JP2008540685A - Ａ１アデノシンレセプターアゴニスト - Google Patents

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Publication number

JP2008540685A

JP2008540685A JP2008512588A JP2008512588A JP2008540685A JP 2008540685 A JP2008540685 A JP 2008540685A JP 2008512588 A JP2008512588 A JP 2008512588A JP 2008512588 A JP2008512588 A JP 2008512588A JP 2008540685 A JP2008540685 A JP 2008540685A

Authority

JP

Japan

Prior art keywords

oxolan

hydroxymethyl

purin

dihydroxy

amino

Prior art date

2005-05-19

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.)

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• 239000003379 purinergic P1 receptor agonist Substances 0.000 title description 11
• 229940122614 Adenosine receptor agonist Drugs 0.000 title description 2
• 101150007969 ADORA1 gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 201
• 238000000034 method Methods 0.000 claims abstract description 53
• 102000009346 Adenosine receptors Human genes 0.000 claims abstract description 30
• 108050000203 Adenosine receptors Proteins 0.000 claims abstract description 30
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
• 239000000556 agonist Substances 0.000 claims abstract description 19
• 201000010099 disease Diseases 0.000 claims abstract description 17
• 239000004031 partial agonist Substances 0.000 claims abstract description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 206010003662 Atrial flutter Diseases 0.000 claims abstract description 6
• 208000008589 Obesity Diseases 0.000 claims abstract description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 4
• 235000020824 obesity Nutrition 0.000 claims abstract description 4
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 3
• -1 oxolan-3-ylamino Chemical group 0.000 claims description 147
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 72
• 125000000217 alkyl group Chemical group 0.000 claims description 64
• 125000001072 heteroaryl group Chemical group 0.000 claims description 62
• 125000003118 aryl group Chemical group 0.000 claims description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 35
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
• 125000004258 purin-2-yl group Chemical group [H]N1C2=NC(*)=NC([H])=C2N([H])C1([H])[H] 0.000 claims description 32
• 125000000623 heterocyclic group Chemical group 0.000 claims description 30
• 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 29
• 150000001412 amines Chemical class 0.000 claims description 21
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 20
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 125000003107 substituted aryl group Chemical group 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 125000000304 alkynyl group Chemical group 0.000 claims description 18
• 239000002253 acid Substances 0.000 claims description 17
• 150000002431 hydrogen Chemical class 0.000 claims description 16
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 16
• 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 13
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 12
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 10
• 229960005305 adenosine Drugs 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 239000005973 Carvone Substances 0.000 claims description 9
• 150000002009 diols Chemical class 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 8
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
• 150000003857 carboxamides Chemical class 0.000 claims description 8
• 229940095102 methyl benzoate Drugs 0.000 claims description 7
• 102000005962 receptors Human genes 0.000 claims description 7
• 108020003175 receptors Proteins 0.000 claims description 7
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 6
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 6
• YSHINTPADKRJQC-UZFJHYNOSA-N 1-[6-(cyclopentylamino)-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carbonitrile Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C#N)=NC(NC3CCCC3)=C2N=C1 YSHINTPADKRJQC-UZFJHYNOSA-N 0.000 claims description 5
• KCXUOHHIHWDYEB-ZGOQAQPGSA-N 1-[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-2-yl]pyrazole-4-carboxylic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(O)=O)=NC(N[C@H]3COCC3)=C2N=C1 KCXUOHHIHWDYEB-ZGOQAQPGSA-N 0.000 claims description 5
• 206010003658 Atrial Fibrillation Diseases 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
• XNMZVFLCYIWGKD-PDWWLECJSA-N 1-[6-(cyclopentylamino)-9-[(3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 XNMZVFLCYIWGKD-PDWWLECJSA-N 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 150000002148 esters Chemical class 0.000 claims description 4
• 208000024891 symptom Diseases 0.000 claims description 4
• DUHMXRIMVGVCME-KGAJLJRASA-N (2S,3R,4S,5R)-N-ethyl-3,4-dihydroxy-5-[6-[[(3R)-oxolan-3-yl]amino]-2-(4-pyridin-4-yl-1H-pyrazol-5-yl)purin-9-yl]oxolane-2-carboxamide Chemical compound O[C@H]1[C@@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(C=3C(=CNN=3)C=3C=CN=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 DUHMXRIMVGVCME-KGAJLJRASA-N 0.000 claims description 3
• TVUGHWLRSAWJJM-NOGSCBLWSA-N (2S,3R,4S,5R)-N-ethyl-3,4-dihydroxy-5-[6-[[(3R)-oxolan-3-yl]amino]-2-(4-quinolin-2-yl-1H-pyrazol-5-yl)purin-9-yl]oxolane-2-carboxamide Chemical compound O[C@H]1[C@@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(C=3C(=CNN=3)C=3N=C4C=CC=CC4=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 TVUGHWLRSAWJJM-NOGSCBLWSA-N 0.000 claims description 3
• PXOGHKCTPCVLTB-YEBQIDHKSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-[4-[4-(trifluoromethyl)phenyl]-1h-pyrazol-5-yl]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(C=3C(=CNN=3)C=3C=CC(=CC=3)C(F)(F)F)=NC(N[C@H]3COCC3)=C2N=C1 PXOGHKCTPCVLTB-YEBQIDHKSA-N 0.000 claims description 3
• PGKWCAWAOJZJSK-RNJMTHNFSA-N (2r,5r)-2-[6-[[(1r,2r)-2-hydroxycyclopentyl]amino]-2-(1h-pyrazol-5-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(C3=NNC=C3)=NC(N[C@H]3[C@@H](CCC3)O)=C2N=C1 PGKWCAWAOJZJSK-RNJMTHNFSA-N 0.000 claims description 3
• XKQWZLKQHJDQMF-PDWWLECJSA-N (3r,4s,5r)-2-[6-(cyclohexylamino)-2-(1h-pyrazol-5-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(C3=NNC=C3)=NC(NC3CCCCC3)=C2N=C1 XKQWZLKQHJDQMF-PDWWLECJSA-N 0.000 claims description 3
• OZRVLZWUXQNNGM-XWHOZGLOSA-N (3r,4s,5r)-2-[6-(cyclopentylamino)-2-(1h-pyrazol-5-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(C3=NNC=C3)=NC(NC3CCCC3)=C2N=C1 OZRVLZWUXQNNGM-XWHOZGLOSA-N 0.000 claims description 3
• OLUORQFAPCSAFX-OZLRJOHKSA-N (3r,4s,5r)-2-[6-(cyclopentylamino)-2-(3,5-dimethyl-1h-pyrazol-4-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound CC1=NNC(C)=C1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 OLUORQFAPCSAFX-OZLRJOHKSA-N 0.000 claims description 3
• GVJLUVZSTWCLCB-RANUBIOZSA-N (3s,4r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-pyridin-2-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)C(CO)OC1N1C2=NC(C=3C(=CNN=3)C=3N=CC=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 GVJLUVZSTWCLCB-RANUBIOZSA-N 0.000 claims description 3
• ODVHCXYRIMOIPI-RVKQPBAUSA-N (3s,4r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-pyridin-4-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)C(CO)OC1N1C2=NC(C=3C(=CNN=3)C=3C=CN=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 ODVHCXYRIMOIPI-RVKQPBAUSA-N 0.000 claims description 3
• IYQRLTNIKOKQBM-CVJJTSJDSA-N (3s,4r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-quinolin-2-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)C(CO)OC1N1C2=NC(C=3C(=CNN=3)C=3N=C4C=CC=CC4=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 IYQRLTNIKOKQBM-CVJJTSJDSA-N 0.000 claims description 3
• CXNXHSYDENRKNJ-YSZIWRGASA-N 1-[6-(3-bicyclo[2.2.1]heptanylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxylic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(N3N=CC(=C3)C(O)=O)=NC(NC3C4CCC(C4)C3)=C2N=C1 CXNXHSYDENRKNJ-YSZIWRGASA-N 0.000 claims description 3
• PCXAWUCDSLBQGU-UVLLPENVSA-N 1-[6-(benzylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-n-ethylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NCC)C=NN1C1=NC(NCC=2C=CC=CC=2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 PCXAWUCDSLBQGU-UVLLPENVSA-N 0.000 claims description 3
• DTZUIVIVWXASNR-DYVMYPEFSA-N 1-[6-(benzylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-n-propylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NCCC)C=NN1C1=NC(NCC=2C=CC=CC=2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 DTZUIVIVWXASNR-DYVMYPEFSA-N 0.000 claims description 3
• PCYVLFCVZVITGZ-XZHXJBAPSA-N 1-[6-(cyclohexylamino)-9-[(3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC)C=NN1C1=NC(NC2CCCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 PCYVLFCVZVITGZ-XZHXJBAPSA-N 0.000 claims description 3
• CBRFHOYVUQTTOO-JDYLIUQESA-N 1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-(4-fluorophenyl)sulfonylpyrazole-4-carboxamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NS(=O)(=O)C=3C=CC(F)=CC=3)=NC(NC3CCCC3)=C2N=C1 CBRFHOYVUQTTOO-JDYLIUQESA-N 0.000 claims description 3
• CVJLZKCJMMTTCG-WJDTXIQTSA-N 1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-ethylsulfonylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NS(=O)(=O)CC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3C(C(O)[C@@H](CO)O3)O)C2=N1 CVJLZKCJMMTTCG-WJDTXIQTSA-N 0.000 claims description 3
• XFAKNYIWVXKGND-QEPJRFBGSA-N 1-[6-(cyclopentylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-5-methylpyrazole-3-carboxamide Chemical compound CC1=CC(C(N)=O)=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 XFAKNYIWVXKGND-QEPJRFBGSA-N 0.000 claims description 3
• VRFJZVZCHGTGLD-KHTYJDQRSA-N 1-[6-(cyclopentylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-n,5-dimethylpyrazole-3-carboxamide Chemical compound N1=C(C(=O)NC)C=C(C)N1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 VRFJZVZCHGTGLD-KHTYJDQRSA-N 0.000 claims description 3
• IWRUBXCDPGPIJY-BNCYDMKUSA-N 1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]-N-[(4-fluorophenyl)methyl]pyrazole-4-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NCC=3C=CC(F)=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 IWRUBXCDPGPIJY-BNCYDMKUSA-N 0.000 claims description 3
• ZWZLDRDGBVQOIM-FSVZYJJUSA-N 1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]-N-ethylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NCC)C=NN1C1=NC(N[C@H]2COCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 ZWZLDRDGBVQOIM-FSVZYJJUSA-N 0.000 claims description 3
• TWTGSPIRIYZHEH-GBUDDTMKSA-N 1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]-N-methylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC)C=NN1C1=NC(N[C@H]2COCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 TWTGSPIRIYZHEH-GBUDDTMKSA-N 0.000 claims description 3
• URCQSKDIYCFLMB-DBKKVMMFSA-N 1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]-N-propylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NCCC)C=NN1C1=NC(N[C@H]2COCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 URCQSKDIYCFLMB-DBKKVMMFSA-N 0.000 claims description 3
• PEYFMKGCMFFEJC-SECFDDAWSA-N 1-[9-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound O[C@H]1[C@@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NCC=3C=C(C=C(F)C=3)C(F)(F)F)=NC(N[C@H]3COCC3)=C2N=C1 PEYFMKGCMFFEJC-SECFDDAWSA-N 0.000 claims description 3
• NNRNGRIBVDTFGT-BELNSVPKSA-N 1-[9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(oxolan-3-ylamino)purin-2-yl]-N-(4-fluorophenyl)sulfonylpyrazole-4-carboxamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NS(=O)(=O)C=3C=CC(F)=CC=3)=NC(NC3COCC3)=C2N=C1 NNRNGRIBVDTFGT-BELNSVPKSA-N 0.000 claims description 3
• PDZJFBKMKPQMNE-LMYIUNJJSA-N 1-[9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(1R,2R)-2-hydroxycyclopentyl]amino]purin-2-yl]-N-methylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC)C=NN1C1=NC(N[C@H]2[C@@H](CCC2)O)=C(N=CN2[C@H]3C(C(O)[C@@H](CO)O3)O)C2=N1 PDZJFBKMKPQMNE-LMYIUNJJSA-N 0.000 claims description 3
• XNTCMYPKIKUYFM-CPHBTSCZSA-N 1-[9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-2-yl]pyrazole-4-carboxylic acid Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(O)=O)=NC(N[C@H]3[C@@H](CCC3)O)=C2N=C1 XNTCMYPKIKUYFM-CPHBTSCZSA-N 0.000 claims description 3
• KBBKVKXFWFOKQD-BHHKXNEBSA-N 2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-pyrazin-2-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-3,4-diol Chemical compound OC1C(O)C(CO)OC1N1C2=NC(C=3C(=CNN=3)C=3N=CC=NC=3)=NC(N[C@H]3COCC3)=C2N=C1 KBBKVKXFWFOKQD-BHHKXNEBSA-N 0.000 claims description 3
• HCHFOVLSLKNFNN-BIPMDSTOSA-N 2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-quinazolin-2-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-3,4-diol Chemical compound OC1C(O)C(CO)OC1N1C2=NC(C=3C(=CNN=3)C=3N=C4C=CC=CC4=CN=3)=NC(N[C@H]3COCC3)=C2N=C1 HCHFOVLSLKNFNN-BIPMDSTOSA-N 0.000 claims description 3
• LOTQFGOYLAMHQE-BNCYDMKUSA-N 4-[[[1-[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-2-yl]pyrazole-4-carbonyl]amino]methyl]benzoic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NCC=3C=CC(=CC=3)C(O)=O)=NC(N[C@H]3COCC3)=C2N=C1 LOTQFGOYLAMHQE-BNCYDMKUSA-N 0.000 claims description 3
• YSGVFSDDBDCYFP-NDTDQGAOSA-N 6-[1-[9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-2-yl]pyrazol-4-yl]pyridine-3-carboxylic acid Chemical compound OC1C(O)C(CO)OC1N1C2=NC(N3N=CC(=C3)C=3N=CC(=CC=3)C(O)=O)=NC(N[C@H]3COCC3)=C2N=C1 YSGVFSDDBDCYFP-NDTDQGAOSA-N 0.000 claims description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
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