JP2001507023A - トリアゾロ[4,5−d]ピリミジニル誘導体および医薬としてのその使用 - Google Patents
トリアゾロ[4,5−d]ピリミジニル誘導体および医薬としてのその使用Info
- Publication number
- JP2001507023A JP2001507023A JP52867898A JP52867898A JP2001507023A JP 2001507023 A JP2001507023 A JP 2001507023A JP 52867898 A JP52867898 A JP 52867898A JP 52867898 A JP52867898 A JP 52867898A JP 2001507023 A JP2001507023 A JP 2001507023A
- Authority
- JP
- Japan
- Prior art keywords
- triazolo
- dihydroxy
- pyrimidin
- propylthio
- butylamino
- 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
- -1 Triazolo [4,5-D] pyrimidinyl Chemical class 0.000 title claims abstract description 218
- 239000003814 drug Substances 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims description 176
- 125000006309 butyl amino group Chemical group 0.000 claims description 115
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
- 125000001847 2-phenylcyclopropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1([H])C([H])([H])C1([H])* 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 12
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 9
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 7
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
- 150000003951 lactams Chemical group 0.000 claims description 3
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- 241000927721 Tritia Species 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 2
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims 1
- 150000003857 carboxamides Chemical class 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004001 thioalkyl group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 description 167
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 239000003480 eluent Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 239000003146 anticoagulant agent Substances 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 238000010828 elution Methods 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
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- 239000012141 concentrate Substances 0.000 description 7
- 235000008504 concentrate Nutrition 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
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- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式(I) [式中、 XはOHまたはNHR3であり; R1はC1-6−アルキル、C3-8−シクロアルキルまたはフェニル基であって、そ れぞれの基は場合により1個またはそれ以上のハロゲン原子および/またはOR4 、NR4R5、C1-6−チオアルキルおよび/またはC1-6−アルキル(それ自体、場 合により1個またはそれ以上のハロゲン原子により置換されている)により置換 されており; R2はC1-8−アルキルまたはC2-8−アルケニルであって、それぞれは場合によ り1個またはそれ以上のハロゲン原子および/またはOR4、NR4R5、C1-6−チオ アルキル、C3-8−シクロアルキル、アリールおよび/またはC1-6−アルキル基 により置換されており;またはR2は場合により1個またはそれ以上のハロゲン原 子および/またはOR4、NR4R5、C1-6−チオアルキル、フェニルおよび/または C1-6−アルキル基により置換されているC3-8−シクロアルキル基であって、こ こでの随意のフェニル置換基はさらに場合により1個またはそれ以上のハロゲン 原子および/またはNO2、C(O)R4、OR4、NR4R5、C1-6−チオアルキルおよび/ま たはC1-6−アルキル基により置換されており; R3は水素であるか、または1個またはそれ以上のヒドロキシおよび/またはフ ェニル基並びに場合により1個またはそれ以上のハロゲン原子により置換されて いるC1-6−アルキルであって、ここでそのフェニル基は1 個またはそれ以上のヒドロキシ基および場合により1個またはそれ以上のハロゲ ン原子および/またはNO2、C(O)R4、OR4、NR4R5、C1-6−チオアルキルおよび/ またはC1-6−アルキル基により置換されており;またはR3はC(O)NR4R5またはCO OH基および場合により1個またはそれ以上のハロゲン原子および/またはOR4、C (NH)NR4R5、C(O)NR4R5、フェニルおよび/またはC1-6−アルキル基により置換 されているC1-6−アルキル基であって、ここでそのアルキルは場合により1個 またはそれ以上のヒドロキシおよび/またはフェニル基により置換されており、 そしてそのフェニル基は、場合によりR3で前述した定義のように置換されており ;またはR3は式(i) で表されるラクタム環であって、ここでQは(CH2)m(ここでmは1、2または3 である)部分であり、ZはO、C(O)またはCH2であり; R4およびR5はそれぞれ独立して水素、フェニルまたはC1-6−アルキルであっ て、そのアルキル基は場合により1個またはそれ以上のフェニル基により置換さ れている] で表される化合物またはその塩。 2.R1は場合により1個またはそれ以上のハロゲン原子または1個のCF3基によ り置換されているC1-4−アルキル、C4-8−シクロアルキルまたはフェニル基で ある、請求項1記載の化合物。 3.R2は場合によりフェニルまたはC1-6−チオアルキル基により置換されてい るC1-6−アルキル基であるか、または場合によりフェニルで置換されているC3 -8 −シクロアルキル基である、請求項1または2記載の化合物。 4.XがOHまたはNHR3であり、ここでR3は水素であるか、またはヒドロキシおよ び場合によりC(O)NH2またはジフルオロにより置換されているC1-6−アルキル; C(O)NH2により置換されているC1-6−アルキル;C(O)NHMeにより置換されている C1-6−アルキル;ヒドロキシフェニルおよび場合によりC(O)NR4R5により置換さ れているC1-6−アルキルであるか、またはR3は式 で表されるラクタム環である、請求項1〜3のいずれか1項に記載の化合物。 5.[1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピ ルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2, 3−ジヒドロキシ−シクロペンタンカルボキサミド、 1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピルチ オ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3− ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−(プ ロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]− 2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−( プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル ]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−[1α,2β,3 β,4α(トランス)]]−2,3−ジヒドロキシ−4−[7−[(2−フェニルシクロ プロピル)アミノ]−5−(プロピルチオ) −3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペン タンカルボン酸、 [1S−[1α,2β,3β,4α(トランス)]]−2,3−ジヒドロキシ−4−[7 −[(2−フェニルシクロプロピル)アミノ]−5−(プロピルチオ)−3H−1,2, 3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキサ ミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−(2−フェ ニルエチルアミノ)−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5− d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−(2−フェ ニルエチルアミノ)−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5− d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[2−(メ チルチオ)エチルアミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[2−(メ チルチオ)エチルアミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−[1α,2β,3β,4α(トランス)]]−4−[5−(シクロヘキシルチオ) −7−[2−(フェニルシクロプロピル)アミノ]−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−[1α,2β,3β,4α(トランス)]]−2,3−ジヒドロキシ−4 -[7−[(2−フェニルシクロプロピル)アミノ]−5−(シクロヘキシルチオ)−3 H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタン カルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(3,4−ジ クロロフェニルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3 −イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(3,4−ジ クロロフェニルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3 −イル]−2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−[4−(トリ フルオロメチル)フェニルチオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリ ミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−[4−(トリ フルオロメチル)フェニルチオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリ ミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(フェニル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(フェニル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−( 3,4−ジクロロフェニルチオ)−3H−1,2,3−トリアゾロ[4,5 −d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボキ サミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−(2−ヒドロキシエチル)−シクロペンタンカルボキサミド 、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−(3−ヒドロキシ−2,2−ジフルオロプロピル)−シクロ ペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−(4−ヒドロキシフェニル)エチル]−シクロペンタン カルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−[4−(トリ フルオロメチル)フェニルチオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリ ミジン−3−イル]−2,3−ジヒドロキシ−N−(2−ヒドロキシエチル)−シク ロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−N−[1−(アミノカルボニル)−2−(ヒド ロキシ)エチル]−4−[7−(ブチルアミノ)−5−(プロピルチオ)−3H−1, 2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ− シクロペンタンカルボキサミド、 [1S−[1α(S*),2β,3β,4α]]−4−[7−(ブチルアミノ)−5−(プロ ピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]− N−(テトラヒドロ−3−オキソ−イソオキサゾール−4−イル)−2,3−ジヒ ドロキシ−シクロペンタンカルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−4−[7−(ブチルアミノ)−5 −(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3− イル]−2,3−ジヒドロキシ−N−(2−オキソ−ピロリジン−3−イル)−シク ロペンタンカルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−4−[7−(ブチルアミノ)−5−(プロ ピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]− 2,3−ジヒドロキシ−N−(2,3−ジ−オキソ−ピロリジン−3−イル)−シク ロペンタンカルボキサミド、 [1S−[1α(R*),2β,3β,4α)]−N−[(アミノカルボニル)−メチル]− 4−[7−(ブチルアミノ)−5−(プロピルチオ)−3H−1,2,3−トリアゾロ [4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカ ルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−N−[1−(アミノカルボニル)−2−( 4−ヒドロキシフェニル)エチル]−4−[7−(ブチルアミノ)−5−(プロピルチ オ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3− ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−N−[1−(アミノカルボニル)−2−( ヒドロキシ)エチル]−4−[7−(ブチルアミノ)−5−[4−(トリフルオロメチ ル)フェニルチオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3− イル]−2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−[1α(1R*,2S*),2β,3β,4α)]]−N−[1−(アミノカルボニ ル)−2−(ヒドロキシ)プロピル]−4−[7−(ブチルアミノ)−5−(プロピルチ オ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3− ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−[1α,2β,3β,4α]]−N−[2−(アミノカルボニル)エチル]−4 −[7−(ブチルアミノ)−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4 ,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ− シクロペンタンカルボキサミド、 [1S−[1α,2β,3β,4α]]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−(メチルアミノカルボニル)−エチル]−シクロペンタ ンカルボキサミド、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−2,3−ジヒドロキシ−4− [7−[(2−フェニルシクロプロピル)アミノ]−5−(プロピルチオ)−3H−1, 2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボ ン酸、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−2,3−ジヒドロキシ−4− [7−[(2−フェニルシクロプロピル)アミノ]−5−(プロピルチオ)−3H−1, 2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボ キサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−(シクロブ チルアミノ)−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピ リミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロブチルアミノ)−5−(プ ロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル] −2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−[[ 4−(トリフルオロメチル)フェニル]チオ]−3H−1,2,3−トリアゾロ[4,5 −d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボン 酸、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−[[ 4−(トリフルオロメチル)フェニル]チオ]−3H−1,2,3−トリアゾロ[4,5 −d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボキ サミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−[(3,3,3 −トリフルオロプロピル)チオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリ ミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−[(3,3,3 −トリフルオロプロピル)チオ]−3H−1,2,3−トリアゾロ[4,5−d]ピリ ミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1,4− ジメチルペンチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ [4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1,4− ジメチルペンチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ [4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1−メ チルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5 −d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1−メチ ルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5− d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1,3− ジメチルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−シクロペンタ ンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1,3− ジメチルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(エチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(4−ヒドロキシブチルアミノ)− 5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3 −イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロペンンチルアミノ)−5− (プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イ ル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[5−[(4−ブロモフェニル)チオ]−7 −(ブチルアミノ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3− イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−[(6−ヒドロキシヘキシル)アミ ノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン −3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−[1α,2β,3β,4α(トランス)]]−2,3−ジヒドロキシ−4−[5 −[[4−(トリフルオロメチル)フェニル]チオ]−7−[(2−フェニルシクロプロ ピル)アミノ]−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル] −シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(シクロペ ンチルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル] −2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(3−メ チルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5 −d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−[1α,2β,3β,4α(1R*,2S*)]]−2,3−ジヒドロキシ−4−[ 7−[(2−フェニルシクロプロピル)アミノ]−5−(プロピルチオ)−3H−1, 2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボ ン酸、 [1S−[1α(R*),2β,3β,4α]]−N−(3−アミノ−3−オキソ−2− プロピル)−4−[7−(ブチルアミノ)−5−(プロピルチオ)−3H−1,2,3− トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロ ペンチルカルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−3−[7−(ブチルアミノ)−5−(プロ ピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]− 2,3−ジヒドロキシ−N−[3−ヒドロキシ−1−(メチルアミノ)−1−オキソ −2−プロピル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[3−(ジメチルアミノ)−3−オキソ−プロピル]−シクロ ペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−(ジメチルアミノ)−2−オキソ−エチル]−シクロペ ンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[3−オキソ−3−[(フェニルメチル)アミノ]−プロピル] −シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−(メチルアミノ)−2−オキソ−エチル]−シクロペン タンカルボキサミド、 [1S−[1α(R*),2β,3β,4α]]−N−[4−アミノ−1−(アミノカルボ ニル)−4−オキソ−ブチル]−4−[7−(ブチルアミノ)−5−(プロピルチオ) −3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジ ヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−N−[4−アミノ−1−[(メチルアミノ)カ ルボニル]−4−オキソ−ブチル]−4−[7−(ブチルアミノ)−5−(プロピルチ オ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3− ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α(R*),2β,3β,4α)]−N−[1−(アミノカルボニル)−3− ヒドロキシ−プロピル]−4−[7−(ブチルアミノ)−5−(プロピルチオ)−3H −1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロ キシ−シクロペンタンカルボキサミド、 [1S−(1α(R*),2β,3β,4α)]−N−[1−(アミノカルボニル)−2− ヒドロキシ−エチル)−2,3−ジヒドロキシ−4−[7−[(4−フェニルブチル) アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミ ジン−3−イル]−シクロペンタンカルボキサミド、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−N−[(アミノカルボニル)メ チル]−2,3−ジヒドロキシ−4−[7−[(2−フェニルシクロプロ ピル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d] ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α(R*),2β,3β,4α)]−N−[(1−アミノカルボニル)−4−( メチルアミノ)−4−オキソ−ブチル]−4−[7−(ブチルアミノ)−5−(プロピ ルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2, 3−ジヒドロキシ−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(4−フ ェニルブチル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4, 5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[(1−フ ェニルシクロプロピル)アミノ]−5−(プロピルチオ)−3H−1,2,3−トリア ゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−(2,3−ジヒドロキシプロピル)−シクロペンタンカルボ キサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−ヒドロキシ−2−(4−ヒドロキシフェニル)−エチ ル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[2−ヒドロキシ−2−(3−ヒドロキシフェニル)−エチ ル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[(4−ヒドロキシ−3−メトキシフェニル)−メチル]−シ クロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[(4−ヒドロキシフェニル)−メチル]−シクロペンタンカ ルボキサミド、 [1S−[1α,2β,3β,4α(1R*,2S*)]]−2,3−ジヒドロキシ−N−( 2−ヒドロキシエチル)−4−[7−[(2−フェニルシクロプロピル)アミノ]−5 −(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3− イル]−シクロペンタンカルボキサミド、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−2,3−ジヒドロキシ−N−( 2−ヒドロキシエチル)−4−[7−[(2−フェニルシクロプロピル)アミノ]−5 −(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3− イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[(2−ヒドロキシ−5−ニトロフェニル)メチル]−シクロ ペンタンカルボキサミド、 [1S−[1α,2β,3β,4α(トランス)]]−2,3−ジヒドロキシ−N−(2 −ヒドロキシエチル)−4−[5−[[(4−トリフルオロメチル)フェニル]チオ] −7−[(2−フェニルシクロプロピル)アミノ]−3H−1,2,3−トリアゾロ[ 4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン− 3−イル]−2,3−ジヒドロキシ−N−[(3,4−ヒドロキシフェニル)メチル] −シクロペンタンカルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[(2−ヒドロキシフェニル)メチル]−シクロペンタンカル ボキサミド、 [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−N−[2−ヒドロキ シエチル]−4−[7−[(4−フェニルブチル)アミノ]−5−(プロピルチオ)−3 H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタン カルボキサミド、 [1S−(1α,2β,3β,4α)]−4−[7−(シクロプロピルアミノ)−5−( プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル ]−2,3−ジヒドロキシ−N−(2−ヒドロキシエチル)−シクロペンタンカルボ キサミド、 [1S−[(1α,2β,3β,4α)]−4−[7−(ブチルアミノ)−5−(プロピル チオ)−3H−1,2,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3 −ジヒドロキシ−N−[(3−ヒドロキシフェニル)メチル]−シクロペンタンカル ボキサミド、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−4−[7−[[2−(4−クロロ フェニル)シクロプロピル]アミノ]−5−(プロピルチオ)−3H−1,2,3−ト リアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペ ンタンカルボン酸、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−4−[7−[[2−(4−クロロ フェニル)シクロプロピル]アミノ]−5−(プロピルチオ)−3H−1,2,3−ト リアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シクロペ ンタンカルボキサミド、 [1S−[1α,2β,3β,4α(1R*,2S*)]]−4−[7−[[2−(4− クロロフェニル)シクロプロピル]アミノ]−5−(プロピルチオ)−3H−1,2 ,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−2,3−ジヒドロキシ−シ クロペンタンカルボン酸、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−2,3−ジヒドロキシ−4−[ 5−(メチルチオ)−7−[(2−フェニルシクロプロピル)アミノ]−3H−1,2, 3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸 、 [1S−[1α,2β,3β,4α(1S*,2R*)]]−2,3−ジヒドロキシ−4−[ 5−(メチルチオ)−7−[(2−フェニルシクロプロピル)アミノ]−3H−1,2 ,3−トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボキ サミド, [1S−(1α,2β,3β,4α)]−2,3−ジヒドロキシ−4−[7−[2−(フ ェニルアミノ)エチルアミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾ ロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸、 [1S−(1α,2β,3β,4α)]−4−[7−[2−(4−クロロフェニル)−エ チルアミノ]−5−(プロピルチオ)−3H−1,2,3−トリアゾロ[4,5−d]ピ リミジン−3−イル]−2,3−ジヒドロキシ−シクロペンタンカルボン酸、 [1S−[1α,2β,3β,4α(E)]]−2,3−ジヒドロキシ−4−[7−(3− ヨード−プロパ−2−エニルアミノ)−5−(プロピルチオ)−3H−1,2,3− トリアゾロ[4,5−d]ピリミジン−3−イル]−シクロペンタンカルボン酸 である請求項1記載の化合物およびそれらの医薬的に許容し得る塩。 6.請求項1〜5のいずれか1項に記載の化合物を医薬的に許容し得る希釈剤、 補助剤または担体とともに含有する医薬組成物。 7.治療に使用するための請求項1〜5のいずれか1項に記載の化合物。 8.血小板凝集疾患治療用医薬の製造における請求項1〜5のいずれか1項に記 載の化合物の使用。 9.血小板凝集疾患に罹っている患者に請求項1〜5のいずれか1項に記載の化 合物の治療的に有効な量を投与することからなる該疾患の治療方法。 10.(a)式(II) [式中、R1およびR2は前述の定義を有し、P1は保護基であり、Yは前述の定義 を有するXであるか、またはO−C1-6−アルキル、O−ベンジルまたはNHR7( ここでR7はC(O)OR8基および場合により、1個またはそれ以上のハロゲン原子お よび/またはOR4、C(NH)NR4R5、C(O)NR4R5、フェニルおよび/またはC1-6−ア ルキル基により置換されているC1-6−アルキル基であって、ここでR4およびR5 は前述の定義を有し、そしてR8はC1-6−アルキル基またはベンジルである]の 化合物を脱保護し、次いで場合により (b) こうして得られた式(I)の化合物を適当な酸または塩基と反応させて、 医薬的に許容し得る塩を製造する ことからなる、請求項1に記載の式(I)の化合物の製造方法。 11.請求項10に定義された式(II)の化合物。
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SE9604787-3 | 1996-12-20 | ||
SE9604787A SE9604787D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
SE9604788-1 | 1996-12-20 | ||
SE9604788A SE9604788D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
PCT/SE1997/002091 WO1998028300A1 (en) | 1996-12-20 | 1997-12-12 | Triazolo[4,5-d]pyrimidinyl derivatives and their use as medicaments |
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US (1) | US6297232B1 (ja) |
EP (1) | EP0946561B1 (ja) |
JP (1) | JP4125790B2 (ja) |
AT (1) | ATE213245T1 (ja) |
AU (1) | AU5501598A (ja) |
DE (1) | DE69710490T2 (ja) |
WO (1) | WO1998028300A1 (ja) |
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JP2022541683A (ja) * | 2019-11-13 | 2022-09-26 | 台州市創源工業技術有限公司 | ヒドロキシベンジルアミンの合成方法 |
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SE9702772D0 (sv) * | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
TW530058B (en) * | 1997-07-22 | 2003-05-01 | Astra Pharma Prod | Triazolo [4,5-d]pyrimidine compounos and their use and process for preparation |
SE9702773D0 (sv) * | 1997-07-22 | 1997-07-22 | Astra Pharma Prod | Novel compounds |
KR20010078696A (ko) | 1998-02-17 | 2001-08-21 | 다비드 에 질레스 | 신규한 트리아졸로[4,5-d]피리미딘 화합물 |
SE9802574D0 (sv) * | 1998-07-17 | 1998-07-17 | Astra Pharma Prod | Novel compounds |
TWI229674B (en) * | 1998-12-04 | 2005-03-21 | Astra Pharma Prod | Novel triazolo[4,5-d]pyrimidine compounds, pharmaceutical composition containing the same, their process for preparation and uses |
SE9903290D0 (sv) * | 1999-09-15 | 1999-09-15 | Astra Pharma Prod | Novel compounds |
SE9904128D0 (sv) * | 1999-11-15 | 1999-11-15 | Astra Pharma Prod | Novel compounds |
SE9904129D0 (sv) * | 1999-11-15 | 1999-11-15 | Astra Pharma Prod | Novel compounds |
GB0013488D0 (en) * | 2000-06-02 | 2000-07-26 | Astrazeneca Ab | Chemical compound |
GB0013407D0 (en) * | 2000-06-02 | 2000-07-26 | Astrazeneca Ab | Forms of a chemical compound |
US7018985B1 (en) | 2000-08-21 | 2006-03-28 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
US6897201B2 (en) | 2000-08-21 | 2005-05-24 | Inspire Pharmaceuticals, Inc. | Compositions and methods for the treatment of glaucoma or ocular hypertension |
US7115585B2 (en) | 2000-08-21 | 2006-10-03 | Inspire Pharmaceuticals, Inc. | Compositions for treating epithelial and retinal tissue diseases |
US7452870B2 (en) | 2000-08-21 | 2008-11-18 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with P2Y12 receptor antagonist compound |
US7132408B2 (en) | 2000-08-21 | 2006-11-07 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
US7435724B2 (en) | 2002-02-27 | 2008-10-14 | Inspire Pharmaceutical, Inc. | Degradation-resistant mononucleoside phosphate compounds |
GB0219746D0 (en) * | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
US7335648B2 (en) | 2003-10-21 | 2008-02-26 | Inspire Pharmaceuticals, Inc. | Non-nucleotide composition and method for inhibiting platelet aggregation |
US7368438B2 (en) | 2003-10-21 | 2008-05-06 | Inspire Pharmaceuticals, Inc. | Non-nucleotide compositions and method for inhibiting platelet aggregation |
US7749981B2 (en) * | 2003-10-21 | 2010-07-06 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with non-nucleotide P2Y12 receptor antagonist compound |
US7504497B2 (en) | 2003-10-21 | 2009-03-17 | Inspire Pharmaceuticals, Inc. | Orally bioavailable compounds and methods for inhibiting platelet aggregation |
GB2418425B (en) | 2004-08-11 | 2008-09-03 | Univ Cambridge Tech | Anti-inflammatory agents |
US7932376B2 (en) | 2005-05-05 | 2011-04-26 | Inspire Pharmaceuticals, Inc. | Pyrimidine-based non-nucleotide composition and method for inhibiting platelet aggregation |
CA2612217A1 (en) | 2005-06-15 | 2006-12-21 | Cambridge Enterprise Limited | Anti-inflammatory agents |
US7566722B2 (en) * | 2006-10-31 | 2009-07-28 | Janssen Pharmaceutica, N.V. | Triazolopyrimidine derivatives as ADP P2Y12 receptor antagonists |
JP2010508351A (ja) * | 2006-10-31 | 2010-03-18 | ヤンセン ファーマシューティカ エヌ.ベー. | Adpp2y12レセプターアンタゴニストとしてのトリアゾロピリミジン誘導体 |
US20110144049A1 (en) * | 2009-10-21 | 2011-06-16 | Serebruany Victor L | Treating Cardiac Arrhythmias, Heart Failure, Peripheral Artery Disease and Stroke with Cyclopentyl-Triazolo-Pyrimidine or Derivative Thereof |
CN105061431B (zh) * | 2015-07-28 | 2017-03-29 | 山东百诺医药股份有限公司 | 6‑n‑(2‑(甲硫基)乙基)‑2‑((3,3,3‑三氟丙基)硫代)‑9h‑嘌呤及其制备方法和应用 |
CN111116592A (zh) * | 2019-11-27 | 2020-05-08 | 杭州沧海帆医药科技有限公司 | 嘧啶并三氮唑类化合物及其医药用途 |
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US4742064A (en) | 1985-09-10 | 1988-05-03 | Regents Of The University Of Minnesota | Antiviral carbocyclic analogs of xylofuranosylpurines |
GB8826205D0 (en) | 1988-11-09 | 1988-12-14 | Wellcome Found | Heterocyclic compounds |
BR9609467A (pt) | 1995-07-11 | 1999-03-02 | Astra Pharma Prod | Composto uso de um composto composição farmacéutica e processos para preparação de um composto e tratamento de distúrbios de agregação planquetária |
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- 1997-12-12 US US09/011,992 patent/US6297232B1/en not_active Expired - Fee Related
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JP7349762B2 (ja) | 2019-11-13 | 2023-09-25 | 台州市創源工業技術有限公司 | ヒドロキシベンジルアミンの合成方法 |
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EP0946561B1 (en) | 2002-02-13 |
EP0946561A1 (en) | 1999-10-06 |
ATE213245T1 (de) | 2002-02-15 |
DE69710490D1 (de) | 2002-03-21 |
US6297232B1 (en) | 2001-10-02 |
WO1998028300A1 (en) | 1998-07-02 |
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DE69710490T2 (de) | 2002-10-24 |
AU5501598A (en) | 1998-07-17 |
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