CA2609051A1 - A1 adenosine receptor agonists - Google Patents

Info

Publication number

CA2609051A1

CA2609051A1 CA002609051A CA2609051A CA2609051A1 CA 2609051 A1 CA2609051 A1 CA 2609051A1 CA 002609051 A CA002609051 A CA 002609051A CA 2609051 A CA2609051 A CA 2609051A CA 2609051 A1 CA2609051 A1 CA 2609051A1

Authority

CA

Canada

Prior art keywords

compound

hydroxymethyl

optionally substituted

purin

formula

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000003379 purinergic P1 receptor agonist Substances 0.000 title claims abstract description 14
• 101150007969 ADORA1 gene Proteins 0.000 title claims abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 235
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
• 201000010099 disease Diseases 0.000 claims abstract description 16
• 230000036961 partial effect Effects 0.000 claims abstract description 10
• 206010003662 Atrial flutter Diseases 0.000 claims abstract description 5
• 208000010125 myocardial infarction Diseases 0.000 claims abstract description 3
• 238000000034 method Methods 0.000 claims description 62
• 125000001072 heteroaryl group Chemical group 0.000 claims description 58
• 125000000623 heterocyclic group Chemical group 0.000 claims description 31
• 229910006069 SO3H Inorganic materials 0.000 claims description 29
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
• 229910052739 hydrogen Inorganic materials 0.000 claims description 29
• 239000001257 hydrogen Substances 0.000 claims description 28
• 150000001412 amines Chemical class 0.000 claims description 24
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 23
• 125000003107 substituted aryl group Chemical group 0.000 claims description 21
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
• 125000000304 alkynyl group Chemical group 0.000 claims description 18
• 150000002431 hydrogen Chemical group 0.000 claims description 18
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 17
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 13
• GLZCOFUIJOEDOK-PZGKNFOESA-N ethyl 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]triazole-4-carboxylate Chemical compound N1=NC(C(=O)OCC)=CN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 GLZCOFUIJOEDOK-PZGKNFOESA-N 0.000 claims description 11
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
• 229910052757 nitrogen Inorganic materials 0.000 claims description 9
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000004258 purin-2-yl group Chemical group [H]N1C2=NC(*)=NC([H])=C2N([H])C1([H])[H] 0.000 claims description 8
• SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 7
• 241000124008 Mammalia Species 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 206010003658 Atrial Fibrillation Diseases 0.000 claims description 5
• AMZRGLCQCSEUIU-VGWNDNRCSA-N 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]triazole-4-carboxamide Chemical compound N1=NC(C(=O)N)=CN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 AMZRGLCQCSEUIU-VGWNDNRCSA-N 0.000 claims description 4
• DFMYMVNQKRLFPQ-AARXTDBFSA-N 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]triazole-4-carboxylic acid Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(N3N=NC(=C3)C(O)=O)=NC(NC3CCCC3)=C2N=C1 DFMYMVNQKRLFPQ-AARXTDBFSA-N 0.000 claims description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-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
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• JWFPXVFJPXMSJB-ZOICRDBHSA-N (3r,4s,5r)-2-[2-(5-benzyl-2h-triazol-4-yl)-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(C=3C(=NNN=3)CC=3C=CC=CC=3)=NC(NC3CCCC3)=C2N=C1 JWFPXVFJPXMSJB-ZOICRDBHSA-N 0.000 claims description 3
• NTJFCRDCFITCLR-XWHOZGLOSA-N 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-n-methyltriazole-4-carboxamide Chemical compound N1=NC(C(=O)NC)=CN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 NTJFCRDCFITCLR-XWHOZGLOSA-N 0.000 claims description 3
• YHXWQVHSTXCXDI-NQXOGJLRSA-N 2-(hydroxymethyl)-5-[2-[5-(hydroxymethyl)-2h-triazol-4-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound OC1C(O)C(CO)OC1N1C2=NC(C=3C(=NNN=3)CO)=NC(N[C@H]3COCC3)=C2N=C1 YHXWQVHSTXCXDI-NQXOGJLRSA-N 0.000 claims description 3
• 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 3
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
• 206010019280 Heart failures Diseases 0.000 claims description 3
• 208000008589 Obesity Diseases 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 206010015037 epilepsy Diseases 0.000 claims description 3
• HTPMEIAJHHEDTI-PISZKDOUSA-N ethyl 1-[9-[3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-2-yl]triazole-4-carboxylate Chemical compound N1=NC(C(=O)OCC)=CN1C1=NC(N[C@H]2COCC2)=C(N=CN2C3C(C(O)C(CO)O3)O)C2=N1 HTPMEIAJHHEDTI-PISZKDOUSA-N 0.000 claims description 3
• 235000020824 obesity Nutrition 0.000 claims description 3
• OVNUPUBMAHHKSR-CZQAHURTSA-N 2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]-2-[5-[4-(trifluoromethyl)phenyl]-2h-triazol-4-yl]purin-9-yl]oxolane-3,4-diol Chemical compound OC1C(O)C(CO)OC1N1C2=NC(C=3C(=NNN=3)C=3C=CC(=CC=3)C(F)(F)F)=NC(N[C@H]3COCC3)=C2N=C1 OVNUPUBMAHHKSR-CZQAHURTSA-N 0.000 claims description 2
• 206010002388 Angina unstable Diseases 0.000 claims description 2
• 208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
• 208000007718 Stable Angina Diseases 0.000 claims description 2
• 208000006011 Stroke Diseases 0.000 claims description 2
• 208000007814 Unstable Angina Diseases 0.000 claims description 2
• 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 2
• 230000000747 cardiac effect Effects 0.000 claims description 2
• PQWMKKQJYFGBFK-XAUNWSGPSA-N ethyl 1-[6-(cyclohexylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]triazole-4-carboxylate Chemical compound N1=NC(C(=O)OCC)=CN1C1=NC(NC2CCCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 PQWMKKQJYFGBFK-XAUNWSGPSA-N 0.000 claims description 2
• 208000006575 hypertriglyceridemia Diseases 0.000 claims description 2
• 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 2
• 208000028867 ischemia Diseases 0.000 claims description 2
• DOENXILBZJVYQF-PSBUXNCMSA-N n-[[3-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]triazol-4-yl]methyl]-4-fluorobenzenesulfonamide Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)OC1N1C2=NC(N3C(=CN=N3)CNS(=O)(=O)C=3C=CC(F)=CC=3)=NC(NC3CCCC3)=C2N=C1 DOENXILBZJVYQF-PSBUXNCMSA-N 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
• 125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
• 108010060263 Adenosine A1 Receptor Proteins 0.000 claims 1
• 102000030814 Adenosine A1 receptor Human genes 0.000 claims 1
• 208000031226 Hyperlipidaemia Diseases 0.000 claims 1
• 208000001871 Tachycardia Diseases 0.000 abstract description 2
• 230000006794 tachycardia Effects 0.000 abstract description 2
• 206010002383 Angina Pectoris Diseases 0.000 abstract 1
• 239000011888 foil Substances 0.000 abstract 1
• -1 glucose fatty acid Chemical class 0.000 description 102
• 238000002360 preparation method Methods 0.000 description 71
• 239000000203 mixture Substances 0.000 description 64
• 125000001424 substituent group Chemical group 0.000 description 58
• 125000000217 alkyl group Chemical group 0.000 description 56
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 238000006243 chemical reaction Methods 0.000 description 50
• 239000000243 solution Substances 0.000 description 48
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
• 125000003118 aryl group Chemical group 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
• 239000002904 solvent Substances 0.000 description 37
• 239000000047 product Substances 0.000 description 34
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 32
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
• 239000004480 active ingredient Substances 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
• 125000003545 alkoxy group Chemical group 0.000 description 25
• 125000004093 cyano group Chemical group *C#N 0.000 description 24
• 229910052736 halogen Inorganic materials 0.000 description 24
• 150000002367 halogens Chemical class 0.000 description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
• 229910001868 water Inorganic materials 0.000 description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 21
• 125000004181 carboxyalkyl group Chemical group 0.000 description 21
• 125000000753 cycloalkyl group Chemical group 0.000 description 21
• 239000003826 tablet Substances 0.000 description 21
• 239000004615 ingredient Substances 0.000 description 19
• NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 16
• 125000004432 carbon atom Chemical group C* 0.000 description 16
• 125000000392 cycloalkenyl group Chemical group 0.000 description 16
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 16
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
• 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
• 210000004027 cell Anatomy 0.000 description 14
• 230000000694 effects Effects 0.000 description 14
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
• 108050000203 Adenosine receptors Proteins 0.000 description 13
• 102000009346 Adenosine receptors Human genes 0.000 description 13
• 238000001914 filtration Methods 0.000 description 13
• 150000003839 salts Chemical class 0.000 description 13
• 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 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• DIRLDPKYOATBIA-UHFFFAOYSA-N oxolan-3-yl acetate Chemical compound CC(=O)OC1CCOC1 DIRLDPKYOATBIA-UHFFFAOYSA-N 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 239000007787 solid Substances 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 125000002947 alkylene group Chemical group 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 10
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 10
• 229940093499 ethyl acetate Drugs 0.000 description 10
• 235000019439 ethyl acetate Nutrition 0.000 description 10
• 230000004048 modification Effects 0.000 description 10
• 238000012986 modification Methods 0.000 description 10
• 229930194542 Keto Natural products 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 125000002252 acyl group Chemical group 0.000 description 9
• 125000004423 acyloxy group Chemical group 0.000 description 9
• 239000000556 agonist Substances 0.000 description 9
• 125000004414 alkyl thio group Chemical group 0.000 description 9
• 125000005110 aryl thio group Chemical group 0.000 description 9
• 125000004104 aryloxy group Chemical group 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
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
• 125000004442 acylamino group Chemical group 0.000 description 8
• 125000000033 alkoxyamino group Chemical group 0.000 description 8
• 125000004429 atom Chemical group 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
• 230000027455 binding Effects 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 125000005368 heteroarylthio group Chemical group 0.000 description 8
• 125000004470 heterocyclooxy group Chemical group 0.000 description 8
• 125000004468 heterocyclylthio group Chemical group 0.000 description 8
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
• 150000003573 thiols Chemical group 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 7
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 7
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• 229920002472 Starch Polymers 0.000 description 7
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 238000009472 formulation Methods 0.000 description 7
• 235000019359 magnesium stearate Nutrition 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• MIPHRQMEIYLZFZ-UHFFFAOYSA-N oxolan-3-amine Chemical compound NC1CCOC1 MIPHRQMEIYLZFZ-UHFFFAOYSA-N 0.000 description 7
• 235000019698 starch Nutrition 0.000 description 7
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
• 238000004809 thin layer chromatography Methods 0.000 description 7
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 229960005305 adenosine Drugs 0.000 description 6
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
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• 238000010992 reflux Methods 0.000 description 6
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• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 5
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
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• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
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• 229910052708 sodium Inorganic materials 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
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• PYLVODBGSCAFQR-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-amino-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(N)=NC=1NC1CCCC1 PYLVODBGSCAFQR-IDTAVKCVSA-N 0.000 description 4
• NEGNYVAPZSCQEX-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-azido-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N=[N+]=[N-])=NC(NC3CCCC3)=C2N=C1 NEGNYVAPZSCQEX-IDTAVKCVSA-N 0.000 description 4
• ZZKOIZPFVKEUFP-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)-2-hydrazinylpurin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=12N=CN([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=NC(NN)=NC=1NC1CCCC1 ZZKOIZPFVKEUFP-IDTAVKCVSA-N 0.000 description 4
• SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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