KR20150003903A - 보체 경로 조절제 및 그의 용도 - Google Patents
보체 경로 조절제 및 그의 용도 Download PDFInfo
- Publication number
- KR20150003903A KR20150003903A KR1020147033713A KR20147033713A KR20150003903A KR 20150003903 A KR20150003903 A KR 20150003903A KR 1020147033713 A KR1020147033713 A KR 1020147033713A KR 20147033713 A KR20147033713 A KR 20147033713A KR 20150003903 A KR20150003903 A KR 20150003903A
- Authority
- KR
- South Korea
- Prior art keywords
- methyl
- carbonitrile
- indol
- benzo
- imidazole
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 230000024203 complement activation Effects 0.000 title claims description 68
- 150000001875 compounds Chemical class 0.000 claims abstract description 301
- 238000000034 method Methods 0.000 claims abstract description 82
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 48
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 6
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 355
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 213
- 208000035475 disorder Diseases 0.000 claims description 108
- 201000010099 disease Diseases 0.000 claims description 105
- 150000003839 salts Chemical class 0.000 claims description 96
- 208000002780 macular degeneration Diseases 0.000 claims description 94
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 89
- 238000011282 treatment Methods 0.000 claims description 63
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 60
- NWVGXXPWOYZODV-UHFFFAOYSA-N 1h-imidazole-5-carbonitrile Chemical compound N#CC1=CN=CN1 NWVGXXPWOYZODV-UHFFFAOYSA-N 0.000 claims description 58
- 230000001404 mediated effect Effects 0.000 claims description 54
- 206010061218 Inflammation Diseases 0.000 claims description 50
- 230000004054 inflammatory process Effects 0.000 claims description 50
- 230000000295 complement effect Effects 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 44
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- 239000003814 drug Substances 0.000 claims description 39
- 208000009525 Myocarditis Diseases 0.000 claims description 35
- 206010046851 Uveitis Diseases 0.000 claims description 35
- 208000006673 asthma Diseases 0.000 claims description 35
- 230000037361 pathway Effects 0.000 claims description 35
- 230000010410 reperfusion Effects 0.000 claims description 34
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 208000001344 Macular Edema Diseases 0.000 claims description 32
- 206010025415 Macular oedema Diseases 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 201000010230 macular retinal edema Diseases 0.000 claims description 32
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 31
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 31
- 208000023275 Autoimmune disease Diseases 0.000 claims description 30
- 206010020751 Hypersensitivity Diseases 0.000 claims description 30
- 108010002350 Interleukin-2 Proteins 0.000 claims description 30
- 206010038910 Retinitis Diseases 0.000 claims description 30
- 206010047115 Vasculitis Diseases 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 208000027866 inflammatory disease Diseases 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical class 0.000 claims description 27
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 26
- 208000011580 syndromic disease Diseases 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 238000002560 therapeutic procedure Methods 0.000 claims description 23
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 22
- 230000004913 activation Effects 0.000 claims description 22
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 21
- 201000006417 multiple sclerosis Diseases 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 206010003694 Atrophy Diseases 0.000 claims description 20
- 230000037444 atrophy Effects 0.000 claims description 20
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 208000009137 Behcet syndrome Diseases 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 19
- 208000010125 myocardial infarction Diseases 0.000 claims description 19
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 18
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 18
- 208000015181 infectious disease Diseases 0.000 claims description 18
- 208000028867 ischemia Diseases 0.000 claims description 18
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 17
- 206010006482 Bronchospasm Diseases 0.000 claims description 17
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 17
- 206010070476 Haemodialysis complication Diseases 0.000 claims description 17
- 208000000616 Hemoptysis Diseases 0.000 claims description 17
- 208000012902 Nervous system disease Diseases 0.000 claims description 17
- 208000025966 Neurological disease Diseases 0.000 claims description 17
- 208000030852 Parasitic disease Diseases 0.000 claims description 17
- 208000018737 Parkinson disease Diseases 0.000 claims description 17
- 206010037457 Pulmonary vasculitis Diseases 0.000 claims description 17
- 206010063897 Renal ischaemia Diseases 0.000 claims description 17
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 17
- 230000007815 allergy Effects 0.000 claims description 17
- 230000007885 bronchoconstriction Effects 0.000 claims description 17
- 208000007475 hemolytic anemia Diseases 0.000 claims description 17
- 210000003975 mesenteric artery Anatomy 0.000 claims description 17
- 201000008383 nephritis Diseases 0.000 claims description 17
- 230000002062 proliferating effect Effects 0.000 claims description 17
- 230000002685 pulmonary effect Effects 0.000 claims description 17
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 17
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 17
- 230000009529 traumatic brain injury Effects 0.000 claims description 17
- 208000035473 Communicable disease Diseases 0.000 claims description 16
- 208000000059 Dyspnea Diseases 0.000 claims description 16
- 206010013975 Dyspnoeas Diseases 0.000 claims description 16
- 206010019668 Hepatic fibrosis Diseases 0.000 claims description 16
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 16
- 208000008589 Obesity Diseases 0.000 claims description 16
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 16
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 16
- 206010040047 Sepsis Diseases 0.000 claims description 16
- 101150046432 Tril gene Proteins 0.000 claims description 16
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 16
- 206010028417 myasthenia gravis Diseases 0.000 claims description 16
- 235000020824 obesity Nutrition 0.000 claims description 16
- 230000002980 postoperative effect Effects 0.000 claims description 16
- 231100000419 toxicity Toxicity 0.000 claims description 16
- 230000001988 toxicity Effects 0.000 claims description 16
- NICYTXJGZRYCEQ-UHFFFAOYSA-N 3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2N=CNC2=C1 NICYTXJGZRYCEQ-UHFFFAOYSA-N 0.000 claims description 15
- 208000004232 Enteritis Diseases 0.000 claims description 15
- 208000004454 Hyperalgesia Diseases 0.000 claims description 15
- 208000035154 Hyperesthesia Diseases 0.000 claims description 15
- 238000002399 angioplasty Methods 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 208000011231 Crohn disease Diseases 0.000 claims description 14
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 14
- 208000026935 allergic disease Diseases 0.000 claims description 14
- 244000309466 calf Species 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 230000009610 hypersensitivity Effects 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- PSLMIXGNCNQQRY-UHFFFAOYSA-N ethyl 1-benzothiophene-2-carboxylate Chemical compound C1=CC=C2SC(C(=O)OCC)=CC2=C1 PSLMIXGNCNQQRY-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- YWBCSLQTTRDWOU-UHFFFAOYSA-N 2-[1-(5-ethyl-7-methyl-1h-indol-4-yl)-1-methoxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(OC)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 YWBCSLQTTRDWOU-UHFFFAOYSA-N 0.000 claims description 8
- GQHLENKHMIFXHS-UHFFFAOYSA-N 2-[1-hydroxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 GQHLENKHMIFXHS-UHFFFAOYSA-N 0.000 claims description 8
- KSWFTFBEOXGXPU-UHFFFAOYSA-N 2-[1-methoxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(C)(OC)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 KSWFTFBEOXGXPU-UHFFFAOYSA-N 0.000 claims description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 8
- 230000002207 retinal effect Effects 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- QCBKRGBKYBRIBW-GKOSEXJESA-N 2-[1-(5-methoxy-7-methyl-1h-indol-4-yl)-1-(trideuteriomethoxy)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC=C(C#N)C=C2NC=1C(C)(OC([2H])([2H])[2H])C1=C(OC)C=C(C)C2=C1C=CN2 QCBKRGBKYBRIBW-GKOSEXJESA-N 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 238000001631 haemodialysis Methods 0.000 claims description 6
- 230000000322 hemodialysis Effects 0.000 claims description 6
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 6
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 6
- XQDAKZJVIKDSCF-UHFFFAOYSA-N 1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC=NC2=C1 XQDAKZJVIKDSCF-UHFFFAOYSA-N 0.000 claims description 5
- CGLIDKMUNVHAHJ-UHFFFAOYSA-N 2-[1-hydroxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 CGLIDKMUNVHAHJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- VFNCCHPOOUQFTB-UHFFFAOYSA-N 2-[(3-chloro-5-methoxy-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C(Cl)=CNC4=C(C)C=C3OC)=NC2=C1 VFNCCHPOOUQFTB-UHFFFAOYSA-N 0.000 claims description 4
- ILRCDGRTLHACEO-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 ILRCDGRTLHACEO-UHFFFAOYSA-N 0.000 claims description 4
- CJCDUWWDLYRXMX-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-hydroxymethyl]-4-methyl-1h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1C CJCDUWWDLYRXMX-UHFFFAOYSA-N 0.000 claims description 4
- PXNRTYRAHJZFCO-UHFFFAOYSA-N 2-[(5,7-dimethyl-3-phenyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound C12=C(C(O)C=3NC4=CC=C(C=C4N=3)C#N)C(C)=CC(C)=C2NC=C1C1=CC=CC=C1 PXNRTYRAHJZFCO-UHFFFAOYSA-N 0.000 claims description 4
- YBKUHYRADHOKPI-UHFFFAOYSA-N 2-[(5-chloro-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C(Cl)C=C(C=4NC=CC=43)C)=NC2=C1 YBKUHYRADHOKPI-UHFFFAOYSA-N 0.000 claims description 4
- NJOJBJOCIYCZOT-UHFFFAOYSA-N 2-[(5-ethoxy-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3OCC)=NC2=C1 NJOJBJOCIYCZOT-UHFFFAOYSA-N 0.000 claims description 4
- XOGKPRPIAZIAAB-UHFFFAOYSA-N 2-[(5-ethyl-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 XOGKPRPIAZIAAB-UHFFFAOYSA-N 0.000 claims description 4
- BXPMFXKYCJRRRD-UHFFFAOYSA-N 2-[(5-ethyl-7-methyl-1h-indol-4-yl)-methoxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(OC)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 BXPMFXKYCJRRRD-UHFFFAOYSA-N 0.000 claims description 4
- IGYZWJYCDZDCGH-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 IGYZWJYCDZDCGH-UHFFFAOYSA-N 0.000 claims description 4
- QOWJIYKJRYIXLK-UHFFFAOYSA-N 2-[1-(5-bromo-7-methyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C(Br)C=C(C=4NC=CC=43)C)=NC2=C1 QOWJIYKJRYIXLK-UHFFFAOYSA-N 0.000 claims description 4
- PRMNYNUSJPZLFN-UHFFFAOYSA-N 2-[1-(5-chloro-7-methyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C(Cl)C=C(C=4NC=CC=43)C)=NC2=C1 PRMNYNUSJPZLFN-UHFFFAOYSA-N 0.000 claims description 4
- GGMDGBGXROIQMS-UHFFFAOYSA-N 2-[1-(5-cyclopropyl-7-methyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(O)C=1C=2C=CNC=2C(C)=CC=1C1CC1 GGMDGBGXROIQMS-UHFFFAOYSA-N 0.000 claims description 4
- FJAGSNSDKXEGDI-UHFFFAOYSA-N 2-[1-(5-cyclopropyl-7-methyl-1h-indol-4-yl)-1-methoxyethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2OC=1C(C)(OC)C(C=1C=CNC=1C(C)=C1)=C1C1CC1 FJAGSNSDKXEGDI-UHFFFAOYSA-N 0.000 claims description 4
- YWGPLGLNPXQJBT-UHFFFAOYSA-N 2-[1-(5-ethoxy-7-methyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OCC)=NC2=C1 YWGPLGLNPXQJBT-UHFFFAOYSA-N 0.000 claims description 4
- LWIUTERINFAUGJ-UHFFFAOYSA-N 2-[1-(5-ethyl-7-methyl-1h-indol-4-yl)-1-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 LWIUTERINFAUGJ-UHFFFAOYSA-N 0.000 claims description 4
- QWHRNESVNDHDPP-UHFFFAOYSA-N 2-[1-amino-1-(5,7-dimethyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(N)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 QWHRNESVNDHDPP-UHFFFAOYSA-N 0.000 claims description 4
- JBUQWZQKVOMXHM-UHFFFAOYSA-N 2-[1-amino-1-(5-bromo-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(N)C3=C(Br)C=C(C=4NC=CC=43)C)=NC2=C1 JBUQWZQKVOMXHM-UHFFFAOYSA-N 0.000 claims description 4
- CSCYUIHDRJAFQA-UHFFFAOYSA-N 2-[1-amino-1-(5-cyclopropyl-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(N)C=1C=2C=CNC=2C(C)=CC=1C1CC1 CSCYUIHDRJAFQA-UHFFFAOYSA-N 0.000 claims description 4
- QIALYZISUDQIOX-UHFFFAOYSA-N 2-[1-amino-1-(5-ethyl-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(C)(N)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 QIALYZISUDQIOX-UHFFFAOYSA-N 0.000 claims description 4
- IKAAPGCDXGGGNY-UHFFFAOYSA-N 2-[1-amino-1-(5-ethyl-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(N)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 IKAAPGCDXGGGNY-UHFFFAOYSA-N 0.000 claims description 4
- XIIBTHYUKHRNKU-UHFFFAOYSA-N 2-[1-amino-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(C)(N)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 XIIBTHYUKHRNKU-UHFFFAOYSA-N 0.000 claims description 4
- LSTLZVVIZOILKX-UHFFFAOYSA-N 2-[1-amino-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(N)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 LSTLZVVIZOILKX-UHFFFAOYSA-N 0.000 claims description 4
- ANVKEYGMSCEJJK-UHFFFAOYSA-N 2-[1-amino-2,2,2-trifluoro-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(N)(C3=C4C=CNC4=C(C)C=C3OC)C(F)(F)F)=NC2=C1 ANVKEYGMSCEJJK-UHFFFAOYSA-N 0.000 claims description 4
- FGGUCKRQQREHSH-UHFFFAOYSA-N 2-[1-hydroxy-1-(7-methyl-5-propan-2-yl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3C(C)C)=NC2=C1 FGGUCKRQQREHSH-UHFFFAOYSA-N 0.000 claims description 4
- JDQMGQFRFUJDRM-UHFFFAOYSA-N 2-[1-hydroxy-1-(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OC(C)C)=NC2=C1 JDQMGQFRFUJDRM-UHFFFAOYSA-N 0.000 claims description 4
- KXKHCXNKUSWQEL-UHFFFAOYSA-N 2-[1-hydroxy-1-(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)propyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(O)(CC)C1=C(OC(C)C)C=C(C)C2=C1C=CN2 KXKHCXNKUSWQEL-UHFFFAOYSA-N 0.000 claims description 4
- OJWKBVFOIPIVOU-UHFFFAOYSA-N 2-[1-hydroxy-1-[7-methyl-5-(2-methylpropyl)-1h-indol-4-yl]ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3CC(C)C)=NC2=C1 OJWKBVFOIPIVOU-UHFFFAOYSA-N 0.000 claims description 4
- QCBKRGBKYBRIBW-UHFFFAOYSA-N 2-[1-methoxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(OC)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 QCBKRGBKYBRIBW-UHFFFAOYSA-N 0.000 claims description 4
- MFQDWDBJGYHEEJ-UHFFFAOYSA-N 2-[1-methoxy-1-(5-methoxy-7-methyl-2,3-dihydro-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(OC)C3=C4CCNC4=C(C)C=C3OC)=NC2=C1 MFQDWDBJGYHEEJ-UHFFFAOYSA-N 0.000 claims description 4
- CJMHEBKUNRTLGO-UHFFFAOYSA-N 2-[1-methoxy-1-[7-methyl-5-(2-methylpropyl)-1h-indol-4-yl]ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(OC)C1=C(CC(C)C)C=C(C)C2=C1C=CN2 CJMHEBKUNRTLGO-UHFFFAOYSA-N 0.000 claims description 4
- QCBKRGBKYBRIBW-BMSJAHLVSA-N 2-[2,2,2-trideuterio-1-methoxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC=C(C#N)C=C2NC=1C(OC)(C([2H])([2H])[2H])C1=C(OC)C=C(C)C2=C1C=CN2 QCBKRGBKYBRIBW-BMSJAHLVSA-N 0.000 claims description 4
- ASPBAGOUFGGOGF-UHFFFAOYSA-N 2-[[5-(difluoromethoxy)-7-methyl-1h-indol-4-yl]-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C(OC(F)F)C=C(C=4NC=CC=43)C)=NC2=C1 ASPBAGOUFGGOGF-UHFFFAOYSA-N 0.000 claims description 4
- OXTHNEBFHYPPPK-UHFFFAOYSA-N 2-[[5-(ethoxymethyl)-7-methyl-1h-indol-4-yl]-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3COCC)=NC2=C1 OXTHNEBFHYPPPK-UHFFFAOYSA-N 0.000 claims description 4
- YYOJNPFZBYGPMG-UHFFFAOYSA-N 2-[amino-(5,7-dimethyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 YYOJNPFZBYGPMG-UHFFFAOYSA-N 0.000 claims description 4
- RNYNYMOJXCPLSD-UHFFFAOYSA-N 2-[amino-(5-ethyl-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 RNYNYMOJXCPLSD-UHFFFAOYSA-N 0.000 claims description 4
- VUJKCTHMMLHKEU-UHFFFAOYSA-N 2-[amino-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 VUJKCTHMMLHKEU-UHFFFAOYSA-N 0.000 claims description 4
- SUFMRMDRJXDVBE-UHFFFAOYSA-N 2-[amino-(7-methyl-5-methylsulfonyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C(C=C(C=4NC=CC=43)C)S(C)(=O)=O)=NC2=C1 SUFMRMDRJXDVBE-UHFFFAOYSA-N 0.000 claims description 4
- DWIKNHBTSVPPIB-UHFFFAOYSA-N 2-[amino-(7-methyl-5-propan-2-yl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C4C=CNC4=C(C)C=C3C(C)C)=NC2=C1 DWIKNHBTSVPPIB-UHFFFAOYSA-N 0.000 claims description 4
- DKQORYWXWKMNSI-UHFFFAOYSA-N 2-[cyclopropyl-methoxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound COC1=CC(C)=C2NC=CC2=C1C(OC)(C=1NC2=CC=C(C=C2N=1)C#N)C1CC1 DKQORYWXWKMNSI-UHFFFAOYSA-N 0.000 claims description 4
- IAUVRHDNBNIFFB-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 IAUVRHDNBNIFFB-UHFFFAOYSA-N 0.000 claims description 4
- OJTFICBVMWEECK-UHFFFAOYSA-N 2-[hydroxy-(7-methyl-5-propan-2-yl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3C(C)C)=NC2=C1 OJTFICBVMWEECK-UHFFFAOYSA-N 0.000 claims description 4
- MYEDFJLSCXUKNV-UHFFFAOYSA-N 2-[hydroxy-(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3OC(C)C)=NC2=C1 MYEDFJLSCXUKNV-UHFFFAOYSA-N 0.000 claims description 4
- LAHHGIYEZXJIPR-UHFFFAOYSA-N 2-[hydroxy-[5-(hydroxymethyl)-7-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C(CO)C=C(C=4NC=CC=43)C)=NC2=C1 LAHHGIYEZXJIPR-UHFFFAOYSA-N 0.000 claims description 4
- DZTXLONEANMRKP-UHFFFAOYSA-N 2-[hydroxy-[7-methyl-5-(2-methylpropyl)-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3CC(C)C)=NC2=C1 DZTXLONEANMRKP-UHFFFAOYSA-N 0.000 claims description 4
- XBFLRXRIYJBVMA-UHFFFAOYSA-N 2-[methoxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(OC)C1=C(OC)C=C(C)C2=C1C=CN2 XBFLRXRIYJBVMA-UHFFFAOYSA-N 0.000 claims description 4
- QSVDTLWAILRPLP-UHFFFAOYSA-N 2-[methoxy-[7-methyl-5-(2-methylpropyl)-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(OC)C1=C(CC(C)C)C=C(C)C2=C1C=CN2 QSVDTLWAILRPLP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
- PMWSUQJSPJJTBD-UHFFFAOYSA-N 4-(5-cyano-1,3-benzoxazol-2-yl)-4-(5-methoxy-7-methyl-1h-indol-4-yl)butanoic acid Chemical compound N#CC1=CC=C2OC(C(CCC(O)=O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 PMWSUQJSPJJTBD-UHFFFAOYSA-N 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 206010035664 Pneumonia Diseases 0.000 claims description 4
- 208000006193 Pulmonary infarction Diseases 0.000 claims description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 201000006301 pulmonary embolism and infarction Diseases 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 3
- NTXVYWVBRJBBAW-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)-1-methoxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(OC)C1=C(C)C=C(C)C2=C1C=CN2 NTXVYWVBRJBBAW-UHFFFAOYSA-N 0.000 claims description 3
- AGXOXQQOMYCSKD-UHFFFAOYSA-N 2-[1-amino-1-(7-methyl-5-propan-2-yl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(N)C3=C4C=CNC4=C(C)C=C3C(C)C)=NC2=C1 AGXOXQQOMYCSKD-UHFFFAOYSA-N 0.000 claims description 3
- VPSWWSSQMSVZMB-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 VPSWWSSQMSVZMB-UHFFFAOYSA-N 0.000 claims description 3
- XHVUNKMWGYVXME-UHFFFAOYSA-N 3-(5-cyano-1,3-benzoxazol-2-yl)-3-(5-methoxy-7-methyl-1h-indol-4-yl)propanoic acid Chemical compound N#CC1=CC=C2OC(C(CC(O)=O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 XHVUNKMWGYVXME-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 230000002889 sympathetic effect Effects 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- SXFQAFFSEZRQCJ-UHFFFAOYSA-N 1-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2OC=CC2=C1 SXFQAFFSEZRQCJ-UHFFFAOYSA-N 0.000 claims description 2
- DTRBIIDYMYVRNE-UHFFFAOYSA-N 1h-azepine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC=CN1 DTRBIIDYMYVRNE-UHFFFAOYSA-N 0.000 claims description 2
- NBZMCMBKDCBGMD-UHFFFAOYSA-N 2-(5-cyano-1,3-benzoxazol-2-yl)-2-(5-methoxy-7-methyl-1h-indol-4-yl)cyclopropane-1-carboxylic acid Chemical compound COC1=CC(C)=C2NC=CC2=C1C1(C=2OC3=CC=C(C=C3N=2)C#N)CC1C(O)=O NBZMCMBKDCBGMD-UHFFFAOYSA-N 0.000 claims description 2
- OCNYQONLHPUALF-UHFFFAOYSA-N 2-(5-ethyl-7-methyl-1h-indole-4-carbonyl)-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(=O)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 OCNYQONLHPUALF-UHFFFAOYSA-N 0.000 claims description 2
- UXOGBVXCQQBXDQ-UHFFFAOYSA-N 2-(5-methoxy-7-methyl-1h-indole-4-carbonyl)-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(=O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 UXOGBVXCQQBXDQ-UHFFFAOYSA-N 0.000 claims description 2
- IOHQVNMXSZAZNE-UHFFFAOYSA-N 2-[(3-bromo-5,7-dimethyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C(Br)=CNC4=C(C)C=C3C)=NC2=C1 IOHQVNMXSZAZNE-UHFFFAOYSA-N 0.000 claims description 2
- HGPAZNAVBFNGRB-UHFFFAOYSA-N 2-[(3-chloro-5,7-dimethyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C(Cl)=CNC4=C(C)C=C3C)=NC2=C1 HGPAZNAVBFNGRB-UHFFFAOYSA-N 0.000 claims description 2
- LDIJRNJNLMZVSU-UHFFFAOYSA-N 2-[(3-chloro-5-ethyl-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C(Cl)=CNC4=C(C)C=C3CC)=NC2=C1 LDIJRNJNLMZVSU-UHFFFAOYSA-N 0.000 claims description 2
- VDFXPLYUDOTSOU-UHFFFAOYSA-N 2-[(3-cyano-5-ethyl-7-methyl-1h-indol-4-yl)-methoxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(OC)C3=C4C(C#N)=CNC4=C(C)C=C3CC)=NC2=C1 VDFXPLYUDOTSOU-UHFFFAOYSA-N 0.000 claims description 2
- OEMALZRAEYFYPK-UHFFFAOYSA-N 2-[(3-cyano-5-ethyl-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C(C#N)=CNC4=C(C)C=C3CC)=NC2=C1 OEMALZRAEYFYPK-UHFFFAOYSA-N 0.000 claims description 2
- BDNGSXIPEWBYOB-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-(methylamino)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(NC)C1=C(C)C=C(C)C2=C1C=CN2 BDNGSXIPEWBYOB-UHFFFAOYSA-N 0.000 claims description 2
- VVFKCPIALKOFNG-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-ethoxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(OCC)C1=C(C)C=C(C)C2=C1C=CN2 VVFKCPIALKOFNG-UHFFFAOYSA-N 0.000 claims description 2
- KFUUIXWEGVTOFO-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-hydroxy-phenylmethyl]-3h-benzimidazole-5-carbonitrile Chemical compound CC1=CC(C)=C2NC=CC2=C1C(O)(C=1NC2=CC=C(C=C2N=1)C#N)C1=CC=CC=C1 KFUUIXWEGVTOFO-UHFFFAOYSA-N 0.000 claims description 2
- VMYIVVYQIJKCED-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-hydroxymethyl]-1,3-benzothiazole-5-carbonitrile Chemical compound N#CC1=CC=C2SC(C(O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 VMYIVVYQIJKCED-UHFFFAOYSA-N 0.000 claims description 2
- POPKXOXUBQGXGW-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-hydroxymethyl]-1,3-benzothiazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2SC(C(O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 POPKXOXUBQGXGW-UHFFFAOYSA-N 0.000 claims description 2
- IQFUMRWLPWPYRL-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)-methoxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(OC)C1=C(C)C=C(C)C2=C1C=CN2 IQFUMRWLPWPYRL-UHFFFAOYSA-N 0.000 claims description 2
- KBLPJOMEMOKRFI-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3C)=NC2=C1 KBLPJOMEMOKRFI-UHFFFAOYSA-N 0.000 claims description 2
- AGGXEHKQWDKERK-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-4-methyl-1h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3C)=NC2=C1C AGGXEHKQWDKERK-UHFFFAOYSA-N 0.000 claims description 2
- UIEIKFNFQQCALH-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-6-fluoro-1h-benzimidazole-5-carbonitrile Chemical compound N#CC1=C(F)C=C2NC(CC3=C4C=CNC4=C(C)C=C3C)=NC2=C1 UIEIKFNFQQCALH-UHFFFAOYSA-N 0.000 claims description 2
- OALNUHWMHGPMCL-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-6-methoxy-3h-benzimidazole-5-carbonitrile Chemical compound N=1C=2C=C(C#N)C(OC)=CC=2NC=1CC1=C(C)C=C(C)C2=C1C=CN2 OALNUHWMHGPMCL-UHFFFAOYSA-N 0.000 claims description 2
- VGFBHRLKHFVFAZ-UHFFFAOYSA-N 2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-7-fluoro-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC(F)=C2NC(CC3=C4C=CNC4=C(C)C=C3C)=NC2=C1 VGFBHRLKHFVFAZ-UHFFFAOYSA-N 0.000 claims description 2
- LULGUWCHTXACBH-UHFFFAOYSA-N 2-[(5,7-dimethyl-2,3-dihydro-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(C)C=C(C=4NCCC=43)C)=NC2=C1 LULGUWCHTXACBH-UHFFFAOYSA-N 0.000 claims description 2
- OAOXNJLUFZEDNX-UHFFFAOYSA-N 2-[(5-bromo-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C(Br)C=C(C=4NC=CC=43)C)=NC2=C1 OAOXNJLUFZEDNX-UHFFFAOYSA-N 0.000 claims description 2
- KIKKJULCAGWYDM-UHFFFAOYSA-N 2-[(5-cyclopropyl-7-methyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(O)C=1C=2C=CNC=2C(C)=CC=1C1CC1 KIKKJULCAGWYDM-UHFFFAOYSA-N 0.000 claims description 2
- KUAAJSALSJCBCW-UHFFFAOYSA-N 2-[(5-ethenyl-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(C=C)C=C(C=4NC=CC=43)C)=NC2=C1 KUAAJSALSJCBCW-UHFFFAOYSA-N 0.000 claims description 2
- PYNBOQVKIBDKDZ-UHFFFAOYSA-N 2-[(5-ethyl-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 PYNBOQVKIBDKDZ-UHFFFAOYSA-N 0.000 claims description 2
- QMECZXWTARTTNA-UHFFFAOYSA-N 2-[(5-ethyl-7-methyl-1h-indol-4-yl)methyl]-6-fluoro-1h-benzimidazole-5-carbonitrile Chemical compound N#CC1=C(F)C=C2NC(CC3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 QMECZXWTARTTNA-UHFFFAOYSA-N 0.000 claims description 2
- MWYRICYCKGVNCV-UHFFFAOYSA-N 2-[(5-ethyl-7-methyl-3-phenyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound C12=C(C(O)C=3NC4=CC=C(C=C4N=3)C#N)C(CC)=CC(C)=C2NC=C1C1=CC=CC=C1 MWYRICYCKGVNCV-UHFFFAOYSA-N 0.000 claims description 2
- LAPWBHFVIUZSJV-UHFFFAOYSA-N 2-[(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzoxazole-5-carbonitrile Chemical compound N#CC1=CC=C2OC(CC3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 LAPWBHFVIUZSJV-UHFFFAOYSA-N 0.000 claims description 2
- WWGLQGZPKPGYSW-UHFFFAOYSA-N 2-[(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzoxazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2OC(CC3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 WWGLQGZPKPGYSW-UHFFFAOYSA-N 0.000 claims description 2
- HUMSBVXKCJIPRW-UHFFFAOYSA-N 2-[(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 HUMSBVXKCJIPRW-UHFFFAOYSA-N 0.000 claims description 2
- UXSBDZJOPDOHFR-UHFFFAOYSA-N 2-[(6-cyano-1h-benzimidazol-2-yl)-(5,7-dimethyl-1h-indol-4-yl)methoxy]acetic acid Chemical compound N#CC1=CC=C2NC(C(OCC(O)=O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 UXSBDZJOPDOHFR-UHFFFAOYSA-N 0.000 claims description 2
- FVULBLKMKDXUHP-UHFFFAOYSA-N 2-[(7-bromo-5-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(Br)C=C3C)=NC2=C1 FVULBLKMKDXUHP-UHFFFAOYSA-N 0.000 claims description 2
- WALZKUHYDOWXPR-UHFFFAOYSA-N 2-[(7-chloro-5-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(Cl)C=C3C)=NC2=C1 WALZKUHYDOWXPR-UHFFFAOYSA-N 0.000 claims description 2
- KQAUIIMURTXSTO-UHFFFAOYSA-N 2-[(7-ethyl-5-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(C)C=C(C=4NC=CC=43)CC)=NC2=C1 KQAUIIMURTXSTO-UHFFFAOYSA-N 0.000 claims description 2
- CHYNZHKLBXVICT-UHFFFAOYSA-N 2-[(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3OC(C)C)=NC2=C1 CHYNZHKLBXVICT-UHFFFAOYSA-N 0.000 claims description 2
- VWUMFVVEDWQBLZ-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)-1-(methylamino)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(NC)C1=C(C)C=C(C)C2=C1C=CN2 VWUMFVVEDWQBLZ-UHFFFAOYSA-N 0.000 claims description 2
- USOQBJKEQJLSQC-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)-1-hydroxypropyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(O)(CC)C1=C(C)C=C(C)C2=C1C=CN2 USOQBJKEQJLSQC-UHFFFAOYSA-N 0.000 claims description 2
- YWQMLZGTPRPLQB-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)-2-hydroxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(CO)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 YWQMLZGTPRPLQB-UHFFFAOYSA-N 0.000 claims description 2
- FBAWAWQJXKWWIY-UHFFFAOYSA-N 2-[1-(5,7-dimethyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)C1=C(C)C=C(C)C2=C1C=CN2 FBAWAWQJXKWWIY-UHFFFAOYSA-N 0.000 claims description 2
- YFRDQYUJRRSHLD-UHFFFAOYSA-N 2-[1-(5-ethyl-7-methyl-1h-indol-4-yl)ethenyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(=C)C3=C4C=CNC4=C(C)C=C3CC)=NC2=C1 YFRDQYUJRRSHLD-UHFFFAOYSA-N 0.000 claims description 2
- DLTBKERUKVCPOX-UHFFFAOYSA-N 2-[1-(5-methoxy-7-methyl-1h-indol-4-yl)ethenyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(=C)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 DLTBKERUKVCPOX-UHFFFAOYSA-N 0.000 claims description 2
- JCTYYTYFUKFUGV-UHFFFAOYSA-N 2-[1-(dimethylamino)-1-(5,7-dimethyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(N(C)C)C1=C(C)C=C(C)C2=C1C=CN2 JCTYYTYFUKFUGV-UHFFFAOYSA-N 0.000 claims description 2
- BPJQFPFODKZMBY-UHFFFAOYSA-N 2-[1-amino-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzothiazole-5-carbonitrile Chemical compound N#CC1=CC=C2SC(C(C)(N)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 BPJQFPFODKZMBY-UHFFFAOYSA-N 0.000 claims description 2
- OTCXYEYLERDSOS-UHFFFAOYSA-N 2-[1-hydroxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzothiazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2SC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 OTCXYEYLERDSOS-UHFFFAOYSA-N 0.000 claims description 2
- IYDSGMAEVJWECV-UHFFFAOYSA-N 2-[1-hydroxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3OC)=CC2=C1 IYDSGMAEVJWECV-UHFFFAOYSA-N 0.000 claims description 2
- QQBFPYDIFQVZKL-UHFFFAOYSA-N 2-[1-hydroxy-1-(7-methyl-5-propyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(O)C3=C4C=CNC4=C(C)C=C3CCC)=NC2=C1 QQBFPYDIFQVZKL-UHFFFAOYSA-N 0.000 claims description 2
- YOQFSMWHBFHTRJ-UHFFFAOYSA-N 2-[1-methoxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-1,3-benzothiazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2SC(C(C)(OC)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 YOQFSMWHBFHTRJ-UHFFFAOYSA-N 0.000 claims description 2
- COZLPXCZMCGACN-UHFFFAOYSA-N 2-[1-methoxy-1-(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(C)(OC)C1=C(OC(C)C)C=C(C)C2=C1C=CN2 COZLPXCZMCGACN-UHFFFAOYSA-N 0.000 claims description 2
- LZKQLEIQSXRSDS-UHFFFAOYSA-N 2-[2-(5-methoxy-7-methyl-1h-indol-4-yl)propan-2-yl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(C)(C)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 LZKQLEIQSXRSDS-UHFFFAOYSA-N 0.000 claims description 2
- XWCAPPDSQGDTKV-UHFFFAOYSA-N 2-[3-hydroxy-1-(5-methoxy-7-methyl-1h-indol-4-yl)propyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(CCO)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 XWCAPPDSQGDTKV-UHFFFAOYSA-N 0.000 claims description 2
- FIKIOPFYWCWFJL-UHFFFAOYSA-N 2-[[5-(2-methoxyethoxy)-7-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3OCCOC)=NC2=C1 FIKIOPFYWCWFJL-UHFFFAOYSA-N 0.000 claims description 2
- BLAZOYVQNMECDY-UHFFFAOYSA-N 2-[[5-(aminomethyl)-7-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(CN)C=C(C=4NC=CC=43)C)=NC2=C1 BLAZOYVQNMECDY-UHFFFAOYSA-N 0.000 claims description 2
- JACSIGWOSBFRKZ-UHFFFAOYSA-N 2-[[5-(difluoromethoxy)-7-methyl-1h-indol-4-yl]-(methylamino)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(NC)C1=C(OC(F)F)C=C(C)C2=C1C=CN2 JACSIGWOSBFRKZ-UHFFFAOYSA-N 0.000 claims description 2
- NRQLDZDGQNQTCB-UHFFFAOYSA-N 2-[[5-(hydroxymethyl)-7-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(CO)C=C(C=4NC=CC=43)C)=NC2=C1 NRQLDZDGQNQTCB-UHFFFAOYSA-N 0.000 claims description 2
- KZLIGWPOHPSTGF-UHFFFAOYSA-N 2-[[5-(methoxymethyl)-7-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3COC)=NC2=C1 KZLIGWPOHPSTGF-UHFFFAOYSA-N 0.000 claims description 2
- MQTLFIWLHJBGFM-UHFFFAOYSA-N 2-[[5-ethyl-7-methyl-3-(1H-pyrazol-5-yl)-1H-indol-4-yl]methyl]-3H-benzimidazole-5-carbonitrile Chemical compound C12=C(CC=3NC4=CC=C(C=C4N=3)C#N)C(CC)=CC(C)=C2NC=C1C1=CC=NN1 MQTLFIWLHJBGFM-UHFFFAOYSA-N 0.000 claims description 2
- HIGAIWMFFYEBBS-UHFFFAOYSA-N 2-[[7-(hydroxymethyl)-5-methyl-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(CO)C=C3C)=NC2=C1 HIGAIWMFFYEBBS-UHFFFAOYSA-N 0.000 claims description 2
- AARLXYWDGUDDFG-FIBGUPNXSA-N 2-[[7-chloro-5-(trideuteriomethoxy)-1h-indol-4-yl]-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(C(O)C3=C4C=CNC4=C(Cl)C=C3OC([2H])([2H])[2H])=NC2=C1 AARLXYWDGUDDFG-FIBGUPNXSA-N 0.000 claims description 2
- VAMSKYRVTYQOCJ-FIBGUPNXSA-N 2-[[7-chloro-5-(trideuteriomethoxy)-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(CC3=C4C=CNC4=C(Cl)C=C3OC([2H])([2H])[2H])=NC2=C1 VAMSKYRVTYQOCJ-FIBGUPNXSA-N 0.000 claims description 2
- HUMSBVXKCJIPRW-BMSJAHLVSA-N 2-[[7-methyl-5-(trideuteriomethoxy)-1h-indol-4-yl]methyl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(CC3=C4C=CNC4=C(C)C=C3OC([2H])([2H])[2H])=NC2=C1 HUMSBVXKCJIPRW-BMSJAHLVSA-N 0.000 claims description 2
- NNENMQPRLQIBLU-UHFFFAOYSA-N 2-[amino-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzothiazole-5-carbonitrile Chemical compound N#CC1=CC=C2SC(C(N)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 NNENMQPRLQIBLU-UHFFFAOYSA-N 0.000 claims description 2
- XALHUCWIXWTHBW-UHFFFAOYSA-N 2-[amino-(7-methyl-5-propan-2-yloxy-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)C3=C4C=CNC4=C(C)C=C3OC(C)C)=NC2=C1 XALHUCWIXWTHBW-UHFFFAOYSA-N 0.000 claims description 2
- GKRKTUYVCRTWFA-UHFFFAOYSA-N 2-[cyclopropyl-(5,7-dimethyl-1h-indol-4-yl)-hydroxymethyl]-3h-benzimidazole-5-carbonitrile Chemical compound CC1=CC(C)=C2NC=CC2=C1C(O)(C=1NC2=CC=C(C=C2N=1)C#N)C1CC1 GKRKTUYVCRTWFA-UHFFFAOYSA-N 0.000 claims description 2
- LRWVUESOAFUXCR-UHFFFAOYSA-N 2-[dimethylamino-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N(C)C)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 LRWVUESOAFUXCR-UHFFFAOYSA-N 0.000 claims description 2
- SJADXMXNFBIUKV-UHFFFAOYSA-N 2-[hydroxy-(3,5,7-trimethyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C=3C(C)=CC(C)=C4NC=C(C=34)C)=NC2=C1 SJADXMXNFBIUKV-UHFFFAOYSA-N 0.000 claims description 2
- WTUDBLTZDXJDGD-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzothiazole-5-carbonitrile Chemical compound N#CC1=CC=C2SC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 WTUDBLTZDXJDGD-UHFFFAOYSA-N 0.000 claims description 2
- AZDHGCPPLMLQAM-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1,3-benzothiazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2SC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=NC2=C1 AZDHGCPPLMLQAM-UHFFFAOYSA-N 0.000 claims description 2
- NAZVMHGVZWQHTJ-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1-benzofuran-5-carbonitrile Chemical compound N#CC1=CC=C2OC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=CC2=C1 NAZVMHGVZWQHTJ-UHFFFAOYSA-N 0.000 claims description 2
- AVZMBPQXEUNKNA-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1-benzofuran-6-carbonitrile Chemical compound C1=C(C#N)C=C2OC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=CC2=C1 AVZMBPQXEUNKNA-UHFFFAOYSA-N 0.000 claims description 2
- SJBSLRPTKRCSHX-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=CC2=C1 SJBSLRPTKRCSHX-UHFFFAOYSA-N 0.000 claims description 2
- UPJXSCZMRLDZEZ-UHFFFAOYSA-N 2-[hydroxy-(5-methoxy-7-methyl-1h-indol-4-yl)methyl]-1h-indole-6-carbonitrile Chemical compound C1=C(C#N)C=C2NC(C(O)C3=C4C=CNC4=C(C)C=C3OC)=CC2=C1 UPJXSCZMRLDZEZ-UHFFFAOYSA-N 0.000 claims description 2
- AWEKIGKASDAVHS-UHFFFAOYSA-N 2-[hydroxy-(7-methyl-5-methylsulfonyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(O)C3=C(C=C(C=4NC=CC=43)C)S(C)(=O)=O)=NC2=C1 AWEKIGKASDAVHS-UHFFFAOYSA-N 0.000 claims description 2
- QXLHLZQFAWQOSZ-UHFFFAOYSA-N 3-aminoimidazole-4-carbonitrile Chemical compound NN1C=NC=C1C#N QXLHLZQFAWQOSZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 2
- OPNYCIZQHWJJTQ-UHFFFAOYSA-N 6-chloro-2-[(5,7-dimethyl-1h-indol-4-yl)methyl]-1h-benzimidazole-5-carbonitrile Chemical compound N#CC1=C(Cl)C=C2NC(CC3=C4C=CNC4=C(C)C=C3C)=NC2=C1 OPNYCIZQHWJJTQ-UHFFFAOYSA-N 0.000 claims description 2
- RXEMEINZCDZQAT-UHFFFAOYSA-N COc1cc(C)c2[nH]ccc2c1C(O)(n1cnc2cc(ccc12)C#N)C(F)(F)F Chemical compound COc1cc(C)c2[nH]ccc2c1C(O)(n1cnc2cc(ccc12)C#N)C(F)(F)F RXEMEINZCDZQAT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- CWJRNKXXSWYYTJ-UHFFFAOYSA-N ethyl 1,3-benzoxazole-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)=NC2=C1 CWJRNKXXSWYYTJ-UHFFFAOYSA-N 0.000 claims description 2
- BVMLORWKLKKXMZ-UHFFFAOYSA-N n-[(6-cyano-1h-benzimidazol-2-yl)-(5,7-dimethyl-1h-indol-4-yl)methyl]acetamide Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(NC(=O)C)C1=C(C)C=C(C)C2=C1C=CN2 BVMLORWKLKKXMZ-UHFFFAOYSA-N 0.000 claims description 2
- IXFBFZDUWTYPCQ-UHFFFAOYSA-N n-[(6-cyano-1h-benzimidazol-2-yl)-(5,7-dimethyl-1h-indol-4-yl)methyl]methanesulfonamide Chemical compound N#CC1=CC=C2NC(C(NS(C)(=O)=O)C3=C4C=CNC4=C(C)C=C3C)=NC2=C1 IXFBFZDUWTYPCQ-UHFFFAOYSA-N 0.000 claims description 2
- VFUZACHIBHOAEY-UHFFFAOYSA-N n-[[4-[(6-cyano-1h-benzimidazol-2-yl)methyl]-7-methyl-1h-indol-5-yl]methyl]acetamide Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(C)C=C3CNC(=O)C)=NC2=C1 VFUZACHIBHOAEY-UHFFFAOYSA-N 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- 102000000588 Interleukin-2 Human genes 0.000 claims 4
- 206010038687 Respiratory distress Diseases 0.000 claims 2
- PJHOULGFTAXRPG-HPRDVNIFSA-N [2H]C([2H])([2H])OC(C1=NC2=C(N1)C=CC(=C2)C#N)(C1=C(OC)C=C(C)C2=C1C=CN2)C(F)(F)F Chemical compound [2H]C([2H])([2H])OC(C1=NC2=C(N1)C=CC(=C2)C#N)(C1=C(OC)C=C(C)C2=C1C=CN2)C(F)(F)F PJHOULGFTAXRPG-HPRDVNIFSA-N 0.000 claims 2
- 230000002612 cardiopulmonary effect Effects 0.000 claims 2
- 201000010002 cicatricial pemphigoid Diseases 0.000 claims 2
- BSNIXNVMYNRRMG-UHFFFAOYSA-N 1,3-oxazole-5-carbonitrile Chemical compound N#CC1=CN=CO1 BSNIXNVMYNRRMG-UHFFFAOYSA-N 0.000 claims 1
- 208000002691 Choroiditis Diseases 0.000 claims 1
- 208000010164 Multifocal Choroiditis Diseases 0.000 claims 1
- 206010029240 Neuritis Diseases 0.000 claims 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims 1
- 101800000989 Oxytocin Proteins 0.000 claims 1
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 claims 1
- 208000003971 Posterior uveitis Diseases 0.000 claims 1
- 230000005784 autoimmunity Effects 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 125000006437 ethyl cyclopropyl group Chemical group 0.000 claims 1
- 230000002710 gonadal effect Effects 0.000 claims 1
- 229960001723 oxytocin Drugs 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 84
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 70
- 229930195712 glutamate Natural products 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 238000006243 chemical reaction Methods 0.000 description 48
- 239000002904 solvent Substances 0.000 description 36
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 35
- 239000002253 acid Substances 0.000 description 35
- 239000002585 base Substances 0.000 description 33
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 32
- 102000003712 Complement factor B Human genes 0.000 description 31
- 108090000056 Complement factor B Proteins 0.000 description 31
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 31
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 30
- 229940092714 benzenesulfonic acid Drugs 0.000 description 28
- 102100020873 Interleukin-2 Human genes 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 18
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 17
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 17
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 17
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 17
- 239000000651 prodrug Substances 0.000 description 17
- 229940002612 prodrug Drugs 0.000 description 17
- 238000011069 regeneration method Methods 0.000 description 17
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 16
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 16
- 229910019142 PO4 Inorganic materials 0.000 description 16
- 125000003118 aryl group Chemical group 0.000 description 16
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 16
- 239000010452 phosphate Substances 0.000 description 16
- 230000008929 regeneration Effects 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- 230000017423 tissue regeneration Effects 0.000 description 16
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 15
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 15
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
- 229910002651 NO3 Inorganic materials 0.000 description 15
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 15
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 15
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 15
- 235000010323 ascorbic acid Nutrition 0.000 description 15
- 239000011668 ascorbic acid Substances 0.000 description 15
- 229940009098 aspartate Drugs 0.000 description 15
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 15
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 15
- 229940043264 dodecyl sulfate Drugs 0.000 description 15
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 15
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 15
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 15
- 210000005036 nerve Anatomy 0.000 description 15
- QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 15
- 229940049964 oleate Drugs 0.000 description 15
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 15
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 15
- 229940095064 tartrate Drugs 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- OZLTWYYNOLDSIP-UHFFFAOYSA-N 2-azidopropane Chemical compound CC(C)N=[N+]=[N-] OZLTWYYNOLDSIP-UHFFFAOYSA-N 0.000 description 14
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 14
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 14
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 14
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 14
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 14
- 150000001299 aldehydes Chemical class 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 14
- 229940072107 ascorbate Drugs 0.000 description 14
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 14
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 230000000302 ischemic effect Effects 0.000 description 14
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 14
- 229940001447 lactate Drugs 0.000 description 14
- 229940099584 lactobionate Drugs 0.000 description 14
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 14
- 125000005487 naphthalate group Chemical group 0.000 description 14
- 235000001968 nicotinic acid Nutrition 0.000 description 14
- 239000011664 nicotinic acid Substances 0.000 description 14
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 14
- 229940116351 sebacate Drugs 0.000 description 14
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 14
- 229940114926 stearate Drugs 0.000 description 14
- 229940086735 succinate Drugs 0.000 description 14
- 229940071103 sulfosalicylate Drugs 0.000 description 14
- 206010067632 Cartilage atrophy Diseases 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 13
- 208000010378 Pulmonary Embolism Diseases 0.000 description 13
- 206010037596 Pyelonephritis Diseases 0.000 description 13
- 230000008021 deposition Effects 0.000 description 13
- 208000026278 immune system disease Diseases 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 229910052805 deuterium Inorganic materials 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 150000002825 nitriles Chemical class 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 108010053085 Complement Factor H Proteins 0.000 description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 238000010511 deprotection reaction Methods 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 230000002265 prevention Effects 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 102100035432 Complement factor H Human genes 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 230000004154 complement system Effects 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 239000012039 electrophile Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000007429 general method Methods 0.000 description 8
- 150000002430 hydrocarbons Chemical group 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 238000010348 incorporation Methods 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000002576 ketones Chemical class 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000002054 transplantation Methods 0.000 description 8
- 230000004393 visual impairment Effects 0.000 description 8
- 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 7
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 7
- 241000721454 Pemphigus Species 0.000 description 7
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 7
- 125000003282 alkyl amino group Chemical group 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
- 230000007850 degeneration Effects 0.000 description 6
- 125000004663 dialkyl amino group Chemical group 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 125000004470 heterocyclooxy group Chemical group 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 239000003755 preservative agent Substances 0.000 description 6
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 5
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 5
- 102100022133 Complement C3 Human genes 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 125000004122 cyclic group Chemical group 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 229910052749 magnesium Inorganic materials 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 238000005935 nucleophilic addition reaction Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229940083542 sodium Drugs 0.000 description 5
- 235000015424 sodium Nutrition 0.000 description 5
- 239000011877 solvent mixture Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 239000011701 zinc Substances 0.000 description 5
- 229910052725 zinc Inorganic materials 0.000 description 5
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 208000019693 Lung disease Diseases 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 238000006069 Suzuki reaction reaction Methods 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 125000005907 alkyl ester group Chemical group 0.000 description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004104 aryloxy group Chemical group 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 210000003161 choroid Anatomy 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000000428 dust Substances 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 206010025135 lupus erythematosus Diseases 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 125000004043 oxo group Chemical group O=* 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 210000000608 photoreceptor cell Anatomy 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 235000011118 potassium hydroxide Nutrition 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 210000001525 retina Anatomy 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 235000016804 zinc Nutrition 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- YGPVRHHGKCQSIL-UHFFFAOYSA-N 5-methoxy-7-methyl-1h-indole Chemical compound COC1=CC(C)=C2NC=CC2=C1 YGPVRHHGKCQSIL-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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 108010028780 Complement C3 Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 101000901154 Homo sapiens Complement C3 Proteins 0.000 description 3
- 101000710032 Homo sapiens Complement factor B Proteins 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 241000288906 Primates Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 210000001775 bruch membrane Anatomy 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 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 3
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Substances [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N n-propyl alcohol Natural products CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000002777 nucleoside Substances 0.000 description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 3
- 125000006684 polyhaloalkyl group Polymers 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229960003975 potassium Drugs 0.000 description 3
- 230000000750 progressive effect Effects 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- CESUXLKAADQNTB-UHFFFAOYSA-N tert-butanesulfinamide Chemical compound CC(C)(C)S(N)=O CESUXLKAADQNTB-UHFFFAOYSA-N 0.000 description 3
- RSPKBJLYYKOYLJ-UHFFFAOYSA-N tert-butyl 3-(3-hydroxyphenyl)piperazine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCNC1C1=CC=CC(O)=C1 RSPKBJLYYKOYLJ-UHFFFAOYSA-N 0.000 description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 229910052721 tungsten Inorganic materials 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 description 2
- WQADWIOXOXRPLN-UHFFFAOYSA-N 1,3-dithiane Chemical compound C1CSCSC1 WQADWIOXOXRPLN-UHFFFAOYSA-N 0.000 description 2
- LOZWAPSEEHRYPG-UHFFFAOYSA-N 1,4-dithiane Chemical compound C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 2
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 2
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010060937 Amniotic cavity infection Diseases 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 208000037157 Azotemia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 208000008158 Chorioamnionitis Diseases 0.000 description 2
- 102000004381 Complement C2 Human genes 0.000 description 2
- 108090000955 Complement C2 Proteins 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 206010012692 Diabetic uveitis Diseases 0.000 description 2
- 238000009007 Diagnostic Kit Methods 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 206010053177 Epidermolysis Diseases 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 208000001034 Frostbite Diseases 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000029422 Hypernatremia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000003623 Hypoalbuminemia Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 201000006165 Kuhnt-Junius degeneration Diseases 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 2
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 206010025421 Macule Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010029113 Neovascularisation Diseases 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 108090000742 Neurotrophin 3 Proteins 0.000 description 2
- 102100029268 Neurotrophin-3 Human genes 0.000 description 2
- 102000003683 Neurotrophin-4 Human genes 0.000 description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 201000011152 Pemphigus Diseases 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- 201000007737 Retinal degeneration Diseases 0.000 description 2
- 206010038848 Retinal detachment Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000009830 antibody antigen interaction Effects 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 239000010425 asbestos Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- REROKLPNVNAPBD-UHFFFAOYSA-N azane;tetrahydrate Chemical compound N.O.O.O.O REROKLPNVNAPBD-UHFFFAOYSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 229910052790 beryllium Inorganic materials 0.000 description 2
- ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 201000004709 chorioretinitis Diseases 0.000 description 2
- 239000002817 coal dust Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229940121394 complement c5 inhibitor Drugs 0.000 description 2
- 239000002720 complement component C5 inhibitor Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000012973 diazabicyclooctane Substances 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 125000004982 dihaloalkyl group Chemical group 0.000 description 2
- 208000011325 dry age related macular degeneration Diseases 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 238000004193 electrokinetic chromatography Methods 0.000 description 2
- 239000003792 electrolyte Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000003821 enantio-separation Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 102000054766 genetic haplotypes Human genes 0.000 description 2
- 230000024924 glomerular filtration Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000006750 hematuria Diseases 0.000 description 2
- 230000002439 hemostatic effect Effects 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 231100000021 irritant Toxicity 0.000 description 2
- 208000037906 ischaemic injury Diseases 0.000 description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- BMFVGAAISNGQNM-UHFFFAOYSA-N isopentylamine Chemical compound CC(C)CCN BMFVGAAISNGQNM-UHFFFAOYSA-N 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 208000018769 loss of vision Diseases 0.000 description 2
- 231100000864 loss of vision Toxicity 0.000 description 2
- 229940076783 lucentis Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 125000006682 monohaloalkyl group Chemical group 0.000 description 2
- 150000002772 monosaccharides Chemical class 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 229940053128 nerve growth factor Drugs 0.000 description 2
- 210000005157 neural retina Anatomy 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 229940097998 neurotrophin 4 Drugs 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 201000001976 pemphigus vulgaris Diseases 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229960005141 piperazine Drugs 0.000 description 2
- 230000010118 platelet activation Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 150000003141 primary amines Chemical class 0.000 description 2
- 208000011511 primary membranoproliferative glomerulonephritis Diseases 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 201000008171 proliferative glomerulonephritis Diseases 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 201000001474 proteinuria Diseases 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000004258 retinal degeneration Effects 0.000 description 2
- 230000004264 retinal detachment Effects 0.000 description 2
- 230000004283 retinal dysfunction Effects 0.000 description 2
- 229910052895 riebeckite Inorganic materials 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 2
- 229960002218 sodium chlorite Drugs 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003797 solvolysis reaction Methods 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 208000009852 uremia Diseases 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- WXWLHDCCGVWTDZ-UHFFFAOYSA-N (2e)-2-[(2e,4z)-5-[1-[6-(2,5-dioxopyrrolidin-1-yl)oxy-6-oxohexyl]-3,3-dimethyl-5-sulfoindol-1-ium-2-yl]penta-2,4-dienylidene]-1-ethyl-3,3-dimethylindole-5-sulfonate Chemical compound CC1(C)C2=CC(S([O-])(=O)=O)=CC=C2[N+](CC)=C1\C=C\C=C\C=C(C(C1=CC(=CC=C11)S(O)(=O)=O)(C)C)\N1CCCCCC(=O)ON1C(=O)CCC1=O WXWLHDCCGVWTDZ-UHFFFAOYSA-N 0.000 description 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 1
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- JTNQFJPZRTURSI-LLVKDONJSA-N (3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](CC(O)=O)C1=CC=CC=C1 JTNQFJPZRTURSI-LLVKDONJSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
- 229940044613 1-propanol Drugs 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- VEKMJKMSTPFHQD-UHFFFAOYSA-N 1h-benzimidazole-2-carbonitrile Chemical class C1=CC=C2NC(C#N)=NC2=C1 VEKMJKMSTPFHQD-UHFFFAOYSA-N 0.000 description 1
- 125000003562 2,2-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- IWWLVWWEZSOTJH-UHFFFAOYSA-N 2,3-dihydroxy-4-(4-methylbenzoyl)oxy-4-oxobutanoic acid Chemical compound CC1=CC=C(C(=O)OC(=O)C(O)C(O)C(O)=O)C=C1 IWWLVWWEZSOTJH-UHFFFAOYSA-N 0.000 description 1
- 125000003660 2,3-dimethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- BYYLHNPEMQMIFB-UHFFFAOYSA-N 2-[(5-chloro-7-methyl-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C(Cl)C=C(C=4NC=CC=43)C)=NC2=C1 BYYLHNPEMQMIFB-UHFFFAOYSA-N 0.000 description 1
- ZHJGLFCMWLAANC-UHFFFAOYSA-N 2-[(7-fluoro-5-methoxy-1h-indol-4-yl)methyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(CC3=C4C=CNC4=C(F)C=C3OC)=NC2=C1 ZHJGLFCMWLAANC-UHFFFAOYSA-N 0.000 description 1
- HVHPRSQXTSJQJT-UHFFFAOYSA-N 2-[1-(5-cyclopropyl-7-methyl-1h-indol-4-yl)-2,2,2-trifluoro-1-(methylamino)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N=1C2=CC(C#N)=CC=C2NC=1C(NC)(C(F)(F)F)C(C=1C=CNC=1C(C)=C1)=C1C1CC1 HVHPRSQXTSJQJT-UHFFFAOYSA-N 0.000 description 1
- NTBOIAVZHFCBRE-UHFFFAOYSA-N 2-[1-(6-fluoro-5-methoxy-7-methyl-1h-indol-4-yl)-1-methoxyethyl]-3h-benzimidazole-5-carbonitrile Chemical compound C1=C(C#N)C=C2NC(C(C)(OC)C3=C4C=CNC4=C(C)C(F)=C3OC)=NC2=C1 NTBOIAVZHFCBRE-UHFFFAOYSA-N 0.000 description 1
- OJPVIRTVYXTSRA-UHFFFAOYSA-N 2-[1-amino-2,2,2-trifluoro-1-(5-methoxy-7-methyl-1h-indol-4-yl)ethyl]-3h-benzimidazole-5-carbonitrile Chemical compound N#CC1=CC=C2NC(C(N)(C3=C4C=CNC4=C(C)C=C3OC)C(F)(F)F)=NC2=C1 OJPVIRTVYXTSRA-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- SQUUGFCETPITLP-UHFFFAOYSA-N 2-bromo-4-methyl-5-nitrobenzonitrile Chemical compound CC1=CC(Br)=C(C#N)C=C1[N+]([O-])=O SQUUGFCETPITLP-UHFFFAOYSA-N 0.000 description 1
- QVOBSRFDFRRCNC-UHFFFAOYSA-N 2-chloro-4-methyl-5-nitrobenzoic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C=C1[N+]([O-])=O QVOBSRFDFRRCNC-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-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
- CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 description 1
- LAVZKLJDKGRZJG-UHFFFAOYSA-N 4-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC2=C1C=CN2 LAVZKLJDKGRZJG-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- MTODENNQRUCIFR-UHFFFAOYSA-N 5,7-dimethyl-4-nitro-1h-indole Chemical compound CC1=CC(C)=C2NC=CC2=C1[N+]([O-])=O MTODENNQRUCIFR-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- LMIQERWZRIFWNZ-UHFFFAOYSA-N 5-hydroxyindole Chemical compound OC1=CC=C2NC=CC2=C1 LMIQERWZRIFWNZ-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- HXFLZWAZSSPLCO-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptyl Chemical group C1[C-]2C([CH2+])([CH2-])[C+]1CCC2 HXFLZWAZSSPLCO-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 102000005590 Anaphylatoxin C5a Receptor Human genes 0.000 description 1
- 108010059426 Anaphylatoxin C5a Receptor Proteins 0.000 description 1
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 1
- 208000035913 Atypical hemolytic uremic syndrome Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 238000006159 Bartoli reaction Methods 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- NTCZEFJAVGRVBG-UHFFFAOYSA-N CC(C)(C(Cl)(Cl)Cl)[ClH]C(O)=O Chemical compound CC(C)(C(Cl)(Cl)Cl)[ClH]C(O)=O NTCZEFJAVGRVBG-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
- 108010078015 Complement C3b Proteins 0.000 description 1
- 102100031506 Complement C5 Human genes 0.000 description 1
- 102000016550 Complement Factor H Human genes 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 238000012286 ELISA Assay Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 102100027285 Fanconi anemia group B protein Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101000808726 Homo sapiens Age-related maculopathy susceptibility protein 2 Proteins 0.000 description 1
- 101000941598 Homo sapiens Complement C5 Proteins 0.000 description 1
- 101000737554 Homo sapiens Complement factor D Proteins 0.000 description 1
- 101000914679 Homo sapiens Fanconi anemia group B protein Proteins 0.000 description 1
- 208000021710 Hyperpigmentation disease Diseases 0.000 description 1
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 1
- 108010005716 Interferon beta-1a Proteins 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229910013063 LiBF 4 Inorganic materials 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
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 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
- 108700005075 Regulator Genes Proteins 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 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 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940005553 analgesics and anesthetics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000005349 anion exchange Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229910052789 astatine Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229940003504 avonex Drugs 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 235000012216 bentonite Nutrition 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
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 208000027119 bilirubin metabolic disease Diseases 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 125000005382 boronyl group Chemical group 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229940043430 calcium compound Drugs 0.000 description 1
- 150000001674 calcium compounds Chemical class 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- DUIPMINAGWHGFI-UHFFFAOYSA-M chloromethylidene-methyl-phenylazanium;chloride Chemical compound [Cl-].ClC=[N+](C)C1=CC=CC=C1 DUIPMINAGWHGFI-UHFFFAOYSA-M 0.000 description 1
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229960002436 cladribine Drugs 0.000 description 1
- 238000003181 co-melting Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 230000004456 color vision Effects 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000012875 competitive assay Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940127271 compound 49 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000006003 dichloroethyl group Chemical group 0.000 description 1
- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000012990 dithiocarbamate Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
- YIOAXIIZOXTUQR-UHFFFAOYSA-N ethyl 1h-azepine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=CN1 YIOAXIIZOXTUQR-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 229940125397 factor b inhibitor Drugs 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 101150118163 h gene Proteins 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000006881 hemostatic dysfunction Effects 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 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 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000045507 human CFD Human genes 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 208000036796 hyperbilirubinemia Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 150000003949 imides Chemical group 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000006317 isomerization reaction Methods 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 230000009916 joint effect Effects 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 238000010983 kinetics study Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Inorganic materials [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- IVMHDOBGNQOUHO-UHFFFAOYSA-N oxathiane Chemical compound C1CCSOC1 IVMHDOBGNQOUHO-UHFFFAOYSA-N 0.000 description 1
- OOFGXDQWDNJDIS-UHFFFAOYSA-N oxathiolane Chemical compound C1COSC1 OOFGXDQWDNJDIS-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 239000006174 pH buffer Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- NFIYTPYOYDDLGO-UHFFFAOYSA-N phosphoric acid;sodium Chemical compound [Na].OP(O)(O)=O NFIYTPYOYDDLGO-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940093956 potassium carbonate Drugs 0.000 description 1
- 229940093932 potassium hydroxide Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 150000003246 quinazolines Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 231100000241 scar Toxicity 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
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 229940055944 soliris Drugs 0.000 description 1
- 239000008137 solubility enhancer Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960003080 taurine Drugs 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
- WMHPXNKSNATFKJ-UHFFFAOYSA-N tert-butyl 3-[3-[2-(phenylmethoxycarbonylamino)ethoxy]phenyl]piperazine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCNC1C1=CC=CC(OCCNC(=O)OCC=2C=CC=CC=2)=C1 WMHPXNKSNATFKJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ZHSKFONQCREGOG-UHFFFAOYSA-N triethyl(trifluoromethyl)silane Chemical compound CC[Si](CC)(CC)C(F)(F)F ZHSKFONQCREGOG-UHFFFAOYSA-N 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Transplantation (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Child & Adolescent Psychology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Vascular Medicine (AREA)
- Psychology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261642798P | 2012-05-04 | 2012-05-04 | |
| US61/642,798 | 2012-05-04 | ||
| US201361782820P | 2013-03-14 | 2013-03-14 | |
| US61/782,820 | 2013-03-14 | ||
| PCT/IB2013/053546 WO2013164802A1 (en) | 2012-05-04 | 2013-05-03 | Complement pathway modulators and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20150003903A true KR20150003903A (ko) | 2015-01-09 |
Family
ID=48626502
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147033713A Withdrawn KR20150003903A (ko) | 2012-05-04 | 2013-05-03 | 보체 경로 조절제 및 그의 용도 |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP2855456B1 (https=) |
| JP (1) | JP6180514B2 (https=) |
| KR (1) | KR20150003903A (https=) |
| CN (1) | CN104603127B (https=) |
| AP (1) | AP2014008040A0 (https=) |
| AR (1) | AR090945A1 (https=) |
| AU (1) | AU2013255470B2 (https=) |
| BR (1) | BR112014027359A2 (https=) |
| CA (1) | CA2872000A1 (https=) |
| CL (1) | CL2014002919A1 (https=) |
| CR (1) | CR20140508A (https=) |
| EA (1) | EA027113B1 (https=) |
| ES (1) | ES2630079T3 (https=) |
| HK (1) | HK1206017A1 (https=) |
| IL (1) | IL235362A0 (https=) |
| MX (1) | MX2014013428A (https=) |
| PE (1) | PE20150623A1 (https=) |
| PH (1) | PH12014502462A1 (https=) |
| PL (1) | PL2855456T3 (https=) |
| PT (1) | PT2855456T (https=) |
| SG (1) | SG11201406973PA (https=) |
| TN (1) | TN2014000449A1 (https=) |
| TW (1) | TW201348199A (https=) |
| UY (1) | UY34781A (https=) |
| WO (1) | WO2013164802A1 (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2970269B1 (en) * | 2013-03-14 | 2017-04-19 | Novartis AG | 2-(1h-indol-4-ylmethyl)-3h-imidazo[4,5-b]pyridine-6-carbonitrile derivatives as complement factor b inhibitors useful for the treatment of ophthalmic diseases |
| JO3425B1 (ar) | 2013-07-15 | 2019-10-20 | Novartis Ag | مشتقات البابيريدينيل-اندول واستخدامها كعامل متمم لمثبطات b |
| EP3089963A1 (en) * | 2013-10-30 | 2016-11-09 | Novartis AG | 2-benzyl-benzimidazole complement factor b inhibitors and uses thereof |
| CN103755622A (zh) * | 2013-12-25 | 2014-04-30 | 华东理工大学 | 合成4,5,6,7-四氘代吲哚-3-乙酸的方法 |
| WO2017035408A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Compounds for treatment of immune and inflammatory disorders |
| AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
| TWI854164B (zh) | 2016-02-01 | 2024-09-01 | 美商百歐克斯製藥公司 | 苯并吡唑化合物及其類似物 |
| RU2018145364A (ru) * | 2016-06-27 | 2020-07-28 | Ачиллион Фармасьютикалс, Инк. | Хиназолиновые и индольные соединения для лечения медицинских нарушений |
| CN110603252A (zh) | 2017-03-01 | 2019-12-20 | 艾其林医药公司 | 用于治疗医学障碍的芳基、杂芳基和杂环药物化合物 |
| TWI873092B (zh) * | 2018-04-06 | 2025-02-21 | 美商百歐克斯製藥公司 | 取代的苯并呋喃、苯并吡咯、苯并噻吩及結構相關的補體抑制劑 |
| WO2020041301A1 (en) | 2018-08-20 | 2020-02-27 | Achillion Pharmaceuticals, Inc. | Pharmaceutical compounds for the treatment of complement factor d medical disorders |
| WO2020051532A2 (en) | 2018-09-06 | 2020-03-12 | Achillion Pharmaceuticals, Inc. | Macrocyclic compounds for the treatment of medical disorders |
| US11814363B2 (en) | 2018-09-06 | 2023-11-14 | Achillion Pharmaceuticals, Inc. | Morphic forms of danicopan |
| BR112021005506A2 (pt) | 2018-09-25 | 2021-06-15 | Achillion Pharmaceuticals, Inc. | formas mórficas de inibidores de fator complementar d |
| WO2021168320A1 (en) | 2020-02-20 | 2021-08-26 | Achillion Pharmaceuticals, Inc. | Heteroaryl compounds for treatment of complement factor d mediated disorders |
| CA3179686A1 (en) * | 2020-04-07 | 2021-10-14 | UCB Biopharma SRL | Difluorocyclohexyl derivatives as il-17 modulators |
| CN114057758A (zh) | 2020-08-07 | 2022-02-18 | 上海美悦生物科技发展有限公司 | 补体因子b抑制剂及其药物组合物、制备方法和用途 |
| EP4194449A4 (en) | 2020-08-07 | 2024-03-20 | Shanghai Meiyue Biotech Development Co., Ltd. | Heterocyclic compound, preparation method therefor and use thereof |
| WO2022066774A1 (en) | 2020-09-23 | 2022-03-31 | Achillion Pharmaceuticals, Inc. | Pharmaceutical compounds for the treatment of complement mediated disorders |
| US20240287034A1 (en) * | 2021-06-03 | 2024-08-29 | Chinook Therapeutics, Inc. | Substituted indole compounds and methods of use thereof |
| CA3242815A1 (en) | 2022-01-26 | 2023-08-03 | Shanghai Meiyue Biotech Development Co., Ltd. | Salt type and crystal form of complement factor b inhibitor, and preparation method therefor and application thereof |
| CN119137099A (zh) * | 2022-04-01 | 2024-12-13 | 诺华股份有限公司 | 补体因子b抑制剂及其用途 |
| EP4617266A1 (en) | 2022-11-11 | 2025-09-17 | Shanghai Yisheng Biopharmaceutical company Limited | Piperidine-substituted benzoic acid compound, and pharmaceutical composition and use thereof |
| JP2026502231A (ja) * | 2022-12-31 | 2026-01-21 | チューハイ ユナイテッド ラボラトリーズ シーオー．，エルティーディー． | 補体因子ｂ阻害剤、その医薬組成物および使用 |
| IL325759A (en) | 2023-07-04 | 2026-03-01 | Sitala Bio Ltd | History of 2-(1H-indol-4-yl)methyl)2H-indazole as factor B inhibitors |
| IL325760A (en) | 2023-07-04 | 2026-03-01 | Sitala Bio Ltd | History of 2-(1H-indol-4-yl)methyl)-isoindoline as factor B inhibitors |
| WO2025008516A2 (en) | 2023-07-06 | 2025-01-09 | Sitala Bio Ltd | Novel compounds |
| WO2025008517A1 (en) | 2023-07-06 | 2025-01-09 | Sitala Bio Ltd | Indole derivatives with factor b inhibitory activity |
| CN119371402A (zh) | 2023-07-26 | 2025-01-28 | 上海美悦生物科技发展有限公司 | 螺环烯基类或氮杂烯基类化合物及其药物组合物、制备方法和用途 |
| WO2025172535A1 (en) | 2024-02-15 | 2025-08-21 | Sitala Bio Ltd | Indole and benzimidazole compounds as factor b inhibitors |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT72878B (en) | 1980-04-24 | 1983-03-29 | Merck & Co Inc | Process for preparing mannich-base hydroxamic acid pro-drugs for the improved delivery of non-steroidal anti-inflammatory agents |
| GB8420919D0 (en) * | 1984-08-17 | 1984-09-19 | Beecham Group Plc | Compounds |
| DE19545464A1 (de) * | 1995-12-06 | 1997-06-12 | Bayer Ag | Benzimidazol-isoindoleninfarbstoffe |
| CN100415723C (zh) * | 2000-01-17 | 2008-09-03 | 帝人株式会社 | 苯并咪唑衍生物 |
| WO2004078163A2 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| GB0400781D0 (en) * | 2004-01-14 | 2004-02-18 | Novartis Ag | Organic compounds |
| US7488752B2 (en) * | 2004-10-08 | 2009-02-10 | Schering Corporation | Thrombin receptor antagonists |
| WO2007034277A1 (en) * | 2005-09-19 | 2007-03-29 | Pfizer Products Inc. | Aryl substituted imidazo [4,5-c] pyridine compounds as c3a receptor antagonists |
| EP2046741B1 (en) * | 2006-07-03 | 2012-10-31 | Proximagen Ltd. | Indoles as 5-ht6 modulators |
| JO3265B1 (ar) * | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| CA2965223C (en) * | 2008-12-22 | 2019-09-24 | Chemocentryx, Inc. | C5ar antagonists |
| AU2010216239B2 (en) * | 2009-02-18 | 2012-06-14 | Amgen Inc. | Indole/benzimidazole compounds as mTOR kinase inhibitors |
| EP2447263A1 (en) * | 2010-09-27 | 2012-05-02 | Bioprojet | Benzazole derivatives as histamine H4 receptor ligands |
| US8846656B2 (en) * | 2011-07-22 | 2014-09-30 | Novartis Ag | Tetrahydropyrido-pyridine and tetrahydropyrido-pyrimidine compounds and use thereof as C5a receptor modulators |
-
2013
- 2013-05-03 EP EP13729096.1A patent/EP2855456B1/en active Active
- 2013-05-03 KR KR1020147033713A patent/KR20150003903A/ko not_active Withdrawn
- 2013-05-03 EA EA201492023A patent/EA027113B1/ru not_active IP Right Cessation
- 2013-05-03 MX MX2014013428A patent/MX2014013428A/es unknown
- 2013-05-03 PT PT137290961T patent/PT2855456T/pt unknown
- 2013-05-03 CN CN201380035327.6A patent/CN104603127B/zh not_active Expired - Fee Related
- 2013-05-03 AP AP2014008040A patent/AP2014008040A0/xx unknown
- 2013-05-03 BR BR112014027359A patent/BR112014027359A2/pt not_active IP Right Cessation
- 2013-05-03 SG SG11201406973PA patent/SG11201406973PA/en unknown
- 2013-05-03 ES ES13729096T patent/ES2630079T3/es active Active
- 2013-05-03 PE PE2014001943A patent/PE20150623A1/es not_active Application Discontinuation
- 2013-05-03 JP JP2015509561A patent/JP6180514B2/ja not_active Expired - Fee Related
- 2013-05-03 CA CA2872000A patent/CA2872000A1/en not_active Abandoned
- 2013-05-03 AU AU2013255470A patent/AU2013255470B2/en not_active Ceased
- 2013-05-03 TW TW102115970A patent/TW201348199A/zh unknown
- 2013-05-03 UY UY0001034781A patent/UY34781A/es not_active Application Discontinuation
- 2013-05-03 WO PCT/IB2013/053546 patent/WO2013164802A1/en not_active Ceased
- 2013-05-03 PL PL13729096T patent/PL2855456T3/pl unknown
- 2013-05-03 HK HK15106552.0A patent/HK1206017A1/xx unknown
- 2013-05-06 AR ARP130101533A patent/AR090945A1/es unknown
-
2014
- 2014-10-22 TN TN2014000449A patent/TN2014000449A1/fr unknown
- 2014-10-27 IL IL235362A patent/IL235362A0/en unknown
- 2014-10-28 CL CL2014002919A patent/CL2014002919A1/es unknown
- 2014-11-04 PH PH12014502462A patent/PH12014502462A1/en unknown
- 2014-11-04 CR CR20140508A patent/CR20140508A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013255470A1 (en) | 2014-11-13 |
| EP2855456B1 (en) | 2017-03-29 |
| IL235362A0 (en) | 2014-12-31 |
| CR20140508A (es) | 2015-03-13 |
| HK1206017A1 (en) | 2015-12-31 |
| AU2013255470B2 (en) | 2015-09-17 |
| CL2014002919A1 (es) | 2015-07-03 |
| WO2013164802A1 (en) | 2013-11-07 |
| PH12014502462A1 (en) | 2014-12-22 |
| AP2014008040A0 (en) | 2014-10-31 |
| TW201348199A (zh) | 2013-12-01 |
| PL2855456T3 (pl) | 2017-09-29 |
| BR112014027359A2 (pt) | 2017-07-18 |
| CN104603127A (zh) | 2015-05-06 |
| CA2872000A1 (en) | 2013-11-07 |
| JP6180514B2 (ja) | 2017-08-16 |
| EA201492023A1 (ru) | 2015-03-31 |
| PT2855456T (pt) | 2017-07-10 |
| UY34781A (es) | 2013-12-31 |
| SG11201406973PA (en) | 2014-12-30 |
| AR090945A1 (es) | 2014-12-17 |
| CN104603127B (zh) | 2016-10-05 |
| TN2014000449A1 (en) | 2016-03-30 |
| JP2015515976A (ja) | 2015-06-04 |
| ES2630079T3 (es) | 2017-08-17 |
| MX2014013428A (es) | 2015-02-04 |
| PE20150623A1 (es) | 2015-05-17 |
| EA027113B1 (ru) | 2017-06-30 |
| EP2855456A1 (en) | 2015-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20150003903A (ko) | 보체 경로 조절제 및 그의 용도 | |
| US9056874B2 (en) | Complement pathway modulators and uses thereof | |
| JP5921572B2 (ja) | 加齢性黄斑変性症（ａｍｄ）の処置に有用なインドール化合物またはそのアナログ | |
| JP6387391B2 (ja) | 眼科疾患の処置に有用な補体因子Ｂ阻害剤としての２−（１Ｈ−インドール−４−イルメチル）−３Ｈ−イミダゾ［４，５−ｂ］ピリジン−６−カルボニトリル誘導体 | |
| EP2867225B1 (en) | Pyrrolidine derivatives and their use as complement pathway modulators | |
| US8492393B2 (en) | Heterobicyclic carboxamides as inhibitors for kinases | |
| EP2867229B1 (en) | Pyrrolidine derivatives and their use as complement pathway modulators | |
| US9388199B2 (en) | Pyrrolidine derivatives and their use as complement pathway modulators | |
| JP2017508788A (ja) | 補体媒介障害の治療のためのエーテル化合物 | |
| CA2988338A1 (en) | Nrf2 regulators | |
| KR20150035766A (ko) | 피롤리딘 유도체 및 보체 경로 조절제로서의 그의 용도 | |
| CN104684910A (zh) | 补体途经调节剂及其用途 | |
| CN107635995A (zh) | 作为atx抑制剂的二环化合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20141201 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |