KR20040039394A

KR20040039394A - 선택적 ｉｎｏｓ 억제제를 사용한 신경보호적 치료 방법

선택적 ｉｎｏｓ 억제제를 사용한 신경보호적 치료 방법 Download PDF

Info

Publication number: KR20040039394A
Authority: KR; South Korea
Prior art keywords: alkyl; halo; alkoxy; product; group
Prior art date: 2001-09-24
Legal status : Withdrawn

Application number

KR10-2004-7004170A

Other languages

English (en)

Korean (ko)

Inventor

매닝파멜라티

코너제인알

Original Assignee

파마시아 코포레이션

Priority date

2001-09-24

Filing date

2002-09-24

Publication date

2004-05-10

2002-09-24 Application filed by 파마시아 코포레이션 filed Critical 파마시아 코포레이션

2004-05-10 Publication of KR20040039394A publication Critical patent/KR20040039394A/ko

Status Withdrawn legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 79
230000000324 neuroprotective effect Effects 0.000 title claims abstract description 10
239000003112 inhibitor Substances 0.000 title description 25
101100396994 Drosophila melanogaster Inos gene Proteins 0.000 title 1
229940124639 Selective inhibitor Drugs 0.000 claims abstract description 16
108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims abstract description 13
230000000626 neurodegenerative effect Effects 0.000 claims abstract description 13
230000002265 prevention Effects 0.000 claims abstract description 12
102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 121
-1 heteroaralkoxy Chemical group 0.000 claims description 121
125000005843 halogen group Chemical group 0.000 claims description 114
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 103
125000003545 alkoxy group Chemical group 0.000 claims description 100
229910052739 hydrogen Inorganic materials 0.000 claims description 58
150000003839 salts Chemical class 0.000 claims description 57
125000000217 alkyl group Chemical group 0.000 claims description 55
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 49
125000000623 heterocyclic group Chemical group 0.000 claims description 35
235000012054 meals Nutrition 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 28
229910052757 nitrogen Inorganic materials 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
SVSARCCKBMZNMR-UHFFFAOYSA-N [1-[2-[methyl-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethyl]amino]ethyl]pyridin-4-ylidene]methyl-oxoazanium;dichloride Chemical compound [Cl-].[Cl-].C1=CC(=C[NH+]=O)C=CN1CCN(C)CCN1C=CC(=C[NH+]=O)C=C1 SVSARCCKBMZNMR-UHFFFAOYSA-N 0.000 claims description 23
229910052736 halogen Inorganic materials 0.000 claims description 23
125000000753 cycloalkyl group Chemical group 0.000 claims description 22
125000003118 aryl group Chemical group 0.000 claims description 21
125000001072 heteroaryl group Chemical group 0.000 claims description 21
150000002367 halogens Chemical class 0.000 claims description 20
125000001424 substituent group Chemical group 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
125000004429 atom Chemical group 0.000 claims description 17
208000014674 injury Diseases 0.000 claims description 17
229910052799 carbon Inorganic materials 0.000 claims description 16
206010008118 cerebral infarction Diseases 0.000 claims description 13
201000006474 Brain Ischemia Diseases 0.000 claims description 12
206010008120 Cerebral ischaemia Diseases 0.000 claims description 12
208000015122 neurodegenerative disease Diseases 0.000 claims description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
208000024827 Alzheimer disease Diseases 0.000 claims description 8
206010010904 Convulsion Diseases 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 8
230000008733 trauma Effects 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
201000006417 multiple sclerosis Diseases 0.000 claims description 7
230000002159 abnormal effect Effects 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
125000001188 haloalkyl group Chemical group 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
206010015037 epilepsy Diseases 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
239000000651 prodrug Substances 0.000 claims description 5
229940002612 prodrug Drugs 0.000 claims description 5
206010012289 Dementia Diseases 0.000 claims description 4
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
125000004438 haloalkoxy group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
125000005354 acylalkyl group Chemical group 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
125000005530 alkylenedioxy group Chemical group 0.000 claims description 3
125000005466 alkylenyl group Chemical group 0.000 claims description 3
125000003435 aroyl group Chemical group 0.000 claims description 3
125000005018 aryl alkenyl group Chemical group 0.000 claims description 3
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 3
125000001769 aryl amino group Chemical group 0.000 claims description 3
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 3
125000005421 aryl sulfonamido group Chemical group 0.000 claims description 3
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
125000005110 aryl thio group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000001589 carboacyl group Chemical group 0.000 claims description 3
125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 3
125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
125000004967 formylalkyl group Chemical group 0.000 claims description 3
125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 3
125000004995 haloalkylthio group Chemical group 0.000 claims description 3
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 3
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
125000005241 heteroarylamino group Chemical group 0.000 claims description 3
125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 3
125000005553 heteroaryloxy group Chemical group 0.000 claims description 3
125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 3
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 3
125000005368 heteroarylthio group Chemical group 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
239000011593 sulfur Substances 0.000 claims description 3
208000030507 AIDS Diseases 0.000 claims description 2
229940119568 Inducible nitric oxide synthase inhibitor Drugs 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
201000010901 lateral sclerosis Diseases 0.000 claims 1
208000005264 motor neuron disease Diseases 0.000 claims 1
230000005856 abnormality Effects 0.000 abstract description 16
238000002560 therapeutic procedure Methods 0.000 abstract description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 403
239000000047 product Substances 0.000 description 340
239000000243 solution Substances 0.000 description 221
239000000203 mixture Substances 0.000 description 165
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 159
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 152
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
235000019439 ethyl acetate Nutrition 0.000 description 134
229940093499 ethyl acetate Drugs 0.000 description 114
239000003921 oil Substances 0.000 description 114
235000019198 oils Nutrition 0.000 description 113
238000006243 chemical reaction Methods 0.000 description 108
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 105
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 102
239000011541 reaction mixture Substances 0.000 description 101
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 100
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 92
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 85
239000007787 solid Substances 0.000 description 78
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 75
239000012044 organic layer Substances 0.000 description 67
239000002904 solvent Substances 0.000 description 61
239000010410 layer Substances 0.000 description 59
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 57
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
239000007858 starting material Substances 0.000 description 51
239000000706 filtrate Substances 0.000 description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
239000000463 material Substances 0.000 description 38
239000000460 chlorine Substances 0.000 description 37
239000012267 brine Substances 0.000 description 35
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
239000000741 silica gel Substances 0.000 description 32
229910002027 silica gel Inorganic materials 0.000 description 32
229960001866 silicon dioxide Drugs 0.000 description 32
238000000746 purification Methods 0.000 description 31
229920006395 saturated elastomer Polymers 0.000 description 30
239000013058 crude material Substances 0.000 description 29
238000003818 flash chromatography Methods 0.000 description 29
238000004458 analytical method Methods 0.000 description 28
229960004132 diethyl ether Drugs 0.000 description 28
238000003756 stirring Methods 0.000 description 28
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 27
229960000583 acetic acid Drugs 0.000 description 27
102000008299 Nitric Oxide Synthase Human genes 0.000 description 26
108010021487 Nitric Oxide Synthase Proteins 0.000 description 26
230000002829 reductive effect Effects 0.000 description 26
238000004128 high performance liquid chromatography Methods 0.000 description 25
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
238000010992 reflux Methods 0.000 description 25
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 25
239000012043 crude product Substances 0.000 description 24
239000002002 slurry Substances 0.000 description 24
238000004809 thin layer chromatography Methods 0.000 description 24
239000011734 sodium Substances 0.000 description 22
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
235000011054 acetic acid Nutrition 0.000 description 20
238000001816 cooling Methods 0.000 description 20
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
230000001225 therapeutic effect Effects 0.000 description 20
239000002253 acid Substances 0.000 description 19
125000004432 carbon atom Chemical group C* 0.000 description 18
238000004587 chromatography analysis Methods 0.000 description 18
229940086542 triethylamine Drugs 0.000 description 18
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 16
230000006378 damage Effects 0.000 description 16
150000002431 hydrogen Chemical class 0.000 description 16
150000003254 radicals Chemical class 0.000 description 16
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
239000012230 colorless oil Substances 0.000 description 15
239000000377 silicon dioxide Substances 0.000 description 15
239000011701 zinc Substances 0.000 description 15
238000007906 compression Methods 0.000 description 14
230000006835 compression Effects 0.000 description 14
230000000694 effects Effects 0.000 description 14
238000004007 reversed phase HPLC Methods 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
210000004027 cell Anatomy 0.000 description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
102000004190 Enzymes Human genes 0.000 description 12
108090000790 Enzymes Proteins 0.000 description 12
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
230000004770 neurodegeneration Effects 0.000 description 12
210000003169 central nervous system Anatomy 0.000 description 11
239000002244 precipitate Substances 0.000 description 11
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 10
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 10
241000700159 Rattus Species 0.000 description 10
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 10
238000004440 column chromatography Methods 0.000 description 10
235000019253 formic acid Nutrition 0.000 description 10
210000001525 retina Anatomy 0.000 description 10
229910052938 sodium sulfate Inorganic materials 0.000 description 10
235000011152 sodium sulphate Nutrition 0.000 description 10
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 9
229930064664 L-arginine Natural products 0.000 description 9
235000014852 L-arginine Nutrition 0.000 description 9
208000027418 Wounds and injury Diseases 0.000 description 9
150000001299 aldehydes Chemical class 0.000 description 9
150000001409 amidines Chemical class 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
238000010438 heat treatment Methods 0.000 description 9
229920001467 poly(styrenesulfonates) Polymers 0.000 description 9
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
RKRLQDJTVWZXMM-UHFFFAOYSA-N 3-methyl-2h-1,2,4-oxadiazol-5-one Chemical compound CC1=NC(=O)ON1 RKRLQDJTVWZXMM-UHFFFAOYSA-N 0.000 description 8
208000010412 Glaucoma Diseases 0.000 description 8
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
238000003556 assay Methods 0.000 description 8
239000002585 base Substances 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 8
238000004108 freeze drying Methods 0.000 description 8
239000007788 liquid Substances 0.000 description 8
230000007246 mechanism Effects 0.000 description 8
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 8
239000012071 phase Substances 0.000 description 8
229920000642 polymer Polymers 0.000 description 8
238000004366 reverse phase liquid chromatography Methods 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 7
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 7
RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 7
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
239000012359 Methanesulfonyl chloride Substances 0.000 description 7
235000011089 carbon dioxide Nutrition 0.000 description 7
229960002173 citrulline Drugs 0.000 description 7
230000000875 corresponding effect Effects 0.000 description 7
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 7
239000002158 endotoxin Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000012362 glacial acetic acid Substances 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
238000002844 melting Methods 0.000 description 7
230000008018 melting Effects 0.000 description 7
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
230000008569 process Effects 0.000 description 7
239000011347 resin Substances 0.000 description 7
229920005989 resin Polymers 0.000 description 7
210000003994 retinal ganglion cell Anatomy 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 6
229910004373 HOAc Inorganic materials 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
235000019502 Orange oil Nutrition 0.000 description 6
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
229940024606 amino acid Drugs 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
239000011575 calcium Substances 0.000 description 6
238000004296 chiral HPLC Methods 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
239000007789 gas Substances 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
230000001939 inductive effect Effects 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
230000004410 intraocular pressure Effects 0.000 description 6
239000011981 lindlar catalyst Substances 0.000 description 6
201000006938 muscular dystrophy Diseases 0.000 description 6
210000003739 neck Anatomy 0.000 description 6
239000010502 orange oil Substances 0.000 description 6
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 6
230000002441 reversible effect Effects 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
VQGCWTDMOOOHCH-PFPYCLJUSA-N (z,2s)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C\CC[C@H](N)C(O)=O VQGCWTDMOOOHCH-PFPYCLJUSA-N 0.000 description 5
RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 5
102100022397 Nitric oxide synthase, brain Human genes 0.000 description 5
101710111444 Nitric oxide synthase, brain Proteins 0.000 description 5
101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
235000001014 amino acid Nutrition 0.000 description 5
239000000872 buffer Substances 0.000 description 5
239000002775 capsule Substances 0.000 description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
235000013477 citrulline Nutrition 0.000 description 5
239000013078 crystal Substances 0.000 description 5
230000001419 dependent effect Effects 0.000 description 5
201000010099 disease Diseases 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
239000000428 dust Substances 0.000 description 5
239000003480 eluent Substances 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000006260 foam Substances 0.000 description 5
238000005984 hydrogenation reaction Methods 0.000 description 5
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Inorganic materials [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 5
230000004112 neuroprotection Effects 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
238000000926 separation method Methods 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
239000000126 substance Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
210000001519 tissue Anatomy 0.000 description 5
CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 description 5
229910052725 zinc Inorganic materials 0.000 description 5
MAGCVRLGTQSVGF-WCCKRBBISA-N (2r)-2-amino-2-methyl-3-sulfanylpropanoic acid;hydrochloride Chemical compound Cl.SC[C@@](N)(C)C(O)=O MAGCVRLGTQSVGF-WCCKRBBISA-N 0.000 description 4
VQGCWTDMOOOHCH-DKCNVOGISA-N (e,2s)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C/CC[C@H](N)C(O)=O VQGCWTDMOOOHCH-DKCNVOGISA-N 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
101001124991 Homo sapiens Nitric oxide synthase, inducible Proteins 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
208000034189 Sclerosis Diseases 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
150000001413 amino acids Chemical class 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000006727 cell loss Effects 0.000 description 4
235000015165 citric acid Nutrition 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
229940093915 gynecological organic acid Drugs 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
238000001727 in vivo Methods 0.000 description 4
230000000302 ischemic effect Effects 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
238000004949 mass spectrometry Methods 0.000 description 4
GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
235000010446 mineral oil Nutrition 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
210000003733 optic disk Anatomy 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
235000005985 organic acids Nutrition 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000000527 sonication Methods 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
CPUSCHYXEUZMSV-ZETCQYMHSA-N (2s)-2,6-diamino-2-methylhexanoic acid Chemical class OC(=O)[C@](N)(C)CCCCN CPUSCHYXEUZMSV-ZETCQYMHSA-N 0.000 description 3
GPMLMWSFTHYNMU-GOJXHPMJSA-N (e,2s)-2-amino-7-(1-aminoethylideneamino)-6-fluoro-2-methylhept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C/CC[C@](C)(N)C(O)=O GPMLMWSFTHYNMU-GOJXHPMJSA-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
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
102000000584 Calmodulin Human genes 0.000 description 3
108010041952 Calmodulin Proteins 0.000 description 3
239000004215 Carbon black (E152) Substances 0.000 description 3
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
208000003098 Ganglion Cysts Diseases 0.000 description 3
101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
MCYHPZGUONZRGO-VKHMYHEASA-N L-cysteine methyl ester hydrochloride Natural products COC(=O)[C@@H](N)CS MCYHPZGUONZRGO-VKHMYHEASA-N 0.000 description 3
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
229930182816 L-glutamine Natural products 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
229910002651 NO3 Inorganic materials 0.000 description 3
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
208000005400 Synovial Cyst Diseases 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
235000010323 ascorbic acid Nutrition 0.000 description 3
239000011668 ascorbic acid Substances 0.000 description 3
229960005070 ascorbic acid Drugs 0.000 description 3
230000009286 beneficial effect Effects 0.000 description 3
LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
229910002091 carbon monoxide Inorganic materials 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
238000002648 combination therapy Methods 0.000 description 3
ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 3
230000001066 destructive effect Effects 0.000 description 3
150000005690 diesters Chemical class 0.000 description 3
238000004821 distillation Methods 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000003821 enantio-separation Methods 0.000 description 3
230000003511 endothelial effect Effects 0.000 description 3
239000000066 endothelium dependent relaxing factor Substances 0.000 description 3
210000003989 endothelium vascular Anatomy 0.000 description 3
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 3
YJSIYYFSBCZIMG-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate;hydrochloride Chemical compound Cl.CCOC(=O)C(N)=O YJSIYYFSBCZIMG-UHFFFAOYSA-N 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000000174 gluconic acid Substances 0.000 description 3
235000012208 gluconic acid Nutrition 0.000 description 3
229960002989 glutamic acid Drugs 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
229930195733 hydrocarbon Natural products 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
150000002466 imines Chemical class 0.000 description 3
239000012535 impurity Substances 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
230000000670 limiting effect Effects 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
150000004702 methyl esters Chemical class 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
238000002156 mixing Methods 0.000 description 3
150000004682 monohydrates Chemical class 0.000 description 3
210000005036 nerve Anatomy 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
125000004430 oxygen atom Chemical group O* 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
230000001575 pathological effect Effects 0.000 description 3
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 3
208000032253 retinal ischemia Diseases 0.000 description 3
229910001220 stainless steel Inorganic materials 0.000 description 3
239000010935 stainless steel Substances 0.000 description 3
150000003457 sulfones Chemical class 0.000 description 3
150000003462 sulfoxides Chemical class 0.000 description 3
125000004434 sulfur atom Chemical group 0.000 description 3
239000006228 supernatant Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
PVNUIRUAPVSSOK-UHFFFAOYSA-N tert-butylimino(tripyrrolidin-1-yl)-$l^{5}-phosphane Chemical compound C1CCCN1P(N1CCCC1)(=NC(C)(C)C)N1CCCC1 PVNUIRUAPVSSOK-UHFFFAOYSA-N 0.000 description 3
230000002792 vascular Effects 0.000 description 3
238000005406 washing Methods 0.000 description 3
RDZZYSHKEABCLK-LURJTMIESA-N (2r)-2-amino-3-(2-aminoethylsulfanyl)-2-methylpropanoic acid Chemical compound OC(=O)[C@](N)(C)CSCCN RDZZYSHKEABCLK-LURJTMIESA-N 0.000 description 2
NNJQSTNVPJLAPP-JZGIKJSDSA-N (2r)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfanyl]-2-methylpropanoic acid;dihydrochloride Chemical compound Cl.Cl.CC(=N)NCCSC[C@](C)(N)C(O)=O NNJQSTNVPJLAPP-JZGIKJSDSA-N 0.000 description 2
HXKKHQJGJAFBHI-VKHMYHEASA-N (2s)-1-aminopropan-2-ol Chemical compound C[C@H](O)CN HXKKHQJGJAFBHI-VKHMYHEASA-N 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
GPMLMWSFTHYNMU-VMKBVTSJSA-N (e,2r)-2-amino-7-(1-aminoethylideneamino)-6-fluoro-2-methylhept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C/CC[C@@](C)(N)C(O)=O GPMLMWSFTHYNMU-VMKBVTSJSA-N 0.000 description 2
ZLBLGYXDADNGOG-DKCNVOGISA-N (e,2s)-2-amino-6-fluoro-7-[1-(hydroxyamino)ethylideneamino]hept-5-enoic acid Chemical compound ON=C(C)NC\C(F)=C/CC[C@H](N)C(O)=O ZLBLGYXDADNGOG-DKCNVOGISA-N 0.000 description 2
XRYVIWRHMIMIDT-ATPLWMGHSA-N (z,2s)-2-amino-7-(1-aminoethylideneamino)-2-methylhept-5-enoic acid Chemical compound CC(=N)NC\C=C/CC[C@](C)(N)C(O)=O XRYVIWRHMIMIDT-ATPLWMGHSA-N 0.000 description 2
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 2
FJJYHTVHBVXEEQ-UHFFFAOYSA-N 2,2-dimethylpropanal Chemical compound CC(C)(C)C=O FJJYHTVHBVXEEQ-UHFFFAOYSA-N 0.000 description 2
RYZAKOLTPLYZGH-UHFFFAOYSA-N 2-[fluorooxy(hydroxy)phosphoryl]acetic acid Chemical compound OC(=O)CP(O)(=O)OF RYZAKOLTPLYZGH-UHFFFAOYSA-N 0.000 description 2
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 2
VSCBATMPTLKTOV-UHFFFAOYSA-N 2-tert-butylimino-n,n-diethyl-1,3-dimethyl-1,3,2$l^{5}-diazaphosphinan-2-amine Chemical compound CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C VSCBATMPTLKTOV-UHFFFAOYSA-N 0.000 description 2
PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical compound O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 description 2
BIGWXAGEQONZGD-UHFFFAOYSA-N 2h-oxadiazol-5-one Chemical compound O=C1C=NNO1 BIGWXAGEQONZGD-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
VMSHSTRJSCOQPT-UHFFFAOYSA-N 5-(oxan-2-yloxy)pent-2-en-1-ol Chemical compound OCC=CCCOC1CCCCO1 VMSHSTRJSCOQPT-UHFFFAOYSA-N 0.000 description 2
KFJFUCUVVHTXHH-UHFFFAOYSA-N 5-(oxan-2-yloxy)pent-2-yn-1-ol Chemical compound OCC#CCCOC1CCCCO1 KFJFUCUVVHTXHH-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
208000029483 Acquired immunodeficiency Diseases 0.000 description 2
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Substances 0.000 description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
229920002785 Croscarmellose sodium Polymers 0.000 description 2
108090000695 Cytokines Proteins 0.000 description 2
102000004127 Cytokines Human genes 0.000 description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
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 2
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
GHSJKUNUIHUPDF-BYPYZUCNSA-N L-thialysine Chemical compound NCCSC[C@H](N)C(O)=O GHSJKUNUIHUPDF-BYPYZUCNSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 2
102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 2
LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
102000001708 Protein Isoforms Human genes 0.000 description 2
108010029485 Protein Isoforms Proteins 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
208000017442 Retinal disease Diseases 0.000 description 2
206010038923 Retinopathy Diseases 0.000 description 2
206010039710 Scleroderma Diseases 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
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 2
239000007983 Tris buffer Substances 0.000 description 2
108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
206010046851 Uveitis Diseases 0.000 description 2
NNECWOFSXHUSKH-UHFFFAOYSA-N [K].CC1=NOC(=O)N1 Chemical compound [K].CC1=NOC(=O)N1 NNECWOFSXHUSKH-UHFFFAOYSA-N 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000003463 adsorbent Substances 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 2
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
239000003125 aqueous solvent Substances 0.000 description 2
230000003140 astrocytic effect Effects 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
229940092714 benzenesulfonic acid Drugs 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
RKYZDASODLLCMM-VIFPVBQESA-N benzyl n-[(2s)-2-hydroxypropyl]carbamate Chemical compound C[C@H](O)CNC(=O)OCC1=CC=CC=C1 RKYZDASODLLCMM-VIFPVBQESA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000037396 body weight Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
229940045348 brown mixture Drugs 0.000 description 2
ARUJJNVNLJPSDO-UHFFFAOYSA-N butanamide;hydrochloride Chemical compound Cl.CCCC(N)=O ARUJJNVNLJPSDO-UHFFFAOYSA-N 0.000 description 2
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 2
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
210000000845 cartilage Anatomy 0.000 description 2
208000015114 central nervous system disease Diseases 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000011097 chromatography purification Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
230000001276 controlling effect Effects 0.000 description 2
229960001681 croscarmellose sodium Drugs 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
150000004683 dihydrates Chemical class 0.000 description 2
NCBFTYFOPLPRBX-UHFFFAOYSA-N dimethyl azodicarboxylate Substances COC(=O)N=NC(=O)OC NCBFTYFOPLPRBX-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000004406 elevated intraocular pressure Effects 0.000 description 2
210000002889 endothelial cell Anatomy 0.000 description 2
210000003038 endothelium Anatomy 0.000 description 2
230000002255 enzymatic effect Effects 0.000 description 2
239000002024 ethyl acetate extract Substances 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000000799 fluorescence microscopy Methods 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
DVGHHMFBFOTGLM-UHFFFAOYSA-L fluorogold Chemical compound F[Au][Au]F DVGHHMFBFOTGLM-UHFFFAOYSA-L 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
239000011630 iodine Substances 0.000 description 2
150000003951 lactams Chemical class 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
229960000448 lactic acid Drugs 0.000 description 2
YPJRHEKCFKOVRT-UHFFFAOYSA-N lerociclib Chemical compound C1CN(C(C)C)CCN1C(C=N1)=CC=C1NC1=NC=C(C=C2N3C4(CCCCC4)CNC2=O)C3=N1 YPJRHEKCFKOVRT-UHFFFAOYSA-N 0.000 description 2
238000011068 loading method Methods 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
239000011976 maleic acid Substances 0.000 description 2
239000001630 malic acid Substances 0.000 description 2
235000011090 malic acid Nutrition 0.000 description 2
229940099690 malic acid Drugs 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
NCBFTYFOPLPRBX-AATRIKPKSA-N methyl (ne)-n-methoxycarbonyliminocarbamate Chemical compound COC(=O)\N=N\C(=O)OC NCBFTYFOPLPRBX-AATRIKPKSA-N 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
239000007758 minimum essential medium Substances 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
238000011859 neuroprotective therapy Methods 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
239000000236 nitric oxide synthase inhibitor Substances 0.000 description 2
210000001328 optic nerve Anatomy 0.000 description 2
150000002923 oximes Chemical class 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229960003531 phenolsulfonphthalein Drugs 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
150000004714 phosphonium salts Chemical class 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
229910000343 potassium bisulfate Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
NDJBHBQUEAGIOB-UHFFFAOYSA-N propan-2-yl trifluoromethanesulfonate Chemical compound CC(C)OS(=O)(=O)C(F)(F)F NDJBHBQUEAGIOB-UHFFFAOYSA-N 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
230000004224 protection Effects 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
238000010791 quenching Methods 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000004044 response Effects 0.000 description 2
230000002207 retinal effect Effects 0.000 description 2
CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 2
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
238000010898 silica gel chromatography Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
235000011006 sodium potassium tartrate Nutrition 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
238000012360 testing method Methods 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
238000005292 vacuum distillation Methods 0.000 description 2
238000007738 vacuum evaporation Methods 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
DHJNMQLRMOVIRR-VIFPVBQESA-N (2S)-2-[2-(1-aminoethylideneamino)ethylsulfanylmethoxy]-3-hydroxy-2-(methylamino)propanoic acid Chemical compound N=C(C)NCCSCO[C@@](NC)(CO)C(=O)O DHJNMQLRMOVIRR-VIFPVBQESA-N 0.000 description 1
WZCRLODIBIRXSM-FZMZJTMJSA-N (2S,4S)-3-benzyl-2-tert-butyl-4-methyl-1,3-oxazolidin-5-one Chemical compound C[C@H]1C(=O)O[C@H](N1CC2=CC=CC=C2)C(C)(C)C WZCRLODIBIRXSM-FZMZJTMJSA-N 0.000 description 1
CPUSCHYXEUZMSV-SSDOTTSWSA-N (2r)-2,6-diamino-2-methylhexanoic acid Chemical class OC(=O)[C@@](N)(C)CCCCN CPUSCHYXEUZMSV-SSDOTTSWSA-N 0.000 description 1
NWBJAUFHPXRBKI-QMMMGPOBSA-N (2r)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfanyl]-2-methylpropanoic acid Chemical compound CC(=N)NCCSC[C@](C)(N)C(O)=O NWBJAUFHPXRBKI-QMMMGPOBSA-N 0.000 description 1
ZXQNVEYPDCBTLD-CYQMCQFNSA-N (2r)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfinyl]-2-methylpropanoic acid Chemical compound CC(=N)NCCS(=O)C[C@](C)(N)C(O)=O ZXQNVEYPDCBTLD-CYQMCQFNSA-N 0.000 description 1
ADDDJEDAMMOVRD-QMMMGPOBSA-N (2r)-2-amino-3-[2-(1-aminoethylideneamino)ethylsulfonyl]-2-methylpropanoic acid Chemical compound CC(=N)NCCS(=O)(=O)C[C@](C)(N)C(O)=O ADDDJEDAMMOVRD-QMMMGPOBSA-N 0.000 description 1
FUOUNKGLDGJSME-JIZZDEOASA-N (2r)-2-amino-3-sulfanylpropanoic acid;dihydrochloride Chemical compound Cl.Cl.SC[C@H](N)C(O)=O FUOUNKGLDGJSME-JIZZDEOASA-N 0.000 description 1
UBXPAGGJJMSWLC-SNVBAGLBSA-N (2r)-4-hydroxy-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound OCC[C@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 UBXPAGGJJMSWLC-SNVBAGLBSA-N 0.000 description 1
YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 1
VQCFYKBTJKIGNX-QMTHXVAHSA-N (2r,4r)-3-benzoyl-2-tert-butyl-4-methyl-1,3-oxazolidin-5-one Chemical compound CC(C)(C)[C@H]1OC(=O)[C@@H](C)N1C(=O)C1=CC=CC=C1 VQCFYKBTJKIGNX-QMTHXVAHSA-N 0.000 description 1
XQMCAYQHEBZGJA-GXFFZTMASA-N (2r,5s)-5-methyl-3-phenyl-2-propan-2-yl-2,5-dihydro-1,4-oxazin-6-one Chemical compound CC(C)[C@H]1OC(=O)[C@H](C)N=C1C1=CC=CC=C1 XQMCAYQHEBZGJA-GXFFZTMASA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
AQTUACKQXJNHFQ-LURJTMIESA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCC(O)=O AQTUACKQXJNHFQ-LURJTMIESA-N 0.000 description 1
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
239000001586 (Z)-pent-2-en-1-ol Substances 0.000 description 1
AWZAWNNQJYZQAS-ONEGZZNKSA-N (e)-2-amino-6-(1-aminoethylideneamino)-2-methylhex-4-enoic acid Chemical compound CC(=N)NC\C=C\CC(C)(N)C(O)=O AWZAWNNQJYZQAS-ONEGZZNKSA-N 0.000 description 1
DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
AWZAWNNQJYZQAS-CDAZIORVSA-N (e,2r)-2-amino-6-(1-aminoethylideneamino)-2-methylhex-4-enoic acid Chemical compound CC(=N)NC\C=C\C[C@@](C)(N)C(O)=O AWZAWNNQJYZQAS-CDAZIORVSA-N 0.000 description 1
VQGCWTDMOOOHCH-HOOMWESVSA-N (e,2r)-2-amino-7-(1-aminoethylideneamino)-6-fluorohept-5-enoic acid Chemical compound CC(=N)NC\C(F)=C/CC[C@@H](N)C(O)=O VQGCWTDMOOOHCH-HOOMWESVSA-N 0.000 description 1
AWZAWNNQJYZQAS-NWALNABHSA-N (e,2s)-2-amino-6-(1-aminoethylideneamino)-2-methylhex-4-enoic acid Chemical compound CC(=N)NC\C=C\C[C@](C)(N)C(O)=O AWZAWNNQJYZQAS-NWALNABHSA-N 0.000 description 1
WHPRNFUINHDPKP-DKCNVOGISA-N (e,2s)-2-amino-7-(1-aminoethylideneamino)-6-fluoro-n-(2h-tetrazol-5-yl)hept-5-enamide Chemical compound CC(=N)NC\C(F)=C/CC[C@H](N)C(=O)NC1=NN=NN1 WHPRNFUINHDPKP-DKCNVOGISA-N 0.000 description 1
BUWVIKSJDLQOIV-IYNCYZAOSA-N (e,2s)-2-amino-7-(1-aminoethylideneamino)-6-methylhept-5-enoic acid Chemical compound CC(=N)NC\C(C)=C\CC[C@H](N)C(O)=O BUWVIKSJDLQOIV-IYNCYZAOSA-N 0.000 description 1
HDJKVYMFCYFQRH-KHVHVRLGSA-N (e,2s)-2-amino-7-(1-aminoethylideneamino)hept-5-enoic acid Chemical compound CC(=N)NC\C=C\CC[C@H](N)C(O)=O HDJKVYMFCYFQRH-KHVHVRLGSA-N 0.000 description 1
XRYVIWRHMIMIDT-TZGMSPROSA-N (z,2r)-2-amino-7-(1-aminoethylideneamino)-2-methylhept-5-enoic acid Chemical compound CC(=N)NC\C=C/CC[C@@](C)(N)C(O)=O XRYVIWRHMIMIDT-TZGMSPROSA-N 0.000 description 1
BUWVIKSJDLQOIV-WYDVEAGSSA-N (z,2s)-2-amino-7-(1-aminoethylideneamino)-6-methylhept-5-enoic acid Chemical compound CC(=N)NC\C(C)=C/CC[C@H](N)C(O)=O BUWVIKSJDLQOIV-WYDVEAGSSA-N 0.000 description 1
HDJKVYMFCYFQRH-LTMVXPGCSA-N (z,2s)-2-amino-7-(1-aminoethylideneamino)hept-5-enoic acid Chemical compound CC(=N)NC\C=C/CC[C@H](N)C(O)=O HDJKVYMFCYFQRH-LTMVXPGCSA-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
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
QBDAFARLDLCWAT-UHFFFAOYSA-N 2,3-dihydropyran-6-one Chemical compound O=C1OCCC=C1 QBDAFARLDLCWAT-UHFFFAOYSA-N 0.000 description 1
BJSVKBGQDHUBHZ-UHFFFAOYSA-N 2,4,6-trifluoroaniline Chemical compound NC1=C(F)C=C(F)C=C1F BJSVKBGQDHUBHZ-UHFFFAOYSA-N 0.000 description 1
FKBVEVWCVMZYQU-UHFFFAOYSA-N 2-(4-chlorobut-3-enyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC=CCl)C(=O)C2=C1 FKBVEVWCVMZYQU-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
KRWHENRFQNDYML-UHFFFAOYSA-N 2-[(3,4-dichlorophenyl)methylideneamino]-2-methylpropanoic acid Chemical compound CC(C(=O)O)(C)N=CC1=CC(=C(C=C1)Cl)Cl KRWHENRFQNDYML-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
AWZAWNNQJYZQAS-UHFFFAOYSA-N 2-amino-6-(1-aminoethylideneamino)-2-methylhex-4-enoic acid Chemical compound CC(N)=NCC=CCC(C)(N)C(O)=O AWZAWNNQJYZQAS-UHFFFAOYSA-N 0.000 description 1
PAGXFZPVIMEVBG-UHFFFAOYSA-N 2-aminohept-5-enoic acid Chemical compound CC=CCCC(N)C(O)=O PAGXFZPVIMEVBG-UHFFFAOYSA-N 0.000 description 1
BZZVUZRTCAMISL-UHFFFAOYSA-N 2-but-3-enoxyoxane Chemical compound C=CCCOC1CCCCO1 BZZVUZRTCAMISL-UHFFFAOYSA-N 0.000 description 1
ZQZSNKJFOFAJQX-UHFFFAOYSA-N 2-but-3-ynoxyoxane Chemical compound C#CCCOC1CCCCO1 ZQZSNKJFOFAJQX-UHFFFAOYSA-N 0.000 description 1
OAWGYHQRRDKKPP-UHFFFAOYSA-N 2-fluoro-2-phosphonoacetic acid Chemical compound OC(=O)C(F)P(O)(O)=O OAWGYHQRRDKKPP-UHFFFAOYSA-N 0.000 description 1
YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 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
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 description 1
JVSMPWHQUPKRNV-UHFFFAOYSA-N 2h-tetrazol-5-amine;hydrate Chemical compound O.NC=1N=NNN=1 JVSMPWHQUPKRNV-UHFFFAOYSA-N 0.000 description 1
ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
ZURLOZJIDLZAOI-UHFFFAOYSA-N 3,4-dihydropyrazol-5-one Chemical class O=C1CCN=N1 ZURLOZJIDLZAOI-UHFFFAOYSA-N 0.000 description 1
WGWCJTNWUFFGFH-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxypropanal Chemical compound CC(C)(C)[Si](C)(C)OCCC=O WGWCJTNWUFFGFH-UHFFFAOYSA-N 0.000 description 1
UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
VDMYBCMYQVQLTR-UHFFFAOYSA-N 4-(5-hydroxypent-2-enyl)-3-methyl-1,2,4-oxadiazol-5-one Chemical compound CC1=NOC(=O)N1CC=CCCO VDMYBCMYQVQLTR-UHFFFAOYSA-N 0.000 description 1
NRWICHBDAPRDAC-UHFFFAOYSA-N 4-(5-iodopent-2-enyl)-3-methyl-1,2,4-oxadiazol-5-one Chemical compound CC1=NOC(=O)N1CC=CCCI NRWICHBDAPRDAC-UHFFFAOYSA-N 0.000 description 1
XLTUHEHHGFWZRN-XYOKQWHBSA-N 4-[(e)-5-[tert-butyl(dimethyl)silyl]oxy-2-fluoropent-2-enyl]-3-methyl-1,2,4-oxadiazol-5-one Chemical compound CC1=NOC(=O)N1C\C(F)=C/CCO[Si](C)(C)C(C)(C)C XLTUHEHHGFWZRN-XYOKQWHBSA-N 0.000 description 1
229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
WZMVOYWYTWFJTK-UHFFFAOYSA-N 5-(3-methyl-5-oxo-1,2,4-oxadiazol-4-yl)pent-3-enyl methanesulfonate Chemical compound CC1=NOC(=O)N1CC=CCCOS(C)(=O)=O WZMVOYWYTWFJTK-UHFFFAOYSA-N 0.000 description 1
OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
MSTWLYMERHJCFZ-UHFFFAOYSA-N CC1=NOCN1CC=CCCO Chemical compound CC1=NOCN1CC=CCCO MSTWLYMERHJCFZ-UHFFFAOYSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
238000005821 Claisen rearrangement reaction Methods 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
229930182847 D-glutamic acid Natural products 0.000 description 1
150000008564 D-lysines Chemical class 0.000 description 1
229920002271 DEAE-Sepharose Polymers 0.000 description 1
GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
206010021143 Hypoxia Diseases 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
235000019766 L-Lysine Nutrition 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 description 1
ZGEYCCHDTIDZAE-BYPYZUCNSA-N L-glutamic acid 5-methyl ester Chemical compound COC(=O)CC[C@H](N)C(O)=O ZGEYCCHDTIDZAE-BYPYZUCNSA-N 0.000 description 1
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 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
WHOHXJZQBJXAKL-DFWYDOINSA-N Mecysteine hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CS WHOHXJZQBJXAKL-DFWYDOINSA-N 0.000 description 1
241001272720 Medialuna californiensis Species 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 description 1
NTWVQPHTOUKMDI-YFKPBYRVSA-N N-Methyl-arginine Chemical compound CN[C@H](C(O)=O)CCCN=C(N)N NTWVQPHTOUKMDI-YFKPBYRVSA-N 0.000 description 1
NTNWOCRCBQPEKQ-UHFFFAOYSA-N NG-mono-methyl-L-arginine Natural products CN=C(N)NCCCC(N)C(O)=O NTNWOCRCBQPEKQ-UHFFFAOYSA-N 0.000 description 1
206010056677 Nerve degeneration Diseases 0.000 description 1
101710138657 Neurotoxin Proteins 0.000 description 1
SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
206010063837 Reperfusion injury Diseases 0.000 description 1
206010038910 Retinitis Diseases 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
239000004280 Sodium formate Substances 0.000 description 1
102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
206010042618 Surgical procedure repeated Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
VQLUPQZRPTXJSH-HNNXBMFYSA-N [(2s)-1-(phenylmethoxycarbonylamino)propan-2-yl] 4-methylbenzenesulfonate Chemical compound C([C@H](C)OS(=O)(=O)C=1C=CC(C)=CC=1)NC(=O)OCC1=CC=CC=C1 VQLUPQZRPTXJSH-HNNXBMFYSA-N 0.000 description 1
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000009692 acute damage Effects 0.000 description 1
238000013019 agitation Methods 0.000 description 1
IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
239000000908 ammonium hydroxide Substances 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000009697 arginine Nutrition 0.000 description 1
230000004872 arterial blood pressure Effects 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
210000004462 astrocytic glia Anatomy 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
125000004069 aziridinyl group Chemical group 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
229960004365 benzoic acid Drugs 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
FKWDZIFOVOUDAG-JTQLQIEISA-N benzyl n-[(3s)-2-oxooxolan-3-yl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N[C@H]1CCOC1=O FKWDZIFOVOUDAG-JTQLQIEISA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000002146 bilateral effect Effects 0.000 description 1
230000035587 bioadhesion Effects 0.000 description 1
230000008238 biochemical pathway Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
OTJZCIYGRUNXTP-UHFFFAOYSA-N but-3-yn-1-ol Chemical compound OCCC#C OTJZCIYGRUNXTP-UHFFFAOYSA-N 0.000 description 1
239000002021 butanolic extract Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000005341 cation exchange Methods 0.000 description 1
239000003729 cation exchange resin Substances 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000008568 cell cell communication Effects 0.000 description 1
230000005779 cell damage Effects 0.000 description 1
208000037887 cell injury Diseases 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
210000001638 cerebellum Anatomy 0.000 description 1
208000026106 cerebrovascular disease Diseases 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
150000003841 chloride salts Chemical class 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
229960004106 citric acid Drugs 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
239000012045 crude solution Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
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 1
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
229960002433 cysteine Drugs 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
238000010908 decantation Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
125000000532 dioxanyl group Chemical group 0.000 description 1
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
238000007907 direct compression Methods 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
238000009826 distribution Methods 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
230000003628 erosive effect Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-M ethanimidate Chemical compound CC([O-])=N DLFVBJFMPXGRIB-UHFFFAOYSA-M 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
JCXLZWMDXJFOOI-UHFFFAOYSA-N ethyl 2-aminopropanoate;hydron;chloride Chemical compound [Cl-].CCOC(=O)C(C)[NH3+] JCXLZWMDXJFOOI-UHFFFAOYSA-N 0.000 description 1
WUHVJSONZHSDFC-UHFFFAOYSA-N ethyl 2-chloro-2-fluoroacetate Chemical compound CCOC(=O)C(F)Cl WUHVJSONZHSDFC-UHFFFAOYSA-N 0.000 description 1
BVSRWCMAJISCTD-UHFFFAOYSA-N ethyl 2-diethoxyphosphorylpropanoate Chemical compound CCOC(=O)C(C)P(=O)(OCC)OCC BVSRWCMAJISCTD-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
JMIAPORGEDIDLT-UHFFFAOYSA-N ethyl ethanimidate Chemical compound CCOC(C)=N JMIAPORGEDIDLT-UHFFFAOYSA-N 0.000 description 1
UVECLJDRPFNRRQ-UHFFFAOYSA-N ethyl trifluoromethanesulfonate Chemical compound CCOS(=O)(=O)C(F)(F)F UVECLJDRPFNRRQ-UHFFFAOYSA-N 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
239000012467 final product Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
238000005187 foaming Methods 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000012634 fragment Substances 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000008014 freezing Effects 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
229960003711 glyceryl trinitrate Drugs 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000010931 gold Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
210000003128 head Anatomy 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
238000003364 immunohistochemistry Methods 0.000 description 1
230000001976 improved effect Effects 0.000 description 1
239000005414 inactive ingredient Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000000411 inducer Substances 0.000 description 1
230000007574 infarction Effects 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
230000035990 intercellular signaling Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
210000000936 intestine Anatomy 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
UUSXSNJAQDJKCG-UHFFFAOYSA-N iodo(methoxy)methane Chemical compound COCI UUSXSNJAQDJKCG-UHFFFAOYSA-N 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
230000002427 irreversible effect Effects 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
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
238000011813 knockout mouse model Methods 0.000 description 1
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
238000002372 labelling Methods 0.000 description 1
229940099563 lactobionic acid Drugs 0.000 description 1
150000002596 lactones Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229940046892 lead acetate Drugs 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
210000002540 macrophage Anatomy 0.000 description 1
YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 description 1
229940098895 maleic acid Drugs 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
239000012528 membrane Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
WIWSDBBLQCFGOL-YFKPBYRVSA-N methyl (2r)-2-amino-3-(2-aminoethylsulfanyl)propanoate Chemical compound COC(=O)[C@@H](N)CSCCN WIWSDBBLQCFGOL-YFKPBYRVSA-N 0.000 description 1
IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
PNZOSXMTHXKHTO-QZPNVGJNSA-N methyl (z,2s)-2-amino-7-(1-aminoethylideneamino)-2-methylhept-5-enoate Chemical compound COC(=O)[C@@](C)(N)CC\C=C/CNC(C)=N PNZOSXMTHXKHTO-QZPNVGJNSA-N 0.000 description 1
SKCGPSUDIYTVPG-UHFFFAOYSA-N methyl 2-[(3,4-dichlorophenyl)methylideneamino]propanoate Chemical compound COC(=O)C(C)N=CC1=CC=C(Cl)C(Cl)=C1 SKCGPSUDIYTVPG-UHFFFAOYSA-N 0.000 description 1
QMXXGLLLHHRPKA-UHFFFAOYSA-N methyl 2-[(4-chlorophenyl)methylideneamino]acetate Chemical compound COC(=O)CN=CC1=CC=C(Cl)C=C1 QMXXGLLLHHRPKA-UHFFFAOYSA-N 0.000 description 1
PVSJXEDBEXYLML-UHFFFAOYSA-N methyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate Chemical compound COC(=O)CP(=O)(OCC(F)(F)F)OCC(F)(F)F PVSJXEDBEXYLML-UHFFFAOYSA-N 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
244000005700 microbiome Species 0.000 description 1
210000000274 microglia Anatomy 0.000 description 1
238000000520 microinjection Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
239000004090 neuroprotective agent Substances 0.000 description 1
239000002581 neurotoxin Substances 0.000 description 1
231100000618 neurotoxin Toxicity 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical compound O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 description 1
125000000466 oxiranyl group Chemical group 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000001991 pathophysiological effect Effects 0.000 description 1
230000018052 penile erection Effects 0.000 description 1
230000035699 permeability Effects 0.000 description 1
210000001539 phagocyte Anatomy 0.000 description 1
239000002831 pharmacologic agent Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 1
PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical compound [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
238000000711 polarimetry Methods 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
DBSKLZRMGLQODM-UHFFFAOYSA-M potassium 3-methyl-5-oxo-1,2,4-oxadiazole-2-carboxylate Chemical compound CC=1N(OC(N=1)=O)C(=O)[O-].[K+] DBSKLZRMGLQODM-UHFFFAOYSA-M 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
201000006366 primary open angle glaucoma Diseases 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
238000005086 pumping Methods 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
230000000171 quenching effect Effects 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
238000011552 rat model Methods 0.000 description 1
238000004064 recycling Methods 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
229960004889 salicylic acid Drugs 0.000 description 1
FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 1
229960004617 sapropterin Drugs 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
239000001476 sodium potassium tartrate Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012453 solvate Substances 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229960004274 stearic acid Drugs 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
229950000244 sulfanilic acid Drugs 0.000 description 1
229940032330 sulfuric acid Drugs 0.000 description 1
210000003863 superior colliculi Anatomy 0.000 description 1
239000013589 supplement Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000013077 target material Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 1
FVQYBAASQSUZOP-UHFFFAOYSA-N tert-butyl n-(4-chlorobut-2-ynyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC#CCCl FVQYBAASQSUZOP-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
230000036962 time dependent Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
238000010361 transduction Methods 0.000 description 1
230000026683 transduction Effects 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000013598 vector Substances 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1