TW202342034A - 心肺病症之治療 - Google Patents

Info

Publication number

TW202342034A

TW202342034A TW111150447A TW111150447A TW202342034A TW 202342034 A TW202342034 A TW 202342034A TW 111150447 A TW111150447 A TW 111150447A TW 111150447 A TW111150447 A TW 111150447A TW 202342034 A TW202342034 A TW 202342034A

Authority

TW

Taiwan

Prior art keywords

ethyl

formula

chloro

methoxy

phenyl

Prior art date

2021-12-29

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 title claims abstract description 225
• 230000002612 cardiopulmonary effect Effects 0.000 title claims abstract description 144
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 493
• 208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 339
• 150000004682 monohydrates Chemical class 0.000 claims abstract description 230
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 167
• 239000004480 active ingredient Substances 0.000 claims abstract description 153
• 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims abstract description 112
• 239000002552 dosage form Substances 0.000 claims abstract description 83
• 208000019693 Lung disease Diseases 0.000 claims abstract description 66
• 230000001684 chronic effect Effects 0.000 claims abstract description 54
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 49
• 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 claims abstract description 41
• 201000010099 disease Diseases 0.000 claims abstract description 33
• 239000000203 mixture Substances 0.000 claims description 283
• 150000001875 compounds Chemical class 0.000 claims description 252
• 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 claims description 224
• 229960001375 lactose Drugs 0.000 claims description 223
• 239000008101 lactose Substances 0.000 claims description 222
• 239000000843 powder Substances 0.000 claims description 187
• 238000009472 formulation Methods 0.000 claims description 153
• 230000005855 radiation Effects 0.000 claims description 145
• 229910017488 Cu K Inorganic materials 0.000 claims description 134
• 229910017541 Cu-K Inorganic materials 0.000 claims description 133
• 239000003814 drug Substances 0.000 claims description 130
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 127
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 114
• 229940079593 drug Drugs 0.000 claims description 108
• 238000000034 method Methods 0.000 claims description 100
• 210000004072 lung Anatomy 0.000 claims description 94
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 88
• 239000002775 capsule Substances 0.000 claims description 57
• 239000008194 pharmaceutical composition Substances 0.000 claims description 45
• 201000006306 Cor pulmonale Diseases 0.000 claims description 44
• WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 claims description 41
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
• 229940112141 dry powder inhaler Drugs 0.000 claims description 34
• -1 4-Carboxyphenyl Chemical group 0.000 claims description 32
• 239000003795 chemical substances by application Substances 0.000 claims description 32
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 18
• 239000013078 crystal Substances 0.000 claims description 17
• 229960001021 lactose monohydrate Drugs 0.000 claims description 16
• 230000000144 pharmacologic effect Effects 0.000 claims description 14
• 230000004048 modification Effects 0.000 claims description 10
• 238000012986 modification Methods 0.000 claims description 10
• 239000004305 biphenyl Substances 0.000 claims description 9
• 235000010290 biphenyl Nutrition 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• 239000008177 pharmaceutical agent Substances 0.000 claims description 3
• 150000003839 salts Chemical class 0.000 abstract description 24
• 239000007902 hard capsule Substances 0.000 abstract description 20
• 239000000546 pharmaceutical excipient Substances 0.000 abstract description 19
• 239000012453 solvate Substances 0.000 abstract description 16
• 150000004677 hydrates Chemical class 0.000 abstract description 12
• 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 224
• 239000002245 particle Substances 0.000 description 187
• 208000035475 disorder Diseases 0.000 description 125
• 230000000052 comparative effect Effects 0.000 description 91
• 230000000694 effects Effects 0.000 description 54
• 230000002685 pulmonary effect Effects 0.000 description 42
• 239000000443 aerosol Substances 0.000 description 41
• 239000010419 fine particle Substances 0.000 description 41
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 230000009471 action Effects 0.000 description 39
• 239000008186 active pharmaceutical agent Substances 0.000 description 39
• 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 description 38
• 229940088679 drug related substance Drugs 0.000 description 38
• 230000009885 systemic effect Effects 0.000 description 36
• 238000002156 mixing Methods 0.000 description 31
• 208000006673 asthma Diseases 0.000 description 27
• 235000002639 sodium chloride Nutrition 0.000 description 27
• 239000007787 solid Substances 0.000 description 27
• 239000000126 substance Substances 0.000 description 27
• 230000009467 reduction Effects 0.000 description 26
• 239000000243 solution Substances 0.000 description 26
• BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 25
• 239000000047 product Substances 0.000 description 22
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 229910001868 water Inorganic materials 0.000 description 21
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
• 230000036772 blood pressure Effects 0.000 description 20
• BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 20
• 238000002441 X-ray diffraction Methods 0.000 description 19
• 230000003182 bronchodilatating effect Effects 0.000 description 19
• 238000002360 preparation method Methods 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
• 238000011049 filling Methods 0.000 description 18
• 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 17
• 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 17
• 238000009826 distribution Methods 0.000 description 17
• 230000001976 improved effect Effects 0.000 description 17
• 230000006872 improvement Effects 0.000 description 17
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
• 239000010410 layer Substances 0.000 description 16
• 238000004519 manufacturing process Methods 0.000 description 16
• 244000309715 mini pig Species 0.000 description 16
• 229940125526 sGC activator Drugs 0.000 description 16
• 239000002904 solvent Substances 0.000 description 16
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
• 230000004872 arterial blood pressure Effects 0.000 description 15
• 230000027455 binding Effects 0.000 description 15
• 238000009739 binding Methods 0.000 description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 14
• 238000002425 crystallisation Methods 0.000 description 14
• 238000000151 deposition Methods 0.000 description 14
• 230000008021 deposition Effects 0.000 description 14
• 150000004683 dihydrates Chemical class 0.000 description 14
• 210000001147 pulmonary artery Anatomy 0.000 description 14
• 241000282412 Homo Species 0.000 description 13
• 239000002253 acid Substances 0.000 description 13
• 230000008025 crystallization Effects 0.000 description 13
• 238000012377 drug delivery Methods 0.000 description 13
• 238000005259 measurement Methods 0.000 description 13
• 230000036593 pulmonary vascular resistance Effects 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 238000004458 analytical method Methods 0.000 description 12
• 230000007883 bronchodilation Effects 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 230000002265 prevention Effects 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 239000012190 activator Substances 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 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 11
• 239000012071 phase Substances 0.000 description 11
• 235000018102 proteins Nutrition 0.000 description 11
• 108090000623 proteins and genes Proteins 0.000 description 11
• 102000004169 proteins and genes Human genes 0.000 description 11
• 239000000523 sample Substances 0.000 description 11
• 238000005160 1H NMR spectroscopy Methods 0.000 description 10
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 229960003065 bosentan Drugs 0.000 description 10
• SXTRWVVIEPWAKM-UHFFFAOYSA-N bosentan hydrate Chemical compound O.COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SXTRWVVIEPWAKM-UHFFFAOYSA-N 0.000 description 10
• 201000009267 bronchiectasis Diseases 0.000 description 10
• 239000000969 carrier Substances 0.000 description 10
• 230000000004 hemodynamic effect Effects 0.000 description 10
• 229960003310 sildenafil Drugs 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 9
• 241000219109 Citrullus Species 0.000 description 9
• 235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 238000010171 animal model Methods 0.000 description 9
• 230000009286 beneficial effect Effects 0.000 description 9
• 238000013461 design Methods 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 230000003285 pharmacodynamic effect Effects 0.000 description 9
• 238000011084 recovery Methods 0.000 description 9
• 230000000241 respiratory effect Effects 0.000 description 9
• 229940127296 soluble guanylate cyclase stimulator Drugs 0.000 description 9
• 230000002459 sustained effect Effects 0.000 description 9
• 208000024891 symptom Diseases 0.000 description 9
• 238000009423 ventilation Methods 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• 206010020772 Hypertension Diseases 0.000 description 8
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 239000000556 agonist Substances 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 210000005120 human airway smooth muscle cell Anatomy 0.000 description 8
• 229960002240 iloprost Drugs 0.000 description 8
• 230000004199 lung function Effects 0.000 description 8
• UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 8
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
• 238000012552 review Methods 0.000 description 8
• 230000024883 vasodilation Effects 0.000 description 8
• 241000282472 Canis lupus familiaris Species 0.000 description 7
• 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 7
• 230000004913 activation Effects 0.000 description 7
• 235000021028 berry Nutrition 0.000 description 7
• 238000011161 development Methods 0.000 description 7
• 230000018109 developmental process Effects 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• 230000004054 inflammatory process Effects 0.000 description 7
• 238000001990 intravenous administration Methods 0.000 description 7
• 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 7
• 210000002345 respiratory system Anatomy 0.000 description 7
• 229960000529 riociguat Drugs 0.000 description 7
• WXXSNCNJFUAIDG-UHFFFAOYSA-N riociguat Chemical compound N1=C(N)C(N(C)C(=O)OC)=C(N)N=C1C(C1=CC=CN=C11)=NN1CC1=CC=CC=C1F WXXSNCNJFUAIDG-UHFFFAOYSA-N 0.000 description 7
• 229910001220 stainless steel Inorganic materials 0.000 description 7
• 239000010935 stainless steel Substances 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• 102000001554 Hemoglobins Human genes 0.000 description 6
• 108010054147 Hemoglobins Proteins 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 208000037883 airway inflammation Diseases 0.000 description 6
• 239000005557 antagonist Substances 0.000 description 6
• 230000008901 benefit Effects 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 210000004204 blood vessel Anatomy 0.000 description 6
• 238000006243 chemical reaction Methods 0.000 description 6
• WPYWMXNXEZFMAK-UHFFFAOYSA-N cinaciguat Chemical compound C=1C=C(C(O)=O)C=CC=1CN(CCCCC(=O)O)CCC1=CC=CC=C1OCC(C=C1)=CC=C1CCC1=CC=CC=C1 WPYWMXNXEZFMAK-UHFFFAOYSA-N 0.000 description 6
• 230000007423 decrease Effects 0.000 description 6
• 210000002216 heart Anatomy 0.000 description 6
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
• 210000000214 mouth Anatomy 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 239000003921 oil Substances 0.000 description 6
• 235000019198 oils Nutrition 0.000 description 6
• 210000000056 organ Anatomy 0.000 description 6
• 210000002381 plasma Anatomy 0.000 description 6
• 230000036470 plasma concentration Effects 0.000 description 6
• 230000002035 prolonged effect Effects 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• 230000011664 signaling Effects 0.000 description 6
• 238000007910 systemic administration Methods 0.000 description 6
• 230000008685 targeting Effects 0.000 description 6
• 229940124549 vasodilator Drugs 0.000 description 6
• 239000003071 vasodilator agent Substances 0.000 description 6
• 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 5
• 229940127291 Calcium channel antagonist Drugs 0.000 description 5
• 201000003883 Cystic fibrosis Diseases 0.000 description 5
• 206010021143 Hypoxia Diseases 0.000 description 5
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
• 238000001069 Raman spectroscopy Methods 0.000 description 5
• 208000002200 Respiratory Hypersensitivity Diseases 0.000 description 5
• 230000010085 airway hyperresponsiveness Effects 0.000 description 5
• 238000013459 approach Methods 0.000 description 5
• 210000004027 cell Anatomy 0.000 description 5
• 229950002128 cinaciguat Drugs 0.000 description 5
• 238000011157 data evaluation Methods 0.000 description 5
• 230000002526 effect on cardiovascular system Effects 0.000 description 5
• 238000002474 experimental method Methods 0.000 description 5
• 239000011521 glass Substances 0.000 description 5
• 150000003278 haem Chemical group 0.000 description 5
• 230000036541 health Effects 0.000 description 5
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 230000014759 maintenance of location Effects 0.000 description 5
• 230000036542 oxidative stress Effects 0.000 description 5
• 239000000825 pharmaceutical preparation Substances 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• 230000019491 signal transduction Effects 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 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 5
• 229960005032 treprostinil Drugs 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• 238000000825 ultraviolet detection Methods 0.000 description 5
• 230000000304 vasodilatating effect Effects 0.000 description 5
• 239000003643 water by type Substances 0.000 description 5
• 238000005303 weighing Methods 0.000 description 5
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 102000002045 Endothelin Human genes 0.000 description 4
• 108050009340 Endothelin Proteins 0.000 description 4
• 229940118365 Endothelin receptor antagonist Drugs 0.000 description 4
• 229930195725 Mannitol Natural products 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 241000282898 Sus scrofa Species 0.000 description 4
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
• 229960004373 acetylcholine Drugs 0.000 description 4
• 230000001070 adhesive effect Effects 0.000 description 4
• 239000003146 anticoagulant agent Substances 0.000 description 4
• 210000003123 bronchiole Anatomy 0.000 description 4
• HDFUYKDOTXOIBD-GWHBCOKCSA-N butyl (5S)-5-[2-(4-butoxycarbonylphenyl)ethyl-[2-[2-[[2-chloro-4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]ethyl]amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate Chemical compound CCCCOC(C1=CC=C(CCN(CCC(C=CC=C2)=C2OCC(C=CC(C2=CC=C(C(F)(F)F)C=C2)=C2)=C2Cl)[C@@H](CCC2)C(C=C3)=C2N=C3C(OCCCC)=O)C=C1)=O HDFUYKDOTXOIBD-GWHBCOKCSA-N 0.000 description 4
• 239000000480 calcium channel blocker Substances 0.000 description 4
• 239000012876 carrier material Substances 0.000 description 4
• 230000006735 deficit Effects 0.000 description 4
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
• 230000004064 dysfunction Effects 0.000 description 4
• 239000002308 endothelin receptor antagonist Substances 0.000 description 4
• 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 4
• 238000005516 engineering process Methods 0.000 description 4
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 238000002664 inhalation therapy Methods 0.000 description 4
• 239000003112 inhibitor Substances 0.000 description 4
• 238000011866 long-term treatment Methods 0.000 description 4
• 239000000594 mannitol Substances 0.000 description 4
• 235000010355 mannitol Nutrition 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 4
• 208000005069 pulmonary fibrosis Diseases 0.000 description 4
• 238000004007 reversed phase HPLC Methods 0.000 description 4
• 238000000926 separation method Methods 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 238000001694 spray drying Methods 0.000 description 4
• 238000003860 storage Methods 0.000 description 4
• 238000013517 stratification Methods 0.000 description 4
• 238000004809 thin layer chromatography Methods 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• UGYRMZVUHVMADQ-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinoline-2-carboxylic acid Chemical compound C1CCCC2=NC(C(=O)O)=CC=C21 UGYRMZVUHVMADQ-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 3
• 101710095468 Cyclase Proteins 0.000 description 3
• QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 108010078321 Guanylate Cyclase Proteins 0.000 description 3
• 102000014469 Guanylate cyclase Human genes 0.000 description 3
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 3
• 101000998623 Homo sapiens NADH-cytochrome b5 reductase 3 Proteins 0.000 description 3
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
• 102100033153 NADH-cytochrome b5 reductase 3 Human genes 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 208000027418 Wounds and injury Diseases 0.000 description 3
• 239000000853 adhesive Substances 0.000 description 3
• 238000005280 amorphization Methods 0.000 description 3
• 229940127218 antiplatelet drug Drugs 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• 230000037396 body weight Effects 0.000 description 3
• 238000004364 calculation method Methods 0.000 description 3
• 239000001569 carbon dioxide Substances 0.000 description 3
• 229910002092 carbon dioxide Inorganic materials 0.000 description 3
• 230000015556 catabolic process Effects 0.000 description 3
• DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 3
• 230000004087 circulation Effects 0.000 description 3
• 239000011362 coarse particle Substances 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 238000006731 degradation reaction Methods 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 230000008030 elimination Effects 0.000 description 3
• 238000003379 elimination reaction Methods 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• 230000001747 exhibiting effect Effects 0.000 description 3
• 230000002349 favourable effect Effects 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 238000000227 grinding Methods 0.000 description 3
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
• 239000005414 inactive ingredient Substances 0.000 description 3
• 229940125369 inhaled corticosteroids Drugs 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 208000014674 injury Diseases 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
• 230000002045 lasting effect Effects 0.000 description 3
• 229940125389 long-acting beta agonist Drugs 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 229910052757 nitrogen Inorganic materials 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
• 238000001556 precipitation Methods 0.000 description 3
• 230000004088 pulmonary circulation Effects 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 230000029058 respiratory gaseous exchange Effects 0.000 description 3
• 238000012216 screening Methods 0.000 description 3
• 238000010956 selective crystallization Methods 0.000 description 3
• 238000007873 sieving Methods 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000012085 test solution Substances 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000009424 thromboembolic effect Effects 0.000 description 3
• LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 210000003437 trachea Anatomy 0.000 description 3
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 3
• 229930195727 α-lactose Natural products 0.000 description 3
• 229930195724 β-lactose Natural products 0.000 description 3
• NSFIAKFOCAEBER-QZTJIDSGSA-N (2s,3s)-2,3-dihydroxy-2,3-bis(4-methylphenyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1[C@@](O)(C(O)=O)[C@](O)(C(O)=O)C1=CC=C(C)C=C1 NSFIAKFOCAEBER-QZTJIDSGSA-N 0.000 description 2
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
• OFJRNBWSFXEHSA-UHFFFAOYSA-N 2-(3-amino-1,2-benzoxazol-5-yl)-n-[4-[2-[(dimethylamino)methyl]imidazol-1-yl]-2-fluorophenyl]-5-(trifluoromethyl)pyrazole-3-carboxamide Chemical compound CN(C)CC1=NC=CN1C(C=C1F)=CC=C1NC(=O)C1=CC(C(F)(F)F)=NN1C1=CC=C(ON=C2N)C2=C1 OFJRNBWSFXEHSA-UHFFFAOYSA-N 0.000 description 2
• 108010077593 ACE-011 Proteins 0.000 description 2
• WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• 206010003645 Atopy Diseases 0.000 description 2
• 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 description 2
• 206010006440 Bronchial obstruction Diseases 0.000 description 2
• 206010006482 Bronchospasm Diseases 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• 244000223760 Cinnamomum zeylanicum Species 0.000 description 2
• IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
• 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 208000029523 Interstitial Lung disease Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 239000002145 L01XE14 - Bosutinib Substances 0.000 description 2
• KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 2
• 108010058846 Ovalbumin Proteins 0.000 description 2
• 108090000854 Oxidoreductases Proteins 0.000 description 2
• 102000004316 Oxidoreductases Human genes 0.000 description 2
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• 108091006335 Prostaglandin I receptors Proteins 0.000 description 2
• 238000001237 Raman spectrum Methods 0.000 description 2
• GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 2
• 241000282887 Suidae Species 0.000 description 2
• 239000005463 Tandutinib Substances 0.000 description 2
• 108090000190 Thrombin Proteins 0.000 description 2
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
• 108010063130 Type II Bone Morphogenetic Protein Receptors Proteins 0.000 description 2
• 230000001594 aberrant effect Effects 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 230000006978 adaptation Effects 0.000 description 2
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
• 239000013566 allergen Substances 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound 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 description 2
• 229960002414 ambrisentan Drugs 0.000 description 2
• 229940127219 anticoagulant drug Drugs 0.000 description 2
• 229960004676 antithrombotic agent Drugs 0.000 description 2
• 210000001367 artery Anatomy 0.000 description 2
• 238000000889 atomisation Methods 0.000 description 2
• WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 2
• 229960003644 aztreonam Drugs 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 229960000074 biopharmaceutical Drugs 0.000 description 2
• 230000017531 blood circulation Effects 0.000 description 2
• 229960003736 bosutinib Drugs 0.000 description 2
• UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 description 2
• 210000000621 bronchi Anatomy 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 239000007963 capsule composition Substances 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 238000000451 chemical ionisation Methods 0.000 description 2
• 235000017803 cinnamon Nutrition 0.000 description 2
• MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
• 238000005352 clarification Methods 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 230000001010 compromised effect Effects 0.000 description 2
• 239000012141 concentrate Substances 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 239000003246 corticosteroid Substances 0.000 description 2
• 229960001334 corticosteroids Drugs 0.000 description 2
• FEJVSJIALLTFRP-LJQANCHMSA-N darusentan Chemical compound COC1=CC(OC)=NC(O[C@H](C(O)=O)C(OC)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 FEJVSJIALLTFRP-LJQANCHMSA-N 0.000 description 2
• 229950008833 darusentan Drugs 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000007812 deficiency Effects 0.000 description 2
• 229940124447 delivery agent Drugs 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• 229910003460 diamond Inorganic materials 0.000 description 2
• 239000010432 diamond Substances 0.000 description 2
• 238000000113 differential scanning calorimetry Methods 0.000 description 2
• 230000006806 disease prevention Effects 0.000 description 2
• 238000011833 dog model Methods 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000013583 drug formulation Substances 0.000 description 2
• 229940126534 drug product Drugs 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000003480 eluent Substances 0.000 description 2
• 230000003073 embolic effect Effects 0.000 description 2
• 230000007613 environmental effect Effects 0.000 description 2
• 229940088598 enzyme Drugs 0.000 description 2
• KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical class 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
• IRHAMPQRHIQLLU-UHFFFAOYSA-N ethyl 5-[2-[2-[[2-chloro-4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]ethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate Chemical compound C1CCC2=NC(C(=O)OCC)=CC=C2C1N(C(=O)OC(C)(C)C)CCC1=CC=CC=C1OCC(C(=C1)Cl)=CC=C1C1=CC=C(C(F)(F)F)C=C1 IRHAMPQRHIQLLU-UHFFFAOYSA-N 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 230000004907 flux Effects 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 238000005194 fractionation Methods 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
• 230000002068 genetic effect Effects 0.000 description 2
• 239000003119 guanylate cyclase activator Substances 0.000 description 2
• 230000001435 haemodynamic effect Effects 0.000 description 2
• 230000004217 heart function Effects 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 102000052502 human ELANE Human genes 0.000 description 2
• 230000004047 hyperresponsiveness Effects 0.000 description 2
• 230000001146 hypoxic effect Effects 0.000 description 2
• 238000009863 impact test Methods 0.000 description 2
• 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
• 230000003434 inspiratory effect Effects 0.000 description 2
• 230000002427 irreversible effect Effects 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
• 229940011051 isopropyl acetate Drugs 0.000 description 2
• GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 230000033001 locomotion Effects 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 238000002483 medication Methods 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 description 2
• 229960004378 nintedanib Drugs 0.000 description 2
• XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 2
• 231100000957 no side effect Toxicity 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 210000001331 nose Anatomy 0.000 description 2
• 238000011369 optimal treatment Methods 0.000 description 2
• 238000005457 optimization Methods 0.000 description 2
• 229940092253 ovalbumin Drugs 0.000 description 2
• 238000006213 oxygenation reaction Methods 0.000 description 2
• 230000004963 pathophysiological condition Effects 0.000 description 2
• 230000037361 pathway Effects 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• 230000010412 perfusion Effects 0.000 description 2
• 230000035699 permeability Effects 0.000 description 2
• 229940127557 pharmaceutical product Drugs 0.000 description 2
• 210000003800 pharynx Anatomy 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 230000000019 pro-fibrinolytic effect Effects 0.000 description 2
• 230000001737 promoting effect Effects 0.000 description 2
• 150000003815 prostacyclins Chemical class 0.000 description 2
• 238000003908 quality control method Methods 0.000 description 2
• LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 2
• 238000011552 rat model Methods 0.000 description 2
• 229940044601 receptor agonist Drugs 0.000 description 2
• 239000000018 receptor agonist Substances 0.000 description 2
• 229960002052 salbutamol Drugs 0.000 description 2
• 229960004017 salmeterol Drugs 0.000 description 2
• 238000005070 sampling Methods 0.000 description 2
• PHWXUGHIIBDVKD-UHFFFAOYSA-N sitaxentan Chemical compound CC1=NOC(NS(=O)(=O)C2=C(SC=C2)C(=O)CC=2C(=CC=3OCOC=3C=2)C)=C1Cl PHWXUGHIIBDVKD-UHFFFAOYSA-N 0.000 description 2
• 229960002578 sitaxentan Drugs 0.000 description 2
• 210000002460 smooth muscle Anatomy 0.000 description 2
• 229950002894 sotatercept Drugs 0.000 description 2
• 238000004611 spectroscopical analysis Methods 0.000 description 2
• 238000013125 spirometry Methods 0.000 description 2
• 238000011301 standard therapy Methods 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 229950009893 tandutinib Drugs 0.000 description 2
• UXXQOJXBIDBUAC-UHFFFAOYSA-N tandutinib Chemical compound COC1=CC2=C(N3CCN(CC3)C(=O)NC=3C=CC(OC(C)C)=CC=3)N=CN=C2C=C1OCCCN1CCCCC1 UXXQOJXBIDBUAC-UHFFFAOYSA-N 0.000 description 2
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 2
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
• 229960004072 thrombin Drugs 0.000 description 2
• 229940110309 tiotropium Drugs 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 238000011269 treatment regimen Methods 0.000 description 2
• 230000002792 vascular Effects 0.000 description 2
• 239000003981 vehicle Substances 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• MGLIYKZFLDTAMW-GFCCVEGCSA-N (1R)-1-(1-isoquinolin-5-ylsulfonylpiperidin-4-yl)ethanamine Chemical compound C[C@@H](N)C1CCN(CC1)S(=O)(=O)C1=CC=CC2=C1C=CN=C2 MGLIYKZFLDTAMW-GFCCVEGCSA-N 0.000 description 1
• WCWUXEGQKLTGDX-LLVKDONJSA-N (2R)-1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methyl-6-pyrrolo[2,1-f][1,2,4]triazinyl]oxy]-2-propanol Chemical compound C1=C2NC(C)=CC2=C(F)C(OC2=NC=NN3C=C(C(=C32)C)OC[C@H](O)C)=C1 WCWUXEGQKLTGDX-LLVKDONJSA-N 0.000 description 1
• DMYZJLOWGSRVKP-RTBURBONSA-N (2r,4r)-1-n-(4-chlorophenyl)-4-hydroxy-2-n-[4-(3-oxomorpholin-4-yl)phenyl]pyrrolidine-1,2-dicarboxamide Chemical compound N1([C@H](C[C@H](C1)O)C(=O)NC=1C=CC(=CC=1)N1C(COCC1)=O)C(=O)NC1=CC=C(Cl)C=C1 DMYZJLOWGSRVKP-RTBURBONSA-N 0.000 description 1
• FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
• LJCBAPRMNYSDOP-LVCYMWGESA-N (2s)-3-(7-carbamimidoylnaphthalen-2-yl)-2-[4-[(3s)-1-ethanimidoylpyrrolidin-3-yl]oxyphenyl]propanoic acid;hydron;chloride;pentahydrate Chemical compound O.O.O.O.O.Cl.C1N(C(=N)C)CC[C@@H]1OC1=CC=C([C@H](CC=2C=C3C=C(C=CC3=CC=2)C(N)=N)C(O)=O)C=C1 LJCBAPRMNYSDOP-LVCYMWGESA-N 0.000 description 1
• AFXLPCNTPZQBIC-HOTGVXAUSA-N (2s)-4-(ethylamino)-1-[4-[[(2s)-4-(ethylamino)-2-hydroxybutyl]amino]butylamino]butan-2-ol Chemical compound CCNCC[C@H](O)CNCCCCNC[C@@H](O)CCNCC AFXLPCNTPZQBIC-HOTGVXAUSA-N 0.000 description 1
• CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
• OSJVTYVKQNOXPP-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CCC2=C1 OSJVTYVKQNOXPP-UHFFFAOYSA-N 0.000 description 1
• MJEREOGWNZGKRN-UHFFFAOYSA-N 1-(4-aminophenyl)-8-[4-(4-fluorophenyl)-4-oxobutyl]-1,3,8-triazaspiro[4.5]decan-4-one Chemical group C1=CC(N)=CC=C1N1C2(CCN(CCCC(=O)C=3C=CC(F)=CC=3)CC2)C(=O)NC1 MJEREOGWNZGKRN-UHFFFAOYSA-N 0.000 description 1
• NHEVHPNUCRJMMU-UHFFFAOYSA-N 1-(bromomethyl)-2-chloro-4-[4-(trifluoromethyl)phenyl]benzene Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=C(CBr)C(Cl)=C1 NHEVHPNUCRJMMU-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
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
• GKHIVNAUVKXIIY-UHFFFAOYSA-N 2-[3-[4-(1h-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-n-propan-2-ylacetamide Chemical compound CC(C)NC(=O)COC1=CC=CC(C=2N=C3C=CC=CC3=C(NC=3C=C4C=NNC4=CC=3)N=2)=C1 GKHIVNAUVKXIIY-UHFFFAOYSA-N 0.000 description 1
• QHVBWSIFLCIXBD-UHFFFAOYSA-N 2-[[2-[3-(diaminomethylidene)-6-oxocyclohexa-1,4-dien-1-yl]oxy-3,5-difluoro-6-[3-(1-methyl-4,5-dihydroimidazol-2-yl)phenoxy]pyridin-4-yl]-methylamino]acetic acid Chemical compound N=1C(OC=2C=C(C=CC=2)C=2N(CCN=2)C)=C(F)C(N(CC(O)=O)C)=C(F)C=1OC1=CC(=C(N)N)C=CC1=O QHVBWSIFLCIXBD-UHFFFAOYSA-N 0.000 description 1
• KVTHPKXDLVYNCH-UHFFFAOYSA-N 2-iodoethylbenzene Chemical compound ICCC1=CC=CC=C1 KVTHPKXDLVYNCH-UHFFFAOYSA-N 0.000 description 1
• OOUGLTULBSNHNF-UHFFFAOYSA-N 3-[5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2N=C(ON=2)C=2C(=CC=CC=2)F)=C1 OOUGLTULBSNHNF-UHFFFAOYSA-N 0.000 description 1
• NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 1
• NOBZETMXGVAWIM-UHFFFAOYSA-N 4-[(2-carbamimidoyl-3,4-dihydro-1h-isoquinolin-7-yl)oxymethyl]-1-pyridin-4-ylpiperidine-4-carboxylic acid;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=C2CN(C(=N)N)CCC2=CC=C1OCC(CC1)(C(O)=O)CCN1C1=CC=NC=C1 NOBZETMXGVAWIM-UHFFFAOYSA-N 0.000 description 1
• XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
• QFCXANHHBCGMAS-UHFFFAOYSA-N 4-[[4-(4-chloroanilino)furo[2,3-d]pyridazin-7-yl]oxymethyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(COC=2C=3OC=CC=3C(NC=3C=CC(Cl)=CC=3)=NN=2)=C1 QFCXANHHBCGMAS-UHFFFAOYSA-N 0.000 description 1
• OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
• LAZGCPTWUHKDLC-UHFFFAOYSA-N 5-amino-5,6,7,8-tetrahydroquinoline-2-carboxylic acid Chemical class OC(=O)C1=CC=C2C(N)CCCC2=N1 LAZGCPTWUHKDLC-UHFFFAOYSA-N 0.000 description 1
• YIEAVVIJPFEHCX-UHFFFAOYSA-N 5-ethyl-2-[5-[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl-2-propoxyphenyl]-7-propyl-4a,7a-dihydro-3H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound CCCOC1=CC=C(C=C1C1=NC2C(N(CC)C=C2CCC)C(=O)N1)S(=O)(=O)N1CCN(CCO)CC1 YIEAVVIJPFEHCX-UHFFFAOYSA-N 0.000 description 1
• RCJYGWGQCPDYSL-HZPDHXFCSA-N 7-[(3-bromo-4-methoxyphenyl)methyl]-1-ethyl-8-[[(1r,2r)-2-hydroxycyclopentyl]amino]-3-(2-hydroxyethyl)purine-2,6-dione Chemical compound C=1C=C(OC)C(Br)=CC=1CN1C=2C(=O)N(CC)C(=O)N(CCO)C=2N=C1N[C@@H]1CCC[C@H]1O RCJYGWGQCPDYSL-HZPDHXFCSA-N 0.000 description 1
• 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 1
• 102000017904 ADRA2C Human genes 0.000 description 1
• 108010059616 Activins Proteins 0.000 description 1
• 102000005606 Activins Human genes 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 208000000884 Airway Obstruction Diseases 0.000 description 1
• 102000005862 Angiotensin II Human genes 0.000 description 1
• 101800000733 Angiotensin-2 Proteins 0.000 description 1
• QNZCBYKSOIHPEH-UHFFFAOYSA-N Apixaban Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(CC2)C=3C=CC(=CC=3)N3C(CCCC3)=O)=C2C(C(N)=O)=N1 QNZCBYKSOIHPEH-UHFFFAOYSA-N 0.000 description 1
• 101100481033 Arabidopsis thaliana TGA7 gene Proteins 0.000 description 1
• 240000005528 Arctium lappa Species 0.000 description 1
• 206010063659 Aversion Diseases 0.000 description 1
• 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
• 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
• 208000009079 Bronchial Spasm Diseases 0.000 description 1
• 208000014181 Bronchial disease Diseases 0.000 description 1
• 206010006448 Bronchiolitis Diseases 0.000 description 1
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 239000005461 Canertinib Substances 0.000 description 1
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
• 102100035882 Catalase Human genes 0.000 description 1
• 108010053835 Catalase Proteins 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 108091006146 Channels Proteins 0.000 description 1
• 206010008469 Chest discomfort Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 208000027932 Collagen disease Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 208000028399 Critical Illness Diseases 0.000 description 1
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
• 244000241257 Cucumis melo Species 0.000 description 1
• 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• 108030005700 Cytochrome-b5 reductases Proteins 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
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
• 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
• 235000017274 Diospyros sandwicensis Nutrition 0.000 description 1
• 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
• 208000000059 Dyspnea Diseases 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 208000005189 Embolism Diseases 0.000 description 1
• 238000005079 FT-Raman Methods 0.000 description 1
• 229940123583 Factor Xa inhibitor Drugs 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 208000015872 Gaucher disease Diseases 0.000 description 1
• 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 1
• 208000031886 HIV Infections Diseases 0.000 description 1
• 208000037357 HIV infectious disease Diseases 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
• 208000021124 Heritable pulmonary arterial hypertension Diseases 0.000 description 1
• 101000720032 Homo sapiens Alpha-2C adrenergic receptor Proteins 0.000 description 1
• 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 description 1
• 101000588476 Homo sapiens [heparan sulfate]-glucosamine N-sulfotransferase NDST3 Proteins 0.000 description 1
• 206010021133 Hypoventilation Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
• 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
• 108010005716 Interferon beta-1a Proteins 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
• 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
• 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
• 239000002138 L01XE21 - Regorafenib Substances 0.000 description 1
• 239000002139 L01XE22 - Masitinib Substances 0.000 description 1
• UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 description 1
• 241000282838 Lama Species 0.000 description 1
• 201000005099 Langerhans cell histiocytosis Diseases 0.000 description 1
• XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
• GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 description 1
• 229940110339 Long-acting muscarinic antagonist Drugs 0.000 description 1
• 208000032376 Lung infection Diseases 0.000 description 1
• 206010025219 Lymphangioma Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
• 239000000006 Nitroglycerin Substances 0.000 description 1
• 208000011623 Obstructive Lung disease Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 102000004020 Oxygenases Human genes 0.000 description 1
• 108090000417 Oxygenases Proteins 0.000 description 1
• 208000031816 Pathologic Dilatation Diseases 0.000 description 1
• 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 1
• 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
• 108010094028 Prothrombin Proteins 0.000 description 1
• 102100027378 Prothrombin Human genes 0.000 description 1
• 208000011191 Pulmonary vascular disease Diseases 0.000 description 1
• 208000014777 Pulmonary venoocclusive disease Diseases 0.000 description 1
• 208000035977 Rare disease Diseases 0.000 description 1
• 208000037656 Respiratory Sounds Diseases 0.000 description 1
• 206010039163 Right ventricular failure Diseases 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 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
• 101000712605 Theromyzon tessulatum Theromin Proteins 0.000 description 1
• 102000002933 Thioredoxin Human genes 0.000 description 1
• 102000013090 Thioredoxin-Disulfide Reductase Human genes 0.000 description 1
• 108010079911 Thioredoxin-disulfide reductase Proteins 0.000 description 1
• 229940122388 Thrombin inhibitor Drugs 0.000 description 1
• 208000001435 Thromboembolism Diseases 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 208000024799 Thyroid disease Diseases 0.000 description 1
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
• 206010047139 Vasoconstriction Diseases 0.000 description 1
• 206010069675 Ventilation perfusion mismatch Diseases 0.000 description 1
• 206010047924 Wheezing Diseases 0.000 description 1
• IYOZTVGMEWJPKR-IJLUTSLNSA-N Y-27632 Chemical compound C1C[C@@H]([C@H](N)C)CC[C@@H]1C(=O)NC1=CC=NC=C1 IYOZTVGMEWJPKR-IJLUTSLNSA-N 0.000 description 1
• FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
• OQQVFCKUDYMWGV-UHFFFAOYSA-N [5-[1-(phenylmethyl)-3-indazolyl]-2-furanyl]methanol Chemical compound O1C(CO)=CC=C1C(C1=CC=CC=C11)=NN1CC1=CC=CC=C1 OQQVFCKUDYMWGV-UHFFFAOYSA-N 0.000 description 1
• IXQHNBONEVULTL-UHFFFAOYSA-N [O-][n+]1cc(Cl)c(NC(=O)c2ccc(OC(F)F)c3oc4ccncc4c23)c(Cl)c1 Chemical compound [O-][n+]1cc(Cl)c(NC(=O)c2ccc(OC(F)F)c3oc4ccncc4c23)c(Cl)c1 IXQHNBONEVULTL-UHFFFAOYSA-N 0.000 description 1
• 102100031395 [heparan sulfate]-glucosamine N-sulfotransferase NDST3 Human genes 0.000 description 1
• 229960000446 abciximab Drugs 0.000 description 1
• CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000000488 activin Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 230000009798 acute exacerbation Effects 0.000 description 1
• 206010069351 acute lung injury Diseases 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000005054 agglomeration Methods 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000003915 air pollution Methods 0.000 description 1
• GRTOGORTSDXSFK-XJTZBENFSA-N ajmalicine Chemical compound C1=CC=C2C(CCN3C[C@@H]4[C@H](C)OC=C([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 GRTOGORTSDXSFK-XJTZBENFSA-N 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
• 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
• 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 208000008445 altitude sickness Diseases 0.000 description 1
• LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 1
• 229960004821 amikacin Drugs 0.000 description 1
• 150000001412 amines 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
• 238000012801 analytical assay Methods 0.000 description 1
• 208000000252 angiomatosis Diseases 0.000 description 1
• 229950006323 angiotensin ii Drugs 0.000 description 1
• 229960004977 anhydrous lactose Drugs 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000002590 anti-leukotriene effect Effects 0.000 description 1
• 230000001022 anti-muscarinic effect Effects 0.000 description 1
• 230000003055 anti-obstructive effect Effects 0.000 description 1
• 239000003698 antivitamin K Substances 0.000 description 1
• 229960003886 apixaban Drugs 0.000 description 1
• 239000002830 appetite depressant Substances 0.000 description 1
• 229960003995 ataluren Drugs 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000001746 atrial effect Effects 0.000 description 1
• 229960000307 avanafil Drugs 0.000 description 1
• WEAJZXNPAWBCOA-INIZCTEOSA-N avanafil Chemical compound C1=C(Cl)C(OC)=CC=C1CNC1=NC(N2[C@@H](CCC2)CO)=NC=C1C(=O)NCC1=NC=CC=N1 WEAJZXNPAWBCOA-INIZCTEOSA-N 0.000 description 1
• 229960003005 axitinib Drugs 0.000 description 1
• RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 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
• 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
• 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
• 239000002876 beta blocker Substances 0.000 description 1
• 229940097320 beta blocking agent Drugs 0.000 description 1
• 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 1
• OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
• 108010055460 bivalirudin Proteins 0.000 description 1
• 229960001500 bivalirudin Drugs 0.000 description 1
• 230000007885 bronchoconstriction Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• BSFNCVQFIPAHLO-YTTGMZPUSA-N butyl (5S)-5-[2-(4-butoxycarbonylphenyl)ethyl-[2-(2-hydroxyphenyl)ethyl]amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate Chemical compound CCCCOC(C1=CC=C(CCN(CCC(C=CC=C2)=C2O)[C@@H](CCC2)C(C=C3)=C2N=C3C(OCCCC)=O)C=C1)=O BSFNCVQFIPAHLO-YTTGMZPUSA-N 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 229950002826 canertinib Drugs 0.000 description 1
• OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 230000002802 cardiorespiratory effect Effects 0.000 description 1
• 239000000679 carrageenan Substances 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 229940113118 carrageenan Drugs 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 229960002412 cediranib Drugs 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• UHZZMRAGKVHANO-UHFFFAOYSA-M chlormequat chloride Chemical compound [Cl-].C[N+](C)(C)CCCl UHZZMRAGKVHANO-UHFFFAOYSA-M 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 229960003405 ciprofloxacin Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
• 229960003009 clopidogrel Drugs 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 230000003750 conditioning effect Effects 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 description 1
• 239000004913 cyclooctene Substances 0.000 description 1
• 229930182912 cyclosporin Natural products 0.000 description 1
• 229960003850 dabigatran Drugs 0.000 description 1
• YBSJFWOBGCMAKL-UHFFFAOYSA-N dabigatran Chemical compound N=1C2=CC(C(=O)N(CCC(O)=O)C=3N=CC=CC=3)=CC=C2N(C)C=1CNC1=CC=C(C(N)=N)C=C1 YBSJFWOBGCMAKL-UHFFFAOYSA-N 0.000 description 1
• 229950003418 dasantafil Drugs 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 238000002716 delivery method Methods 0.000 description 1
• CARVNSROHCBVAO-BUGJESOBSA-N depelestat Chemical compound O=C([C@H](C(C)C)NC(=O)CNC(=O)[C@@H]1CSSC[C@@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H]2C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H]3CSSC[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=4C=CC(O)=CC=4)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC=4C=CC(O)=CC=4)NC(=O)[C@H]4N(CCC4)C(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC3=O)C(C)C)CSSC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(C)C)[C@@H](C)CC)C(C)C)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O)N1CCC[C@H]1C(O)=O CARVNSROHCBVAO-BUGJESOBSA-N 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• 229960004166 diltiazem Drugs 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
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229960002768 dipyridamole Drugs 0.000 description 1
• IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
• XRKMNJXYOFSTBE-UHFFFAOYSA-N disodium;iron(4+);nitroxyl anion;pentacyanide;dihydrate Chemical compound O.O.[Na+].[Na+].[Fe+4].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].O=[N-] XRKMNJXYOFSTBE-UHFFFAOYSA-N 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 238000009513 drug distribution Methods 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 238000002036 drum drying Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229960000622 edoxaban Drugs 0.000 description 1
• PSMMNJNZVZZNOI-SJILXJHISA-N edoxaban tosylate hydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.N([C@H]1CC[C@@H](C[C@H]1NC(=O)C=1SC=2CN(C)CCC=2N=1)C(=O)N(C)C)C(=O)C(=O)NC1=CC=C(Cl)C=N1 PSMMNJNZVZZNOI-SJILXJHISA-N 0.000 description 1
• 229960001123 epoprostenol Drugs 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
• FXTUOOHJPWVRKS-UHFFFAOYSA-N ethyl 5-[2-[2-[[2-chloro-4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]ethyl-[2-(4-methoxycarbonylphenyl)ethyl]amino]-5,6,7,8-tetrahydroquinoline-2-carboxylate Chemical compound C1CCC2=NC(C(=O)OCC)=CC=C2C1N(CCC=1C(=CC=CC=1)OCC=1C(=CC(=CC=1)C=1C=CC(=CC=1)C(F)(F)F)Cl)CCC1=CC=C(C(=O)OC)C=C1 FXTUOOHJPWVRKS-UHFFFAOYSA-N 0.000 description 1
• MXFKQFYUKHITMN-UHFFFAOYSA-N ethyl 5-[2-[2-[[2-chloro-4-[4-(trifluoromethyl)phenyl]phenyl]methoxy]phenyl]ethylamino]-5,6,7,8-tetrahydroquinoline-2-carboxylate;dihydrochloride Chemical compound Cl.Cl.C1CCC2=NC(C(=O)OCC)=CC=C2C1NCCC1=CC=CC=C1OCC(C(=C1)Cl)=CC=C1C1=CC=C(C(F)(F)F)C=C1 MXFKQFYUKHITMN-UHFFFAOYSA-N 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 1
• 229960002435 fasudil Drugs 0.000 description 1
• 229950010034 fidexaban Drugs 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
• 229960001318 fondaparinux Drugs 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229960002584 gefitinib Drugs 0.000 description 1
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229960003711 glyceryl trinitrate Drugs 0.000 description 1
• 208000007345 glycogen storage disease Diseases 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 229940029575 guanosine Drugs 0.000 description 1
• 229920000591 gum Polymers 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 239000002628 heparin derivative Substances 0.000 description 1
• 239000000833 heterodimer Substances 0.000 description 1
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 230000009610 hypersensitivity Effects 0.000 description 1
• 208000018875 hypoxemia Diseases 0.000 description 1
• 229960003943 hypromellose Drugs 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 230000001861 immunosuppressant effect Effects 0.000 description 1
• 239000003018 immunosuppressive agent Substances 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000012000 impulse oscillometry Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 239000001023 inorganic pigment Substances 0.000 description 1
• 229960004461 interferon beta-1a Drugs 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000037041 intracellular level Effects 0.000 description 1
• 150000008040 ionic compounds Chemical class 0.000 description 1
• OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
• 229960001888 ipratropium Drugs 0.000 description 1
• 229960001361 ipratropium bromide Drugs 0.000 description 1
• KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
• UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
• 239000002085 irritant Substances 0.000 description 1
• 231100000021 irritant Toxicity 0.000 description 1
• MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
• 229960000201 isosorbide dinitrate Drugs 0.000 description 1
• YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
• 229960003827 isosorbide mononitrate Drugs 0.000 description 1
• PURKAOJPTOLRMP-UHFFFAOYSA-N ivacaftor Chemical compound C1=C(O)C(C(C)(C)C)=CC(C(C)(C)C)=C1NC(=O)C1=CNC2=CC=CC=C2C1=O PURKAOJPTOLRMP-UHFFFAOYSA-N 0.000 description 1
• 229960004508 ivacaftor Drugs 0.000 description 1
• 238000009533 lab test Methods 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• 210000000867 larynx Anatomy 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
• 229950001845 lestaurtinib Drugs 0.000 description 1
• 229960003376 levofloxacin Drugs 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• MVYUCRDXZXLFSB-UHFFFAOYSA-N lodenafil Chemical compound CCCC1=NN(C)C(C(N=2)=O)=C1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N(CC1)CCN1CCOC(=O)OCCN(CC1)CCN1S(=O)(=O)C(C=1)=CC=C(OCC)C=1C(N1)=NC(=O)C2=C1C(CCC)=NN2C MVYUCRDXZXLFSB-UHFFFAOYSA-N 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• UFSKUSARDNFIRC-UHFFFAOYSA-N lumacaftor Chemical compound N1=C(C=2C=C(C=CC=2)C(O)=O)C(C)=CC=C1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 UFSKUSARDNFIRC-UHFFFAOYSA-N 0.000 description 1
• 229960000998 lumacaftor Drugs 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 108700025647 major vault Proteins 0.000 description 1
• 230000036244 malformation Effects 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• 229960004655 masitinib Drugs 0.000 description 1
• WJEOLQLKVOPQFV-UHFFFAOYSA-N masitinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3SC=C(N=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 WJEOLQLKVOPQFV-UHFFFAOYSA-N 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 231100000682 maximum tolerated dose Toxicity 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• DKWNMCUOEDMMIN-PKOBYXMFSA-N melagatran Chemical compound C1=CC(C(=N)N)=CC=C1CNC(=O)[C@H]1N(C(=O)[C@H](NCC(O)=O)C2CCCCC2)CC1 DKWNMCUOEDMMIN-PKOBYXMFSA-N 0.000 description 1
• 229960002137 melagatran Drugs 0.000 description 1
• 239000000155 melt Substances 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229940071648 metered dose inhaler Drugs 0.000 description 1
• FEBZFUASXKRIMS-UHFFFAOYSA-N methyl 4-(2-iodoethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCI)C=C1 FEBZFUASXKRIMS-UHFFFAOYSA-N 0.000 description 1
• 230000004089 microcirculation Effects 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 238000003801 milling Methods 0.000 description 1
• 229950002245 mirodenafil Drugs 0.000 description 1
• XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 1
• 229960004027 molsidomine Drugs 0.000 description 1
• HFCWZVGKWGOBKV-QNGWXLTQSA-N mosliciguat Chemical compound OC(=O)C1=CC=C(CCN(CCC2=CC=CC=C2OCC3=CC=C(C=C3Cl)C4=CC=C(C=C4)C(F)(F)F)[C@H]5CCCC6=C5C=CC(=N6)C(O)=O)C=C1 HFCWZVGKWGOBKV-QNGWXLTQSA-N 0.000 description 1
• 210000003205 muscle Anatomy 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 229920005615 natural polymer Polymers 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 239000002547 new drug Substances 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
• 229960001346 nilotinib Drugs 0.000 description 1
• HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
• VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
• MVPQUSQUURLQKF-MCPDASDXSA-E nonasodium;(2s,3s,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3s,4s,5r,6r)-2-carboxylato-4,5-dimethoxy-6-[(2r,3r,4s,5r,6s)-6-methoxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-4,5-disulfonatooxy-2-(sulfonatooxymethyl)oxan-3-yl]oxy-4,5-di Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S(=O)(=O)O[C@@H]1[C@@H](OS([O-])(=O)=O)[C@@H](OC)O[C@H](COS([O-])(=O)=O)[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@@H]2[C@@H]([C@@H](OS([O-])(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](OC)[C@H](O[C@@H]4[C@@H]([C@@H](OC)[C@H](OC)[C@@H](COS([O-])(=O)=O)O4)OC)[C@H](O3)C([O-])=O)OC)[C@@H](COS([O-])(=O)=O)O2)OS([O-])(=O)=O)[C@H](C([O-])=O)O1 MVPQUSQUURLQKF-MCPDASDXSA-E 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• 208000001797 obstructive sleep apnea Diseases 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
• 239000010502 orange oil Substances 0.000 description 1
• 210000004789 organ system Anatomy 0.000 description 1
• 229940082615 organic nitrates used in cardiac disease Drugs 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 244000045947 parasite Species 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 238000003921 particle size analysis Methods 0.000 description 1
• 230000007310 pathophysiology Effects 0.000 description 1
• 229960000639 pazopanib Drugs 0.000 description 1
• CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
• 229950006299 pelitinib Drugs 0.000 description 1
• WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 description 1
• 230000002688 persistence Effects 0.000 description 1
• 208000004594 persistent fetal circulation syndrome Diseases 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 238000011170 pharmaceutical development Methods 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
• 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000036314 physical performance Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 238000013310 pig model Methods 0.000 description 1
• 229960003073 pirfenidone Drugs 0.000 description 1
• ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
• 239000000902 placebo Substances 0.000 description 1
• 229940068196 placebo Drugs 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 208000007232 portal hypertension Diseases 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 150000003141 primary amines Chemical group 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
• VBVQTIZAMNWWJI-UHFFFAOYSA-N propan-2-yl n-[4,6-diamino-2-[1-[(2-fluorophenyl)methyl]pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl]-n-methylcarbamate Chemical compound N1=C(N)C(N(C)C(=O)OC(C)C)=C(N)N=C1C(C1=CC=CN=C11)=NN1CC1=CC=CC=C1F VBVQTIZAMNWWJI-UHFFFAOYSA-N 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 229940039716 prothrombin Drugs 0.000 description 1
• 238000009613 pulmonary function test Methods 0.000 description 1
• 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
• 230000008704 pulmonary vasodilation Effects 0.000 description 1
• 229950010535 razaxaban Drugs 0.000 description 1
• 229940045847 receptor mimetic Drugs 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 229960004836 regorafenib Drugs 0.000 description 1
• FNHKPVJBJVTLMP-UHFFFAOYSA-N regorafenib Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(F)C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 FNHKPVJBJVTLMP-UHFFFAOYSA-N 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 238000012827 research and development Methods 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 229950010037 revamilast Drugs 0.000 description 1
• 239000003590 rho kinase inhibitor Substances 0.000 description 1
• 230000000630 rising effect Effects 0.000 description 1
• 229960001148 rivaroxaban Drugs 0.000 description 1
• KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
• MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
• 229960002586 roflumilast Drugs 0.000 description 1
• UDOFUJZUXCZXKD-VYAAASJMSA-N s-(fluoromethyl) (6s,8s,9r,10s,11s,13s,14s,16r,17r)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carbothioate;n-[2-hydroxy-5-[1-hydroxy-2-[1-(4-methoxyphenyl)propan-2-ylamino]ethyl]phenyl Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O UDOFUJZUXCZXKD-VYAAASJMSA-N 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 238000007127 saponification reaction Methods 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 238000013341 scale-up Methods 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 208000037812 secondary pulmonary hypertension Diseases 0.000 description 1
• 238000004062 sedimentation Methods 0.000 description 1
• 238000005204 segregation Methods 0.000 description 1
• 229950003647 semaxanib Drugs 0.000 description 1
• WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 1
• 230000001235 sensitizing effect Effects 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 229940127211 short-acting beta 2 agonist Drugs 0.000 description 1
• 208000013220 shortness of breath Diseases 0.000 description 1
• 238000005029 sieve analysis Methods 0.000 description 1
• 238000010334 sieve classification Methods 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• BTGNGJJLZOIYID-UHFFFAOYSA-N sivelestat Chemical compound C1=CC(OC(=O)C(C)(C)C)=CC=C1S(=O)(=O)NC1=CC=CC=C1C(=O)NCC(O)=O BTGNGJJLZOIYID-UHFFFAOYSA-N 0.000 description 1
• 229950009343 sivelestat Drugs 0.000 description 1
• 201000002859 sleep apnea Diseases 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229940083618 sodium nitroprusside Drugs 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000010911 splenectomy Methods 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000013112 stability test Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 229960001796 sunitinib Drugs 0.000 description 1
• WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
• 230000008093 supporting effect Effects 0.000 description 1
• 230000003746 surface roughness Effects 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 208000037905 systemic hypertension Diseases 0.000 description 1
• 229960000835 tadalafil Drugs 0.000 description 1
• IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229950004186 telatinib Drugs 0.000 description 1
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
• 238000001757 thermogravimetry curve Methods 0.000 description 1
• 108060008226 thioredoxin Proteins 0.000 description 1
• 229940094937 thioredoxin Drugs 0.000 description 1
• 239000003868 thrombin inhibitor Substances 0.000 description 1
• 230000001732 thrombotic effect Effects 0.000 description 1
• 208000021510 thyroid gland disease Diseases 0.000 description 1
• PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
• 229960005001 ticlopidine Drugs 0.000 description 1
• 229960000257 tiotropium bromide Drugs 0.000 description 1
• 229960003425 tirofiban Drugs 0.000 description 1
• COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 1
• OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
• HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
• 229940038773 trisodium citrate Drugs 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 229960000438 udenafil Drugs 0.000 description 1
• IYFNEFQTYQPVOC-UHFFFAOYSA-N udenafil Chemical compound C1=C(C=2NC=3C(CCC)=NN(C)C=3C(=O)N=2)C(OCCC)=CC=C1S(=O)(=O)NCCC1CCCN1C IYFNEFQTYQPVOC-UHFFFAOYSA-N 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 229960002381 vardenafil Drugs 0.000 description 1
• 230000025033 vasoconstriction Effects 0.000 description 1
• 229950000578 vatalanib Drugs 0.000 description 1
• YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
• 229940105295 ventavis Drugs 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 229960001722 verapamil Drugs 0.000 description 1
• 229940019333 vitamin k antagonists Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000002023 wood Substances 0.000 description 1
• ZXIBCJHYVWYIKI-PZJWPPBQSA-N ximelagatran Chemical compound C1([C@@H](NCC(=O)OCC)C(=O)N2[C@@H](CC2)C(=O)NCC=2C=CC(=CC=2)C(\N)=N\O)CCCCC1 ZXIBCJHYVWYIKI-PZJWPPBQSA-N 0.000 description 1
• 229960001522 ximelagatran Drugs 0.000 description 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1