TW201506024A

TW201506024A - 作為有效ｒｏｃｋ抑制劑的三環甲醯胺衍生物

作為有效ｒｏｃｋ抑制劑的三環甲醯胺衍生物 Download PDF

Info

Publication number: TW201506024A
Authority: TW; Taiwan
Prior art keywords: substituted; alkyl; chr; independently selected; group
Prior art date: 2013-07-02

Application number

TW103122739A

Other languages

English (en)

Chinese (zh)

Inventor

彌米Ｌ關

胡子倫

王彩蘭

夏倫巴薩帕帕提爾

Original Assignee

必治妥美雅史谷比公司

Priority date

2013-07-02

Filing date

2014-07-01

Publication date

2015-02-16

2014-07-01 Application filed by 必治妥美雅史谷比公司 filed Critical 必治妥美雅史谷比公司

2015-02-16 Publication of TW201506024A publication Critical patent/TW201506024A/zh

Links

239000011435 rock Substances 0.000 title abstract description 36
239000003112 inhibitor Substances 0.000 title abstract description 10
229940053202 antiepileptics carboxamide derivative Drugs 0.000 title 1
230000003389 potentiating effect Effects 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 170
150000003839 salts Chemical class 0.000 claims abstract description 64
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
125000000217 alkyl group Chemical group 0.000 claims description 528
229910020008 S(O) Inorganic materials 0.000 claims description 370
125000000623 heterocyclic group Chemical group 0.000 claims description 253
229910052731 fluorine Inorganic materials 0.000 claims description 193
229910052794 bromium Inorganic materials 0.000 claims description 185
229910052801 chlorine Inorganic materials 0.000 claims description 185
229910052739 hydrogen Inorganic materials 0.000 claims description 178
125000001424 substituent group Chemical group 0.000 claims description 172
125000002837 carbocyclic group Chemical group 0.000 claims description 171
229910052799 carbon Inorganic materials 0.000 claims description 156
-1 substituted Chemical class 0.000 claims description 124
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 98
125000000753 cycloalkyl group Chemical group 0.000 claims description 89
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 88
229910052757 nitrogen Inorganic materials 0.000 claims description 81
125000004433 nitrogen atom Chemical group N* 0.000 claims description 67
229910052760 oxygen Inorganic materials 0.000 claims description 61
125000003118 aryl group Chemical group 0.000 claims description 60
229910002091 carbon monoxide Inorganic materials 0.000 claims description 56
125000003342 alkenyl group Chemical group 0.000 claims description 53
125000004452 carbocyclyl group Chemical group 0.000 claims description 48
150000001721 carbon Chemical group 0.000 claims description 47
125000000304 alkynyl group Chemical group 0.000 claims description 44
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 39
125000001072 heteroaryl group Chemical group 0.000 claims description 38
125000005842 heteroatom Chemical group 0.000 claims description 34
238000011282 treatment Methods 0.000 claims description 31
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
201000010099 disease Diseases 0.000 claims description 22
125000004432 carbon atom Chemical group C* 0.000 claims description 21
239000003814 drug Substances 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
125000004429 atom Chemical group 0.000 claims description 13
239000003937 drug carrier Substances 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
238000006467 substitution reaction Methods 0.000 claims description 11
206010020772 Hypertension Diseases 0.000 claims description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims description 9
208000024172 Cardiovascular disease Diseases 0.000 claims description 9
101000669921 Homo sapiens Rho-associated protein kinase 2 Proteins 0.000 claims description 8
102100039314 Rho-associated protein kinase 2 Human genes 0.000 claims description 8
230000002265 prevention Effects 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
208000010228 Erectile Dysfunction Diseases 0.000 claims description 6
150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
201000001881 impotence Diseases 0.000 claims description 6
206010019280 Heart failures Diseases 0.000 claims description 5
206010028980 Neoplasm Diseases 0.000 claims description 5
125000004122 cyclic group Chemical group 0.000 claims description 5
208000001286 intracranial vasospasm Diseases 0.000 claims description 5
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
206010002383 Angina Pectoris Diseases 0.000 claims description 4
206010003225 Arteriospasm coronary Diseases 0.000 claims description 4
201000001320 Atherosclerosis Diseases 0.000 claims description 4
208000003890 Coronary Vasospasm Diseases 0.000 claims description 4
208000010412 Glaucoma Diseases 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
201000011634 coronary artery vasospasm Diseases 0.000 claims description 4
125000000547 substituted alkyl group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
208000037803 restenosis Diseases 0.000 claims description 3
208000020431 spinal cord injury Diseases 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
201000006474 Brain Ischemia Diseases 0.000 claims 1
101150063022 CHRD gene Proteins 0.000 claims 1
206010007572 Cardiac hypertrophy Diseases 0.000 claims 1
208000006029 Cardiomegaly Diseases 0.000 claims 1
206010008120 Cerebral ischaemia Diseases 0.000 claims 1
208000035473 Communicable disease Diseases 0.000 claims 1
101100274355 Danio rerio chd gene Proteins 0.000 claims 1
206010061218 Inflammation Diseases 0.000 claims 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
208000001132 Osteoporosis Diseases 0.000 claims 1
206010008118 cerebral infarction Diseases 0.000 claims 1
230000003073 embolic effect Effects 0.000 claims 1
230000004054 inflammatory process Effects 0.000 claims 1
208000031225 myocardial ischemia Diseases 0.000 claims 1
230000004770 neurodegeneration Effects 0.000 claims 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 1
125000004426 substituted alkynyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 74
230000002526 effect on cardiovascular system Effects 0.000 abstract description 6
230000003176 fibrotic effect Effects 0.000 abstract description 4
210000002460 smooth muscle Anatomy 0.000 abstract description 4
230000001363 autoimmune Effects 0.000 abstract 1
208000027866 inflammatory disease Diseases 0.000 abstract 1
230000002981 neuropathic effect Effects 0.000 abstract 1
230000000771 oncological effect Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 294
239000000543 intermediate Substances 0.000 description 253
235000019439 ethyl acetate Nutrition 0.000 description 140
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 138
239000000460 chlorine Substances 0.000 description 131
239000000243 solution Substances 0.000 description 116
238000006243 chemical reaction Methods 0.000 description 113
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 108
238000005481 NMR spectroscopy Methods 0.000 description 105
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 97
239000002904 solvent Substances 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
239000007787 solid Substances 0.000 description 69
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
239000011541 reaction mixture Substances 0.000 description 58
239000000203 mixture Substances 0.000 description 56
229910052786 argon Inorganic materials 0.000 description 54
235000002639 sodium chloride Nutrition 0.000 description 53
239000012071 phase Substances 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
238000000746 purification Methods 0.000 description 36
239000012453 solvate Substances 0.000 description 36
238000004128 high performance liquid chromatography Methods 0.000 description 35
239000002253 acid Substances 0.000 description 34
239000002585 base Substances 0.000 description 34
239000012267 brine Substances 0.000 description 31
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
238000004587 chromatography analysis Methods 0.000 description 30
239000000651 prodrug Substances 0.000 description 30
229940002612 prodrug Drugs 0.000 description 30
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
238000004366 reverse phase liquid chromatography Methods 0.000 description 29
229910052938 sodium sulfate Inorganic materials 0.000 description 28
235000011152 sodium sulphate Nutrition 0.000 description 28
239000012043 crude product Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000007821 HATU Substances 0.000 description 25
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
239000003153 chemical reaction reagent Substances 0.000 description 23
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
239000000725 suspension Substances 0.000 description 22
150000002148 esters Chemical class 0.000 description 21
239000012074 organic phase Substances 0.000 description 21
230000008878 coupling Effects 0.000 description 19
238000010168 coupling process Methods 0.000 description 19
238000005859 coupling reaction Methods 0.000 description 19
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
101150003085 Pdcl gene Proteins 0.000 description 17
229910052796 boron Inorganic materials 0.000 description 15
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
230000000694 effects Effects 0.000 description 15
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
150000001412 amines Chemical class 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
229920006395 saturated elastomer Polymers 0.000 description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
150000001299 aldehydes Chemical class 0.000 description 10
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
238000010828 elution Methods 0.000 description 10
239000011734 sodium Substances 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 9
229940079593 drug Drugs 0.000 description 9
239000010410 layer Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 8
239000005695 Ammonium acetate Substances 0.000 description 8
101100356682 Caenorhabditis elegans rho-1 gene Proteins 0.000 description 8
101150111584 RHOA gene Proteins 0.000 description 8
238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 8
235000019257 ammonium acetate Nutrition 0.000 description 8
229940043376 ammonium acetate Drugs 0.000 description 8
238000001914 filtration Methods 0.000 description 8
125000002971 oxazolyl group Chemical group 0.000 description 8
230000002441 reversible effect Effects 0.000 description 8
108010041788 rho-Associated Kinases Proteins 0.000 description 8
102000000568 rho-Associated Kinases Human genes 0.000 description 8
229940124597 therapeutic agent Drugs 0.000 description 8
208000006011 Stroke Diseases 0.000 description 7
238000003556 assay Methods 0.000 description 7
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 7
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 7
239000002245 particle Substances 0.000 description 7
230000008569 process Effects 0.000 description 7
239000000047 product Substances 0.000 description 7
239000003643 water by type Substances 0.000 description 7
IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
239000013543 active substance Substances 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000000463 material Substances 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
238000002360 preparation method Methods 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 5
NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical class BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000003513 alkali Substances 0.000 description 5
125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
235000015165 citric acid Nutrition 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 5
238000009472 formulation Methods 0.000 description 5
125000001188 haloalkyl group Chemical group 0.000 description 5
150000003840 hydrochlorides Chemical class 0.000 description 5
125000000842 isoxazolyl group Chemical group 0.000 description 5
239000007937 lozenge Substances 0.000 description 5
229910052751 metal Inorganic materials 0.000 description 5
239000002184 metal Substances 0.000 description 5
231100000252 nontoxic Toxicity 0.000 description 5
230000003000 nontoxic effect Effects 0.000 description 5
125000004430 oxygen atom Chemical group O* 0.000 description 5
125000003226 pyrazolyl group Chemical group 0.000 description 5
125000004076 pyridyl group Chemical group 0.000 description 5
238000010791 quenching Methods 0.000 description 5
238000006798 ring closing metathesis reaction Methods 0.000 description 5
230000019491 signal transduction Effects 0.000 description 5
IMRGVWZLCZERSQ-UHFFFAOYSA-N 4-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1Cl IMRGVWZLCZERSQ-UHFFFAOYSA-N 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
239000007818 Grignard reagent Substances 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
125000002527 bicyclic carbocyclic group Chemical group 0.000 description 4
230000037396 body weight Effects 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000000969 carrier Substances 0.000 description 4
NGOGFTYYXHNFQH-UHFFFAOYSA-N fasudil Chemical compound C=1C=CC2=CN=CC=C2C=1S(=O)(=O)N1CCCNCC1 NGOGFTYYXHNFQH-UHFFFAOYSA-N 0.000 description 4
229960002435 fasudil Drugs 0.000 description 4
239000012467 final product Substances 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
150000004795 grignard reagents Chemical class 0.000 description 4
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
125000002883 imidazolyl group Chemical group 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
208000017169 kidney disease Diseases 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 4
125000001624 naphthyl group Chemical group 0.000 description 4
IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000004033 plastic Substances 0.000 description 4
229920003023 plastic Polymers 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
125000003373 pyrazinyl group Chemical group 0.000 description 4
125000002098 pyridazinyl group Chemical group 0.000 description 4
125000000168 pyrrolyl group Chemical group 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
239000008107 starch Substances 0.000 description 4
239000000126 substance Substances 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
125000003831 tetrazolyl group Chemical group 0.000 description 4
125000000335 thiazolyl group Chemical group 0.000 description 4
125000001544 thienyl group Chemical group 0.000 description 4
CJWGCBRQAHCVHW-SSDOTTSWSA-N (1r)-1-(3-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC([C@@H](C)N)=C1 CJWGCBRQAHCVHW-SSDOTTSWSA-N 0.000 description 3
LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 3
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
IDDDVXIUIXWAGJ-DDSAHXNVSA-N 4-[(1r)-1-aminoethyl]-n-pyridin-4-ylcyclohexane-1-carboxamide;dihydrochloride Chemical compound Cl.Cl.C1CC([C@H](N)C)CCC1C(=O)NC1=CC=NC=C1 IDDDVXIUIXWAGJ-DDSAHXNVSA-N 0.000 description 3
150000005751 4-halopyridines Chemical class 0.000 description 3
101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 3
101100132433 Arabidopsis thaliana VIII-1 gene Proteins 0.000 description 3
101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
239000005711 Benzoic acid Substances 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
108091000080 Phosphotransferase Proteins 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
206010063837 Reperfusion injury Diseases 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
125000005605 benzo group Chemical group 0.000 description 3
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
235000010233 benzoic acid Nutrition 0.000 description 3
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
230000036772 blood pressure Effects 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
235000008504 concentrate Nutrition 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
229940093915 gynecological organic acid Drugs 0.000 description 3
125000004438 haloalkoxy group Chemical group 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
230000004047 hyperresponsiveness Effects 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
125000002757 morpholinyl group Chemical group 0.000 description 3
239000003921 oil Substances 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
235000005985 organic acids Nutrition 0.000 description 3
125000001715 oxadiazolyl group Chemical group 0.000 description 3
125000000160 oxazolidinyl group Chemical group 0.000 description 3
239000000123 paper Substances 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
102000020233 phosphotransferase Human genes 0.000 description 3
125000003367 polycyclic group Chemical group 0.000 description 3
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
208000002815 pulmonary hypertension Diseases 0.000 description 3
125000000714 pyrimidinyl group Chemical group 0.000 description 3
125000005493 quinolyl group Chemical group 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
241000894007 species Species 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
238000012360 testing method Methods 0.000 description 3
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
125000001113 thiadiazolyl group Chemical group 0.000 description 3
125000004306 triazinyl group Chemical group 0.000 description 3
125000001425 triazolyl group Chemical group 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
QGCLEUGNYRXBMZ-ZCFIWIBFSA-N (1r)-1-(4-fluorophenyl)ethanamine Chemical compound C[C@@H](N)C1=CC=C(F)C=C1 QGCLEUGNYRXBMZ-ZCFIWIBFSA-N 0.000 description 2
UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 2
GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 2
CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 2
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 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 2
HZIDIMMRFXPNBG-UHFFFAOYSA-N CN(CCN1C(C2=CN=CC=C2C2=C1C=C(C=C2)C(=O)O)=O)C Chemical compound CN(CCN1C(C2=CN=CC=C2C2=C1C=C(C=C2)C(=O)O)=O)C HZIDIMMRFXPNBG-UHFFFAOYSA-N 0.000 description 2
229930186147 Cephalosporin Natural products 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
201000000057 Coronary Stenosis Diseases 0.000 description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
CAKMPENPSABJHS-UHFFFAOYSA-N FC=1C=NC=CC1C1=C(C=C(C(=O)OC)C=C1)C(C)O Chemical compound FC=1C=NC=CC1C1=C(C=C(C(=O)OC)C=C1)C(C)O CAKMPENPSABJHS-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
208000022559 Inflammatory bowel disease Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
150000001204 N-oxides Chemical class 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
208000012902 Nervous system disease Diseases 0.000 description 2
208000025966 Neurological disease Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
229920000954 Polyglycolide Polymers 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
230000001594 aberrant effect Effects 0.000 description 2
230000002159 abnormal effect Effects 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
235000010323 ascorbic acid Nutrition 0.000 description 2
239000011668 ascorbic acid Substances 0.000 description 2
229960005070 ascorbic acid Drugs 0.000 description 2
230000008901 benefit Effects 0.000 description 2
125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 2
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000011111 cardboard Substances 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
230000012292 cell migration Effects 0.000 description 2
229940124587 cephalosporin Drugs 0.000 description 2
150000001780 cephalosporins Chemical class 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
229920001577 copolymer Polymers 0.000 description 2
208000029078 coronary artery disease Diseases 0.000 description 2
239000007822 coupling agent Substances 0.000 description 2
239000013058 crude material Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
238000013461 design Methods 0.000 description 2
229910052805 deuterium Inorganic materials 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000007884 disintegrant Substances 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
150000003948 formamides Chemical class 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
150000002334 glycols Chemical class 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
125000005945 imidazopyridyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000004968 inflammatory condition Effects 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
239000011630 iodine Substances 0.000 description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
125000005956 isoquinolyl group Chemical group 0.000 description 2
125000001786 isothiazolyl group Chemical group 0.000 description 2
125000000468 ketone group Chemical group 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000002502 liposome Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
GPMSTDWXXKAKCT-UHFFFAOYSA-N methyl 3-amino-4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C(N)=C1 GPMSTDWXXKAKCT-UHFFFAOYSA-N 0.000 description 2
JJOPQUXTGOWGLS-UHFFFAOYSA-N methyl 4-bromo-3-methylsulfanylbenzoate Chemical compound COC(=O)c1ccc(Br)c(SC)c1 JJOPQUXTGOWGLS-UHFFFAOYSA-N 0.000 description 2
SNZRPPBWRSEVIU-UHFFFAOYSA-N methyl 4-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC=C1Cl SNZRPPBWRSEVIU-UHFFFAOYSA-N 0.000 description 2
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
BREREXQRUUGQSH-MRXNPFEDSA-N n-[(6-methoxypyridin-2-yl)methylidene]-2-methylpropane-2-sulfinamide Chemical compound COC1=CC=CC(C=N[S@](=O)C(C)(C)C)=N1 BREREXQRUUGQSH-MRXNPFEDSA-N 0.000 description 2
YAEUSJDMKPZVRM-PWYDHBKHSA-N n-[1-(6-methoxypyridin-2-yl)ethyl]-2-methylpropane-2-sulfinamide Chemical compound COC1=CC=CC(C(C)N[S@](=O)C(C)(C)C)=N1 YAEUSJDMKPZVRM-PWYDHBKHSA-N 0.000 description 2
230000008692 neointimal formation Effects 0.000 description 2
208000004296 neuralgia Diseases 0.000 description 2
208000021722 neuropathic pain Diseases 0.000 description 2
238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
238000004806 packaging method and process Methods 0.000 description 2
239000003182 parenteral nutrition solution Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
150000003904 phospholipids Chemical class 0.000 description 2
229920000747 poly(lactic acid) Polymers 0.000 description 2
125000005575 polycyclic aromatic hydrocarbon group Chemical group 0.000 description 2
229920000728 polyester Polymers 0.000 description 2
239000004633 polyglycolic acid Substances 0.000 description 2
239000004626 polylactic acid Substances 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000009862 primary prevention Effects 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000011160 research Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
230000009863 secondary prevention Effects 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
150000003413 spiro compounds Chemical class 0.000 description 2
238000011699 spontaneously hypertensive rat Methods 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000003826 tablet Substances 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
239000002691 unilamellar liposome Substances 0.000 description 2
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
IPMGDPJDHDVXRQ-OGFXRTJISA-N (1r)-1-(3-methoxyphenyl)ethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC([C@@H](C)N)=C1 IPMGDPJDHDVXRQ-OGFXRTJISA-N 0.000 description 1
KRRWAASSBQOAHT-MRVPVSSYSA-N (1s)-2-azido-1-phenylethanamine Chemical compound [N-]=[N+]=NC[C@@H](N)C1=CC=CC=C1 KRRWAASSBQOAHT-MRVPVSSYSA-N 0.000 description 1
XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
GRRIMVWABNHKBX-UHFFFAOYSA-N (3-methoxyphenyl)methanamine Chemical compound COC1=CC=CC(CN)=C1 GRRIMVWABNHKBX-UHFFFAOYSA-N 0.000 description 1
CVDISKDRAMAPKZ-VHSXEESVSA-N (3S,4R)-3-amino-4-phenylpyrrolidine-1-carboxylic acid Chemical compound N[C@@H]1CN(C[C@H]1C1=CC=CC=C1)C(=O)O CVDISKDRAMAPKZ-VHSXEESVSA-N 0.000 description 1
125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
NQMOEOWCGIQVCO-UHFFFAOYSA-N 1-(6-methoxypyridin-2-yl)ethanamine Chemical compound COC1=CC=CC(C(C)N)=N1 NQMOEOWCGIQVCO-UHFFFAOYSA-N 0.000 description 1
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
WIZIBEDAPVILNL-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine-2,3-dione Chemical compound C1=CC=C2C(=O)C(=O)NC2=N1 WIZIBEDAPVILNL-UHFFFAOYSA-N 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
WEBZWISZCKYJDN-UHFFFAOYSA-N 2-(6-methoxypyridin-2-yl)ethanamine Chemical compound COC1=CC=CC(CCN)=N1 WEBZWISZCKYJDN-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
QQLWZJPMEHSISU-UHFFFAOYSA-N 2-bromo-5-fluoro-4-iodopyridine Chemical compound FC1=CN=C(Br)C=C1I QQLWZJPMEHSISU-UHFFFAOYSA-N 0.000 description 1
UODINHBLNPPDPD-UHFFFAOYSA-N 2-bromo-5-fluoropyridine Chemical compound FC1=CC=C(Br)N=C1 UODINHBLNPPDPD-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000006040 2-hexenyl group Chemical group 0.000 description 1
LIQLYTSJSBMCAH-UHFFFAOYSA-N 2-hydroxy-5-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=C(O)C(C(O)=O)=C1 LIQLYTSJSBMCAH-UHFFFAOYSA-N 0.000 description 1
125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
VDDMEGHGVOOGSO-UHFFFAOYSA-N 2-naphthalen-1-yl-1,3-oxazolidine Chemical compound N1CCOC1C1=CC=CC2=CC=CC=C12 VDDMEGHGVOOGSO-UHFFFAOYSA-N 0.000 description 1
125000006024 2-pentenyl group Chemical group 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
125000006041 3-hexenyl group Chemical group 0.000 description 1
GHKILJGWQPBQGL-UHFFFAOYSA-N 3-methoxypyridine-2-carbaldehyde Chemical compound COC1=CC=CN=C1C=O GHKILJGWQPBQGL-UHFFFAOYSA-N 0.000 description 1
JGEKZHVMIZHOGQ-UHFFFAOYSA-N 3-o-tert-butyl 1-o-methyl 4-(trifluoromethylsulfonyloxy)benzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C(C(=O)OC(C)(C)C)=C1 JGEKZHVMIZHOGQ-UHFFFAOYSA-N 0.000 description 1
JWUHENPHQGCXTG-UHFFFAOYSA-N 4-(2-fluoro-4-methoxycarbonylphenyl)pyridine-3-carboxylic acid Chemical compound FC1=CC(C(=O)OC)=CC=C1C1=CC=NC=C1C(O)=O JWUHENPHQGCXTG-UHFFFAOYSA-N 0.000 description 1
PAJSESFUWIYFNF-UHFFFAOYSA-N 4-bromo-3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(O)=C1 PAJSESFUWIYFNF-UHFFFAOYSA-N 0.000 description 1
RUTNWXBHRAIQSP-UHFFFAOYSA-N 4-bromo-3-methoxyaniline Chemical compound COC1=CC(N)=CC=C1Br RUTNWXBHRAIQSP-UHFFFAOYSA-N 0.000 description 1
TWBFZKKJFREYES-UHFFFAOYSA-N 4-bromo-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1Br TWBFZKKJFREYES-UHFFFAOYSA-N 0.000 description 1
KWVXDZLVCISXIB-UHFFFAOYSA-M 4-bromo-3-methylbenzoate Chemical compound CC1=CC(C([O-])=O)=CC=C1Br KWVXDZLVCISXIB-UHFFFAOYSA-M 0.000 description 1
SWZRBNKRTCXHPT-UHFFFAOYSA-N 4-chloro-2,5-difluoropyridine Chemical compound FC1=CC(Cl)=C(F)C=N1 SWZRBNKRTCXHPT-UHFFFAOYSA-N 0.000 description 1
APSSAJKZELMQNM-UHFFFAOYSA-N 4-chloro-5-fluoropyrimidine Chemical compound FC1=CN=CN=C1Cl APSSAJKZELMQNM-UHFFFAOYSA-N 0.000 description 1
125000006042 4-hexenyl group Chemical group 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
VSGODVJOLOLNMX-UHFFFAOYSA-N 5-(bromomethyl)-2-fluorobenzoic acid Chemical compound OC(=O)C1=CC(CBr)=CC=C1F VSGODVJOLOLNMX-UHFFFAOYSA-N 0.000 description 1
DDOFUMWLNSICHU-UHFFFAOYSA-N 5-bromo-4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=C(Br)C=N1 DDOFUMWLNSICHU-UHFFFAOYSA-N 0.000 description 1
125000006043 5-hexenyl group Chemical group 0.000 description 1
125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
CJWVZPXVOMRBJS-UHFFFAOYSA-N 5h-chromeno[3,4-c]pyridin-8-amine Chemical compound N1=CC=C2C3=CC=C(N)C=C3OCC2=C1 CJWVZPXVOMRBJS-UHFFFAOYSA-N 0.000 description 1
125000004008 6 membered carbocyclic group Chemical group 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
YDNWTNODZDSPNZ-UHFFFAOYSA-N 6-methoxypyridine-2-carbaldehyde Chemical compound COC1=CC=CC(C=O)=N1 YDNWTNODZDSPNZ-UHFFFAOYSA-N 0.000 description 1
PQLUEGQCTHEXAL-UHFFFAOYSA-N 9h-pyrido[3,4-b]indole-7-carboxylic acid Chemical compound N1=CC=C2C3=CC=C(C(=O)O)C=C3NC2=C1 PQLUEGQCTHEXAL-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
102100023818 ADP-ribosylation factor 3 Human genes 0.000 description 1
102000007469 Actins Human genes 0.000 description 1
108010085238 Actins Proteins 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
102400000345 Angiotensin-2 Human genes 0.000 description 1
101800000733 Angiotensin-2 Proteins 0.000 description 1
108010011485 Aspartame Proteins 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
239000004342 Benzoyl peroxide Substances 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
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 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
VXFFQRVAXFTHOP-UHFFFAOYSA-N C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C#N Chemical compound C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C#N VXFFQRVAXFTHOP-UHFFFAOYSA-N 0.000 description 1
LOAGQASREWMUCM-UHFFFAOYSA-N C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C(=O)NCC=1C=C(C=CC=1)C=1SC=C(N=1)C(=O)O Chemical compound C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C(=O)NCC=1C=C(C=CC=1)C=1SC=C(N=1)C(=O)O LOAGQASREWMUCM-UHFFFAOYSA-N 0.000 description 1
GDZAUIQAWIHZHF-UHFFFAOYSA-N C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C(=O)O Chemical compound C1=C2C(=CN=C1)COC=1C=C(C=CC=12)C(=O)O GDZAUIQAWIHZHF-UHFFFAOYSA-N 0.000 description 1
HMCNDYQBHJDBKF-UHFFFAOYSA-N C1=CC2=C3C=CN=CC3=CN=C2C=C1C(=O)N Chemical compound C1=CC2=C3C=CN=CC3=CN=C2C=C1C(=O)N HMCNDYQBHJDBKF-UHFFFAOYSA-N 0.000 description 1
SXZJUBJSRPSDLE-UHFFFAOYSA-N C1=NC=CC2=C1OC1=C2C=CC(=C1)C(=O)O Chemical compound C1=NC=CC2=C1OC1=C2C=CC(=C1)C(=O)O SXZJUBJSRPSDLE-UHFFFAOYSA-N 0.000 description 1
PWNGFGDXPUEFOM-UHFFFAOYSA-N CC1OC=2C=C(C=CC=2C=2C1=CN=CC=2)C(=O)NCC=1C=C(C(=O)O)C=CC=1 Chemical compound CC1OC=2C=C(C=CC=2C=2C1=CN=CC=2)C(=O)NCC=1C=C(C(=O)O)C=CC=1 PWNGFGDXPUEFOM-UHFFFAOYSA-N 0.000 description 1
FEEYKGKDRAJFDP-UHFFFAOYSA-N CCOC(=O)c1csc(n1)-c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 Chemical compound CCOC(=O)c1csc(n1)-c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 FEEYKGKDRAJFDP-UHFFFAOYSA-N 0.000 description 1
SMLZGNOAEWXLOT-UHFFFAOYSA-N CCn1c2cc(ccc2c2ccncc2c1=O)C(=O)OC Chemical compound CCn1c2cc(ccc2c2ccncc2c1=O)C(=O)OC SMLZGNOAEWXLOT-UHFFFAOYSA-N 0.000 description 1
IXBLUTWFVTVZOV-FQEVSTJZSA-N COC(=O)[C@@H](NC(=O)c1ccc-2c(OCc3cnccc-23)c1)c1ccccc1Cl Chemical compound COC(=O)[C@@H](NC(=O)c1ccc-2c(OCc3cnccc-23)c1)c1ccccc1Cl IXBLUTWFVTVZOV-FQEVSTJZSA-N 0.000 description 1
MPOVZJDNPONVJX-UHFFFAOYSA-N COC(=O)c1cc(Cl)ccc1-c1ccncc1F Chemical compound COC(=O)c1cc(Cl)ccc1-c1ccncc1F MPOVZJDNPONVJX-UHFFFAOYSA-N 0.000 description 1
XIGWFOPNODKWCW-UHFFFAOYSA-N COC(=O)c1ccc(c(CO)c1)-c1cc(Br)ncc1F Chemical compound COC(=O)c1ccc(c(CO)c1)-c1cc(Br)ncc1F XIGWFOPNODKWCW-UHFFFAOYSA-N 0.000 description 1
CUYJLORZVQEYGU-UHFFFAOYSA-N COC(=O)c1ccc(c(CO)c1)-c1cc(F)ncc1F Chemical compound COC(=O)c1ccc(c(CO)c1)-c1cc(F)ncc1F CUYJLORZVQEYGU-UHFFFAOYSA-N 0.000 description 1
PGJLSVJWPDKHMB-UHFFFAOYSA-N COC(=O)c1ccc(c(CO)c1)-c1ccncc1F Chemical compound COC(=O)c1ccc(c(CO)c1)-c1ccncc1F PGJLSVJWPDKHMB-UHFFFAOYSA-N 0.000 description 1
YFJQDTSEYXZFSP-UHFFFAOYSA-N COC(=O)c1ccc(c(F)c1)-c1cc(NC(C)=O)ncc1CO Chemical compound COC(=O)c1ccc(c(F)c1)-c1cc(NC(C)=O)ncc1CO YFJQDTSEYXZFSP-UHFFFAOYSA-N 0.000 description 1
VHKMSENVJPTNHK-UHFFFAOYSA-N COC(=O)c1ccc(c(N)c1)-c1ccncc1C(O)=O Chemical compound COC(=O)c1ccc(c(N)c1)-c1ccncc1C(O)=O VHKMSENVJPTNHK-UHFFFAOYSA-N 0.000 description 1
VXADPVVATFTMNO-UHFFFAOYSA-N COC(=O)c1ccc(c(N)c1)-c1ccncc1F Chemical compound COC(=O)c1ccc(c(N)c1)-c1ccncc1F VXADPVVATFTMNO-UHFFFAOYSA-N 0.000 description 1
VDZIMWJGCDJHSH-UHFFFAOYSA-N COC(=O)c1ccc(c(c1)C(=O)OC(C)(C)C)-c1ccncc1F Chemical compound COC(=O)c1ccc(c(c1)C(=O)OC(C)(C)C)-c1ccncc1F VDZIMWJGCDJHSH-UHFFFAOYSA-N 0.000 description 1
XDZQUMZUBIAUOB-UHFFFAOYSA-N COC(=O)c1ccc(c(c1)C(O)=O)-c1ccncc1F Chemical compound COC(=O)c1ccc(c(c1)C(O)=O)-c1ccncc1F XDZQUMZUBIAUOB-UHFFFAOYSA-N 0.000 description 1
HXZJFTIDZBKGFX-UHFFFAOYSA-N COC(=O)c1ccc2c(c1)oc1cnccc21 Chemical compound COC(=O)c1ccc2c(c1)oc1cnccc21 HXZJFTIDZBKGFX-UHFFFAOYSA-N 0.000 description 1
ADYQKAYUEMIWDX-UHFFFAOYSA-N COC(=O)c1ccc2c3ccncc3n(C)c(=O)c2c1 Chemical compound COC(=O)c1ccc2c3ccncc3n(C)c(=O)c2c1 ADYQKAYUEMIWDX-UHFFFAOYSA-N 0.000 description 1
SQYQKJZDVFVROX-UHFFFAOYSA-N COC(=O)c1cccc(CNC(=O)c2ccc-3c(OC(C)c4cnccc-34)c2)c1 Chemical compound COC(=O)c1cccc(CNC(=O)c2ccc-3c(OC(C)c4cnccc-34)c2)c1 SQYQKJZDVFVROX-UHFFFAOYSA-N 0.000 description 1
PGBWRDRCWRRROQ-UHFFFAOYSA-N COC(=O)c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 Chemical compound COC(=O)c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 PGBWRDRCWRRROQ-UHFFFAOYSA-N 0.000 description 1
QXSHXSNJOFFSJP-UHFFFAOYSA-N COC(=O)c1cnccc1-c1ccc(cc1OC)C#N Chemical compound COC(=O)c1cnccc1-c1ccc(cc1OC)C#N QXSHXSNJOFFSJP-UHFFFAOYSA-N 0.000 description 1
LYGASPBHZSCYDL-UHFFFAOYSA-N COCCn1c2cc(ccc2c2ccncc2c1=O)C(O)=O Chemical compound COCCn1c2cc(ccc2c2ccncc2c1=O)C(O)=O LYGASPBHZSCYDL-UHFFFAOYSA-N 0.000 description 1
PVXGUMORIMJFSS-GOSISDBHSA-N C[C@@H](NC(=O)c1ccc2c(c1)n(CCN1CCCC1)c(=O)c1cnccc21)c1ccc(F)cc1 Chemical compound C[C@@H](NC(=O)c1ccc2c(c1)n(CCN1CCCC1)c(=O)c1cnccc21)c1ccc(F)cc1 PVXGUMORIMJFSS-GOSISDBHSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
MZVSDJGCELEHMH-FQEVSTJZSA-N ClC1=C(C=CC=C1)[C@@H](C(=O)NC)NC(=O)C=1C=CC2=C(C=1)OCC1=CN=CC=C12 Chemical compound ClC1=C(C=CC=C1)[C@@H](C(=O)NC)NC(=O)C=1C=CC2=C(C=1)OCC1=CN=CC=C12 MZVSDJGCELEHMH-FQEVSTJZSA-N 0.000 description 1
NYMNZQPSAGXAGY-UHFFFAOYSA-N ClC1=CC(=NC=C1C)NC(C)=O Chemical compound ClC1=CC(=NC=C1C)NC(C)=O NYMNZQPSAGXAGY-UHFFFAOYSA-N 0.000 description 1
PPDRBCDBSXNJHR-UHFFFAOYSA-N ClC=1C=CC(=C(C=1)C(C)(C)O)C1=C(C=NC=C1)F Chemical compound ClC=1C=CC(=C(C=1)C(C)(C)O)C1=C(C=NC=C1)F PPDRBCDBSXNJHR-UHFFFAOYSA-N 0.000 description 1
SWQZWXCOPYYYCU-UHFFFAOYSA-N Cn1c2cnccc2c2ccc(cc12)C(O)=O Chemical compound Cn1c2cnccc2c2ccc(cc12)C(O)=O SWQZWXCOPYYYCU-UHFFFAOYSA-N 0.000 description 1
206010011089 Coronary artery stenosis Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-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 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
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
102400000686 Endothelin-1 Human genes 0.000 description 1
101800004490 Endothelin-1 Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
YDENOUIDHCMFFC-UHFFFAOYSA-N FC=1C=C(C(=O)OC)C=CC=1C1=C(C=NC=C1)C(C)O Chemical compound FC=1C=C(C(=O)OC)C=CC=1C1=C(C=NC=C1)C(C)O YDENOUIDHCMFFC-UHFFFAOYSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108010068370 Glutens Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
101000684275 Homo sapiens ADP-ribosylation factor 3 Proteins 0.000 description 1
101001000061 Homo sapiens Protein phosphatase 1 regulatory subunit 12A Proteins 0.000 description 1
101001130437 Homo sapiens Ras-related protein Rap-2b Proteins 0.000 description 1
101000669917 Homo sapiens Rho-associated protein kinase 1 Proteins 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
IHIRNKBZPKOLQH-UHFFFAOYSA-N IC=1C=CC2=C(C=1)OCC1=CN=CC=C12 Chemical compound IC=1C=CC2=C(C=1)OCC1=CN=CC=C12 IHIRNKBZPKOLQH-UHFFFAOYSA-N 0.000 description 1
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II 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](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108010037801 Myosin-Light-Chain Phosphatase Proteins 0.000 description 1
102000011131 Myosin-Light-Chain Phosphatase Human genes 0.000 description 1
QLPRQVVECWBUJT-UHFFFAOYSA-N NC=1C=C2C(=CN=1)COC=1C=C(C=CC=12)C(=O)O Chemical compound NC=1C=C2C(=CN=1)COC=1C=C(C=CC=12)C(=O)O QLPRQVVECWBUJT-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
NEIYQLBLJRQJJM-IBGZPJMESA-N OC(=O)[C@@H](NC(=O)c1ccc-2c(OCc3cnccc-23)c1)c1ccccc1Cl Chemical compound OC(=O)[C@@H](NC(=O)c1ccc-2c(OCc3cnccc-23)c1)c1ccccc1Cl NEIYQLBLJRQJJM-IBGZPJMESA-N 0.000 description 1
KTPHVYBIUOAWMJ-UHFFFAOYSA-N OC(=O)c1ccc2c(c1)[nH]c(=O)c1cnccc21 Chemical compound OC(=O)c1ccc2c(c1)[nH]c(=O)c1cnccc21 KTPHVYBIUOAWMJ-UHFFFAOYSA-N 0.000 description 1
CEZVZFAVCIZSIS-UHFFFAOYSA-N OC(=O)c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 Chemical compound OC(=O)c1cccc(CNC(=O)c2ccc-3c(OCc4cnccc-34)c2)c1 CEZVZFAVCIZSIS-UHFFFAOYSA-N 0.000 description 1
PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 1
REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001710 Polyorthoester Polymers 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
102100036547 Protein phosphatase 1 regulatory subunit 12A Human genes 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
208000002200 Respiratory Hypersensitivity Diseases 0.000 description 1
102100039313 Rho-associated protein kinase 1 Human genes 0.000 description 1
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
108091027076 Spiegelmer Proteins 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
238000006069 Suzuki reaction reaction Methods 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000050488 Urotensin II Human genes 0.000 description 1
108010018369 Urotensin II Proteins 0.000 description 1
206010047295 Ventricular hypertrophy Diseases 0.000 description 1
208000027418 Wounds and injury 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
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
QMCZMSKKAHWYBJ-GFCCVEGCSA-N [(2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylethyl] methanesulfonate Chemical compound CC(C)(C)OC(=O)N[C@H](COS(C)(=O)=O)C1=CC=CC=C1 QMCZMSKKAHWYBJ-GFCCVEGCSA-N 0.000 description 1
CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
239000000654 additive Substances 0.000 description 1
239000000853 adhesive Substances 0.000 description 1
230000001070 adhesive effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
208000037883 airway inflammation Diseases 0.000 description 1
150000001336 alkenes Chemical group 0.000 description 1
125000006177 alkyl benzyl group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229920000469 amphiphilic block copolymer Polymers 0.000 description 1
229950006323 angiotensin ii Drugs 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
239000011260 aqueous acid Substances 0.000 description 1
125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
238000010420 art technique Methods 0.000 description 1
239000000605 aspartame Substances 0.000 description 1
IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
235000010357 aspartame Nutrition 0.000 description 1
229960003438 aspartame Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
239000000440 bentonite Substances 0.000 description 1
229910000278 bentonite Inorganic materials 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
239000000480 calcium channel blocker Substances 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
235000011132 calcium sulphate Nutrition 0.000 description 1
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical group 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000021164 cell adhesion Effects 0.000 description 1
230000003915 cell function Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
125000003636 chemical group Chemical group 0.000 description 1
230000035605 chemotaxis Effects 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
150000005698 chloropyrimidines Chemical class 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
239000006071 cream Substances 0.000 description 1
229920006037 cross link polymer Polymers 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
230000021953 cytokinesis Effects 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
150000001975 deuterium Chemical group 0.000 description 1
238000011161 development Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
102000038379 digestive enzymes Human genes 0.000 description 1
108091007734 digestive enzymes Proteins 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
238000009510 drug design Methods 0.000 description 1
238000009509 drug development Methods 0.000 description 1
239000003596 drug target Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000012636 effector Substances 0.000 description 1
238000000132 electrospray ionisation Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002124 endocrine Effects 0.000 description 1
XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
CNHISCQPKKGDPO-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(Br)=N1 CNHISCQPKKGDPO-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000003709 fluoroalkyl group Chemical group 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
125000001207 fluorophenyl group Chemical group 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000003205 fragrance Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
230000006870 function Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
239000003292 glue Substances 0.000 description 1
235000021312 gluten Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000004995 haloalkylthio group Chemical group 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000003862 health status Effects 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
125000006343 heptafluoro propyl group Chemical group 0.000 description 1
125000005980 hexynyl group Chemical group 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
239000000017 hydrogel Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
238000013299 hypertensive rat model Methods 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
125000004926 indolenyl group Chemical group 0.000 description 1
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 1
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
230000007574 infarction Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
229940006461 iodide ion Drugs 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
230000000622 irritating effect Effects 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical compound C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
239000003446 ligand Substances 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
230000003908 liver function Effects 0.000 description 1
238000011866 long-term treatment Methods 0.000 description 1
VFZXMEQGIIWBFJ-UHFFFAOYSA-M magnesium;cyclopropane;bromide Chemical compound [Mg+2].[Br-].C1C[CH-]1 VFZXMEQGIIWBFJ-UHFFFAOYSA-M 0.000 description 1
DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
238000002483 medication Methods 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
BIECSXCXIXHDBC-UHFFFAOYSA-N methyl 2-bromo-5-chlorobenzoate Chemical compound COC(=O)C1=CC(Cl)=CC=C1Br BIECSXCXIXHDBC-UHFFFAOYSA-N 0.000 description 1
OWBKDJSKHXGOJY-UHFFFAOYSA-N methyl 3-(aminomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CN)=C1 OWBKDJSKHXGOJY-UHFFFAOYSA-N 0.000 description 1
NHZFATNHCDEQSO-UHFFFAOYSA-N methyl 4-(3-fluoropyridin-4-yl)-3-hydroxybenzoate Chemical compound FC=1C=NC=CC=1C1=C(C=C(C(=O)OC)C=C1)O NHZFATNHCDEQSO-UHFFFAOYSA-N 0.000 description 1
DSKIZIITNIWKOS-UHFFFAOYSA-N methyl 4-bromo-3-(dibromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(Br)C(C(Br)Br)=C1 DSKIZIITNIWKOS-UHFFFAOYSA-N 0.000 description 1
YOIIBAQYFWZDPX-UHFFFAOYSA-N methyl 4-bromo-3-(hydroxymethyl)benzoate Chemical compound COC(=O)C1=CC=C(Br)C(CO)=C1 YOIIBAQYFWZDPX-UHFFFAOYSA-N 0.000 description 1
AQKRLPBNVUWCMY-UHFFFAOYSA-N methyl 4-bromo-3-(methylamino)benzoate Chemical compound CNC1=CC(C(=O)OC)=CC=C1Br AQKRLPBNVUWCMY-UHFFFAOYSA-N 0.000 description 1
URENGDOGLKEOKE-UHFFFAOYSA-N methyl 5-(aminomethyl)-2-fluorobenzoate Chemical compound COC(=O)C1=CC(CN)=CC=C1F URENGDOGLKEOKE-UHFFFAOYSA-N 0.000 description 1
KFHGSZPAIKDNFD-UHFFFAOYSA-N methyl 5-(azidomethyl)-2-fluorobenzoate Chemical compound COC(=O)C1=CC(CN=[N+]=[N-])=CC=C1F KFHGSZPAIKDNFD-UHFFFAOYSA-N 0.000 description 1
TVHLOZRVUXGWTI-UHFFFAOYSA-N methyl 5-oxo-6h-benzo[c][2,7]naphthyridine-8-carboxylate Chemical compound N1=CC=C2C3=CC=C(C(=O)OC)C=C3NC(=O)C2=C1 TVHLOZRVUXGWTI-UHFFFAOYSA-N 0.000 description 1
229940095102 methyl benzoate Drugs 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
230000005012 migration Effects 0.000 description 1
238000013508 migration Methods 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
201000006417 multiple sclerosis Diseases 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
UIGOMFDGHINZOC-UHFFFAOYSA-N n-(4-chloro-5-ethenylpyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(C=C)C=N1 UIGOMFDGHINZOC-UHFFFAOYSA-N 0.000 description 1
AJORAFCTYBOMAV-UHFFFAOYSA-N n-(5-bromo-4-chloropyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(Br)C=N1 AJORAFCTYBOMAV-UHFFFAOYSA-N 0.000 description 1
DVRUQNLSZFAFOD-CQSZACIVSA-N n-[(1r)-1-(3-methoxyphenyl)ethyl]-5h-chromeno[3,4-c]pyridine-8-carboxamide Chemical compound COC1=CC=CC([C@@H](C)NC(=O)C=2C=C3C(C4=CC=NC=C4CO3)=CC=2)=C1 DVRUQNLSZFAFOD-CQSZACIVSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
NSBIQPJIWUJBBX-UHFFFAOYSA-N n-methoxyaniline Chemical compound CONC1=CC=CC=C1 NSBIQPJIWUJBBX-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000007971 neurological deficit Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000002547 new drug Substances 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
229960002748 norepinephrine Drugs 0.000 description 1
NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000008520 organization Effects 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000037361 pathway Effects 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000005981 pentynyl group Chemical group 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
125000005561 phenanthryl group Chemical group 0.000 description 1
FLHQDVBEWAULIZ-UHFFFAOYSA-N phenol;prop-2-enamide Chemical compound NC(=O)C=C.OC1=CC=CC=C1 FLHQDVBEWAULIZ-UHFFFAOYSA-N 0.000 description 1
229950000688 phenothiazine Drugs 0.000 description 1
125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
239000006187 pill Substances 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000656 polylysine Polymers 0.000 description 1
229920006324 polyoxymethylene Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000009117 preventive therapy Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
238000010926 purge Methods 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000016487 regulation of smooth muscle contraction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000007634 remodeling Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
230000007017 scission Effects 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
230000016160 smooth muscle contraction Effects 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000007614 solvation Methods 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
229910052712 strontium Inorganic materials 0.000 description 1
CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
YALHCTUQSQRCSX-UHFFFAOYSA-N sulfane sulfuric acid Chemical compound S.OS(O)(=O)=O YALHCTUQSQRCSX-UHFFFAOYSA-N 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
FVRFUTSYZGORBM-UHFFFAOYSA-N tert-butyl n-(4-bromo-3-methoxyphenyl)carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=CC=C1Br FVRFUTSYZGORBM-UHFFFAOYSA-N 0.000 description 1
DIFATXRZXSUITE-LLVKDONJSA-N tert-butyl n-[(1s)-2-azido-1-phenylethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CN=[N+]=[N-])C1=CC=CC=C1 DIFATXRZXSUITE-LLVKDONJSA-N 0.000 description 1
IBDIOGYTZBKRGI-LLVKDONJSA-N tert-butyl n-[(1s)-2-hydroxy-1-phenylethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)C1=CC=CC=C1 IBDIOGYTZBKRGI-LLVKDONJSA-N 0.000 description 1
KHUOILLIYICVLY-UHFFFAOYSA-N tert-butyl n-[4-[3-(hydroxymethyl)pyridin-4-yl]-3-methoxyphenyl]carbamate Chemical compound COC1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC=NC=C1CO KHUOILLIYICVLY-UHFFFAOYSA-N 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
125000005309 thioalkoxy group Chemical group 0.000 description 1
125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
230000037317 transdermal delivery Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000000844 transformation Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1
PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1