JP2013533882A5 - - Google Patents
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- JP2013533882A5 JP2013533882A5 JP2013518651A JP2013518651A JP2013533882A5 JP 2013533882 A5 JP2013533882 A5 JP 2013533882A5 JP 2013518651 A JP2013518651 A JP 2013518651A JP 2013518651 A JP2013518651 A JP 2013518651A JP 2013533882 A5 JP2013533882 A5 JP 2013533882A5
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- JP
- Japan
- Prior art keywords
- optionally substituted
- methyl
- trihydropurine
- pyrazol
- dione
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 239000000203 mixture Substances 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 claims description 21
- 229940121359 adenosine receptor antagonist Drugs 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- -1 cyclic xanthine derivative Chemical class 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 10
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000651 prodrug Substances 0.000 claims description 8
- 229940002612 prodrug Drugs 0.000 claims description 8
- 210000001147 pulmonary artery Anatomy 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 229940044551 receptor antagonist Drugs 0.000 claims description 8
- 239000002464 receptor antagonist Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 150000004866 oxadiazoles Chemical class 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 6
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 6
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 4
- 102000008186 Collagen Human genes 0.000 claims description 4
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 4
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 4
- 108090001007 Interleukin-8 Proteins 0.000 claims description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 4
- 208000000924 Right ventricular hypertrophy Diseases 0.000 claims description 4
- 125000000732 arylene group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 229920001436 collagen Polymers 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 4
- 108091007167 extracellular matrix enzymes Proteins 0.000 claims description 4
- 102000036444 extracellular matrix enzymes Human genes 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 4
- 125000005549 heteroarylene group Chemical group 0.000 claims description 4
- 230000004199 lung function Effects 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 230000008719 thickening Effects 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 230000002861 ventricular Effects 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 3
- 230000035488 systolic blood pressure Effects 0.000 claims description 3
- FJOWCRNUYDSBQY-UHFFFAOYSA-N 1,3-dipropyl-8-(1h-pyrazol-4-yl)-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C=1C=NNC=1 FJOWCRNUYDSBQY-UHFFFAOYSA-N 0.000 claims description 2
- RAFXNBDJRQNLBT-UHFFFAOYSA-N 1,3-dipropyl-8-[1-(pyridin-2-ylmethyl)pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=CC=N1 RAFXNBDJRQNLBT-UHFFFAOYSA-N 0.000 claims description 2
- VKTXMHRAIBKAOF-UHFFFAOYSA-N 1,3-dipropyl-8-[1-[2-[3-(trifluoromethyl)phenyl]ethyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CCC1=CC=CC(C(F)(F)F)=C1 VKTXMHRAIBKAOF-UHFFFAOYSA-N 0.000 claims description 2
- NNBVIKCVEVSEMX-UHFFFAOYSA-N 1,3-dipropyl-8-[1-[[3-(2h-tetrazol-5-yl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC(C=1)=CC=CC=1C1=NN=NN1 NNBVIKCVEVSEMX-UHFFFAOYSA-N 0.000 claims description 2
- IDMQLXNSDSLNNR-UHFFFAOYSA-N 1,3-dipropyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 IDMQLXNSDSLNNR-UHFFFAOYSA-N 0.000 claims description 2
- YTNFLFXQFWBCKN-UHFFFAOYSA-N 1,3-dipropyl-8-[1-[[5-[4-(trifluoromethyl)phenyl]-1,2-oxazol-3-yl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC(=NO1)C=C1C1=CC=C(C(F)(F)F)C=C1 YTNFLFXQFWBCKN-UHFFFAOYSA-N 0.000 claims description 2
- GMFXXXZLTVVYHB-UHFFFAOYSA-N 1,3-dipropyl-8-[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=C(C(F)(F)F)N=C1 GMFXXXZLTVVYHB-UHFFFAOYSA-N 0.000 claims description 2
- FOPDIVBIDYTGMD-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-ethyl-8-[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound O=C1N(CC)C=2N=C(C3=CN(CC=4C=NC(=CC=4)C(F)(F)F)N=C3)NC=2C(=O)N1CC1CC1 FOPDIVBIDYTGMD-UHFFFAOYSA-N 0.000 claims description 2
- NUMOUMWZKQANSP-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-methyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound O=C1N(C)C=2N=C(C3=CN(CC=4C=C(C=CC=4)C(F)(F)F)N=C3)NC=2C(=O)N1CC1CC1 NUMOUMWZKQANSP-UHFFFAOYSA-N 0.000 claims description 2
- VURXLJUOHZZJBM-UHFFFAOYSA-N 1-(cyclopropylmethyl)-8-[1-(pyridin-2-ylmethyl)pyrazol-4-yl]-3,7-dihydropurine-2,6-dione Chemical compound O=C1NC=2N=C(C3=CN(CC=4N=CC=CC=4)N=C3)NC=2C(=O)N1CC1CC1 VURXLJUOHZZJBM-UHFFFAOYSA-N 0.000 claims description 2
- JBGRNTKBOQPADE-UHFFFAOYSA-N 1-butyl-8-[1-[(3-fluorophenyl)methyl]pyrazol-4-yl]-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCCC)C(=O)NC=2N=C1C(=C1)C=NN1CC1=CC=CC(F)=C1 JBGRNTKBOQPADE-UHFFFAOYSA-N 0.000 claims description 2
- QSEYHOMIGYEFFY-UHFFFAOYSA-N 1-butyl-8-[1-[[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]pyrazol-4-yl]-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCCC)C(=O)NC=2N=C1C(=C1)C=NN1CC(N=1)=NOC=1C1=CC=C(Cl)C=C1 QSEYHOMIGYEFFY-UHFFFAOYSA-N 0.000 claims description 2
- MYEOAOVDIBWJEL-UHFFFAOYSA-N 1-butyl-8-[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCCC)C(=O)NC=2N=C1C(=C1)C=NN1CC1=CC=C(C(F)(F)F)N=C1 MYEOAOVDIBWJEL-UHFFFAOYSA-N 0.000 claims description 2
- NHFVPOFRVAXYBX-UHFFFAOYSA-N 1-ethyl-8-[1-[(3-fluorophenyl)methyl]pyrazol-4-yl]-3-methyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CC)C(=O)N(C)C=2N=C1C(=C1)C=NN1CC1=CC=CC(F)=C1 NHFVPOFRVAXYBX-UHFFFAOYSA-N 0.000 claims description 2
- SEKFWEUZFWPIIW-UHFFFAOYSA-N 1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-3,7-dihydropurine-2,6-dione Chemical group N1C=2C(=O)N(CCC)C(=O)NC=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 SEKFWEUZFWPIIW-UHFFFAOYSA-N 0.000 claims description 2
- UDNGNWOKQLQPJV-UHFFFAOYSA-N 2-[4-[6-oxo-1-(2-oxopropyl)-3-propyl-2,7-dihydropurin-8-yl]-1H-pyrazol-5-yl]-2-phenylacetic acid Chemical compound O=C(CN1CN(C=2N=C(NC=2C1=O)C=1C(=NNC=1)C(C(=O)O)C1=CC=CC=C1)CCC)C UDNGNWOKQLQPJV-UHFFFAOYSA-N 0.000 claims description 2
- AZIMJLTVUFLESS-UHFFFAOYSA-N 3-[[4-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)-1h-pyrazol-5-yl]methyl]benzoic acid Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CNN=C1CC1=CC=CC(C(O)=O)=C1 AZIMJLTVUFLESS-UHFFFAOYSA-N 0.000 claims description 2
- FSZJGDMXEQVTPM-UHFFFAOYSA-N 3-butan-2-yl-1-methyl-8-(1h-pyrazol-4-yl)-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(C)C(=O)N(C(C)CC)C=2N=C1C=1C=NNC=1 FSZJGDMXEQVTPM-UHFFFAOYSA-N 0.000 claims description 2
- RGSFBJFXDRCAQB-UHFFFAOYSA-N 3-ethyl-1-propyl-8-[1-(pyridin-2-ylmethyl)pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=CC=N1 RGSFBJFXDRCAQB-UHFFFAOYSA-N 0.000 claims description 2
- KOYXXLLNCXWUNF-UHFFFAOYSA-N 3-ethyl-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 KOYXXLLNCXWUNF-UHFFFAOYSA-N 0.000 claims description 2
- TXEFUDYEMBGBMN-UHFFFAOYSA-N 3-ethyl-1-propyl-8-[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=C(C(F)(F)F)N=C1 TXEFUDYEMBGBMN-UHFFFAOYSA-N 0.000 claims description 2
- BWVLVKYENDCAHC-UHFFFAOYSA-N 3-methyl-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(C)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 BWVLVKYENDCAHC-UHFFFAOYSA-N 0.000 claims description 2
- VKONPLGZIZPWGJ-UHFFFAOYSA-N 4-[[4-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)pyrazol-1-yl]methyl]benzoic acid Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=C(C(O)=O)C=C1 VKONPLGZIZPWGJ-UHFFFAOYSA-N 0.000 claims description 2
- BKVOEOMEFAFQJL-UHFFFAOYSA-N 6-[[4-(2,6-dioxo-1,3-dipropyl-7h-purin-8-yl)-1h-pyrazol-5-yl]methyl]pyridine-2-carboxylic acid Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1=CNN=C1CC1=CC=CC(C(O)=O)=N1 BKVOEOMEFAFQJL-UHFFFAOYSA-N 0.000 claims description 2
- KAYVCWBEIZTVCN-UHFFFAOYSA-N 8-(1-benzylpyrazol-4-yl)-1-propyl-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)NC=2N=C1C(=C1)C=NN1CC1=CC=CC=C1 KAYVCWBEIZTVCN-UHFFFAOYSA-N 0.000 claims description 2
- INMYJCHAOZGGBA-UHFFFAOYSA-N 8-[1-(2-phenylethyl)pyrazol-4-yl]-1-propyl-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)NC=2N=C1C(=C1)C=NN1CCC1=CC=CC=C1 INMYJCHAOZGGBA-UHFFFAOYSA-N 0.000 claims description 2
- BXQRCUSBUDNKKE-UHFFFAOYSA-N 8-[1-[(2-methoxyphenyl)methyl]pyrazol-4-yl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=CC=C1OC BXQRCUSBUDNKKE-UHFFFAOYSA-N 0.000 claims description 2
- HDWMDKHMNFXXDV-UHFFFAOYSA-N 8-[1-[(3-fluorophenyl)methyl]pyrazol-4-yl]-1,3-dimethyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(C)C(=O)N(C)C=2N=C1C(=C1)C=NN1CC1=CC=CC(F)=C1 HDWMDKHMNFXXDV-UHFFFAOYSA-N 0.000 claims description 2
- NJXVKVMVLZPERB-UHFFFAOYSA-N 8-[1-[(3-fluorophenyl)methyl]pyrazol-4-yl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(F)=C1 NJXVKVMVLZPERB-UHFFFAOYSA-N 0.000 claims description 2
- HLTWCJCIPYYETO-UHFFFAOYSA-N 8-[1-[[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]pyrazol-4-yl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(=C1)C=NN1CC(ON=1)=NC=1C1=CC=C(Cl)C=C1 HLTWCJCIPYYETO-UHFFFAOYSA-N 0.000 claims description 2
- HWHLLTUJISZFDN-UHFFFAOYSA-N 8-[1-[[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]pyrazol-4-yl]-1-propyl-3,7-dihydropurine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)NC=2N=C1C(=C1)C=NN1CC(N=1)=NOC=1C1=CC=C(Cl)C=C1 HWHLLTUJISZFDN-UHFFFAOYSA-N 0.000 claims description 2
- PSHSAHVUUAGSSH-UHFFFAOYSA-N 8-[1-[[5-(4-chlorophenyl)-1,2-oxazol-3-yl]methyl]pyrazol-4-yl]-3-ethyl-1-propyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC(=NO1)C=C1C1=CC=C(Cl)C=C1 PSHSAHVUUAGSSH-UHFFFAOYSA-N 0.000 claims description 2
- JNJWKLSCJORTLT-UHFFFAOYSA-N 8-[4-[[5-(2-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]phenyl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(C=C1)=CC=C1OCC(N=1)=NOC=1C1=CC=CC=C1OC JNJWKLSCJORTLT-UHFFFAOYSA-N 0.000 claims description 2
- AHJHSANRNGKAFS-UHFFFAOYSA-N 8-[4-[[5-(3-methoxyphenyl)-1,2,4-oxadiazol-3-yl]methoxy]phenyl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(C=C1)=CC=C1OCC(N=1)=NOC=1C1=CC=CC(OC)=C1 AHJHSANRNGKAFS-UHFFFAOYSA-N 0.000 claims description 2
- LHMYROXNDKDUQN-UHFFFAOYSA-N 8-[4-[[5-(4-fluorophenyl)-1,2,4-oxadiazol-3-yl]methoxy]phenyl]-1,3-dipropyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C(C=C1)=CC=C1OCC(N=1)=NOC=1C1=CC=C(F)C=C1 LHMYROXNDKDUQN-UHFFFAOYSA-N 0.000 claims description 2
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- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
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- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical group O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 claims description 2
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| PCT/US2011/042379 WO2012003220A1 (en) | 2010-06-30 | 2011-06-29 | Use of a2b adenosine receptor antagonists for treating pulmonary hypertension |
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| US7317017B2 (en) * | 2002-11-08 | 2008-01-08 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| JP2017048116A (ja) * | 2014-01-10 | 2017-03-09 | 国立研究開発法人国立国際医療研究センター | 肺高血圧症治療薬 |
| WO2019157337A1 (en) * | 2018-02-08 | 2019-08-15 | Pulmokine, Inc. | Formulations of kinase inhibitors and prostanoids |
| ES2975753T3 (es) | 2018-03-05 | 2024-07-12 | Teon Therapeutics Inc | Antagonistas del receptor de adenosina y usos de los mismos |
| WO2022187649A1 (en) * | 2021-03-05 | 2022-09-09 | Tosk, Inc. | Uridine phosphorylase inhibitors to prevent or treat drug-induced pulmonary dysfunction |
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| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
| US5364620A (en) | 1983-12-22 | 1994-11-15 | Elan Corporation, Plc | Controlled absorption diltiazem formulation for once daily administration |
| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
| US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
| US4902514A (en) | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
| US6117878A (en) | 1998-02-24 | 2000-09-12 | University Of Virginia | 8-phenyl- or 8-cycloalkyl xanthine antagonists of A2B human adenosine receptors |
| GB0028383D0 (en) | 2000-11-21 | 2001-01-03 | Novartis Ag | Organic compounds |
| DE60206756T2 (de) | 2001-06-29 | 2006-07-13 | CV Therapeutics, Inc., Palo Alto | Purin derivate als a2b adenosin rezeptor antagonisten |
| UA80258C2 (en) * | 2001-09-06 | 2007-09-10 | Biogen Inc | Methods of treating pulmonary disease |
| DK1444233T3 (da) * | 2001-11-09 | 2011-10-17 | Gilead Palo Alto Inc | A2B-adenosinreceptorantagonister |
| US7125993B2 (en) | 2001-11-09 | 2006-10-24 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| US6977300B2 (en) * | 2001-11-09 | 2005-12-20 | Cv Therapeutics, Inc. | A2B adenosine receptor antagonists |
| DE10303639B4 (de) | 2003-01-30 | 2016-05-25 | Zf Friedrichshafen Ag | Vorrichtung zur Steuerung einer hydraulisch betätigbaren Kupplung eines Automatgetriebes |
| US20050101608A1 (en) * | 2003-09-24 | 2005-05-12 | Santel Donald J. | Iloprost in combination therapies for the treatment of pulmonary arterial hypertension |
| EP1799221A1 (en) | 2004-10-15 | 2007-06-27 | Cv Therapeutics, Inc. | Method of preventing and treating airway remodeling and pulmonary inflammation using a2b adenosine receptor antagonists |
| US7601723B2 (en) * | 2005-02-25 | 2009-10-13 | Pgx Health, Llc | Pyridyl substituted xanthines |
| EP1891070A1 (en) | 2005-06-16 | 2008-02-27 | Cv Therapeutics, Inc. | Prodrugs of a2b adenosine receptor antagonists |
| ES2274712B1 (es) | 2005-10-06 | 2008-03-01 | Laboratorios Almirall S.A. | Nuevos derivados imidazopiridina. |
| US7767685B2 (en) * | 2006-06-29 | 2010-08-03 | King Pharmaceuticals Research And Development, Inc. | Adenosine A2B receptor antagonists |
| EP2101777B1 (en) * | 2006-12-12 | 2015-05-20 | Gilead Sciences, Inc. | Composition for treating a pulmonary hypertension |
| EP2268641B1 (en) | 2008-03-26 | 2014-09-03 | Advinus Therapeutics Pvt. Ltd. | Heterocyclic compounds as adenosine receptor antagonist |
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- 2011-06-29 US US13/172,609 patent/US20120003329A1/en not_active Abandoned
- 2011-06-29 JP JP2013518651A patent/JP2013533882A/ja active Pending
- 2011-06-29 EA EA201291274A patent/EA201291274A1/ru unknown
- 2011-06-29 AU AU2011271510A patent/AU2011271510A1/en not_active Abandoned
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- 2011-06-29 WO PCT/US2011/042379 patent/WO2012003220A1/en not_active Ceased
- 2011-06-29 CA CA2802891A patent/CA2802891A1/en not_active Abandoned
- 2011-06-29 EP EP11730524.3A patent/EP2595630A1/en not_active Withdrawn
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