2018-06-14 | ダナ−ファーバー キャンサー インスティテュート, インコーポレイテッド | サイクリン依存性キナーゼの阻害剤 |
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