CA2553630A1 - Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof - Google Patents
Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof Download PDFInfo
- Publication number
- CA2553630A1 CA2553630A1 CA002553630A CA2553630A CA2553630A1 CA 2553630 A1 CA2553630 A1 CA 2553630A1 CA 002553630 A CA002553630 A CA 002553630A CA 2553630 A CA2553630 A CA 2553630A CA 2553630 A1 CA2553630 A1 CA 2553630A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- kpu
- atom
- nitro
- heteroaryl
- 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.)
- Abandoned
Links
- 230000015572 biosynthetic process Effects 0.000 title description 26
- 238000003786 synthesis reaction Methods 0.000 title description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 287
- 238000000034 method Methods 0.000 claims abstract description 155
- 239000000203 mixture Substances 0.000 claims abstract description 86
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims abstract description 35
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 21
- 230000002792 vascular Effects 0.000 claims abstract description 20
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims abstract description 18
- 230000035755 proliferation Effects 0.000 claims abstract description 18
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 claims abstract description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 184
- -1 amino, substituted amino, nitro, azido, substituted nitro, phenyl Chemical group 0.000 claims description 139
- 125000001072 heteroaryl group Chemical group 0.000 claims description 89
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 64
- 102000004243 Tubulin Human genes 0.000 claims description 59
- 108090000704 Tubulin Proteins 0.000 claims description 59
- 239000003814 drug Substances 0.000 claims description 57
- 238000011282 treatment Methods 0.000 claims description 54
- 125000003118 aryl group Chemical group 0.000 claims description 52
- 229910052757 nitrogen Inorganic materials 0.000 claims description 46
- 210000005166 vasculature Anatomy 0.000 claims description 45
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 42
- 125000003107 substituted aryl group Chemical group 0.000 claims description 41
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 241001465754 Metazoa Species 0.000 claims description 36
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 33
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 31
- 125000004434 sulfur atom Chemical group 0.000 claims description 31
- 201000011510 cancer Diseases 0.000 claims description 30
- 210000001519 tissue Anatomy 0.000 claims description 29
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 229920006395 saturated elastomer Polymers 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000006686 (C1-C24) alkyl group Chemical group 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 20
- 230000001965 increasing effect Effects 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 125000002252 acyl group Chemical group 0.000 claims description 13
- 208000002780 macular degeneration Diseases 0.000 claims description 13
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 10
- 206010038923 Retinopathy Diseases 0.000 claims description 9
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 8
- 206010009192 Circulatory collapse Diseases 0.000 claims description 8
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 5
- 206010011017 Corneal graft rejection Diseases 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 208000001132 Osteoporosis Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 230000001613 neoplastic effect Effects 0.000 claims description 5
- 201000003142 neovascular glaucoma Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 230000008685 targeting Effects 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 2
- 210000002216 heart Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 208000017442 Retinal disease Diseases 0.000 claims 3
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 1
- 150000003935 benzaldehydes Chemical class 0.000 abstract description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 155
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 147
- 210000004027 cell Anatomy 0.000 description 136
- 238000004949 mass spectrometry Methods 0.000 description 127
- 230000000694 effects Effects 0.000 description 113
- 108010054981 dehydrophenylahistin Proteins 0.000 description 107
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 95
- UNRCMCRRFYFGFX-TYPNBTCFSA-N plinabulin Chemical compound N1C=NC(\C=C/2C(NC(=C\C=3C=CC=CC=3)/C(=O)N\2)=O)=C1C(C)(C)C UNRCMCRRFYFGFX-TYPNBTCFSA-N 0.000 description 87
- 239000000243 solution Substances 0.000 description 73
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 72
- 102000029749 Microtubule Human genes 0.000 description 72
- 108091022875 Microtubule Proteins 0.000 description 72
- 229960001338 colchicine Drugs 0.000 description 72
- 150000003839 salts Chemical class 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- 210000004688 microtubule Anatomy 0.000 description 49
- 229940121375 antifungal agent Drugs 0.000 description 46
- 229940079593 drug Drugs 0.000 description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 36
- 229930012538 Paclitaxel Natural products 0.000 description 36
- 229960001592 paclitaxel Drugs 0.000 description 36
- 229940063683 taxotere Drugs 0.000 description 36
- 238000009739 binding Methods 0.000 description 35
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 230000004614 tumor growth Effects 0.000 description 33
- 238000004128 high performance liquid chromatography Methods 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 230000000843 anti-fungal effect Effects 0.000 description 28
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 28
- 208000015181 infectious disease Diseases 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 25
- 238000009472 formulation Methods 0.000 description 25
- 230000004048 modification Effects 0.000 description 25
- 238000012986 modification Methods 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000006116 polymerization reaction Methods 0.000 description 24
- 239000003429 antifungal agent Substances 0.000 description 23
- 230000008569 process Effects 0.000 description 23
- GWMHBVLPNWHWGW-CNYBTUBUSA-N (3s,6z)-3-benzyl-6-[[5-(2-methylbut-3-en-2-yl)-1h-imidazol-4-yl]methylidene]piperazine-2,5-dione Chemical compound N1C=NC(\C=C/2C(N[C@@H](CC=3C=CC=CC=3)C(=O)N\2)=O)=C1C(C)(C=C)C GWMHBVLPNWHWGW-CNYBTUBUSA-N 0.000 description 21
- 230000003389 potentiating effect Effects 0.000 description 21
- 238000013414 tumor xenograft model Methods 0.000 description 21
- 206010017533 Fungal infection Diseases 0.000 description 20
- 208000031888 Mycoses Diseases 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- 210000004881 tumor cell Anatomy 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- 208000029742 colonic neoplasm Diseases 0.000 description 19
- 229940002612 prodrug Drugs 0.000 description 19
- 239000000651 prodrug Substances 0.000 description 19
- 239000000126 substance Substances 0.000 description 19
- 239000000725 suspension Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000001704 evaporation Methods 0.000 description 18
- 230000008020 evaporation Effects 0.000 description 18
- 238000007920 subcutaneous administration Methods 0.000 description 18
- 230000001472 cytotoxic effect Effects 0.000 description 17
- 230000002401 inhibitory effect Effects 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 17
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 17
- 229910000024 caesium carbonate Inorganic materials 0.000 description 16
- 238000011010 flushing procedure Methods 0.000 description 16
- 244000053095 fungal pathogen Species 0.000 description 16
- 238000001802 infusion Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 206010006187 Breast cancer Diseases 0.000 description 15
- 230000000259 anti-tumor effect Effects 0.000 description 15
- 239000002246 antineoplastic agent Substances 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 208000026310 Breast neoplasm Diseases 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 239000011369 resultant mixture Substances 0.000 description 14
- 239000004066 vascular targeting agent Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 241000700159 Rattus Species 0.000 description 13
- 230000017531 blood circulation Effects 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000007423 decrease Effects 0.000 description 13
- 235000019439 ethyl acetate Nutrition 0.000 description 13
- 238000007912 intraperitoneal administration Methods 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- 229910052760 oxygen Inorganic materials 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 12
- 238000003556 assay Methods 0.000 description 12
- 238000011888 autopsy Methods 0.000 description 12
- 238000002648 combination therapy Methods 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 101150041968 CDC13 gene Proteins 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 230000003013 cytotoxicity Effects 0.000 description 11
- 231100000135 cytotoxicity Toxicity 0.000 description 11
- VWLWTJHKQHRTNC-UHFFFAOYSA-L dipotassium;8-anilino-5-(4-anilino-5-sulfonatonaphthalen-1-yl)naphthalene-1-sulfonate Chemical compound [K+].[K+].C=12C(S(=O)(=O)[O-])=CC=CC2=C(C=2C3=CC=CC(=C3C(NC=3C=CC=CC=3)=CC=2)S([O-])(=O)=O)C=CC=1NC1=CC=CC=C1 VWLWTJHKQHRTNC-UHFFFAOYSA-L 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 230000001717 pathogenic effect Effects 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 229920000642 polymer Polymers 0.000 description 11
- 230000036515 potency Effects 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- 208000023958 prostate neoplasm Diseases 0.000 description 11
- 238000006467 substitution reaction Methods 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- 108010036949 Cyclosporine Proteins 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 230000006907 apoptotic process Effects 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 10
- 230000012010 growth Effects 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 238000001228 spectrum Methods 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 241000222122 Candida albicans Species 0.000 description 9
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 9
- 229930105110 Cyclosporin A Natural products 0.000 description 9
- 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 9
- 241001529936 Murinae Species 0.000 description 9
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 9
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 9
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 125000001246 bromo group Chemical group Br* 0.000 description 9
- 229960001265 ciclosporin Drugs 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 230000007246 mechanism Effects 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 230000005012 migration Effects 0.000 description 9
- 238000013508 migration Methods 0.000 description 9
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 9
- 230000002265 prevention Effects 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 238000009097 single-agent therapy Methods 0.000 description 9
- 239000000375 suspending agent Substances 0.000 description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 8
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 241000699660 Mus musculus Species 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 8
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 8
- 229960003942 amphotericin b Drugs 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 239000012829 chemotherapy agent Substances 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 231100000433 cytotoxic Toxicity 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 8
- 125000002883 imidazolyl group Chemical group 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 201000001441 melanoma Diseases 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 238000011580 nude mouse model Methods 0.000 description 8
- 239000002674 ointment Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- 230000035699 permeability Effects 0.000 description 8
- 235000018102 proteins Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- CBBKKVPJPRZOCM-UHFFFAOYSA-N 1,4-diacetylpiperazine-2,5-dione Chemical compound CC(=O)N1CC(=O)N(C(C)=O)CC1=O CBBKKVPJPRZOCM-UHFFFAOYSA-N 0.000 description 7
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 7
- 241000233866 Fungi Species 0.000 description 7
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 206010061418 Zygomycosis Diseases 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000000577 adipose tissue Anatomy 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 230000003247 decreasing effect Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 239000001963 growth medium Substances 0.000 description 7
- 238000000338 in vitro Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 208000020816 lung neoplasm Diseases 0.000 description 7
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 7
- 229960001156 mitoxantrone Drugs 0.000 description 7
- 201000007524 mucormycosis Diseases 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 238000011255 standard chemotherapy Methods 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- 229940077476 2,5-piperazinedione Drugs 0.000 description 6
- 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 6
- 229920002307 Dextran Polymers 0.000 description 6
- IIUZTXTZRGLYTI-UHFFFAOYSA-N Dihydrogriseofulvin Natural products COC1CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 IIUZTXTZRGLYTI-UHFFFAOYSA-N 0.000 description 6
- 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 6
- UXWOXTQWVMFRSE-UHFFFAOYSA-N Griseoviridin Natural products O=C1OC(C)CC=C(C(NCC=CC=CC(O)CC(O)C2)=O)SCC1NC(=O)C1=COC2=N1 UXWOXTQWVMFRSE-UHFFFAOYSA-N 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 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 6
- DDUHZTYCFQRHIY-UHFFFAOYSA-N Negwer: 6874 Natural products COC1=CC(=O)CC(C)C11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-UHFFFAOYSA-N 0.000 description 6
- 206010039491 Sarcoma Diseases 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 210000001072 colon Anatomy 0.000 description 6
- 238000001493 electron microscopy Methods 0.000 description 6
- 210000002889 endothelial cell Anatomy 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 238000005755 formation reaction Methods 0.000 description 6
- DDUHZTYCFQRHIY-RBHXEPJQSA-N griseofulvin Chemical compound COC1=CC(=O)C[C@@H](C)[C@@]11C(=O)C(C(OC)=CC(OC)=C2Cl)=C2O1 DDUHZTYCFQRHIY-RBHXEPJQSA-N 0.000 description 6
- 229960002867 griseofulvin Drugs 0.000 description 6
- 238000010820 immunofluorescence microscopy Methods 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000002502 liposome Substances 0.000 description 6
- 239000011777 magnesium Substances 0.000 description 6
- 229910052749 magnesium Inorganic materials 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 230000008092 positive effect Effects 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 238000013207 serial dilution Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000003381 stabilizer Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 5
- ZZOBLCHCPLOXCE-UHFFFAOYSA-N Arthripur Chemical compound CN1C(C)=C(I)C(=O)N1C1=CC=CC=C1 ZZOBLCHCPLOXCE-UHFFFAOYSA-N 0.000 description 5
- 108090000397 Caspase 3 Proteins 0.000 description 5
- 102100029855 Caspase-3 Human genes 0.000 description 5
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 5
- 108091000080 Phosphotransferase Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000000149 argon plasma sintering Methods 0.000 description 5
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 5
- 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 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 210000000481 breast Anatomy 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000000576 coating method Methods 0.000 description 5
- 238000004891 communication Methods 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- 229940127089 cytotoxic agent Drugs 0.000 description 5
- 239000008298 dragée Substances 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000002538 fungal effect Effects 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 229960001031 glucose Drugs 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 230000001506 immunosuppresive effect Effects 0.000 description 5
- 238000002513 implantation Methods 0.000 description 5
- 229960004130 itraconazole Drugs 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 210000004072 lung Anatomy 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000017074 necrotic cell death Effects 0.000 description 5
- 230000037361 pathway Effects 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 102000020233 phosphotransferase Human genes 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 210000002307 prostate Anatomy 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- 239000002356 single layer Substances 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 239000011550 stock solution Substances 0.000 description 5
- 235000000346 sugar Nutrition 0.000 description 5
- 239000000829 suppository Substances 0.000 description 5
- 150000003852 triazoles Chemical class 0.000 description 5
- 229920002554 vinyl polymer Polymers 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- YGKOYVNJPRSSRX-UHFFFAOYSA-M (4-dodecylphenyl)methyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCC1=CC=C(C[N+](C)(C)C)C=C1 YGKOYVNJPRSSRX-UHFFFAOYSA-M 0.000 description 4
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 206010007134 Candida infections Diseases 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 229930182816 L-glutamine Natural products 0.000 description 4
- 108091077621 MAPRE family Proteins 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 206010027476 Metastases Diseases 0.000 description 4
- 206010028851 Necrosis Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 201000003984 candidiasis Diseases 0.000 description 4
- 210000000170 cell membrane Anatomy 0.000 description 4
- WDOGQTQEKVLZIJ-WAYWQWQTSA-N combretastatin a-4 phosphate Chemical compound C1=C(OP(O)(O)=O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 WDOGQTQEKVLZIJ-WAYWQWQTSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 238000002784 cytotoxicity assay Methods 0.000 description 4
- 231100000263 cytotoxicity test Toxicity 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 125000004185 ester group Chemical group 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 4
- 229960004884 fluconazole Drugs 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000009499 grossing Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 208000037841 lung tumor Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 150000002829 nitrogen Chemical group 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 4
- 230000002685 pulmonary effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 210000003606 umbilical vein Anatomy 0.000 description 4
- UGBMEXLBFDAOGL-INIZCTEOSA-N zd6126 Chemical compound C1C[C@H](NC(C)=O)C2=CC(OP(O)(O)=O)=CC=C2C2=C1C=C(OC)C(OC)=C2OC UGBMEXLBFDAOGL-INIZCTEOSA-N 0.000 description 4
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
- WWLHYYPFFDHSBF-UHFFFAOYSA-N 5-(2-methylbut-3-en-2-yl)-1h-imidazole-4-carbaldehyde Chemical compound C=CC(C)(C)C=1NC=NC=1C=O WWLHYYPFFDHSBF-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
- 241000228212 Aspergillus Species 0.000 description 3
- 241001225321 Aspergillus fumigatus Species 0.000 description 3
- 241000335423 Blastomyces Species 0.000 description 3
- 206010005098 Blastomycosis Diseases 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 102000011727 Caspases Human genes 0.000 description 3
- 108010076667 Caspases Proteins 0.000 description 3
- 241000223205 Coccidioides immitis Species 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 3
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 3
- 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 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 244000068988 Glycine max Species 0.000 description 3
- 235000010469 Glycine max Nutrition 0.000 description 3
- 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 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 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 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
- 206010054094 Tumour necrosis Diseases 0.000 description 3
- 230000009102 absorption Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 230000002776 aggregation Effects 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000004075 alteration Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 229960000074 biopharmaceutical Drugs 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 229940095731 candida albicans Drugs 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 229960005527 combretastatin A-4 phosphate Drugs 0.000 description 3
- 230000006957 competitive inhibition Effects 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 238000000635 electron micrograph Methods 0.000 description 3
- 210000003527 eukaryotic cell Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 3
- 229960004413 flucytosine Drugs 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 230000000855 fungicidal effect Effects 0.000 description 3
- 230000001408 fungistatic effect Effects 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000005090 green fluorescent protein Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 229960004125 ketoconazole Drugs 0.000 description 3
- 238000012417 linear regression Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- IZLAFAPADUHVEE-UHFFFAOYSA-N methyl 3-hydroxy-2,2-dimethylbutanoate Chemical compound COC(=O)C(C)(C)C(C)O IZLAFAPADUHVEE-UHFFFAOYSA-N 0.000 description 3
- 230000029115 microtubule polymerization Effects 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003068 molecular probe Substances 0.000 description 3
- 230000006911 nucleation Effects 0.000 description 3
- 238000010899 nucleation Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 229940026778 other chemotherapeutics in atc Drugs 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- 238000004062 sedimentation Methods 0.000 description 3
- 239000008159 sesame oil Substances 0.000 description 3
- 235000011803 sesame oil Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 238000004627 transmission electron microscopy Methods 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- NHBJCUUNNHUOOO-UHFFFAOYSA-N 2,2-dimethylbut-3-enoyl chloride Chemical compound C=CC(C)(C)C(Cl)=O NHBJCUUNNHUOOO-UHFFFAOYSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 201000002909 Aspergillosis Diseases 0.000 description 2
- 241000228197 Aspergillus flavus Species 0.000 description 2
- 208000036641 Aspergillus infections Diseases 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 241000228405 Blastomyces dermatitidis Species 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 2
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 2
- 241001480517 Conidiobolus Species 0.000 description 2
- 201000007336 Cryptococcosis Diseases 0.000 description 2
- 241000221204 Cryptococcus neoformans Species 0.000 description 2
- 241000235555 Cunninghamella Species 0.000 description 2
- 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 2
- 206010011878 Deafness Diseases 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 208000000785 Invasive Pulmonary Aspergillosis Diseases 0.000 description 2
- 208000000913 Kidney Calculi Diseases 0.000 description 2
- 244000285963 Kluyveromyces fragilis Species 0.000 description 2
- 229910010084 LiAlH4 Inorganic materials 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 231100000678 Mycotoxin Toxicity 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010029148 Nephrolithiasis Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
- 206010033767 Paracoccidioides infections Diseases 0.000 description 2
- 201000000301 Paracoccidioidomycosis Diseases 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- 238000004617 QSAR study Methods 0.000 description 2
- 208000007135 Retinal Neovascularization Diseases 0.000 description 2
- 241000235527 Rhizopus Species 0.000 description 2
- 240000005384 Rhizopus oryzae Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 206010041736 Sporotrichosis Diseases 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 241000223238 Trichophyton Species 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229940050528 albumin Drugs 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000004645 aluminates Chemical class 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000002827 antifungal susceptibility testing Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 150000001556 benzimidazoles Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 201000008275 breast carcinoma Diseases 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000006369 cell cycle progression Effects 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000007248 cellular mechanism Effects 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 159000000006 cesium salts Chemical class 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 201000003486 coccidioidomycosis Diseases 0.000 description 2
- 239000003240 coconut oil Substances 0.000 description 2
- 235000019864 coconut oil Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229960005537 combretastatin A-4 Drugs 0.000 description 2
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 2
- 229940124301 concurrent medication Drugs 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 210000004748 cultured cell Anatomy 0.000 description 2
- 229960001305 cysteine hydrochloride Drugs 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000000032 diagnostic agent Substances 0.000 description 2
- 229940039227 diagnostic agent Drugs 0.000 description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000009699 differential effect Effects 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 231100000676 disease causative agent Toxicity 0.000 description 2
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 2
- VXNQMUVMEIGUJW-XNOMRPDFSA-L disodium;[2-methoxy-5-[(z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate Chemical compound [Na+].[Na+].C1=C(OP([O-])([O-])=O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 VXNQMUVMEIGUJW-XNOMRPDFSA-L 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 230000002900 effect on cell Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- QUEYGKWZKXHYIL-UHFFFAOYSA-N ethyl 2-chloro-4,4-dimethyl-3-oxohex-5-enoate Chemical compound CCOC(=O)C(Cl)C(=O)C(C)(C)C=C QUEYGKWZKXHYIL-UHFFFAOYSA-N 0.000 description 2
- XBTXDMIYSKXIGL-UHFFFAOYSA-N ethyl 2-chloro-4,4-dimethyl-3-oxopentanoate Chemical compound CCOC(=O)C(Cl)C(=O)C(C)(C)C XBTXDMIYSKXIGL-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000001506 fluorescence spectroscopy Methods 0.000 description 2
- 238000002189 fluorescence spectrum Methods 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229910052734 helium Inorganic materials 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- 229940125721 immunosuppressive agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000004922 lacquer Substances 0.000 description 2
- 229960001375 lactose Drugs 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006194 liquid suspension Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- UHRVSIIJSJKEPO-UHFFFAOYSA-N methyl 2,2-dimethylbut-3-enoate Chemical compound COC(=O)C(C)(C)C=C UHRVSIIJSJKEPO-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- BHIWKHZACMWKOJ-UHFFFAOYSA-N methyl isobutyrate Chemical compound COC(=O)C(C)C BHIWKHZACMWKOJ-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000025090 microtubule depolymerization Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 235000013923 monosodium glutamate Nutrition 0.000 description 2
- 239000002636 mycotoxin Substances 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 2
- 229960003255 natamycin Drugs 0.000 description 2
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 2
- 230000012169 negative regulation of microtubule polymerization Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000006179 pH buffering agent Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 125000005633 phthalidyl group Chemical group 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- 229950011498 plinabulin Drugs 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 230000008261 resistance mechanism Effects 0.000 description 2
- 239000012449 sabouraud dextrose agar Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229940073490 sodium glutamate Drugs 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000005556 structure-activity relationship Methods 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 239000004408 titanium dioxide Substances 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000027 toxicology Toxicity 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- 239000003744 tubulin modulator Substances 0.000 description 2
- 210000001635 urinary tract Anatomy 0.000 description 2
- 201000002327 urinary tract obstruction Diseases 0.000 description 2
- 208000037965 uterine sarcoma Diseases 0.000 description 2
- 210000005167 vascular cell Anatomy 0.000 description 2
- 238000010865 video microscopy Methods 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- YKSVGLFNJPQDJE-YDMQLZBCSA-N (19E,21E,23E,25E,27E,29E,31E)-33-[(2R,3S,4R,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-17-[7-(4-aminophenyl)-5-hydroxy-4-methyl-7-oxoheptan-2-yl]-1,3,5,7,37-pentahydroxy-18-methyl-9,13,15-trioxo-16,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid Chemical compound CC(CC(C)C1OC(=O)CC(=O)CCCC(=O)CC(O)CC(O)CC(O)CC2(O)CC(O)C(C(CC(O[C@@H]3O[C@H](C)[C@@H](O)[C@@H](N)[C@@H]3O)\C=C\C=C\C=C\C=C\C=C\C=C\C=C\C1C)O2)C(O)=O)C(O)CC(=O)C1=CC=C(N)C=C1 YKSVGLFNJPQDJE-YDMQLZBCSA-N 0.000 description 1
- BLSQLHNBWJLIBQ-OZXSUGGESA-N (2R,4S)-terconazole Chemical compound C1CN(C(C)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2N=CN=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 BLSQLHNBWJLIBQ-OZXSUGGESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- LEZWWPYKPKIXLL-UHFFFAOYSA-N 1-{2-(4-chlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl}imidazole Chemical compound C1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 LEZWWPYKPKIXLL-UHFFFAOYSA-N 0.000 description 1
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical class O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
- SCFWAOWWAANBPY-UHFFFAOYSA-N 2,2-dimethyl-3-butenoic acid Chemical compound C=CC(C)(C)C(O)=O SCFWAOWWAANBPY-UHFFFAOYSA-N 0.000 description 1
- XARVANDLQOZMMJ-CHHVJCJISA-N 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-oxo-2-(2-oxoethylamino)ethylidene]amino]oxy-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)O\N=C(/C(=O)NCC=O)C1=CSC(N)=N1 XARVANDLQOZMMJ-CHHVJCJISA-N 0.000 description 1
- NABMTTWARSHKGC-UHFFFAOYSA-N 2-[1-(2-sulfoethyl)piperazin-2-yl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCC1CNCCN1CCS(O)(=O)=O NABMTTWARSHKGC-UHFFFAOYSA-N 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- XQQBUAPQHNYYRS-UHFFFAOYSA-N 2-methylthiophene Chemical group CC1=CC=CS1 XQQBUAPQHNYYRS-UHFFFAOYSA-N 0.000 description 1
- HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- DEKJPODSYVPCPW-ZGZXFVETSA-N 4-(aminomethyl)-N-[(12E,15S)-17,19-diazatricyclo[14.2.1.02,7]nonadeca-1(18),2,4,6,12,16-hexaen-15-yl]cyclohexane-1-carboxamide Chemical compound NCC1CCC(CC1)C(=O)N[C@H]1C\C=C\CCCCc2ccccc2-c2cnc1[nH]2 DEKJPODSYVPCPW-ZGZXFVETSA-N 0.000 description 1
- ILUSBJDVXKZYEP-UHFFFAOYSA-N 4-(aminomethyl)oxan-4-ol;hydrochloride Chemical compound Cl.NCC1(O)CCOCC1 ILUSBJDVXKZYEP-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- NDPDSHFBKCCURT-UHFFFAOYSA-N 5-(2-methylpropyl)-1h-imidazole-4-carbaldehyde Chemical group CC(C)CC=1NC=NC=1C=O NDPDSHFBKCCURT-UHFFFAOYSA-N 0.000 description 1
- FSTXHTKEZGSDNN-UHFFFAOYSA-N 5-tert-butyl-1h-imidazole-4-carbaldehyde Chemical compound CC(C)(C)C=1N=CNC=1C=O FSTXHTKEZGSDNN-UHFFFAOYSA-N 0.000 description 1
- PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
- SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 208000003120 Angiofibroma Diseases 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 241001480043 Arthrodermataceae Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000235579 Basidiobolus Species 0.000 description 1
- 241001480523 Basidiobolus ranarum Species 0.000 description 1
- 241001302652 Bassiana Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DFVYOEWFOJYXQS-UHFFFAOYSA-N CC[K].OC(=O)CC(O)=O Chemical compound CC[K].OC(=O)CC(O)=O DFVYOEWFOJYXQS-UHFFFAOYSA-N 0.000 description 1
- 241000222178 Candida tropicalis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102100027943 Carnitine O-palmitoyltransferase 1, liver isoform Human genes 0.000 description 1
- 101710120614 Carnitine O-palmitoyltransferase 1, liver isoform Proteins 0.000 description 1
- 101710108984 Carnitine O-palmitoyltransferase 1, muscle isoform Proteins 0.000 description 1
- 102100026548 Caspase-8 Human genes 0.000 description 1
- 108090000538 Caspase-8 Proteins 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 206010008803 Chromoblastomycosis Diseases 0.000 description 1
- 208000015116 Chromomycosis Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 241000223203 Coccidioides Species 0.000 description 1
- 241001077262 Conga Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 208000007163 Dermatomycoses Diseases 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108010049047 Echinocandins Proteins 0.000 description 1
- 241000257465 Echinoidea Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001480035 Epidermophyton Species 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000592938 Helminthosporium solani Species 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 241000228404 Histoplasma capsulatum Species 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000007766 Kaposi sarcoma Diseases 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 231100000111 LD50 Toxicity 0.000 description 1
- 241001523528 Loasa Species 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 206010027458 Metastases to lung Diseases 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical class COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- 102000002151 Microfilament Proteins Human genes 0.000 description 1
- 108010040897 Microfilament Proteins Proteins 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 1
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 description 1
- 101000808007 Mus musculus Vascular endothelial growth factor A Proteins 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 241000475481 Nebula Species 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- KYRVNWMVYQXFEU-UHFFFAOYSA-N Nocodazole Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CS1 KYRVNWMVYQXFEU-UHFFFAOYSA-N 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 101150053185 P450 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001537205 Paracoccidioides Species 0.000 description 1
- 241000526686 Paracoccidioides brasiliensis Species 0.000 description 1
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 241000235645 Pichia kudriavzevii Species 0.000 description 1
- NCXMLFZGDNKEPB-UHFFFAOYSA-N Pimaricin Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCC(C)OC(=O)C=CC2OC2CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 NCXMLFZGDNKEPB-UHFFFAOYSA-N 0.000 description 1
- 241000233870 Pneumocystis Species 0.000 description 1
- 229930182764 Polyoxin Natural products 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 241000183024 Populus tremula Species 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 206010037649 Pyogenic granuloma Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 241000293825 Rhinosporidium Species 0.000 description 1
- 241000293824 Rhinosporidium seeberi Species 0.000 description 1
- 241000235402 Rhizomucor Species 0.000 description 1
- 241000593344 Rhizopus microsporus Species 0.000 description 1
- 241000223598 Scedosporium boydii Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 240000002825 Solanum vestissimum Species 0.000 description 1
- 235000018259 Solanum vestissimum Nutrition 0.000 description 1
- 241001149963 Sporothrix schenckii Species 0.000 description 1
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 1
- 108020003891 Squalene monooxygenase Proteins 0.000 description 1
- XJTXBUKLGQCZHC-UHFFFAOYSA-N Steganacin Natural products C1=C2C=3C(OC)=C(OC)C(OC)=CC=3CC3C(=O)OCC3C(OC(C)=O)C2=CC2=C1OCO2 XJTXBUKLGQCZHC-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000390203 Trachoma Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- 241000591119 Trichophyton sp. Species 0.000 description 1
- 241000893966 Trichophyton verrucosum Species 0.000 description 1
- 241000009298 Trigla lyra Species 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 229930183739 Tryprostatin Natural products 0.000 description 1
- 229940122429 Tubulin inhibitor Drugs 0.000 description 1
- 241001238303 Turdus fuscater Species 0.000 description 1
- COQLPRJCUIATTQ-UHFFFAOYSA-N Uranyl acetate Chemical compound O.O.O=[U]=O.CC(O)=O.CC(O)=O COQLPRJCUIATTQ-UHFFFAOYSA-N 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- DOSITEMRMPTXEY-UHFFFAOYSA-N [4-(2-methylbut-3-en-2-yl)-1h-imidazol-5-yl]methanol Chemical compound C=CC(C)(C)C=1N=CNC=1CO DOSITEMRMPTXEY-UHFFFAOYSA-N 0.000 description 1
- 241000222126 [Candida] glabrata Species 0.000 description 1
- 230000005856 abnormality Effects 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000009956 adenocarcinoma Diseases 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid Drugs 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 125000000033 alkoxyamino group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000416 anti-micotic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000001946 anti-microtubular Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940091771 aspergillus fumigatus Drugs 0.000 description 1
- 230000008335 axon cargo transport Effects 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- RIOXQFHNBCKOKP-UHFFFAOYSA-N benomyl Chemical compound C1=CC=C2N(C(=O)NCCCC)C(NC(=O)OC)=NC2=C1 RIOXQFHNBCKOKP-UHFFFAOYSA-N 0.000 description 1
- MITFXPHMIHQXPI-UHFFFAOYSA-N benzoxaprofen Natural products N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- SWLMUYACZKCSHZ-UHFFFAOYSA-N butoconazole Chemical compound C1=CC(Cl)=CC=C1CCC(SC=1C(=CC=CC=1Cl)Cl)CN1C=NC=C1 SWLMUYACZKCSHZ-UHFFFAOYSA-N 0.000 description 1
- 229960005074 butoconazole Drugs 0.000 description 1
- 229960004348 candicidin Drugs 0.000 description 1
- 208000032343 candida glabrata infection Diseases 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000033366 cell cycle process Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 210000004671 cell-free system Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- CWJSHJJYOPWUGX-UHFFFAOYSA-N chlorpropham Chemical compound CC(C)OC(=O)NC1=CC=CC(Cl)=C1 CWJSHJJYOPWUGX-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 1
- 229960004022 clotrimazole Drugs 0.000 description 1
- 150000004814 combretastatins Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000011970 concomitant therapy Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- WKPZKRWOIZKCDN-WAQYZQTGSA-N ctp-11 Chemical compound Cl.C=1C=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=1OC(=O)N(CC1)CCC1N1CCCCC1 WKPZKRWOIZKCDN-WAQYZQTGSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000037304 dermatophytes Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000006389 diacetylation reaction Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical class [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 239000000386 donor Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000013535 dynamic contrast enhanced MRI Methods 0.000 description 1
- 230000008482 dysregulation Effects 0.000 description 1
- 229960003913 econazole Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- HPFGMNPZLRHTIP-UHFFFAOYSA-N ethyl 4,4-dimethyl-3-oxohex-5-enoate Chemical compound CCOC(=O)CC(=O)C(C)(C)C=C HPFGMNPZLRHTIP-UHFFFAOYSA-N 0.000 description 1
- VUYNTIDSHCJIKF-UHFFFAOYSA-N ethyl 4,4-dimethyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)(C)C VUYNTIDSHCJIKF-UHFFFAOYSA-N 0.000 description 1
- AYUWAEAZFKHQMM-UHFFFAOYSA-N ethyl 5-(2-methylbut-3-en-2-yl)-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1N=CNC=1C(C)(C)C=C AYUWAEAZFKHQMM-UHFFFAOYSA-N 0.000 description 1
- ZWLWFCKNFSOIEA-UHFFFAOYSA-N ethyl 5-tert-butyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC=NC=1C(C)(C)C ZWLWFCKNFSOIEA-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 201000005889 eumycotic mycetoma Diseases 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000004508 fractional distillation Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 231100000025 genetic toxicology Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000010651 grapefruit oil Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004470 heterocyclooxy group Chemical group 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000000852 hydrogen donor Substances 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 230000006951 hyperphosphorylation Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000010189 intracellular transport Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 1
- WDAXFOBOLVPGLV-UHFFFAOYSA-N isobutyric acid ethyl ester Natural products CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 150000004715 keto acids Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- CYMNTFYAKOAZRB-UHFFFAOYSA-N methyl 2,2-dimethyl-3-(4-methylphenyl)sulfonyloxybutanoate Chemical compound COC(=O)C(C)(C)C(C)OS(=O)(=O)C1=CC=C(C)C=C1 CYMNTFYAKOAZRB-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002509 miconazole Drugs 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 231100000782 microtubule inhibitor Toxicity 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 239000007758 minimum essential medium Substances 0.000 description 1
- 230000008600 mitotic progression Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- OZGNYLLQHRPOBR-DHZHZOJOSA-N naftifine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OZGNYLLQHRPOBR-DHZHZOJOSA-N 0.000 description 1
- 229960004313 naftifine Drugs 0.000 description 1
- 239000004311 natamycin Substances 0.000 description 1
- 235000010298 natamycin Nutrition 0.000 description 1
- 229950006344 nocodazole Drugs 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/CC/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- IXWNTLSTOZFSCM-YVACAVLKSA-N ombrabulin Chemical compound C1=C(NC(=O)[C@@H](N)CO)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 IXWNTLSTOZFSCM-YVACAVLKSA-N 0.000 description 1
- 229950003600 ombrabulin Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 230000004768 organ dysfunction Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229960003483 oxiconazole Drugs 0.000 description 1
- QRJJEGAJXVEBNE-MOHJPFBDSA-N oxiconazole Chemical compound ClC1=CC(Cl)=CC=C1CO\N=C(C=1C(=CC(Cl)=CC=1)Cl)\CN1C=NC=C1 QRJJEGAJXVEBNE-MOHJPFBDSA-N 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 231100000435 percutaneous penetration Toxicity 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940080469 phosphocellulose Drugs 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000009290 primary effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229930000044 secondary metabolite Natural products 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009943 skeletal muscle blood flow Effects 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- XJTXBUKLGQCZHC-GCKMJXCFSA-N steganacin Chemical compound C1=C2C=3C(OC)=C(OC)C(OC)=CC=3C[C@@H]3C(=O)OC[C@H]3[C@H](OC(C)=O)C2=CC2=C1OCO2 XJTXBUKLGQCZHC-GCKMJXCFSA-N 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 238000002626 targeted therapy Methods 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 229960002722 terbinafine Drugs 0.000 description 1
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 1
- 229960000580 terconazole Drugs 0.000 description 1
- 125000005323 thioketone group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 206010044325 trachoma Diseases 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000000430 tryptophan group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic 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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54207304P | 2004-02-04 | 2004-02-04 | |
| US60/542,073 | 2004-02-04 | ||
| US62426204P | 2004-11-01 | 2004-11-01 | |
| US60/624,262 | 2004-11-01 | ||
| PCT/US2005/003636 WO2005077940A1 (en) | 2004-02-04 | 2005-02-04 | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2553630A1 true CA2553630A1 (en) | 2005-08-25 |
Family
ID=34864489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002553630A Abandoned CA2553630A1 (en) | 2004-02-04 | 2005-02-04 | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1711487A1 (en_2) |
| JP (1) | JP2007520565A (en_2) |
| KR (1) | KR101228104B1 (en_2) |
| AU (1) | AU2005212399B2 (en_2) |
| BR (1) | BRPI0506655A (en_2) |
| CA (1) | CA2553630A1 (en_2) |
| IL (1) | IL176932A0 (en_2) |
| NZ (1) | NZ548659A (en_2) |
| WO (1) | WO2005077940A1 (en_2) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7919497B2 (en) | 2002-08-02 | 2011-04-05 | Nereus Pharmaceuticals, Inc. | Analogs of dehydrophenylahistins and their therapeutic use |
| MXPA05001217A (es) | 2002-08-02 | 2005-05-16 | Nereus Pharmaceuticals Inc | Deshidrofenilahistinas y sus analogos y la sintesis de deshidrofenilahistinas y sus analogos. |
| US7935704B2 (en) | 2003-08-01 | 2011-05-03 | Nereus Pharmaceuticals, Inc. | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof |
| WO2007035841A1 (en) * | 2005-09-21 | 2007-03-29 | Nereus Pharmaceuticals, Inc. | Analogs of dehydrophenylahistins and their therapeutic use |
| US8129527B2 (en) | 2006-11-03 | 2012-03-06 | Nereus Pharmacuticals, Inc. | Analogs of dehydrophenylahistins and their therapeutic use |
| US10596169B2 (en) * | 2013-10-11 | 2020-03-24 | Beyondspring Inc. | Cancer treatment with combination of plinabulin and taxane |
| US20180028531A1 (en) * | 2015-02-12 | 2018-02-01 | BeyondSpring Phamaceuticals, Inc. | Use of plinabulin in combination with immune checkpoint inhibitors |
| JP6769982B2 (ja) | 2015-03-06 | 2020-10-14 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | Ｒａｓ変異と関連するがんの治療方法 |
| KR102623404B1 (ko) * | 2015-03-06 | 2024-01-11 | 비욘드스프링 파마수티컬스, 인코포레이티드. | 뇌 종양 치료 방법 |
| AU2016291708B2 (en) * | 2015-07-13 | 2020-12-24 | Beyondspring Pharmaceuticals, Inc | Plinabulin compositions |
| NZ744854A (en) | 2016-02-08 | 2020-01-31 | Beyondspring Pharmaceuticals Inc | Compositions containing tucaresol or its analogs |
| CA3026455A1 (en) | 2016-06-06 | 2017-12-14 | Beyondspring Pharmaceuticals, Inc. | Use of plinabulin for reducing neutropenia induced by chemotherapeutic agents |
| CN114276332B (zh) | 2016-08-12 | 2023-08-18 | 深圳华大海洋科技有限公司 | 脱氢苯基阿夕斯丁类化合物的多晶型及其制备纯化方法和应用 |
| US11633393B2 (en) | 2017-01-06 | 2023-04-25 | Beyondspring Pharmaceuticals, Inc. | Tubulin binding compounds and therapeutic use thereof |
| CN110381938A (zh) | 2017-02-01 | 2019-10-25 | 大连万春布林医药有限公司 | 减少中性粒细胞缺乏症的方法 |
| JP7280192B2 (ja) * | 2017-03-13 | 2023-05-23 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | プリナブリン組成物及びその使用 |
| AU2019212118A1 (en) | 2018-01-24 | 2020-09-03 | Beyondspring Pharmaceuticals, Inc. | Composition and method for reducing thrombocytopenia via the administration of plinabulin |
| CN108524442B (zh) * | 2018-06-05 | 2022-01-28 | 深圳海王医药科技研究院有限公司 | 一种抗肿瘤药物的注射剂及其制备方法 |
| JP2018199726A (ja) * | 2018-09-26 | 2018-12-20 | ビヨンドスプリング インコーポレイテッド | プリナブリン及びタキサンの組合せがん治療 |
| JP2024513505A (ja) | 2021-04-09 | 2024-03-25 | ビヨンドスプリング ファーマシューティカルズ，インコーポレイテッド | 腫瘍を治療するための組成物及び方法 |
| EP4412613A1 (en) * | 2021-10-07 | 2024-08-14 | Beyondspring Pharmaceuticals, Inc. | Methods for treating cancers and tumors |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3318789C2 (de) * | 1983-05-24 | 1987-04-02 | Eduard Gerlach GmbH Chemische Fabrik, 4990 Lübbecke | Deodorant |
| GB9402807D0 (en) * | 1994-02-14 | 1994-04-06 | Xenova Ltd | Pharmaceutical compounds |
| US6069146A (en) * | 1998-03-25 | 2000-05-30 | The Regents Of The University Of California | Halimide, a cytotoxic marine natural product, and derivatives thereof |
| US6358957B1 (en) * | 1998-11-12 | 2002-03-19 | Nereus Pharmaceuticals, Inc. | Phenylahistin and the phenylahistin analogs, a new class of anti-tumor compounds |
| MXPA02006826A (es) * | 2000-01-18 | 2004-04-05 | Nereus Phamraceuticals Inc | Un inhibidor de division celular y un metodo de produccion del mismo. |
| ATE417614T1 (de) * | 2000-05-09 | 2009-01-15 | Angiorx Corp | Piperazindion-verbindungen |
| MXPA05001217A (es) * | 2002-08-02 | 2005-05-16 | Nereus Pharmaceuticals Inc | Deshidrofenilahistinas y sus analogos y la sintesis de deshidrofenilahistinas y sus analogos. |
-
2005
- 2005-02-04 NZ NZ548659A patent/NZ548659A/en not_active IP Right Cessation
- 2005-02-04 EP EP05712910A patent/EP1711487A1/en not_active Withdrawn
- 2005-02-04 WO PCT/US2005/003636 patent/WO2005077940A1/en active Application Filing
- 2005-02-04 KR KR1020067017883A patent/KR101228104B1/ko not_active Expired - Lifetime
- 2005-02-04 BR BRPI0506655-7A patent/BRPI0506655A/pt not_active IP Right Cessation
- 2005-02-04 AU AU2005212399A patent/AU2005212399B2/en not_active Ceased
- 2005-02-04 CA CA002553630A patent/CA2553630A1/en not_active Abandoned
- 2005-02-04 JP JP2006552282A patent/JP2007520565A/ja active Pending
-
2006
- 2006-07-18 IL IL176932A patent/IL176932A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005212399B2 (en) | 2011-09-22 |
| BRPI0506655A (pt) | 2007-05-08 |
| WO2005077940A1 (en) | 2005-08-25 |
| JP2007520565A (ja) | 2007-07-26 |
| IL176932A0 (en) | 2006-12-10 |
| KR20060124743A (ko) | 2006-12-05 |
| AU2005212399A1 (en) | 2005-08-25 |
| KR101228104B1 (ko) | 2013-02-01 |
| NZ548659A (en) | 2011-01-28 |
| EP1711487A1 (en) | 2006-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7919497B2 (en) | Analogs of dehydrophenylahistins and their therapeutic use | |
| US8129527B2 (en) | Analogs of dehydrophenylahistins and their therapeutic use | |
| CA2494049C (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| AU2005212399B2 (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| WO2007035841A9 (en) | Analogs of dehydrophenylahistins and their therapeutic use | |
| US7935704B2 (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| ZA200607151B (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| CN101633655B (zh) | 脱氢苯基阿夕斯丁及其类似物以及脱氢苯基阿夕斯丁及其类似物的合成 | |
| MXPA06008810A (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| HK1078080B (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof | |
| HK1084388B (en) | Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130204 |