JP2013533882A - 肺高血圧症を処置するためのａ２ｂアデノシン受容体アンタゴニストの使用 - Google Patents
肺高血圧症を処置するためのａ２ｂアデノシン受容体アンタゴニストの使用 Download PDFInfo
- Publication number
- JP2013533882A JP2013533882A JP2013518651A JP2013518651A JP2013533882A JP 2013533882 A JP2013533882 A JP 2013533882A JP 2013518651 A JP2013518651 A JP 2013518651A JP 2013518651 A JP2013518651 A JP 2013518651A JP 2013533882 A JP2013533882 A JP 2013533882A
- Authority
- JP
- Japan
- Prior art keywords
- optionally substituted
- methyl
- dione
- pyrazol
- trihydropurine
- 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
Links
- 208000002815 pulmonary hypertension Diseases 0.000 title claims abstract description 129
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 title claims abstract description 79
- 229940121359 adenosine receptor antagonist Drugs 0.000 title claims abstract description 77
- 101150078577 Adora2b gene Proteins 0.000 title description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims description 120
- 150000001875 compounds Chemical class 0.000 claims description 92
- -1 cyclic xanthine derivative Chemical class 0.000 claims description 84
- 125000000217 alkyl group Chemical group 0.000 claims description 78
- 125000001072 heteroaryl group Chemical group 0.000 claims description 76
- 238000011282 treatment Methods 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 66
- 102000005962 receptors Human genes 0.000 claims description 64
- 108020003175 receptors Proteins 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 41
- 210000004027 cell Anatomy 0.000 claims description 38
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 36
- 101800004490 Endothelin-1 Proteins 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 230000014509 gene expression Effects 0.000 claims description 35
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 210000001147 pulmonary artery Anatomy 0.000 claims description 33
- 125000002947 alkylene group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 25
- 108090001007 Interleukin-8 Proteins 0.000 claims description 23
- 230000002792 vascular Effects 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 20
- 229940002612 prodrug Drugs 0.000 claims description 20
- 210000000329 smooth muscle myocyte Anatomy 0.000 claims description 18
- 230000008719 thickening Effects 0.000 claims description 18
- 125000003107 substituted aryl group Chemical group 0.000 claims description 17
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 17
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 16
- 108010035532 Collagen Proteins 0.000 claims description 14
- 102000008186 Collagen Human genes 0.000 claims description 14
- 229920001436 collagen Polymers 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 13
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 13
- 208000019693 Lung disease Diseases 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 12
- 210000002889 endothelial cell Anatomy 0.000 claims description 11
- 229940044551 receptor antagonist Drugs 0.000 claims description 11
- 239000002464 receptor antagonist Substances 0.000 claims description 11
- 230000002861 ventricular Effects 0.000 claims description 11
- 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 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 102000036444 extracellular matrix enzymes Human genes 0.000 claims description 10
- 108091007167 extracellular matrix enzymes Proteins 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000000732 arylene group Chemical group 0.000 claims description 8
- 125000005549 heteroarylene group Chemical group 0.000 claims description 8
- 230000006872 improvement Effects 0.000 claims description 8
- 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 8
- 230000035488 systolic blood pressure Effects 0.000 claims description 8
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 208000020875 Idiopathic pulmonary arterial hypertension Diseases 0.000 claims description 6
- 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 6
- 229960002414 ambrisentan Drugs 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 238000013508 migration Methods 0.000 claims description 6
- 150000004866 oxadiazoles Chemical class 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 6
- 230000009885 systemic effect Effects 0.000 claims description 6
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 claims description 6
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 5
- 206010021143 Hypoxia Diseases 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 239000002308 endothelin receptor antagonist Substances 0.000 claims description 5
- 230000007954 hypoxia Effects 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 230000002018 overexpression Effects 0.000 claims description 5
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 5
- 230000009325 pulmonary function Effects 0.000 claims description 5
- 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 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 4
- 102100033601 Collagen alpha-1(I) chain Human genes 0.000 claims description 4
- 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 claims description 4
- 101000990912 Homo sapiens Matrilysin Proteins 0.000 claims description 4
- 102100027998 Macrophage metalloelastase Human genes 0.000 claims description 4
- 102100030417 Matrilysin Human genes 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
- 108010029483 alpha 1 Chain Collagen Type I Proteins 0.000 claims description 4
- 239000000480 calcium channel blocker Substances 0.000 claims description 4
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 102100027398 A disintegrin and metalloproteinase with thrombospondin motifs 1 Human genes 0.000 claims description 3
- 102100032635 A disintegrin and metalloproteinase with thrombospondin motifs 8 Human genes 0.000 claims description 3
- 108091005660 ADAMTS1 Proteins 0.000 claims description 3
- 108091005666 ADAMTS8 Proteins 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- 102100031168 CCN family member 2 Human genes 0.000 claims description 3
- 108091007854 Cdh1/Fizzy-related Proteins 0.000 claims description 3
- 102000038594 Cdh1/Fizzy-related Human genes 0.000 claims description 3
- 102100024337 Collagen alpha-1(VIII) chain Human genes 0.000 claims description 3
- 102000010180 Endothelin receptor Human genes 0.000 claims description 3
- 108050001739 Endothelin receptor Proteins 0.000 claims description 3
- 101000777550 Homo sapiens CCN family member 2 Proteins 0.000 claims description 3
- 101000909492 Homo sapiens Collagen alpha-1(VIII) chain Proteins 0.000 claims description 3
- 108090000320 Hyaluronan Synthases Proteins 0.000 claims description 3
- 102100032832 Integrin alpha-7 Human genes 0.000 claims description 3
- HOLLSHYBSWZLEY-UHFFFAOYSA-N [3-ethyl-2,6-dioxo-1-propyl-8-[1-[[3-(trifluoromethyl)phenyl]methyl]pyrazol-4-yl]purin-7-yl] 2-methylbutanoate Chemical compound CCC(C)C(=O)ON1C=2C(=O)N(CCC)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=CC(C(F)(F)F)=C1 HOLLSHYBSWZLEY-UHFFFAOYSA-N 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 108010092830 integrin alpha7beta1 Proteins 0.000 claims description 3
- 238000007918 intramuscular administration Methods 0.000 claims description 3
- 238000007912 intraperitoneal administration Methods 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 3
- 150000003815 prostacyclins Chemical class 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 229940124549 vasodilator Drugs 0.000 claims description 3
- 239000003071 vasodilator agent Substances 0.000 claims description 3
- 108090001005 Interleukin-6 Proteins 0.000 claims description 2
- 206010035664 Pneumonia Diseases 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 229940097217 cardiac glycoside Drugs 0.000 claims description 2
- 239000002368 cardiac glycoside Substances 0.000 claims description 2
- 230000012292 cell migration Effects 0.000 claims description 2
- 239000002934 diuretic Substances 0.000 claims description 2
- 229940030606 diuretics Drugs 0.000 claims description 2
- 229930002534 steroid glycoside Natural products 0.000 claims description 2
- 150000008143 steroidal glycosides Chemical class 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 230000009469 supplementation Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 102400000686 Endothelin-1 Human genes 0.000 claims 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 1
- 102000003918 Hyaluronan Synthases Human genes 0.000 claims 1
- CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical compound COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 claims 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 abstract description 14
- 108090000695 Cytokines Proteins 0.000 abstract description 14
- 208000032594 Vascular Remodeling Diseases 0.000 abstract description 13
- 208000024891 symptom Diseases 0.000 abstract description 9
- 108010012236 Chemokines Proteins 0.000 abstract description 8
- 102000019034 Chemokines Human genes 0.000 abstract description 8
- 229940126062 Compound A Drugs 0.000 description 90
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 90
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 81
- 108010006654 Bleomycin Proteins 0.000 description 78
- 229960001561 bleomycin Drugs 0.000 description 78
- 241000699670 Mus sp. Species 0.000 description 55
- 125000003118 aryl group Chemical group 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 125000001424 substituent group Chemical group 0.000 description 41
- 108050000203 Adenosine receptors Proteins 0.000 description 34
- 102000009346 Adenosine receptors Human genes 0.000 description 34
- 102100033902 Endothelin-1 Human genes 0.000 description 34
- 230000001965 increasing effect Effects 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 33
- 230000002829 reductive effect Effects 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- 210000004072 lung Anatomy 0.000 description 30
- 125000000392 cycloalkenyl group Chemical group 0.000 description 29
- 108010063738 Interleukins Proteins 0.000 description 28
- 102000015696 Interleukins Human genes 0.000 description 28
- 125000003342 alkenyl group Chemical group 0.000 description 26
- 239000005557 antagonist Substances 0.000 description 26
- 230000000694 effects Effects 0.000 description 26
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 26
- 239000002609 medium Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- 239000004480 active ingredient Substances 0.000 description 25
- 230000004913 activation Effects 0.000 description 23
- 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 23
- 229910052736 halogen Inorganic materials 0.000 description 23
- 150000002367 halogens Chemical class 0.000 description 23
- 125000000304 alkynyl group Chemical group 0.000 description 22
- 125000004181 carboxyalkyl group Chemical group 0.000 description 22
- 125000004093 cyano group Chemical group *C#N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 102000004890 Interleukin-8 Human genes 0.000 description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 102000055025 Adenosine deaminases Human genes 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 230000035755 proliferation Effects 0.000 description 20
- 239000004615 ingredient Substances 0.000 description 19
- 239000002953 phosphate buffered saline Substances 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 108090000623 proteins and genes Proteins 0.000 description 19
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 13
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 208000000059 Dyspnea Diseases 0.000 description 12
- 206010013975 Dyspnoeas Diseases 0.000 description 12
- 229960005305 adenosine Drugs 0.000 description 12
- 230000036541 health Effects 0.000 description 12
- 230000008506 pathogenesis Effects 0.000 description 12
- 230000002685 pulmonary effect Effects 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 239000003981 vehicle Substances 0.000 description 12
- 102000001760 Notch3 Receptor Human genes 0.000 description 11
- 108010029756 Notch3 Receptor Proteins 0.000 description 11
- 125000004414 alkyl thio group Chemical group 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- 230000004199 lung function Effects 0.000 description 11
- 238000002965 ELISA Methods 0.000 description 10
- 229930194542 Keto Natural products 0.000 description 10
- 210000001367 artery Anatomy 0.000 description 10
- 125000005110 aryl thio group Chemical group 0.000 description 10
- 231100000673 dose–response relationship Toxicity 0.000 description 10
- 125000000468 ketone group Chemical group 0.000 description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
- 102000004169 proteins and genes Human genes 0.000 description 10
- 208000005069 pulmonary fibrosis Diseases 0.000 description 10
- 230000015590 smooth muscle cell migration Effects 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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
- 125000000033 alkoxyamino group Chemical group 0.000 description 9
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 9
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 9
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 9
- 125000004104 aryloxy group Chemical group 0.000 description 9
- 230000001684 chronic effect Effects 0.000 description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 description 9
- 125000005368 heteroarylthio group Chemical group 0.000 description 9
- 125000004468 heterocyclylthio group Chemical group 0.000 description 9
- 150000003573 thiols Chemical class 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 8
- XNRNNGPBEPRNAR-UHFFFAOYSA-N Thromboxane B2 Natural products CCCCCC(O)C=CC1OC(O)CC(O)C1CC=CCCCC(O)=O XNRNNGPBEPRNAR-UHFFFAOYSA-N 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 150000001540 azides Chemical class 0.000 description 8
- YEWZQCDRZRYAEB-UHFFFAOYSA-N ditert-butyl hydrogen phosphate Chemical compound CC(C)(C)OP(O)(=O)OC(C)(C)C YEWZQCDRZRYAEB-UHFFFAOYSA-N 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
- 230000002757 inflammatory effect Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 208000031467 Pulmonary capillary hemangiomatosis Diseases 0.000 description 7
- 208000014777 Pulmonary venoocclusive disease Diseases 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000003213 activating effect Effects 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 230000037081 physical activity Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 230000007838 tissue remodeling Effects 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102100031519 Collagen alpha-1(VI) chain Human genes 0.000 description 6
- 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 6
- 102000002045 Endothelin Human genes 0.000 description 6
- 108050009340 Endothelin Proteins 0.000 description 6
- 101000941581 Homo sapiens Collagen alpha-1(VI) chain Proteins 0.000 description 6
- 208000004852 Lung Injury Diseases 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 238000000540 analysis of variance Methods 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 238000010586 diagram Methods 0.000 description 6
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 235000021317 phosphate Nutrition 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 210000002460 smooth muscle Anatomy 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000002238 attenuated effect Effects 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 230000001404 mediated effect Effects 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
- 210000003205 muscle Anatomy 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 210000003492 pulmonary vein Anatomy 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 4
- 206010008479 Chest Pain Diseases 0.000 description 4
- 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 description 4
- 208000032862 Clinical Deterioration Diseases 0.000 description 4
- 102100037296 Collagen alpha-1(XXII) chain Human genes 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 101000952998 Homo sapiens Collagen alpha-1(XXII) chain Proteins 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 208000021060 Pulmonary arterial hypertension associated with another disease Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 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 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 4
- 238000003745 diagnosis Methods 0.000 description 4
- LNJAJHJFSKUCIR-UHFFFAOYSA-N ditert-butyl chloromethyl phosphate Chemical compound CC(C)(C)OP(=O)(OCCl)OC(C)(C)C LNJAJHJFSKUCIR-UHFFFAOYSA-N 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 206010016256 fatigue Diseases 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 208000019622 heart disease Diseases 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
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000004237 preparative chromatography Methods 0.000 description 4
- 238000004393 prognosis Methods 0.000 description 4
- 230000000284 resting effect Effects 0.000 description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 description 4
- 208000013220 shortness of breath Diseases 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 4
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- KQCFQSMHNZFZCQ-MCDZGGTQSA-N (2R,3R,4S,5R)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol N-ethylformamide Chemical compound CCNC=O.C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O KQCFQSMHNZFZCQ-MCDZGGTQSA-N 0.000 description 3
- TXDXEUVACFAWQB-UHFFFAOYSA-N 5,6-diamino-1-ethyl-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N)=C(N)N(CC)C1=O TXDXEUVACFAWQB-UHFFFAOYSA-N 0.000 description 3
- JVNIERUYZGPSCA-UHFFFAOYSA-N 6-amino-1-ethyl-5-nitroso-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C(N=O)=C(N)N(CC)C1=O JVNIERUYZGPSCA-UHFFFAOYSA-N 0.000 description 3
- QHEMDIZENXAVRQ-UHFFFAOYSA-N 6-amino-1-ethylpyrimidine-2,4-dione Chemical compound CCN1C(N)=CC(=O)NC1=O QHEMDIZENXAVRQ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000007809 Boyden Chamber assay Methods 0.000 description 3
- 102400000667 Brain natriuretic peptide 32 Human genes 0.000 description 3
- 101800002247 Brain natriuretic peptide 45 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000015872 Gaucher disease Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 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
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000029523 Interstitial Lung disease Diseases 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
- 208000014767 Myeloproliferative disease Diseases 0.000 description 3
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 208000024799 Thyroid disease Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 206010069363 Traumatic lung injury Diseases 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 230000001746 atrial effect Effects 0.000 description 3
- 239000007640 basal medium Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 230000001593 cAMP accumulation Effects 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 239000002975 chemoattractant Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 208000007345 glycogen storage disease Diseases 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 230000000004 hemodynamic effect Effects 0.000 description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 description 3
- 238000003364 immunohistochemistry Methods 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 231100000515 lung injury Toxicity 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000013160 medical therapy Methods 0.000 description 3
- 230000004630 mental health Effects 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- SPJDDRUDFQBAOY-UHFFFAOYSA-N n'-(3-ethyl-2,6-dioxo-1-propylpyrimidin-4-yl)-n,n-dimethylmethanimidamide Chemical compound CCCN1C(=O)C=C(N=CN(C)C)N(CC)C1=O SPJDDRUDFQBAOY-UHFFFAOYSA-N 0.000 description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000006213 oxygenation reaction Methods 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 208000007232 portal hypertension Diseases 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 230000036593 pulmonary vascular resistance Effects 0.000 description 3
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000003653 radioligand binding assay Methods 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000007634 remodeling Methods 0.000 description 3
- 230000029058 respiratory gaseous exchange Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000010911 splenectomy Methods 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 108700012359 toxins Proteins 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-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
- HUJXGQILHAUCCV-MOROJQBDSA-N 3-iodobenzyl-5'-N-methylcarboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C=CC=3)=C2N=C1 HUJXGQILHAUCCV-MOROJQBDSA-N 0.000 description 2
- YPSQTTRYMSZAGR-UHFFFAOYSA-N 6-amino-1-ethyl-3-propylpyrimidine-2,4-dione Chemical compound CCCN1C(=O)C=C(N)N(CC)C1=O YPSQTTRYMSZAGR-UHFFFAOYSA-N 0.000 description 2
- HEHWDTREEVPBPD-UHFFFAOYSA-N 8-[1-[[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-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(ON=1)=NC=1C1=CC=C(Cl)C=C1 HEHWDTREEVPBPD-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
- 102100021407 ATP-dependent RNA helicase DDX18 Human genes 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 description 2
- 108050008407 Bone morphogenetic protein receptor type-2 Proteins 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 208000002330 Congenital Heart Defects Diseases 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 206010014561 Emphysema Diseases 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
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 2
- 108010079345 Follicle Stimulating Hormone Proteins 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
- 229940126656 GS-4224 Drugs 0.000 description 2
- 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 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101001011896 Homo sapiens Matrix metalloproteinase-19 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 206010021133 Hypoventilation Diseases 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 2
- 102000009151 Luteinizing Hormone Human genes 0.000 description 2
- 108010073521 Luteinizing Hormone Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102100030218 Matrix metalloproteinase-19 Human genes 0.000 description 2
- 102100024130 Matrix metalloproteinase-23 Human genes 0.000 description 2
- 102100024131 Matrix metalloproteinase-25 Human genes 0.000 description 2
- 241001465754 Metazoa Species 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
- 208000002193 Pain Diseases 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 206010036653 Presyncope Diseases 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 208000021072 Pulmonary hypertension owing to lung disease and/or hypoxia Diseases 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
- 238000011529 RT qPCR Methods 0.000 description 2
- 206010039163 Right ventricular failure Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 241001147844 Streptomyces verticillus Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 239000007984 Tris EDTA buffer Substances 0.000 description 2
- 206010047139 Vasoconstriction Diseases 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
- 239000013543 active substance Substances 0.000 description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000012491 analyte Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 230000027455 binding Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 210000003678 bronchial smooth muscle cell Anatomy 0.000 description 2
- 201000009267 bronchiectasis Diseases 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 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
- 238000013262 cAMP assay Methods 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
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 238000004113 cell culture Methods 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
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 208000028831 congenital heart disease Diseases 0.000 description 2
- 235000020940 control diet Nutrition 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 238000013016 damping Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000012055 enteric layer Substances 0.000 description 2
- 229960001123 epoprostenol Drugs 0.000 description 2
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 230000005713 exacerbation Effects 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229940028334 follicle stimulating hormone Drugs 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
- 239000008187 granular material Substances 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 239000001963 growth medium Substances 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
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 230000005980 lung dysfunction Effects 0.000 description 2
- 229940040129 luteinizing hormone Drugs 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 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
- 238000002156 mixing Methods 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- CKBHZDKYMHOLNJ-UHFFFAOYSA-N n'-(3-ethyl-2,6-dioxopyrimidin-4-yl)-n,n-dimethylmethanimidamide Chemical compound CCN1C(N=CN(C)C)=CC(=O)NC1=O CKBHZDKYMHOLNJ-UHFFFAOYSA-N 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 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
- 230000008520 organization Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000002085 persistent effect Effects 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
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 229960003415 propylparaben Drugs 0.000 description 2
- 239000003586 protic polar solvent Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- 230000011664 signaling 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
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 230000021595 spermatogenesis Effects 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000008223 sterile water Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000005156 substituted alkylene group Chemical group 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
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 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
- 230000000699 topical effect Effects 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
- 230000007704 transition Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 2
- 208000019553 vascular disease Diseases 0.000 description 2
- 230000025033 vasoconstriction Effects 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 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
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 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
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 1
- 125000005926 1,2-dimethylbutyloxy group Chemical group 0.000 description 1
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- LWLBIEJVVPVPMW-UHFFFAOYSA-N 1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole Chemical compound FC(F)(F)C1=CC=CC(CN2N=CC=C2)=C1 LWLBIEJVVPVPMW-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
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-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
- ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical compound C1NC=CO1 ZABMHLDQFJHDSC-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
- 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
- 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
- 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
- UWWGEIHSFZWTAF-UHFFFAOYSA-N 3-ethyl-1-(2-methylpropyl)-8-[1-[[6-(trifluoromethyl)pyridin-3-yl]methyl]pyrazol-4-yl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CC(C)C)C(=O)N(CC)C=2N=C1C(=C1)C=NN1CC1=CC=C(C(F)(F)F)N=C1 UWWGEIHSFZWTAF-UHFFFAOYSA-N 0.000 description 1
- LOGOEBMHHXYBID-MOROJQBDSA-N 3-iodo-4-aminobenzyl-5'-N-methylcarboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C(N)=CC=3)=C2N=C1 LOGOEBMHHXYBID-MOROJQBDSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 102000018918 Activin Receptors Human genes 0.000 description 1
- 108010052946 Activin Receptors 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
- 101100328894 Arabidopsis thaliana COL6 gene Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 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
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 102100029136 Collagen alpha-1(II) chain Human genes 0.000 description 1
- 102100031611 Collagen alpha-1(III) chain Human genes 0.000 description 1
- 102100022145 Collagen alpha-1(IV) chain Human genes 0.000 description 1
- 102100031457 Collagen alpha-1(V) chain Human genes 0.000 description 1
- 102100036217 Collagen alpha-1(X) chain Human genes 0.000 description 1
- 102100033825 Collagen alpha-1(XI) chain Human genes 0.000 description 1
- 102100027442 Collagen alpha-1(XII) chain Human genes 0.000 description 1
- 102100040993 Collagen alpha-1(XIII) chain Human genes 0.000 description 1
- 102100024203 Collagen alpha-1(XIV) chain Human genes 0.000 description 1
- 102100031161 Collagen alpha-1(XIX) chain Human genes 0.000 description 1
- 102100022640 Collagen alpha-1(XV) chain Human genes 0.000 description 1
- 102100028257 Collagen alpha-1(XVI) chain Human genes 0.000 description 1
- 102100028256 Collagen alpha-1(XVII) chain Human genes 0.000 description 1
- 102100031162 Collagen alpha-1(XVIII) chain Human genes 0.000 description 1
- 102100031160 Collagen alpha-1(XX) chain Human genes 0.000 description 1
- 102100040995 Collagen alpha-1(XXI) chain Human genes 0.000 description 1
- 102100036213 Collagen alpha-2(I) chain Human genes 0.000 description 1
- 102100033781 Collagen alpha-2(IV) chain Human genes 0.000 description 1
- 102100030976 Collagen alpha-2(IX) chain Human genes 0.000 description 1
- 102100031502 Collagen alpha-2(V) chain Human genes 0.000 description 1
- 102100033885 Collagen alpha-2(XI) chain Human genes 0.000 description 1
- 102100033780 Collagen alpha-3(IV) chain Human genes 0.000 description 1
- 102100030977 Collagen alpha-3(IX) chain Human genes 0.000 description 1
- 102100031501 Collagen alpha-3(V) chain Human genes 0.000 description 1
- 102100033779 Collagen alpha-4(IV) chain Human genes 0.000 description 1
- 102100033775 Collagen alpha-5(IV) chain Human genes 0.000 description 1
- 102100033773 Collagen alpha-6(IV) chain Human genes 0.000 description 1
- 208000029147 Collagen-vascular disease Diseases 0.000 description 1
- 102100027995 Collagenase 3 Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 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
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010013971 Dyspnoea exertional Diseases 0.000 description 1
- 208000003287 Eisenmenger Complex Diseases 0.000 description 1
- 208000020686 Eisenmenger syndrome Diseases 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102100037241 Endoglin Human genes 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 208000007530 Essential hypertension Diseases 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
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108091006101 Gi proteins Proteins 0.000 description 1
- 102000034354 Gi proteins Human genes 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- 108091006065 Gs proteins Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 101000627872 Homo sapiens 72 kDa type IV collagenase Proteins 0.000 description 1
- 101000771163 Homo sapiens Collagen alpha-1(II) chain Proteins 0.000 description 1
- 101000993285 Homo sapiens Collagen alpha-1(III) chain Proteins 0.000 description 1
- 101000901150 Homo sapiens Collagen alpha-1(IV) chain Proteins 0.000 description 1
- 101000941708 Homo sapiens Collagen alpha-1(V) chain Proteins 0.000 description 1
- 101000875027 Homo sapiens Collagen alpha-1(X) chain Proteins 0.000 description 1
- 101000710623 Homo sapiens Collagen alpha-1(XI) chain Proteins 0.000 description 1
- 101000861874 Homo sapiens Collagen alpha-1(XII) chain Proteins 0.000 description 1
- 101000749004 Homo sapiens Collagen alpha-1(XIII) chain Proteins 0.000 description 1
- 101000909626 Homo sapiens Collagen alpha-1(XIV) chain Proteins 0.000 description 1
- 101000940120 Homo sapiens Collagen alpha-1(XIX) chain Proteins 0.000 description 1
- 101000899935 Homo sapiens Collagen alpha-1(XV) chain Proteins 0.000 description 1
- 101000860648 Homo sapiens Collagen alpha-1(XVI) chain Proteins 0.000 description 1
- 101000860679 Homo sapiens Collagen alpha-1(XVII) chain Proteins 0.000 description 1
- 101000940068 Homo sapiens Collagen alpha-1(XVIII) chain Proteins 0.000 description 1
- 101000940122 Homo sapiens Collagen alpha-1(XX) chain Proteins 0.000 description 1
- 101000748976 Homo sapiens Collagen alpha-1(XXI) chain Proteins 0.000 description 1
- 101000875067 Homo sapiens Collagen alpha-2(I) chain Proteins 0.000 description 1
- 101000710876 Homo sapiens Collagen alpha-2(IV) chain Proteins 0.000 description 1
- 101000919645 Homo sapiens Collagen alpha-2(IX) chain Proteins 0.000 description 1
- 101000941594 Homo sapiens Collagen alpha-2(V) chain Proteins 0.000 description 1
- 101000710619 Homo sapiens Collagen alpha-2(XI) chain Proteins 0.000 description 1
- 101000710873 Homo sapiens Collagen alpha-3(IV) chain Proteins 0.000 description 1
- 101000919644 Homo sapiens Collagen alpha-3(IX) chain Proteins 0.000 description 1
- 101000941596 Homo sapiens Collagen alpha-3(V) chain Proteins 0.000 description 1
- 101000710870 Homo sapiens Collagen alpha-4(IV) chain Proteins 0.000 description 1
- 101000710886 Homo sapiens Collagen alpha-5(IV) chain Proteins 0.000 description 1
- 101000710885 Homo sapiens Collagen alpha-6(IV) chain Proteins 0.000 description 1
- 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 1
- 101001013150 Homo sapiens Interstitial collagenase Proteins 0.000 description 1
- 101001011906 Homo sapiens Matrix metalloproteinase-14 Proteins 0.000 description 1
- 101001011884 Homo sapiens Matrix metalloproteinase-15 Proteins 0.000 description 1
- 101001011886 Homo sapiens Matrix metalloproteinase-16 Proteins 0.000 description 1
- 101001011887 Homo sapiens Matrix metalloproteinase-17 Proteins 0.000 description 1
- 101001013139 Homo sapiens Matrix metalloproteinase-20 Proteins 0.000 description 1
- 101001013142 Homo sapiens Matrix metalloproteinase-21 Proteins 0.000 description 1
- 101000627851 Homo sapiens Matrix metalloproteinase-23 Proteins 0.000 description 1
- 101000627858 Homo sapiens Matrix metalloproteinase-24 Proteins 0.000 description 1
- 101000627852 Homo sapiens Matrix metalloproteinase-25 Proteins 0.000 description 1
- 101000627854 Homo sapiens Matrix metalloproteinase-26 Proteins 0.000 description 1
- 101000627860 Homo sapiens Matrix metalloproteinase-27 Proteins 0.000 description 1
- 101000627861 Homo sapiens Matrix metalloproteinase-28 Proteins 0.000 description 1
- 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 1
- 101000990908 Homo sapiens Neutrophil collagenase Proteins 0.000 description 1
- 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 description 1
- 101000577874 Homo sapiens Stromelysin-2 Proteins 0.000 description 1
- 101000577877 Homo sapiens Stromelysin-3 Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 208000024934 IgG4-related mediastinitis Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 102000004889 Interleukin-6 Human genes 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
- 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
- 102000007547 Laminin Human genes 0.000 description 1
- 108010085895 Laminin Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010049459 Lymphangioleiomyomatosis Diseases 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
- 108091007144 MMP23A Proteins 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 102100030216 Matrix metalloproteinase-14 Human genes 0.000 description 1
- 102100030201 Matrix metalloproteinase-15 Human genes 0.000 description 1
- 102100030200 Matrix metalloproteinase-16 Human genes 0.000 description 1
- 102100030219 Matrix metalloproteinase-17 Human genes 0.000 description 1
- 102100024129 Matrix metalloproteinase-24 Human genes 0.000 description 1
- 102100024128 Matrix metalloproteinase-26 Human genes 0.000 description 1
- 102100024132 Matrix metalloproteinase-27 Human genes 0.000 description 1
- 102100026799 Matrix metalloproteinase-28 Human genes 0.000 description 1
- 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 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
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- FVKPZGAIJRIYTI-UHFFFAOYSA-N N-[6-amino-4-oxo-3-(2-oxopentan-3-yl)-1,2-dihydropyrimidin-5-yl]-1-[[3-(trifluoromethyl)phenyl]methyl]pyrazole-4-carboxamide Chemical compound NC1=C(C(N(CN1)C(C(C)=O)CC)=O)NC(=O)C=1C=NN(C1)CC1=CC(=CC=C1)C(F)(F)F FVKPZGAIJRIYTI-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
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 101150103623 NOTCH3 gene Proteins 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 102100030411 Neutrophil collagenase Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 208000011191 Pulmonary vascular disease Diseases 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
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102100030416 Stromelysin-1 Human genes 0.000 description 1
- 102100028848 Stromelysin-2 Human genes 0.000 description 1
- 102100028847 Stromelysin-3 Human genes 0.000 description 1
- 238000003639 Student–Newman–Keuls (SNK) method Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 206010071436 Systolic dysfunction 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
- 102000004987 Troponin T Human genes 0.000 description 1
- 108090001108 Troponin T Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 206010070995 Vascular compression Diseases 0.000 description 1
- 206010072810 Vascular wall hypertrophy Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- AKZWRTCWNXHHFR-PDIZUQLASA-N [(3S)-oxolan-3-yl] N-[(2S,3S)-4-[(5S)-5-benzyl-3-[(2R)-2-carbamoyloxy-2,3-dihydro-1H-inden-1-yl]-4-oxo-3H-pyrrol-5-yl]-3-hydroxy-1-phenylbutan-2-yl]carbamate Chemical compound NC(=O)O[C@@H]1Cc2ccccc2C1C1C=N[C@](C[C@H](O)[C@H](Cc2ccccc2)NC(=O)O[C@H]2CCOC2)(Cc2ccccc2)C1=O AKZWRTCWNXHHFR-PDIZUQLASA-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
- HVUMOYIDDBPOLL-XGKPLOKHSA-N [2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XGKPLOKHSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 208000017304 adult pulmonary Langerhans cell histiocytosis Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229940053991 aldehydes and derivative Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 208000022531 anorexia Diseases 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
- 239000011260 aqueous acid Substances 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 210000004618 arterial endothelial cell Anatomy 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000037147 athletic performance Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- CREXVNNSNOKDHW-UHFFFAOYSA-N azaniumylideneazanide Chemical group N[N] CREXVNNSNOKDHW-UHFFFAOYSA-N 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229960002890 beraprost Drugs 0.000 description 1
- CTPOHARTNNSRSR-APJZLKAGSA-N beraprost Chemical compound O([C@H]1C[C@@H](O)[C@@H]([C@@H]21)/C=C/[C@@H](O)C(C)CC#CC)C1=C2C=CC=C1CCCC(O)=O CTPOHARTNNSRSR-APJZLKAGSA-N 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
- 238000012925 biological evaluation Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- HRQGCQVOJVTVLU-UHFFFAOYSA-N bis(chloromethyl) ether Chemical compound ClCOCCl HRQGCQVOJVTVLU-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 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
- 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
- 235000001465 calcium Nutrition 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
- 229960001714 calcium phosphate Drugs 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
- 150000001718 carbodiimides Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000037198 cardiovascular physiology Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- VXWDQYHMYFTTBQ-UHFFFAOYSA-N chloromethyl pyridine-3-carboxylate Chemical compound ClCOC(=O)C1=CC=CN=C1 VXWDQYHMYFTTBQ-UHFFFAOYSA-N 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
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 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
- 235000015165 citric acid Nutrition 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
- 230000011382 collagen catabolic process Effects 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 208000030635 congenital pulmonary lymphangiectasia Diseases 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000009547 development abnormality Effects 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002085 enols Chemical class 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
- 150000002170 ethers Chemical class 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
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- WHRIKZCFRVTHJH-UHFFFAOYSA-N ethylhydrazine Chemical compound CCNN WHRIKZCFRVTHJH-UHFFFAOYSA-N 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 235000019634 flavors Nutrition 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
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 238000002825 functional assay Methods 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
- 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
- 238000010353 genetic engineering Methods 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
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 125000005241 heteroarylamino 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
- 239000012456 homogeneous solution Substances 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- NRWCULBPDGBRQD-UHFFFAOYSA-L hydrogen phosphate;tetramethylazanium Chemical compound C[N+](C)(C)C.C[N+](C)(C)C.OP([O-])([O-])=O NRWCULBPDGBRQD-UHFFFAOYSA-L 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 229960002240 iloprost Drugs 0.000 description 1
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 108700016226 indium-bleomycin Proteins 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
- 230000001939 inductive effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 108010067479 inhibin B Proteins 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 238000011813 knockout mouse model Methods 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
- 210000003041 ligament Anatomy 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000011360 lung alveolus development Effects 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000001115 mace Substances 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
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 108090000440 matrix metalloproteinase 25 Proteins 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 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
- 239000001923 methylcellulose Substances 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
- 238000012544 monitoring process Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000007491 morphometric analysis Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000036973 muscularity Effects 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
- HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 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
- 235000003715 nutritional status Nutrition 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 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
- 238000002640 oxygen therapy Methods 0.000 description 1
- 230000020477 pH reduction Effects 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
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 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
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Chemical group 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 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
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 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
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 230000009430 psychological distress Effects 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
- 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
- 238000002106 pulse oximetry Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 229940107700 pyruvic acid Drugs 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
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 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
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 210000000582 semen Anatomy 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000008477 smooth muscle tissue growth Effects 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010288 sodium nitrite 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
- 230000003068 static effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 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
- 230000000638 stimulation Effects 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 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
- 239000003765 sweetening agent Substances 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 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
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity 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
- 238000011269 treatment regimen Methods 0.000 description 1
- 229960005032 treprostinil Drugs 0.000 description 1
- PAJMKGZZBBTTOY-ZFORQUDYSA-N treprostinil Chemical compound C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 PAJMKGZZBBTTOY-ZFORQUDYSA-N 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000005259 triarylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 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
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 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
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Otolaryngology (AREA)
- Dispersion Chemistry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36028910P | 2010-06-30 | 2010-06-30 | |
| US61/360,289 | 2010-06-30 | ||
| PCT/US2011/042379 WO2012003220A1 (en) | 2010-06-30 | 2011-06-29 | Use of a2b adenosine receptor antagonists for treating pulmonary hypertension |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013533882A true JP2013533882A (ja) | 2013-08-29 |
| JP2013533882A5 JP2013533882A5 (https=) | 2014-08-14 |
Family
ID=44343985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013518651A Pending JP2013533882A (ja) | 2010-06-30 | 2011-06-29 | 肺高血圧症を処置するためのａ２ｂアデノシン受容体アンタゴニストの使用 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20120003329A1 (https=) |
| EP (1) | EP2595630A1 (https=) |
| JP (1) | JP2013533882A (https=) |
| KR (1) | KR20130088834A (https=) |
| CN (1) | CN103237548A (https=) |
| AU (1) | AU2011271510A1 (https=) |
| BR (1) | BR112012032766A2 (https=) |
| CA (1) | CA2802891A1 (https=) |
| EA (1) | EA201291274A1 (https=) |
| MX (1) | MX2012015112A (https=) |
| WO (1) | WO2012003220A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024508553A (ja) * | 2021-03-05 | 2024-02-27 | トスク インコーポレーテッド | 薬物誘発性肺機能障害の予防又は処置のためのウリジンホスホリラーゼ阻害剤 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030229106A1 (en) * | 2001-11-09 | 2003-12-11 | Rao Kalla | A2B adenosine receptor antagonists |
| JP2005509036A (ja) * | 2001-11-09 | 2005-04-07 | シーブイ・セラピューティクス・インコーポレイテッド | Ａ２ｂアデノシン受容体アンタゴニスト |
| US20060293283A1 (en) * | 2005-06-16 | 2006-12-28 | Rao Kalla | Prodrugs of A2B adenosine receptor antagonists |
| JP2007506752A (ja) * | 2003-09-24 | 2007-03-22 | コゼリクス、 インク． | 肺動脈高血圧症を治療するための併用療法におけるイロプロスト |
| US20070072843A1 (en) * | 2005-02-25 | 2007-03-29 | Guoquan Wang | Pyridyl substituted xanthines |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| US7125993B2 (en) | 2001-11-09 | 2006-10-24 | 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 |
| 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 |
| 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 |
-
2011
- 2011-06-29 BR BR112012032766A patent/BR112012032766A2/pt not_active IP Right Cessation
- 2011-06-29 KR KR1020137001490A patent/KR20130088834A/ko not_active Withdrawn
- 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
- 2011-06-29 CN CN2011800417298A patent/CN103237548A/zh active Pending
- 2011-06-29 MX MX2012015112A patent/MX2012015112A/es not_active Application Discontinuation
- 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
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030229106A1 (en) * | 2001-11-09 | 2003-12-11 | Rao Kalla | A2B adenosine receptor antagonists |
| JP2005509036A (ja) * | 2001-11-09 | 2005-04-07 | シーブイ・セラピューティクス・インコーポレイテッド | Ａ２ｂアデノシン受容体アンタゴニスト |
| JP2007506752A (ja) * | 2003-09-24 | 2007-03-22 | コゼリクス、 インク． | 肺動脈高血圧症を治療するための併用療法におけるイロプロスト |
| US20070072843A1 (en) * | 2005-02-25 | 2007-03-29 | Guoquan Wang | Pyridyl substituted xanthines |
| US20060293283A1 (en) * | 2005-06-16 | 2006-12-28 | Rao Kalla | Prodrugs of A2B adenosine receptor antagonists |
Non-Patent Citations (4)
| Title |
|---|
| JPN6015021192; Ｊ Ｃｌｉｎ Ｉｎｖｅｓｔ Ｖｏｌ．１６， Ｎｏ．８, 2006, ｐ．２１７３-８２ * |
| JPN6015021194; Ｒｅｓｐｉｒ Ｐｈｙｓｉｏｌ Ｎｅｕｒｏｂｉｏｌ Ｖｏｌ．１７０， Ｎｏ．１, 201001, ｐ．３２-６ * |
| JPN6015021196; Ａｍ Ｊ Ｐｈｙｓｉｏｌ Ｌｕｎｇ Ｃｅｌｌ Ｍｏｌ Ｐｈｙｓｉｏｌ Ｖｏｌ．２９４， Ｎｏ．１, 2008, ｐ．Ｌ２４-３３ * |
| JPN6015021198; Ｐｅｄｉａｔｒ Ｉｎｔ Ｖｏｌ．４７， Ｎｏ．３, 2005, ｐ．２４２-７ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2024508553A (ja) * | 2021-03-05 | 2024-02-27 | トスク インコーポレーテッド | 薬物誘発性肺機能障害の予防又は処置のためのウリジンホスホリラーゼ阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012003220A1 (en) | 2012-01-05 |
| KR20130088834A (ko) | 2013-08-08 |
| AU2011271510A1 (en) | 2013-01-10 |
| CA2802891A1 (en) | 2012-01-05 |
| EA201291274A1 (ru) | 2013-12-30 |
| EP2595630A1 (en) | 2013-05-29 |
| CN103237548A (zh) | 2013-08-07 |
| MX2012015112A (es) | 2013-05-28 |
| US20120003329A1 (en) | 2012-01-05 |
| BR112012032766A2 (pt) | 2019-09-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5250848B2 (ja) | Ａ２ｂアデノシン受容体拮抗物質を用いる肝疾患の予防および処置の方法 | |
| RU2374247C2 (ru) | Способ получения антагонистов аденозиновых рецепторов a2b и промежуточные продукты | |
| ES2959419T3 (es) | Formulaciones secas por aspersión | |
| RU2391103C2 (ru) | Способ предупреждения и лечения ремоделирования дыхательных путей и воспаления легких с применением антагонистов аденозиновых рецепторов a2b | |
| JP2013533882A (ja) | 肺高血圧症を処置するためのａ２ｂアデノシン受容体アンタゴニストの使用 | |
| AU2012254057B2 (en) | Use of A2B adenosine receptor antagonists for treating heart failure and arrhythmia in post-myocardial infarction patients | |
| US20190125756A1 (en) | Method of treating hypertension | |
| AU2012261721A1 (en) | Method of preventing and treating hepatic disease using A2B adenosine receptor antagonists | |
| HK40036372B (zh) | 喷雾干燥制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140627 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140627 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150601 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151027 |