CA2609117A1

CA2609117A1 - A1 adenosine receptor agonists

A1 adenosine receptor agonists Download PDF

Info

Publication number: CA2609117A1
Authority: CA; Canada
Prior art keywords: oxolan; purin; hydroxymethyl; dihydroxy; amino
Prior art date: 2005-05-19
Legal status : Abandoned

Application number

CA002609117A

Other languages

English (en)

French (fr)

Inventor

Elfatih Elzein

Rao Kalla

Thao Perry

Jeff Zablocki

Xiaofen Li

Current Assignee

Gilead Palo Alto Inc

Original Assignee

Individual

Priority date

2005-05-19

Filing date

2006-05-19

Publication date

2006-11-23

2006-05-19 Application filed by Individual filed Critical Individual

2006-11-23 Publication of CA2609117A1 publication Critical patent/CA2609117A1/en

Status Abandoned legal-status Critical Current

Links

239000003379 purinergic P1 receptor agonist Substances 0.000 title claims abstract description 15
101150007969 ADORA1 gene Proteins 0.000 title claims abstract 3
150000001875 compounds Chemical class 0.000 claims abstract description 180
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
201000010099 disease Diseases 0.000 claims abstract description 15
230000036961 partial effect Effects 0.000 claims abstract description 11
206010003662 Atrial flutter Diseases 0.000 claims abstract description 5
208000010125 myocardial infarction Diseases 0.000 claims abstract description 3
-1 1- {9-[(4S,3R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-(cyclopentylamino)purin-2-yl } pyrazol-4-yl Chemical group 0.000 claims description 110
125000000217 alkyl group Chemical group 0.000 claims description 60
125000001072 heteroaryl group Chemical group 0.000 claims description 57
125000004258 purin-2-yl group Chemical group [H]N1C2=NC(*)=NC([H])=C2N([H])C1([H])[H] 0.000 claims description 55
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
238000000034 method Methods 0.000 claims description 49
239000001257 hydrogen Substances 0.000 claims description 35
229910052739 hydrogen Inorganic materials 0.000 claims description 35
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 31
229910006069 SO3H Inorganic materials 0.000 claims description 30
125000000623 heterocyclic group Chemical group 0.000 claims description 30
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
125000000547 substituted alkyl group Chemical group 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
125000003342 alkenyl group Chemical group 0.000 claims description 20
125000003107 substituted aryl group Chemical group 0.000 claims description 20
125000000304 alkynyl group Chemical group 0.000 claims description 18
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 18
150000002431 hydrogen Chemical group 0.000 claims description 17
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 13
150000003857 carboxamides Chemical class 0.000 claims description 12
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 12
JLJZTCJMQJJETK-XAUNWSGPSA-N ethyl 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 JLJZTCJMQJJETK-XAUNWSGPSA-N 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
125000003710 aryl alkyl group Chemical group 0.000 claims description 7
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 6
241000124008 Mammalia Species 0.000 claims description 6
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
206010003658 Atrial Fibrillation Diseases 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
KUOUOSPYKPTVLS-AZCJMIGDSA-N (2r,5r)-2-[2-[4-(aminomethyl)-1h-pyrazol-5-yl]-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound NCC1=CNN=C1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3C(C(O)[C@@H](CO)O3)O)C2=N1 KUOUOSPYKPTVLS-AZCJMIGDSA-N 0.000 claims description 4
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 4
UFDQVJFJDZEQQW-XWHOZGLOSA-N 1-[6-(cyclopentylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxamide Chemical compound C1=C(C(=O)N)C=NN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 UFDQVJFJDZEQQW-XWHOZGLOSA-N 0.000 claims description 4
KQNIKZQXSHVQCH-IKYDMHQPSA-N 1-[6-(cyclopentylamino)-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(NC3CCCC3)=C2N=C1 KQNIKZQXSHVQCH-IKYDMHQPSA-N 0.000 claims description 4
101100516563 Caenorhabditis elegans nhr-6 gene Proteins 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
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
IPODEOBXIPGCDX-XNNBUEOLSA-N (2s,3r,4s,5r)-3,4-dihydroxy-5-[2-[4-(4-methylphenyl)-1h-pyrazol-5-yl]-6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolane-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CNN=C1C1=NC(N[C@H]2COCC2)=C(N=CN2[C@H]3[C@H]([C@@H](O)[C@H](O3)C(O)=O)O)C2=N1 IPODEOBXIPGCDX-XNNBUEOLSA-N 0.000 claims description 3
BOAXJLCXDJALKR-PSBUXNCMSA-N (3r,4s,5r)-2-[2-(4-butyl-3,5-dimethylpyrazol-1-yl)-6-(cyclopentylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound CC1=C(CCCC)C(C)=NN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 BOAXJLCXDJALKR-PSBUXNCMSA-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
UTODEXFTTYUYGE-BEBASYGKSA-N (3r,4s,5r)-2-[6-(cyclopentylamino)-2-(3,5-dimethyl-4-propylpyrazol-1-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound CC1=C(CCC)C(C)=NN1C1=NC(NC2CCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 UTODEXFTTYUYGE-BEBASYGKSA-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
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
BNBLYBZRECFIPT-VGKBRBPRSA-N 1-[6-(benzylamino)-9-[(2r,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(NCC=2C=CC=CC=2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 BNBLYBZRECFIPT-VGKBRBPRSA-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
FKAMQTIHIKDMHS-PDWWLECJSA-N 1-[6-(cyclohexylamino)-9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxamide Chemical compound C1=C(C(=O)N)C=NN1C1=NC(NC2CCCCC2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 FKAMQTIHIKDMHS-PDWWLECJSA-N 0.000 claims description 3
AZAHRMATHOITLE-PZGKNFOESA-N 1-[6-(cyclohexylamino)-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(NC3CCCCC3)=C2N=C1 AZAHRMATHOITLE-PZGKNFOESA-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
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 3
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 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
FLGLKNUAMWXUIF-UHFFFAOYSA-N 2-(hydroxymethyl)-5-[2-[4-(4-methylphenyl)-1h-pyrazol-5-yl]-6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C1=CC(C)=CC=C1C1=CNN=C1C1=NC(NC2COCC2)=C(N=CN2C3C(C(O)C(CO)O3)O)C2=N1 FLGLKNUAMWXUIF-UHFFFAOYSA-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
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
206010019280 Heart failures Diseases 0.000 claims description 3
BYRJMWDDEZQHPO-QMRXYIOLSA-N N-(2-chlorophenyl)sulfonyl-1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-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=CC=3)Cl)=NC(NC3CCCC3)=C2N=C1 BYRJMWDDEZQHPO-QMRXYIOLSA-N 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
150000002148 esters Chemical class 0.000 claims description 3
235000020824 obesity Nutrition 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
WAKSQUVSQMANBK-YHOVATNRSA-N (2S,3R,4S,5R)-N-ethyl-3,4-dihydroxy-5-[2-[4-(4-methylphenyl)-1H-pyrazol-5-yl]-6-[[(3R)-oxolan-3-yl]amino]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=CC(C)=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 WAKSQUVSQMANBK-YHOVATNRSA-N 0.000 claims description 2
ZPDFZGJJWCAMHJ-ZNKWUMMHSA-N (3r,4s,5r)-2-[6-(3-bicyclo[2.2.1]heptanylamino)-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(NC3C4CCC(C4)C3)=C2N=C1 ZPDFZGJJWCAMHJ-ZNKWUMMHSA-N 0.000 claims description 2
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 2
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 2
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 2
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 2
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 2
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 2
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 2
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 2
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 2
UHIBFBGPRDLYDA-HAXDFEGKSA-N 3-[1-[6-(cyclopentylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]-n-methylpropanamide Chemical compound C1=C(CCC(=O)NC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 UHIBFBGPRDLYDA-HAXDFEGKSA-N 0.000 claims description 2
NICOYTPMLIMSPU-MVMYICEXSA-N 4-[[9-[(3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-(4-ethoxycarbonyl-1h-pyrazol-5-yl)purin-6-yl]amino]benzenesulfonic acid Chemical compound CCOC(=O)C1=CNN=C1C1=NC(NC=2C=CC(=CC=2)S(O)(=O)=O)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 NICOYTPMLIMSPU-MVMYICEXSA-N 0.000 claims description 2
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 2
206010002388 Angina unstable Diseases 0.000 claims description 2
208000001145 Metabolic Syndrome Diseases 0.000 claims description 2
QIZCFVIQFAPLDO-BNCYDMKUSA-N N-[(4-chlorophenyl)methyl]-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-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(Cl)=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 QIZCFVIQFAPLDO-BNCYDMKUSA-N 0.000 claims description 2
BVMZPMIJDSIZDM-BNCYDMKUSA-N N-benzyl-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-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=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 BVMZPMIJDSIZDM-BNCYDMKUSA-N 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
CLBNFWHXUDRHMC-OZVUOMPESA-N ethyl 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-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1C1=NC(NC2C3CCC(C3)C2)=C(N=CN2C3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 CLBNFWHXUDRHMC-OZVUOMPESA-N 0.000 claims description 2
DHZQKCYALVWGJR-QTQZEZTPSA-N ethyl 1-[6-(benzylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)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 DHZQKCYALVWGJR-QTQZEZTPSA-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
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
XDBWIAZCKUAKBT-HLHDFFQDSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[2-[4-[hydroxy(phenyl)methyl]-1h-pyrazol-5-yl]-6-[[(3r)-oxolan-3-yl]amino]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(O)C=3C=CC=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 XDBWIAZCKUAKBT-HLHDFFQDSA-N 0.000 claims 1
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 1
COHZYPMNXBGCJQ-CHXMUBILSA-N 1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-(4-methylphenyl)sulfonylpyrazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)C1=CN(C=2N=C3N([C@H]4C(C(O)[C@@H](CO)O4)O)C=NC3=C(NC3CCCC3)N=2)N=C1 COHZYPMNXBGCJQ-CHXMUBILSA-N 0.000 claims 1
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 1
JTZQPUOCFRKMSG-DUWSABPASA-N 1-[9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(1r,2r)-2-hydroxycyclopentyl]amino]purin-2-yl]pyrazole-4-carboxamide Chemical compound C1=C(C(=O)N)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 JTZQPUOCFRKMSG-DUWSABPASA-N 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
ILEPOPLBCRODAE-JDYLIUQESA-N N-(benzenesulfonyl)-1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-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=CC=3)=NC(NC3CCCC3)=C2N=C1 ILEPOPLBCRODAE-JDYLIUQESA-N 0.000 claims 1
MLKBBXUWKQIPIC-CHXMUBILSA-N N-benzylsulfonyl-1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NS(=O)(=O)CC=3C=CC=CC=3)=NC(NC3CCCC3)=C2N=C1 MLKBBXUWKQIPIC-CHXMUBILSA-N 0.000 claims 1
GOISBEJALOZVSK-DXZWLVDASA-N ethyl (e)-3-[1-[6-(cyclopentylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]prop-2-enoate Chemical compound C1=C(/C=C/C(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 GOISBEJALOZVSK-DXZWLVDASA-N 0.000 claims 1
GUBGGPZBPUTRNH-CIVUBGFFSA-N ethyl 3-[1-[6-(cyclopentylamino)-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]propanoate Chemical compound C1=C(CCC(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 GUBGGPZBPUTRNH-CIVUBGFFSA-N 0.000 claims 1
LXOIOPAHNIBTSC-XXXKQHFZSA-N methyl 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]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CNC(=O)C1=CN(C=2N=C3N([C@H]4[C@@H]([C@H](O)[C@@H](CO)O4)O)C=NC3=C(N[C@H]3COCC3)N=2)N=C1 LXOIOPAHNIBTSC-XXXKQHFZSA-N 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
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
125000001424 substituent group Chemical group 0.000 description 70
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
239000000203 mixture Substances 0.000 description 62
238000002360 preparation method Methods 0.000 description 59
239000000243 solution Substances 0.000 description 56
125000003118 aryl group Chemical group 0.000 description 43
238000006243 chemical reaction Methods 0.000 description 41
239000002904 solvent Substances 0.000 description 37
239000000047 product Substances 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
239000004480 active ingredient Substances 0.000 description 29
125000004093 cyano group Chemical group *C#N 0.000 description 28
125000002887 hydroxy group Chemical group [H]O* 0.000 description 26
125000003545 alkoxy group Chemical group 0.000 description 25
229910052736 halogen Inorganic materials 0.000 description 25
150000002367 halogens Chemical class 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
150000001412 amines Chemical class 0.000 description 24
125000004181 carboxyalkyl group Chemical group 0.000 description 22
239000004615 ingredient Substances 0.000 description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
239000003826 tablet Substances 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
230000004048 modification Effects 0.000 description 20
238000012986 modification Methods 0.000 description 20
229910001868 water Inorganic materials 0.000 description 20
125000000753 cycloalkyl group Chemical group 0.000 description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
125000004432 carbon atom Chemical group C* 0.000 description 16
125000000392 cycloalkenyl group Chemical group 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 15
125000003226 pyrazolyl group Chemical group 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
239000011541 reaction mixture Substances 0.000 description 14
108050000203 Adenosine receptors Proteins 0.000 description 13
102000009346 Adenosine receptors Human genes 0.000 description 13
125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 description 13
238000004809 thin layer chromatography Methods 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
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
239000000843 powder Substances 0.000 description 11
239000000725 suspension Substances 0.000 description 11
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 10
230000004224 protection Effects 0.000 description 10
238000010992 reflux Methods 0.000 description 10
235000000346 sugar Nutrition 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
229930194542 Keto Natural products 0.000 description 9
239000002253 acid Substances 0.000 description 9
125000002252 acyl group Chemical group 0.000 description 9
125000004442 acylamino group Chemical group 0.000 description 9
125000004423 acyloxy group Chemical group 0.000 description 9
239000000556 agonist Substances 0.000 description 9
125000002947 alkylene 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
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([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
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 8
125000004429 atom Chemical group 0.000 description 8
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 8
230000027455 binding Effects 0.000 description 8
238000001914 filtration Methods 0.000 description 8
125000004470 heterocyclooxy group Chemical group 0.000 description 8
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 8
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
229920002472 Starch Polymers 0.000 description 7
239000002585 base Substances 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 7
238000010511 deprotection reaction Methods 0.000 description 7
238000009472 formulation Methods 0.000 description 7
125000005368 heteroarylthio group Chemical group 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
239000007787 solid Substances 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
238000003756 stirring Methods 0.000 description 7
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 7
150000003573 thiols Chemical class 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
239000002126 C01EB10 - Adenosine Substances 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
229960005305 adenosine Drugs 0.000 description 6
125000000033 alkoxyamino group Chemical group 0.000 description 6
125000004414 alkyl thio group Chemical group 0.000 description 6
125000006598 aminocarbonylamino group Chemical group 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
238000003556 assay Methods 0.000 description 6
239000002775 capsule Substances 0.000 description 6
229940093499 ethyl acetate Drugs 0.000 description 6
235000019439 ethyl acetate Nutrition 0.000 description 6
125000004468 heterocyclylthio group Chemical group 0.000 description 6
239000007788 liquid Substances 0.000 description 6
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
239000008107 starch Substances 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
229920000168 Microcrystalline cellulose Polymers 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
150000002430 hydrocarbons Chemical group 0.000 description 5
239000000463 material Substances 0.000 description 5
235000019813 microcrystalline cellulose Nutrition 0.000 description 5
239000008108 microcrystalline cellulose Substances 0.000 description 5
229940016286 microcrystalline cellulose Drugs 0.000 description 5
208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
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
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000012981 Hank's balanced salt solution Substances 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical class O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
239000000872 buffer Substances 0.000 description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
125000004185 ester group Chemical class 0.000 description 4
235000021588 free fatty acids Nutrition 0.000 description 4
238000011534 incubation Methods 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012528 membrane Substances 0.000 description 4
150000005830 nonesterified fatty acids Chemical class 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000006187 pill Substances 0.000 description 4
239000003586 protic polar solvent Substances 0.000 description 4
229930195734 saturated hydrocarbon Natural products 0.000 description 4
239000002002 slurry Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
125000005017 substituted alkenyl group Chemical group 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
239000000454 talc Substances 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
235000012222 talc Nutrition 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
230000024883 vasodilation Effects 0.000 description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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 3
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
239000005711 Benzoic acid Substances 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
229930195725 Mannitol Natural products 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
208000003734 Supraventricular Tachycardia Diseases 0.000 description 3
230000004913 activation Effects 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
LDDQLRUQCUTJBB-UHFFFAOYSA-N ammonium fluoride Chemical compound [NH4+].[F-] LDDQLRUQCUTJBB-UHFFFAOYSA-N 0.000 description 3
230000008901 benefit Effects 0.000 description 3
235000010233 benzoic acid Nutrition 0.000 description 3
XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
239000012267 brine Substances 0.000 description 3
235000015165 citric acid Nutrition 0.000 description 3
238000000576 coating method Methods 0.000 description 3
NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 3
230000007423 decrease Effects 0.000 description 3
230000001419 dependent effect Effects 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000012467 final product Substances 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
125000004475 heteroaralkyl group Chemical group 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000594 mannitol Substances 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
239000002609 medium Substances 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
239000001267 polyvinylpyrrolidone Substances 0.000 description 3
229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
230000004044 response Effects 0.000 description 3
230000033764 rhythmic process Effects 0.000 description 3
238000002821 scintillation proximity assay Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
VJVZPTPOYCJFNI-UHFFFAOYSA-M (2-ethoxy-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC(=O)OCC)C1=CC=CC=C1 VJVZPTPOYCJFNI-UHFFFAOYSA-M 0.000 description 2
FLGLKNUAMWXUIF-BIXJFMBOSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[2-[4-(4-methylphenyl)-1h-pyrazol-5-yl]-6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C1=CC(C)=CC=C1C1=CNN=C1C1=NC(NC2COCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 FLGLKNUAMWXUIF-BIXJFMBOSA-N 0.000 description 2
XSMYYYQVWPZWIZ-RTOGKPCTSA-N (2r,3s,4r,5r)-2-[2-chloro-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(Cl)=NC(NC3CCCC3)=C2N=C1 XSMYYYQVWPZWIZ-RTOGKPCTSA-N 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
VYXNKQZQUSYNEI-UHFFFAOYSA-N (4-methylphenyl)sulfonylformamide Chemical compound CC1=CC=C(S(=O)(=O)C(N)=O)C=C1 VYXNKQZQUSYNEI-UHFFFAOYSA-N 0.000 description 2
XJJALRRHDSFIHH-JHZZHVAFSA-N 1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(cyclopentylamino)purin-2-yl]pyrazole-4-carbaldehyde Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC(N3N=CC(C=O)=C3)=NC(NC3CCCC3)=C2N=C1 XJJALRRHDSFIHH-JHZZHVAFSA-N 0.000 description 2
CKXSZXGDJGCGEB-WHJYSPQCSA-N 1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(oxolan-3-ylamino)purin-2-yl]pyrazole-4-carbaldehyde Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC(N3N=CC(C=O)=C3)=NC(NC3COCC3)=C2N=C1 CKXSZXGDJGCGEB-WHJYSPQCSA-N 0.000 description 2
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 description 2
IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 2
BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
101150046889 ADORA3 gene Proteins 0.000 description 2
NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
102000055025 Adenosine deaminases Human genes 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
239000004255 Butylated hydroxyanisole Substances 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000017667 Chronic Disease Diseases 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
108010001483 Glycogen Synthase Proteins 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
102000018697 Membrane Proteins Human genes 0.000 description 2
108010052285 Membrane Proteins Proteins 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical group CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
206010047141 Vasodilatation Diseases 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
210000001789 adipocyte Anatomy 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
230000003243 anti-lipolytic effect Effects 0.000 description 2
239000003429 antifungal agent Substances 0.000 description 2
229940121375 antifungal agent Drugs 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
JEPPYVOSGKWVSJ-UHFFFAOYSA-N bicyclo[2.2.1]heptan-3-amine Chemical compound C1CC2C(N)CC1C2 JEPPYVOSGKWVSJ-UHFFFAOYSA-N 0.000 description 2
229940098773 bovine serum albumin Drugs 0.000 description 2
235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
229940043253 butylated hydroxyanisole Drugs 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
150000007942 carboxylates Chemical class 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
150000003943 catecholamines Chemical class 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
229940075614 colloidal silicon dioxide Drugs 0.000 description 2
238000013270 controlled release Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
229920001577 copolymer Polymers 0.000 description 2
235000005687 corn oil Nutrition 0.000 description 2
239000002285 corn oil Substances 0.000 description 2
125000006165 cyclic alkyl group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
239000008121 dextrose Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
229960004132 diethyl ether Drugs 0.000 description 2
229910001873 dinitrogen Inorganic materials 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
239000002612 dispersion medium Substances 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
239000012055 enteric layer Substances 0.000 description 2
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
HMFLBGNCDZYITR-UHFFFAOYSA-N ethyl 2-formyl-3-oxopropanoate Chemical compound CCOC(=O)C(C=O)C=O HMFLBGNCDZYITR-UHFFFAOYSA-N 0.000 description 2
GUBGGPZBPUTRNH-SXTKRDDTSA-N ethyl 3-[1-[6-(cyclopentylamino)-9-[(2r,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]propanoate Chemical compound C1=C(CCC(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@H]([C@@H](O)[C@H](CO)O3)O)C2=N1 GUBGGPZBPUTRNH-SXTKRDDTSA-N 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000000945 filler Substances 0.000 description 2
235000019634 flavors Nutrition 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
239000007789 gas Substances 0.000 description 2
230000004190 glucose uptake Effects 0.000 description 2
KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
210000002837 heart atrium Anatomy 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
210000003630 histaminocyte Anatomy 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
201000001421 hyperglycemia Diseases 0.000 description 2
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000009871 nonspecific binding Effects 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
MIPHRQMEIYLZFZ-UHFFFAOYSA-N oxolan-3-amine Chemical compound NC1CCOC1 MIPHRQMEIYLZFZ-UHFFFAOYSA-N 0.000 description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
239000002245 particle Substances 0.000 description 2
239000008177 pharmaceutical agent Substances 0.000 description 2
229940124531 pharmaceutical excipient Drugs 0.000 description 2
RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000008569 process Effects 0.000 description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000000159 protein binding assay Methods 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
238000000746 purification Methods 0.000 description 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000000700 radioactive tracer Substances 0.000 description 2
230000000717 retained effect Effects 0.000 description 2
150000008223 ribosides Chemical class 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
239000008247 solid mixture Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
125000005156 substituted alkylene group Chemical group 0.000 description 2
125000004426 substituted alkynyl group Chemical group 0.000 description 2
229940124530 sulfonamide Drugs 0.000 description 2
150000003456 sulfonamides Chemical class 0.000 description 2
150000003457 sulfones Chemical class 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
239000000829 suppository Substances 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
230000002889 sympathetic effect Effects 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
230000009885 systemic effect Effects 0.000 description 2
239000007916 tablet composition Substances 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
125000005500 uronium group Chemical group 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
230000002861 ventricular Effects 0.000 description 2
229920002554 vinyl polymer Polymers 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000000230 xanthan gum Substances 0.000 description 2
235000010493 xanthan gum Nutrition 0.000 description 2
229920001285 xanthan gum Polymers 0.000 description 2
229940082509 xanthan gum Drugs 0.000 description 2
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
ZZKOIZPFVKEUFP-PQKOYNMZSA-N (2R,3R,4S)-2-[6-(cyclopentylamino)-2-hydrazinylpurin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N(N)C1=NC(=C2N=CN(C2=N1)[C@@H]1OC([C@H]([C@H]1O)O)CO)NC1CCCC1 ZZKOIZPFVKEUFP-PQKOYNMZSA-N 0.000 description 1
HJXWZGVMHDPCRS-UUOKFMHZSA-N (2r,3r,4s,5r)-2-(2,6-dichloropurin-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(Cl)=NC(Cl)=C2N=C1 HJXWZGVMHDPCRS-UUOKFMHZSA-N 0.000 description 1
XSMYYYQVWPZWIZ-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-chloro-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(Cl)=NC(NC3CCCC3)=C2N=C1 XSMYYYQVWPZWIZ-IDTAVKCVSA-N 0.000 description 1
OAFLHBZKXOHFIF-CKRXIKOQSA-N (2r,3s,4r,5r)-2-(6-anilino-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=1NC1=CC=CC=C1 OAFLHBZKXOHFIF-CKRXIKOQSA-N 0.000 description 1
XDBWIAZCKUAKBT-FBRPOMKHSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[2-[4-[hydroxy(phenyl)methyl]-1h-pyrazol-5-yl]-6-(oxolan-3-ylamino)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(O)C=3C=CC=CC=3)=NC(NC3COCC3)=C2N=C1 XDBWIAZCKUAKBT-FBRPOMKHSA-N 0.000 description 1
LFOKMAPKIRXQRJ-NNXMZFEESA-N (2r,3s,4r,5r)-2-[2-chloro-6-(cyclopropylamino)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(Cl)=NC(NC3CC3)=C2N=C1 LFOKMAPKIRXQRJ-NNXMZFEESA-N 0.000 description 1
OGCPKCRVEVDGIB-ZRPKBAQZSA-N (2r,3s,4r,5r)-2-[2-chloro-6-(cyclopropylmethylamino)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(Cl)=NC(NCC3CC3)=C2N=C1 OGCPKCRVEVDGIB-ZRPKBAQZSA-N 0.000 description 1
XEAJNSCYKKKRRS-BZWDOIOGSA-N (2r,3s,4r,5r)-2-[2-chloro-6-(oxolan-3-ylamino)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(Cl)=NC(NC3COCC3)=C2N=C1 XEAJNSCYKKKRRS-BZWDOIOGSA-N 0.000 description 1
JFIPRWYUKUMKKU-MYMXGEOPSA-N (2r,3s,4r,5r)-2-[2-chloro-6-(pyridin-2-ylamino)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(Cl)=NC(NC=3N=CC=CC=3)=C2N=C1 JFIPRWYUKUMKKU-MYMXGEOPSA-N 0.000 description 1
XDUYMEMCGJRFPJ-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[2-chloro-6-[(2-fluorophenyl)methylamino]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(Cl)=NC(NCC=3C(=CC=CC=3)F)=C2N=C1 XDUYMEMCGJRFPJ-QOFRNUMZSA-N 0.000 description 1
ALMCMXYPOUDHGX-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[2-chloro-6-[(4-chlorophenyl)methylamino]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(Cl)=NC(NCC=3C=CC(Cl)=CC=3)=C2N=C1 ALMCMXYPOUDHGX-QOFRNUMZSA-N 0.000 description 1
OEZDAHUIVSOFSK-ZRPKBAQZSA-N (2r,3s,4r,5r)-2-[2-hydrazinyl-6-(1h-pyrrol-3-ylamino)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(NN)=NC=1NC=1C=CNC=1 OEZDAHUIVSOFSK-ZRPKBAQZSA-N 0.000 description 1
GWFVMKJTCCFJIJ-BZWDOIOGSA-N (2r,3s,4r,5r)-2-[2-hydrazinyl-6-(oxolan-3-ylamino)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(NN)=NC=1NC1CCOC1 GWFVMKJTCCFJIJ-BZWDOIOGSA-N 0.000 description 1
AXCCRLWIRDCYGA-MYMXGEOPSA-N (2r,3s,4r,5r)-2-[2-hydrazinyl-6-(pyridin-2-ylamino)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(NN)=NC=1NC1=CC=CC=N1 AXCCRLWIRDCYGA-MYMXGEOPSA-N 0.000 description 1
AEOCPQUDPJKEQV-BGGRTOIGSA-N (2r,3s,4r,5r)-2-[6-(3-bicyclo[2.2.1]heptanylamino)-2-chloropurin-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(Cl)=NC(NC3C4CCC(C4)C3)=C2N=C1 AEOCPQUDPJKEQV-BGGRTOIGSA-N 0.000 description 1
HRVFIAYJEMWYTP-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[6-(benzylamino)-2-chloropurin-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(Cl)=NC(NCC=3C=CC=CC=3)=C2N=C1 HRVFIAYJEMWYTP-QOFRNUMZSA-N 0.000 description 1
PHFJSUHHZVSICD-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[6-(benzylamino)-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=1NCC1=CC=CC=C1 PHFJSUHHZVSICD-QOFRNUMZSA-N 0.000 description 1
AZUGBQSWBHGBGT-NNXMZFEESA-N (2r,3s,4r,5r)-2-[6-(cyclopropylamino)-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=1NC1CC1 AZUGBQSWBHGBGT-NNXMZFEESA-N 0.000 description 1
NEBVWKYOCHLYAR-ZRPKBAQZSA-N (2r,3s,4r,5r)-2-[6-(cyclopropylmethylamino)-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=1NCC1CC1 NEBVWKYOCHLYAR-ZRPKBAQZSA-N 0.000 description 1
OBXKFIVJQYNONF-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[6-[(2-fluorophenyl)methylamino]-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=1NCC1=CC=CC=C1F OBXKFIVJQYNONF-QOFRNUMZSA-N 0.000 description 1
VGTHLDAKNJIPLO-QOFRNUMZSA-N (2r,3s,4r,5r)-2-[6-[(4-chlorophenyl)methylamino]-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=1NCC1=CC=C(Cl)C=C1 VGTHLDAKNJIPLO-QOFRNUMZSA-N 0.000 description 1
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 description 1
UEWSREHCRRIXLL-MCSCLANISA-N (2s,3r,4s,5r)-3,4-dihydroxy-5-[6-[[(3r)-oxolan-3-yl]amino]-2-(4-pyridin-4-yl-1h-pyrazol-5-yl)purin-9-yl]oxolane-2-carboxylic acid Chemical compound O1[C@H](C(O)=O)[C@H](O)[C@H](O)[C@@H]1N1C2=NC(C=3C(=CNN=3)C=3C=CN=CC=3)=NC(N[C@H]3COCC3)=C2N=C1 UEWSREHCRRIXLL-MCSCLANISA-N 0.000 description 1
JSPBFRVYJJCXBZ-RMZPNZJBSA-N (3ar,4r,6s,6ar)-2,2-dimethyl-4-[2-[4-(4-methylphenyl)-1h-pyrazol-5-yl]-6-(oxolan-3-ylamino)purin-9-yl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid Chemical compound C1=CC(C)=CC=C1C1=CNN=C1C1=NC(NC2COCC2)=C(N=CN2[C@H]3[C@@H]4OC(C)(C)O[C@H]4[C@H](O3)C(O)=O)C2=N1 JSPBFRVYJJCXBZ-RMZPNZJBSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
VKCIKVLSJLSCPP-AGTGTDPFSA-N 1-(benzenesulfonyl)-n-[1-[6-(cyclopentylamino)-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]formamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(NC(=O)S(=O)(=O)C=4C=CC=CC=4)=C3)=NC(NC3CCCC3)=C2N=C1 VKCIKVLSJLSCPP-AGTGTDPFSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
GZBRVFFTXXCAHH-UHFFFAOYSA-N 2-[2-chloro-6-(methylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(NC)=NC(Cl)=NC=2N1C1OC(CO)C(O)C1O GZBRVFFTXXCAHH-UHFFFAOYSA-N 0.000 description 1
MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical class CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
NICOYTPMLIMSPU-TXRZWFJJSA-N 4-[[9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-(4-ethoxycarbonyl-1h-pyrazol-5-yl)purin-6-yl]amino]benzenesulfonic acid Chemical compound CCOC(=O)C1=CNN=C1C1=NC(NC=2C=CC(=CC=2)S(O)(=O)=O)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C2=N1 NICOYTPMLIMSPU-TXRZWFJJSA-N 0.000 description 1
LFLSATHZMYYIAQ-UHFFFAOYSA-N 4-flourobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(F)C=C1 LFLSATHZMYYIAQ-UHFFFAOYSA-N 0.000 description 1
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
GDRVFDDBLLKWRI-UHFFFAOYSA-N 4H-quinolizine Chemical compound C1=CC=CN2CC=CC=C21 GDRVFDDBLLKWRI-UHFFFAOYSA-N 0.000 description 1
DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
235000006491 Acacia senegal Nutrition 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
102000007470 Adenosine A2B Receptor Human genes 0.000 description 1
108010085273 Adenosine A2B receptor Proteins 0.000 description 1
229940122614 Adenosine receptor agonist Drugs 0.000 description 1
101150051188 Adora2a gene Proteins 0.000 description 1
101150078577 Adora2b gene Proteins 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
241000699800 Cricetinae Species 0.000 description 1
IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
229920003148 Eudragit® E polymer Polymers 0.000 description 1
102000020897 Formins Human genes 0.000 description 1
108091022623 Formins Proteins 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
206010022489 Insulin Resistance Diseases 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
229910010084 LiAlH4 Inorganic materials 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
241001314546 Microtis <orchid> Species 0.000 description 1
SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
235000009421 Myristica fragrans Nutrition 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
PNMQWDMJMYWGGD-JDYLIUQESA-N N-(3-chlorophenyl)sulfonyl-1-[6-(cyclopentylamino)-9-[(2R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carboxamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NS(=O)(=O)C=3C=C(Cl)C=CC=3)=NC(NC3CCCC3)=C2N=C1 PNMQWDMJMYWGGD-JDYLIUQESA-N 0.000 description 1
IIBOGKHTXBPGEI-UHFFFAOYSA-N N-benzylformamide Chemical compound O=CNCC1=CC=CC=C1 IIBOGKHTXBPGEI-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
239000004264 Petrolatum Substances 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920002873 Polyethylenimine Polymers 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
206010042434 Sudden death Diseases 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
239000007984 Tris EDTA buffer Substances 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
ADYSMCWHQQVRKF-XDVJFCRTSA-N [1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]pyrazol-4-yl] N-[(4-chlorophenyl)methyl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(OC(=O)NCC=4C=CC(Cl)=CC=4)=C3)=NC(N[C@H]3COCC3)=C2N=C1 ADYSMCWHQQVRKF-XDVJFCRTSA-N 0.000 description 1
LCYGPTMXTCDOFS-XDVJFCRTSA-N [1-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]pyrazol-4-yl] N-[(4-fluorophenyl)methyl]carbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(OC(=O)NCC=4C=CC(F)=CC=4)=C3)=NC(N[C@H]3COCC3)=C2N=C1 LCYGPTMXTCDOFS-XDVJFCRTSA-N 0.000 description 1
CXGNCSFGUOEDDT-JXOURFHASA-N [1-[9-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-[[(3R)-oxolan-3-yl]amino]purin-2-yl]pyrazol-4-yl] N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]carbamate Chemical compound O[C@H]1[C@@H](O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(OC(=O)NCC=4C=C(C=C(F)C=4)C(F)(F)F)=C3)=NC(N[C@H]3COCC3)=C2N=C1 CXGNCSFGUOEDDT-JXOURFHASA-N 0.000 description 1
LUTUZMPYZCYKNU-VVMMKWPVSA-N [1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(oxolan-3-ylamino)purin-2-yl]pyrazol-4-yl]-phenylmethanol Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC(N3N=CC(=C3)C(O)C=3C=CC=CC=3)=NC(NC3COCC3)=C2N=C1 LUTUZMPYZCYKNU-VVMMKWPVSA-N 0.000 description 1
TUJIQNHJAUNNML-WHJYSPQCSA-N [1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(oxolan-3-ylamino)purin-2-yl]pyrazol-4-yl]methanol Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC(N3N=CC(CO)=C3)=NC(NC3COCC3)=C2N=C1 TUJIQNHJAUNNML-WHJYSPQCSA-N 0.000 description 1
BQOWUDKEXDCGQS-UHFFFAOYSA-N [CH]1CCCC1 Chemical group [CH]1CCCC1 BQOWUDKEXDCGQS-UHFFFAOYSA-N 0.000 description 1
ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
239000003070 absorption delaying agent Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
230000036982 action potential Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000013543 active substance Substances 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
230000003919 adipocyte function Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000008485 antagonism Effects 0.000 description 1
125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
230000001773 anti-convulsant effect Effects 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
229960003965 antiepileptics Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229960003121 arginine Drugs 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
238000003149 assay kit Methods 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000001746 atrial effect Effects 0.000 description 1
210000001992 atrioventricular node Anatomy 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
150000003939 benzylamines Chemical class 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
229960003237 betaine Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000013262 cAMP assay Methods 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000000378 calcium silicate Substances 0.000 description 1
229910052918 calcium silicate Inorganic materials 0.000 description 1
229960003340 calcium silicate Drugs 0.000 description 1
235000012241 calcium silicate Nutrition 0.000 description 1
OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
230000025938 carbohydrate utilization Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000009084 cardiovascular function Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000020411 cell activation Effects 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000006037 cell lysis Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000010267 cellular communication Effects 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000012875 competitive assay Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
238000010276 construction Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229940095074 cyclic amp Drugs 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
238000000586 desensitisation Methods 0.000 description 1
238000003795 desorption Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
125000005266 diarylamine group Chemical group 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
XJWSAJYUBXQQDR-UHFFFAOYSA-M dodecyltrimethylammonium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)C XJWSAJYUBXQQDR-UHFFFAOYSA-M 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
238000001035 drying Methods 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000012636 effector Substances 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
239000002662 enteric coated tablet Substances 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
MKKONPCYMNIYLR-FNLSOWRSSA-N ethyl (E)-3-[1-[9-[(2R,3S,4S,5S)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(cyclopentylamino)purin-2-yl]pyrazol-4-yl]prop-2-enoate Chemical compound C1=C(/C=C/C(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@H]([C@@H](O[Si](C)(C)C(C)(C)C)[C@H](CO[Si](C)(C)C(C)(C)C)O3)O[Si](C)(C)C(C)(C)C)C2=N1 MKKONPCYMNIYLR-FNLSOWRSSA-N 0.000 description 1
GOISBEJALOZVSK-BNRFHEQTSA-N ethyl (e)-3-[1-[6-(cyclopentylamino)-9-[(2r,3s,4r,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]prop-2-enoate Chemical compound C1=C(/C=C/C(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@H]([C@@H](O)[C@H](CO)O3)O)C2=N1 GOISBEJALOZVSK-BNRFHEQTSA-N 0.000 description 1
FSEUBHQAEIMCRH-UTBAFCPYSA-N ethyl 1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(cyclopentylamino)purin-2-yl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1C1=NC(NC2CCCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O3)O[Si](C)(C)C(C)(C)C)C2=N1 FSEUBHQAEIMCRH-UTBAFCPYSA-N 0.000 description 1
AXLZPJCQEMVYRN-KRIJDYEQSA-N ethyl 1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(oxolan-3-ylamino)purin-2-yl]pyrazole-4-carboxylate Chemical compound C1=C(C(=O)OCC)C=NN1C1=NC(NC2COCC2)=C(N=CN2[C@H]3[C@@H]([C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O3)O[Si](C)(C)C(C)(C)C)C2=N1 AXLZPJCQEMVYRN-KRIJDYEQSA-N 0.000 description 1
VGAFAMCHCIRBRS-AJKMGBEJSA-N ethyl 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-carboxylate Chemical compound C1=C(C(=O)OCC)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 VGAFAMCHCIRBRS-AJKMGBEJSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
229940014259 gelatin Drugs 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
229960002442 glucosamine Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
210000002064 heart cell Anatomy 0.000 description 1
125000005241 heteroarylamino group Chemical group 0.000 description 1
125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
229960002885 histidine Drugs 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
239000011539 homogenization buffer Substances 0.000 description 1
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
150000002429 hydrazines Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000003871 intestinal function Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229960003646 lysine Drugs 0.000 description 1
239000001115 mace Substances 0.000 description 1
OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical group [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
208000030159 metabolic disease Diseases 0.000 description 1
229940117841 methacrylic acid copolymer Drugs 0.000 description 1
229920003145 methacrylic acid copolymer Polymers 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
OUPRGRNLSABFMK-RZBJAIAPSA-N methyl 2-[[1-[6-(cyclopentylamino)-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazole-4-carbonyl]sulfamoyl]benzoate Chemical compound COC(=O)C1=CC=CC=C1S(=O)(=O)NC(=O)C1=CN(C=2N=C3N([C@H]4C(C(O)[C@@H](CO)O4)O)C=NC3=C(NC3CCCC3)N=2)N=C1 OUPRGRNLSABFMK-RZBJAIAPSA-N 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UWFCFCVYDFMVRV-AQOIBLHDSA-N n-(benzenesulfonyl)-1-[9-[(2r,3r,4r,5r)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-6-(cyclopentylamino)purin-2-yl]pyrazole-4-carboxamide Chemical compound CC(C)(C)[Si](C)(C)O[C@@H]1[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@H]1N1C2=NC(N3N=CC(=C3)C(=O)NS(=O)(=O)C=3C=CC=CC=3)=NC(NC3CCCC3)=C2N=C1 UWFCFCVYDFMVRV-AQOIBLHDSA-N 0.000 description 1
NNZDKVHCZXNARE-AGTGTDPFSA-N n-[1-[6-(cyclopentylamino)-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]-1-[4-(trifluoromethyl)phenyl]sulfonylformamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(NC(=O)S(=O)(=O)C=4C=CC(=CC=4)C(F)(F)F)=C3)=NC(NC3CCCC3)=C2N=C1 NNZDKVHCZXNARE-AGTGTDPFSA-N 0.000 description 1
BUHVEVBNCOGPCO-LBQDIGMFSA-N n-[[1-[6-(cyclopentylamino)-9-[(2r,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]pyrazol-4-yl]methyl]-4-fluorobenzenesulfonamide Chemical compound OC1C(O)[C@@H](CO)O[C@H]1N1C2=NC(N3N=CC(CNS(=O)(=O)C=4C=CC(F)=CC=4)=C3)=NC(NC3CCCC3)=C2N=C1 BUHVEVBNCOGPCO-LBQDIGMFSA-N 0.000 description 1
HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
230000004112 neuroprotection Effects 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
230000000661 pacemaking effect Effects 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000004031 partial agonist Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229960003742 phenol Drugs 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
239000008213 purified water Substances 0.000 description 1
230000001696 purinergic effect Effects 0.000 description 1
150000003212 purines Chemical class 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000003346 radioligand binding method Methods 0.000 description 1
102000005912 ran GTP Binding Protein Human genes 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000036279 refractory period Effects 0.000 description 1
230000021014 regulation of cell growth Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
229950005741 rolipram Drugs 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
238000007789 sealing Methods 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
210000002027 skeletal muscle Anatomy 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
239000012058 sterile packaged powder Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
229960002385 streptomycin sulfate Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000000153 supplemental effect Effects 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000009747 swallowing Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical class Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
210000001177 vas deferen Anatomy 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
206010047302 ventricular tachycardia Diseases 0.000 description 1
238000003260 vortexing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1