KR20050004155A

KR20050004155A - 선택적 유도성 산화질소 신타아제 억제제를 이용한 호흡기질병 및 질환의 치료 방법

선택적 유도성 산화질소 신타아제 억제제를 이용한 호흡기질병 및 질환의 치료 방법 Download PDF

Info

Publication number: KR20050004155A
Authority: KR; South Korea
Prior art keywords: alkyl; optionally substituted; amino; halo; alkoxy
Prior art date: 2002-05-16
Legal status : Ceased

Application number

KR10-2004-7018523A

Other languages

English (en)

Korean (ko)

Inventor

매닝파멜라티

Original Assignee

파마시아 코포레이션

Priority date

2002-05-16

Filing date

2003-05-16

Publication date

2005-01-12

2003-05-16 Application filed by 파마시아 코포레이션 filed Critical 파마시아 코포레이션

2005-01-12 Publication of KR20050004155A publication Critical patent/KR20050004155A/ko

Status Ceased legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 97
208000023504 respiratory system disease Diseases 0.000 title claims abstract description 41
238000011282 treatment Methods 0.000 title claims description 25
239000003112 inhibitor Substances 0.000 title abstract description 38
101100396994 Drosophila melanogaster Inos gene Proteins 0.000 title 1
108010076864 Nitric Oxide Synthase Type II Proteins 0.000 claims abstract description 8
102000011779 Nitric Oxide Synthase Type II Human genes 0.000 claims abstract description 8
125000000217 alkyl group Chemical group 0.000 claims description 182
-1 heteroaralkoxy Chemical group 0.000 claims description 163
125000005843 halogen group Chemical group 0.000 claims description 151
125000003545 alkoxy group Chemical group 0.000 claims description 139
238000006243 chemical reaction Methods 0.000 claims description 111
229910052739 hydrogen Inorganic materials 0.000 claims description 110
150000001875 compounds Chemical class 0.000 claims description 108
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 104
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 100
208000006673 asthma Diseases 0.000 claims description 78
239000001257 hydrogen Substances 0.000 claims description 76
150000002431 hydrogen Chemical class 0.000 claims description 63
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 57
125000000753 cycloalkyl group Chemical group 0.000 claims description 55
125000000623 heterocyclic group Chemical group 0.000 claims description 54
150000003839 salts Chemical class 0.000 claims description 53
229910052757 nitrogen Inorganic materials 0.000 claims description 49
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 46
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
125000003710 aryl alkyl group Chemical group 0.000 claims description 36
125000003118 aryl group Chemical group 0.000 claims description 33
229910052799 carbon Inorganic materials 0.000 claims description 31
206010006451 bronchitis Diseases 0.000 claims description 28
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 26
125000001072 heteroaryl group Chemical group 0.000 claims description 26
125000003107 substituted aryl group Chemical group 0.000 claims description 24
125000001424 substituent group Chemical group 0.000 claims description 22
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 21
229940119568 Inducible nitric oxide synthase inhibitor Drugs 0.000 claims description 21
201000010099 disease Diseases 0.000 claims description 20
125000001188 haloalkyl group Chemical group 0.000 claims description 20
125000004429 atom Chemical group 0.000 claims description 17
125000005842 heteroatom Chemical group 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
206010006458 Bronchitis chronic Diseases 0.000 claims description 15
208000007451 chronic bronchitis Diseases 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
230000001154 acute effect Effects 0.000 claims description 14
210000004072 lung Anatomy 0.000 claims description 14
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
206010061218 Inflammation Diseases 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 12
230000004054 inflammatory process Effects 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 11
230000005764 inhibitory process Effects 0.000 claims description 11
125000004414 alkyl thio group Chemical group 0.000 claims description 10
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 9
239000000356 contaminant Substances 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
206010035664 Pneumonia Diseases 0.000 claims description 8
229940124639 Selective inhibitor Drugs 0.000 claims description 8
125000004442 acylamino group Chemical group 0.000 claims description 8
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 8
239000013566 allergen Substances 0.000 claims description 8
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
125000004104 aryloxy group Chemical group 0.000 claims description 8
125000004452 carbocyclyl group Chemical group 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
208000002815 pulmonary hypertension Diseases 0.000 claims description 8
241000700605 Viruses Species 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
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 claims description 6
206010003557 Asthma exercise induced Diseases 0.000 claims description 6
208000004657 Exercise-Induced Asthma Diseases 0.000 claims description 6
208000024695 exercise-induced bronchoconstriction Diseases 0.000 claims description 6
150000004682 monohydrates Chemical class 0.000 claims description 6
206010035653 pneumoconiosis Diseases 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
201000003883 Cystic fibrosis Diseases 0.000 claims description 5
206010040047 Sepsis Diseases 0.000 claims description 5
208000027418 Wounds and injury Diseases 0.000 claims description 5
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 5
125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000004438 haloalkoxy group Chemical group 0.000 claims description 5
230000000241 respiratory effect Effects 0.000 claims description 5
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 4
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 claims description 4
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 claims description 4
208000010444 Acidosis Diseases 0.000 claims description 4
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
206010003504 Aspiration Diseases 0.000 claims description 4
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 4
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
241000272201 Columbiformes Species 0.000 claims description 4
206010021143 Hypoxia Diseases 0.000 claims description 4
208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
230000007950 acidosis Effects 0.000 claims description 4
208000026545 acidosis disease Diseases 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000005354 acylalkyl group Chemical group 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 4
150000001345 alkine derivatives Chemical class 0.000 claims description 4
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
125000005530 alkylenedioxy group Chemical group 0.000 claims description 4
125000005466 alkylenyl group Chemical group 0.000 claims description 4
208000008445 altitude sickness Diseases 0.000 claims description 4
125000000539 amino acid group Chemical group 0.000 claims description 4
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
125000003435 aroyl group Chemical group 0.000 claims description 4
125000005018 aryl alkenyl group Chemical group 0.000 claims description 4
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 4
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
125000001769 aryl amino group Chemical group 0.000 claims description 4
125000005141 aryl amino sulfonyl group Chemical group 0.000 claims description 4
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
125000005421 aryl sulfonamido group Chemical group 0.000 claims description 4
125000005110 aryl thio group Chemical group 0.000 claims description 4
125000001589 carboacyl group Chemical group 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
125000004966 cyanoalkyl group Chemical group 0.000 claims description 4
125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 4
125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
230000006378 damage Effects 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 4
125000004967 formylalkyl group Chemical group 0.000 claims description 4
125000004994 halo alkoxy alkyl group Chemical group 0.000 claims description 4
125000004995 haloalkylthio group Chemical group 0.000 claims description 4
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 4
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
125000005241 heteroarylamino group Chemical group 0.000 claims description 4
125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 4
125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
125000005150 heteroarylsulfinyl group Chemical group 0.000 claims description 4
125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
230000007954 hypoxia Effects 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
208000014674 injury Diseases 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
239000000651 prodrug Substances 0.000 claims description 4
229940002612 prodrug Drugs 0.000 claims description 4
229940048914 protamine Drugs 0.000 claims description 4
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
208000011580 syndromic disease Diseases 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims description 4
KAXFOSOXUNYWRV-IYSWYEEDSA-N (2s)-2-amino-3-[(2r)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-IYSWYEEDSA-N 0.000 claims description 3
KAXFOSOXUNYWRV-CAHLUQPWSA-N (2s)-2-amino-3-[(2s)-2-(1-aminoethylideneamino)propyl]sulfanylpropanoic acid Chemical compound CC(=N)N[C@@H](C)CSC[C@@H](N)C(O)=O KAXFOSOXUNYWRV-CAHLUQPWSA-N 0.000 claims description 3
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 claims description 3
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 claims description 3
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206010001029 Acute pulmonary oedema Diseases 0.000 claims description 3
239000004201 L-cysteine Substances 0.000 claims description 3
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230000002401 inhibitory effect Effects 0.000 claims description 3
239000012528 membrane Substances 0.000 claims description 3
230000002688 persistence Effects 0.000 claims description 3
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 claims description 2
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 claims description 2
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 claims description 2
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 claims description 2
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 claims 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 claims description 2
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 claims description 2
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 claims description 2
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 claims description 2
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 claims description 2
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 claims description 2
201000009267 bronchiectasis Diseases 0.000 claims description 2
150000004683 dihydrates Chemical class 0.000 claims description 2
230000001771 impaired effect Effects 0.000 claims description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
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 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 12
150000004684 trihydrates Chemical class 0.000 claims 5
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208000003241 Fat Embolism Diseases 0.000 claims 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 407
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 161
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235000019439 ethyl acetate Nutrition 0.000 description 134
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
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239000007787 solid Substances 0.000 description 77
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239000010410 layer Substances 0.000 description 58
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 54
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239000007858 starting material Substances 0.000 description 49
239000000706 filtrate Substances 0.000 description 46
239000000463 material Substances 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
239000000460 chlorine Substances 0.000 description 37
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 35
239000012267 brine Substances 0.000 description 34
239000013058 crude material Substances 0.000 description 31
239000000741 silica gel Substances 0.000 description 31
229910002027 silica gel Inorganic materials 0.000 description 31
238000000746 purification Methods 0.000 description 30
230000002829 reductive effect Effects 0.000 description 30
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229960004132 diethyl ether Drugs 0.000 description 28
238000003818 flash chromatography Methods 0.000 description 28
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238000003756 stirring Methods 0.000 description 27
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
238000004128 high performance liquid chromatography Methods 0.000 description 25
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
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238000004458 analytical method Methods 0.000 description 21
239000011734 sodium Substances 0.000 description 21
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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
230000035479 physiological effects, processes and functions Effects 0.000 description 1
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229920002401 polyacrylamide Polymers 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
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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238000002360 preparation method Methods 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
238000004237 preparative chromatography Methods 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
NDJBHBQUEAGIOB-UHFFFAOYSA-N propan-2-yl trifluoromethanesulfonate Chemical compound CC(C)OS(=O)(=O)C(F)(F)F NDJBHBQUEAGIOB-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
238000010926 purge Methods 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
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230000009467 reduction Effects 0.000 description 1
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238000001226 reprecipitation Methods 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
230000000630 rising effect Effects 0.000 description 1
VFIZBHJTOHUOEK-UHFFFAOYSA-N s-ethylisothiourea Chemical compound CCSC(N)=N VFIZBHJTOHUOEK-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
208000013220 shortness of breath Diseases 0.000 description 1
229910052708 sodium Inorganic materials 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
235000011006 sodium potassium tartrate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
208000024794 sputum Diseases 0.000 description 1
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239000012258 stirred mixture Substances 0.000 description 1
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238000001356 surgical procedure Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000005062 synaptic transmission Effects 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
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
210000001519 tissue Anatomy 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
230000005945 translocation 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
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
208000026726 vitreous disease Diseases 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1