MXPA05001217A - Deshidrofenilahistinas y sus analogos y la sintesis de deshidrofenilahistinas y sus analogos. - Google Patents

Info

Publication number

MXPA05001217A

MXPA05001217A MXPA05001217A MXPA05001217A MXPA05001217A MX PA05001217 A MXPA05001217 A MX PA05001217A MX PA05001217 A MXPA05001217 A MX PA05001217A MX PA05001217 A MXPA05001217 A MX PA05001217A MX PA05001217 A MXPA05001217 A MX PA05001217A

Authority

MX

Mexico

Prior art keywords

substituted

compound

group

atom

nitro

Prior art date

2002-08-02

Links

• Espacenet
• Global Dossier
• Discuss

• 230000015572 biosynthetic process Effects 0.000 title description 28
• 238000003786 synthesis reaction Methods 0.000 title description 25
• 150000001875 compounds Chemical class 0.000 claims abstract description 254
• 238000000034 method Methods 0.000 claims abstract description 128
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 113
• 239000000203 mixture Substances 0.000 claims abstract description 101
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims abstract description 36
• 150000001299 aldehydes Chemical class 0.000 claims abstract description 25
• 206010017533 Fungal infection Diseases 0.000 claims abstract description 23
• 208000031888 Mycoses Diseases 0.000 claims abstract description 23
• 201000011510 cancer Diseases 0.000 claims abstract description 19
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 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 16
• 150000003935 benzaldehydes Chemical class 0.000 claims abstract description 4
• -1 amino, substituted amino, nitro, azido, substituted nitro, phenyl Chemical group 0.000 claims description 98
• 125000001072 heteroaryl group Chemical group 0.000 claims description 68
• 238000011282 treatment Methods 0.000 claims description 51
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
• 125000003118 aryl group Chemical group 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 40
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
• 125000003545 alkoxy group Chemical group 0.000 claims description 34
• 239000003814 drug Substances 0.000 claims description 33
• 125000005843 halogen group Chemical group 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 32
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 31
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 229920006395 saturated elastomer Polymers 0.000 claims description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims description 29
• 125000003107 substituted aryl group Chemical group 0.000 claims description 29
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 27
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 27
• 229910052717 sulfur Inorganic materials 0.000 claims description 25
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 24
• 125000004434 sulfur atom Chemical group 0.000 claims description 24
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 20
• 238000004519 manufacturing process Methods 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 238000002360 preparation method Methods 0.000 claims description 15
• 230000001472 cytotoxic effect Effects 0.000 claims description 14
• 241000124008 Mammalia Species 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
• 125000002252 acyl group Chemical group 0.000 claims description 12
• 125000003342 alkenyl group Chemical group 0.000 claims description 12
• 125000004414 alkyl thio group Chemical group 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 12
• 230000002265 prevention Effects 0.000 claims description 11
• 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 9
• 125000004432 carbon atom Chemical group C* 0.000 claims description 7
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 230000001613 neoplastic effect Effects 0.000 claims description 3
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims 2
• 125000004043 oxo group Chemical group O=* 0.000 claims 2
• 230000000118 anti-neoplastic effect Effects 0.000 claims 1
• 108010054981 dehydrophenylahistin Proteins 0.000 description 101
• 210000004027 cell Anatomy 0.000 description 96
• 230000000694 effects Effects 0.000 description 91
• 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 81
• 239000000243 solution Substances 0.000 description 72
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 229940121375 antifungal agent Drugs 0.000 description 46
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
• 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 34
• 229940063683 taxotere Drugs 0.000 description 34
• 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 31
• 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 31
• 229930012538 Paclitaxel Natural products 0.000 description 30
• 229960001592 paclitaxel Drugs 0.000 description 30
• 230000004614 tumor growth Effects 0.000 description 30
• 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 29
• 208000015181 infectious disease Diseases 0.000 description 28
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 238000005481 NMR spectroscopy Methods 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
• 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 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• 239000003429 antifungal agent Substances 0.000 description 22
• 239000003795 chemical substances by application Substances 0.000 description 22
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 241001465754 Metazoa Species 0.000 description 21
• 208000029742 colonic neoplasm Diseases 0.000 description 21
• 229940079593 drug Drugs 0.000 description 20
• 238000007920 subcutaneous administration Methods 0.000 description 20
• 210000004881 tumor cell Anatomy 0.000 description 20
• 239000000651 prodrug Substances 0.000 description 19
• 229940002612 prodrug Drugs 0.000 description 19
• 238000012360 testing method Methods 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• 241000699670 Mus sp. Species 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• 229910000024 caesium carbonate Inorganic materials 0.000 description 17
• 238000001704 evaporation Methods 0.000 description 17
• 230000008020 evaporation Effects 0.000 description 17
• 150000003839 salts Chemical class 0.000 description 17
• 239000011734 sodium Substances 0.000 description 17
• 239000002904 solvent Substances 0.000 description 17
• 239000000126 substance Substances 0.000 description 17
• 239000002246 antineoplastic agent Substances 0.000 description 16
• 238000005429 filling process Methods 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000007924 injection Substances 0.000 description 15
• 238000002347 injection Methods 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• 206010006187 Breast cancer Diseases 0.000 description 14
• 208000026310 Breast neoplasm Diseases 0.000 description 14
• 101150041968 CDC13 gene Proteins 0.000 description 14
• 244000053095 fungal pathogen Species 0.000 description 14
• 239000002609 medium Substances 0.000 description 14
• 230000003389 potentiating effect Effects 0.000 description 14
• 102000029749 Microtubule Human genes 0.000 description 13
• 108091022875 Microtubule Proteins 0.000 description 13
• 230000000259 anti-tumor effect Effects 0.000 description 13
• 230000003013 cytotoxicity Effects 0.000 description 13
• 231100000135 cytotoxicity Toxicity 0.000 description 13
• 150000002148 esters Chemical class 0.000 description 13
• 235000019439 ethyl acetate Nutrition 0.000 description 13
• 238000001802 infusion Methods 0.000 description 13
• 238000007912 intraperitoneal administration Methods 0.000 description 13
• 210000004688 microtubule Anatomy 0.000 description 13
• 230000001717 pathogenic effect Effects 0.000 description 13
• 239000000047 product Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• 238000006243 chemical reaction Methods 0.000 description 12
• 229960001338 colchicine Drugs 0.000 description 12
• 230000001965 increasing effect Effects 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
• BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 12
• 238000002560 therapeutic procedure Methods 0.000 description 12
• 241000222122 Candida albicans Species 0.000 description 11
• 241000699666 Mus <mouse, genus> Species 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 238000011888 autopsy Methods 0.000 description 11
• 238000001727 in vivo Methods 0.000 description 11
• 239000003112 inhibitor Substances 0.000 description 11
• 239000000546 pharmaceutical excipient Substances 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• 208000023958 prostate neoplasm Diseases 0.000 description 11
• 230000002829 reductive effect Effects 0.000 description 11
• 229910052708 sodium Inorganic materials 0.000 description 11
• 238000006467 substitution reaction Methods 0.000 description 11
• 210000001519 tissue Anatomy 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
• 238000002648 combination therapy Methods 0.000 description 10
• 230000002538 fungal effect Effects 0.000 description 10
• 230000012010 growth Effects 0.000 description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
• 210000004072 lung Anatomy 0.000 description 10
• 238000009097 single-agent therapy Methods 0.000 description 10
• 239000003826 tablet Substances 0.000 description 10
• 229940077476 2,5-piperazinedione Drugs 0.000 description 9
• 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 9
• 241000233866 Fungi Species 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• 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 9
• 229960003942 amphotericin b Drugs 0.000 description 9
• 210000001072 colon Anatomy 0.000 description 9
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 9
• 238000000338 in vitro Methods 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 239000002207 metabolite Substances 0.000 description 9
• 230000005012 migration Effects 0.000 description 9
• 238000013508 migration Methods 0.000 description 9
• 239000001301 oxygen Substances 0.000 description 9
• 229910052760 oxygen Inorganic materials 0.000 description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
• 241001529936 Murinae Species 0.000 description 8
• 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 8
• 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 8
• 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• 206010061418 Zygomycosis Diseases 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 230000006907 apoptotic process Effects 0.000 description 8
• 150000001721 carbon Chemical group 0.000 description 8
• 239000012829 chemotherapy agent Substances 0.000 description 8
• 238000011156 evaluation Methods 0.000 description 8
• 239000008187 granular material Substances 0.000 description 8
• 208000020816 lung neoplasm Diseases 0.000 description 8
• 230000007246 mechanism Effects 0.000 description 8
• 201000001441 melanoma Diseases 0.000 description 8
• 239000003960 organic solvent Substances 0.000 description 8
• 230000003647 oxidation Effects 0.000 description 8
• 238000007254 oxidation reaction Methods 0.000 description 8
• 210000002307 prostate Anatomy 0.000 description 8
• 238000004007 reversed phase HPLC Methods 0.000 description 8
• 239000000375 suspending agent Substances 0.000 description 8
• 230000001988 toxicity Effects 0.000 description 8
• 231100000419 toxicity Toxicity 0.000 description 8
• 102100033350 ATP-dependent translocase ABCB1 Human genes 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
• 241000699660 Mus musculus Species 0.000 description 7
• PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 7
• 102000004243 Tubulin Human genes 0.000 description 7
• 108090000704 Tubulin Proteins 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
• 239000002775 capsule Substances 0.000 description 7
• 238000011161 development Methods 0.000 description 7
• 230000018109 developmental process Effects 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 239000001963 growth medium Substances 0.000 description 7
• 125000002883 imidazolyl group Chemical group 0.000 description 7
• 239000004615 ingredient Substances 0.000 description 7
• 239000002502 liposome 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
• 238000011580 nude mouse model Methods 0.000 description 7
• 230000036515 potency Effects 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 238000011255 standard chemotherapy Methods 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 238000013414 tumor xenograft model Methods 0.000 description 7
• 125000006686 (C1-C24) alkyl group Chemical group 0.000 description 6
• 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 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 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
• 241000222120 Candida <Saccharomycetales> Species 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
• 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
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 230000022131 cell cycle Effects 0.000 description 6
• 229920002678 cellulose Polymers 0.000 description 6
• 239000001913 cellulose Substances 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 238000005755 formation reaction Methods 0.000 description 6
• 239000007789 gas Substances 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
• 229930195733 hydrocarbon Natural products 0.000 description 6
• 239000001257 hydrogen Substances 0.000 description 6
• 229910052739 hydrogen Inorganic materials 0.000 description 6
• 230000002401 inhibitory effect Effects 0.000 description 6
• 238000001990 intravenous administration Methods 0.000 description 6
• 229960004130 itraconazole Drugs 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 6
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
• 239000002674 ointment Substances 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• 230000008092 positive effect Effects 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 235000000346 sugar Nutrition 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• 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 5
• 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 5
• 206010007134 Candida infections Diseases 0.000 description 5
• 108090000397 Caspase 3 Proteins 0.000 description 5
• 102100029855 Caspase-3 Human genes 0.000 description 5
• 229930105110 Cyclosporin A Natural products 0.000 description 5
• 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 5
• 108010036949 Cyclosporine Proteins 0.000 description 5
• 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 5
• 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 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 229930195725 Mannitol Natural products 0.000 description 5
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
• 238000010171 animal model 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
• 230000037396 body weight Effects 0.000 description 5
• 201000003984 candidiasis Diseases 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 230000008859 change Effects 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 5
• 229960001265 ciclosporin Drugs 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
• 231100000433 cytotoxic Toxicity 0.000 description 5
• 229940127089 cytotoxic agent Drugs 0.000 description 5
• 239000008298 dragée Substances 0.000 description 5
• 239000012091 fetal bovine serum Substances 0.000 description 5
• 229910052731 fluorine Inorganic materials 0.000 description 5
• 239000012634 fragment Substances 0.000 description 5
• 230000008014 freezing Effects 0.000 description 5
• 238000007710 freezing Methods 0.000 description 5
• 229960001031 glucose Drugs 0.000 description 5
• 208000037841 lung tumor Diseases 0.000 description 5
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Inorganic materials O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 5
• 239000000594 mannitol Substances 0.000 description 5
• 235000010355 mannitol Nutrition 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
• 230000035755 proliferation Effects 0.000 description 5
• 201000005825 prostate adenocarcinoma Diseases 0.000 description 5
• 239000011541 reaction mixture Substances 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 241000894007 species Species 0.000 description 5
• 239000007921 spray Substances 0.000 description 5
• 239000003381 stabilizer Substances 0.000 description 5
• 239000000829 suppository Substances 0.000 description 5
• 150000003852 triazoles Chemical class 0.000 description 5
• 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 241000228212 Aspergillus Species 0.000 description 4
• 241001225321 Aspergillus fumigatus Species 0.000 description 4
• 206010005098 Blastomycosis Diseases 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
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• 239000007995 HEPES buffer Substances 0.000 description 4
• 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 4
• 229930182816 L-glutamine Natural products 0.000 description 4
• 206010027476 Metastases Diseases 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
• 239000004902 Softening Agent Substances 0.000 description 4
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
• 241000223229 Trichophyton rubrum Species 0.000 description 4
• 230000004913 activation Effects 0.000 description 4
• 230000002411 adverse Effects 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 239000003242 anti bacterial agent Substances 0.000 description 4
• 239000007900 aqueous suspension Substances 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 238000003556 assay Methods 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
• 229940095731 candida albicans Drugs 0.000 description 4
• 229910002092 carbon dioxide Inorganic materials 0.000 description 4
• 210000000170 cell membrane Anatomy 0.000 description 4
• 230000001413 cellular effect Effects 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• 238000013270 controlled release Methods 0.000 description 4
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• 231100000673 dose–response relationship Toxicity 0.000 description 4
• 125000004185 ester group Chemical group 0.000 description 4
• 210000003527 eukaryotic cell Anatomy 0.000 description 4
• 239000000284 extract 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
• 229910052736 halogen Inorganic materials 0.000 description 4
• 150000002430 hydrocarbons Chemical class 0.000 description 4
• 230000001506 immunosuppresive effect Effects 0.000 description 4
• 238000007918 intramuscular administration Methods 0.000 description 4
• 239000011777 magnesium Substances 0.000 description 4
• 229910052749 magnesium Inorganic materials 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
• 206010061289 metastatic neoplasm Diseases 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
• 150000002829 nitrogen Chemical group 0.000 description 4
• 230000035699 permeability Effects 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 238000012545 processing Methods 0.000 description 4
• 230000002685 pulmonary effect Effects 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 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
• 210000001635 urinary tract Anatomy 0.000 description 4
• 238000005406 washing Methods 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
• 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 3
• DKGPAJORZYZGOY-UHFFFAOYSA-N (4-tert-butyl-1h-imidazol-5-yl)methanol Chemical compound CC(C)(C)C=1N=CNC=1CO DKGPAJORZYZGOY-UHFFFAOYSA-N 0.000 description 3
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
• SCFWAOWWAANBPY-UHFFFAOYSA-N 2,2-dimethyl-3-butenoic acid Chemical compound C=CC(C)(C)C(O)=O SCFWAOWWAANBPY-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
• 229920001817 Agar Polymers 0.000 description 3
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
• 241000335423 Blastomyces Species 0.000 description 3
• 102000011727 Caspases Human genes 0.000 description 3
• 108010076667 Caspases Proteins 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 206010009192 Circulatory collapse Diseases 0.000 description 3
• 241000223205 Coccidioides immitis Species 0.000 description 3
• 229940126657 Compound 17 Drugs 0.000 description 3
• 201000007336 Cryptococcosis Diseases 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
• 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 3
• 229920002307 Dextran Polymers 0.000 description 3
• 241001480036 Epidermophyton floccosum Species 0.000 description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
• 235000010469 Glycine max Nutrition 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• 239000007832 Na2SO4 Substances 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
• 241000700159 Rattus Species 0.000 description 3
• 229920002472 Starch Polymers 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
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000006096 absorbing agent Substances 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 230000006978 adaptation Effects 0.000 description 3
• 210000000577 adipose tissue Anatomy 0.000 description 3
• 239000008272 agar Substances 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 229940088710 antibiotic agent Drugs 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 208000036815 beta tubulin Diseases 0.000 description 3
• 239000006227 byproduct Substances 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 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
• 229910052801 chlorine Inorganic materials 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
• 238000001816 cooling Methods 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 238000002784 cytotoxicity assay Methods 0.000 description 3
• 231100000263 cytotoxicity test Toxicity 0.000 description 3
• 230000007423 decrease Effects 0.000 description 3
• 206010012601 diabetes mellitus Diseases 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 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 3
• 210000002950 fibroblast Anatomy 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 230000000855 fungicidal effect Effects 0.000 description 3
• 230000001408 fungistatic effect Effects 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000014509 gene expression 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
• 125000000623 heterocyclic group Chemical group 0.000 description 3
• 150000002460 imidazoles Chemical class 0.000 description 3
• 238000002513 implantation Methods 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 238000010253 intravenous injection Methods 0.000 description 3
• 150000002500 ions Chemical class 0.000 description 3
• 229960004125 ketoconazole Drugs 0.000 description 3
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 3
• 201000005202 lung cancer Diseases 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 230000009401 metastasis Effects 0.000 description 3
• UHRVSIIJSJKEPO-UHFFFAOYSA-N methyl 2,2-dimethylbut-3-enoate Chemical compound COC(=O)C(C)(C)C=C UHRVSIIJSJKEPO-UHFFFAOYSA-N 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
• 238000002156 mixing Methods 0.000 description 3
• 239000000312 peanut oil Substances 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000001953 sensory effect Effects 0.000 description 3
• 239000008159 sesame oil Substances 0.000 description 3
• 235000011803 sesame oil Nutrition 0.000 description 3
• 230000035939 shock Effects 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 238000002054 transplantation Methods 0.000 description 3
• 229920002554 vinyl polymer Polymers 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
• 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
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• CHZBPWFTYFOPMN-UHFFFAOYSA-N 5-tert-butyl-1h-imidazole-4-carboxylic acid Chemical compound CC(C)(C)C=1N=CNC=1C(O)=O CHZBPWFTYFOPMN-UHFFFAOYSA-N 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• 208000036762 Acute promyelocytic leukaemia Diseases 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
• 208000036641 Aspergillus infections Diseases 0.000 description 2
• 241001480523 Basidiobolus ranarum Species 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
• 241000222178 Candida tropicalis Species 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
• 208000017667 Chronic Disease Diseases 0.000 description 2
• 241001480517 Conidiobolus Species 0.000 description 2
• 241000221204 Cryptococcus neoformans Species 0.000 description 2
• 208000007163 Dermatomycoses Diseases 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
• 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
• 229920000084 Gum arabic Polymers 0.000 description 2
• 241000228404 Histoplasma capsulatum Species 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
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 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
• 241001480037 Microsporum Species 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
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 206010029148 Nephrolithiasis Diseases 0.000 description 2
• BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
• 101150053185 P450 gene Proteins 0.000 description 2
• 241000526686 Paracoccidioides brasiliensis Species 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
• 241000235645 Pichia kudriavzevii Species 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 208000033826 Promyelocytic Acute Leukemia Diseases 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
• 241000293824 Rhinosporidium seeberi Species 0.000 description 2
• 241000235527 Rhizopus Species 0.000 description 2
• 241000593344 Rhizopus microsporus Species 0.000 description 2
• 240000005384 Rhizopus oryzae Species 0.000 description 2
• 235000003976 Ruta Nutrition 0.000 description 2
• 240000005746 Ruta graveolens Species 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 229920002125 Sokalan® Polymers 0.000 description 2
• 241001149963 Sporothrix schenckii Species 0.000 description 2
• 206010041736 Sporotrichosis Diseases 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
• 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
• 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 2
• 241000222126 [Candida] glabrata Species 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
• 230000009102 absorption Effects 0.000 description 2
• 238000010521 absorption reaction Methods 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
• 235000010419 agar Nutrition 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
• 150000003973 alkyl amines Chemical class 0.000 description 2
• 230000000172 allergic effect Effects 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 150000003863 ammonium salts Chemical class 0.000 description 2
• 230000003698 anagen phase Effects 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 229940091771 aspergillus fumigatus Drugs 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 2
• 150000001556 benzimidazoles Chemical class 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 239000000872 buffer Substances 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
• 208000032343 candida glabrata infection Diseases 0.000 description 2
• 150000001720 carbohydrates Chemical class 0.000 description 2
• 235000014633 carbohydrates Nutrition 0.000 description 2
• 239000001569 carbon dioxide Substances 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
• 230000030833 cell death Effects 0.000 description 2
• 230000010261 cell growth 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
• 230000000973 chemotherapeutic effect Effects 0.000 description 2
• 229940044683 chemotherapy drug Drugs 0.000 description 2
• 238000003776 cleavage reaction Methods 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
• 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
• 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
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 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
• 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
• 238000004821 distillation Methods 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 238000009510 drug design Methods 0.000 description 2
• 125000006575 electron-withdrawing group Chemical group 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000003623 enhancer Substances 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
• 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 2
• 230000005284 excitation Effects 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
• 229960004413 flucytosine Drugs 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 238000013467 fragmentation Methods 0.000 description 2
• 238000006062 fragmentation reaction Methods 0.000 description 2
• 239000003205 fragrance Substances 0.000 description 2
• 239000000417 fungicide 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
• 235000011187 glycerol Nutrition 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
• 238000010438 heat treatment Methods 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 239000007943 implant 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
• 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
• 231100000636 lethal dose Toxicity 0.000 description 2
• 230000001665 lethal effect Effects 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 230000031700 light absorption 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
• 238000007726 management method Methods 0.000 description 2
• 229960001855 mannitol Drugs 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 238000002844 melting Methods 0.000 description 2
• 230000008018 melting Effects 0.000 description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
• 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 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
• 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
• 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
• 210000000056 organ Anatomy 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
• 229940026778 other chemotherapeutics in atc Drugs 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
• 238000007911 parenteral administration Methods 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
• 239000006187 pill 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
• 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
• 230000002250 progressing effect Effects 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 238000005086 pumping Methods 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 238000002271 resection Methods 0.000 description 2
• 230000008261 resistance mechanism Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 235000005806 ruta Nutrition 0.000 description 2
• 239000012449 sabouraud dextrose agar Substances 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 239000002356 single layer Substances 0.000 description 2
• 229940073490 sodium glutamate Drugs 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000008107 starch Substances 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
• 125000000547 substituted alkyl group Chemical group 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
• 229940098465 tincture Drugs 0.000 description 2
• 239000004408 titanium dioxide Substances 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 231100000027 toxicology Toxicity 0.000 description 2
• 150000003626 triacylglycerols Chemical class 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• 239000003744 tubulin modulator Substances 0.000 description 2
• 210000005166 vasculature Anatomy 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
• 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 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
• 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 class 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 1
• AANRCAZDPPXTKN-XCMCHEKJSA-N (3z,6z)-3-benzylidene-6-[[5-(2-methylbut-3-en-2-yl)-1h-imidazol-4-yl]methylidene]piperazine-2,5-dione Chemical compound N1C=NC(\C=C/2C(NC(=C\C=3C=CC=CC=3)/C(=O)N\2)=O)=C1C(C)(C=C)C AANRCAZDPPXTKN-XCMCHEKJSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• 125000006033 1,1-dimethyl-2-propenyl group Chemical group 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
• ZQEXIXXJFSQPNA-UHFFFAOYSA-N 1h-imidazole-5-carbaldehyde Chemical class O=CC1=CNC=N1 ZQEXIXXJFSQPNA-UHFFFAOYSA-N 0.000 description 1
• MWDRCHNGEUVBLY-UHFFFAOYSA-N 2,2-dimethyl-3-(4-methylphenyl)sulfonyloxybutanoic acid Chemical compound OC(=O)C(C)(C)C(C)OS(=O)(=O)C1=CC=C(C)C=C1 MWDRCHNGEUVBLY-UHFFFAOYSA-N 0.000 description 1
• NHBJCUUNNHUOOO-UHFFFAOYSA-N 2,2-dimethylbut-3-enoyl chloride Chemical compound C=CC(C)(C)C(Cl)=O NHBJCUUNNHUOOO-UHFFFAOYSA-N 0.000 description 1
• VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-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
• 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
• SKYAOVCQRJIPDR-UHFFFAOYSA-N 4,4-dimethyl-3-oxohex-5-enoic acid Chemical compound C=CC(C)(C)C(=O)CC(O)=O SKYAOVCQRJIPDR-UHFFFAOYSA-N 0.000 description 1
• VKFDNWKLZWLWJW-UHFFFAOYSA-N 4-chloro-3,3-dimethylbut-1-ene Chemical compound ClCC(C)(C)C=C VKFDNWKLZWLWJW-UHFFFAOYSA-N 0.000 description 1
• 150000005168 4-hydroxybenzoic acids Chemical class 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
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
• 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
• 244000245659 Arcangelisia flava Species 0.000 description 1
• 241001480043 Arthrodermataceae Species 0.000 description 1
• 241000228197 Aspergillus flavus 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
• 241000751139 Beauveria 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
• 241000283690 Bos taurus Species 0.000 description 1
• 241000123650 Botrytis cinerea Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• ZKAISLGYPWGEAE-UHFFFAOYSA-N C(C)(=O)OC.C(C(=C)C)(=O)O Chemical compound C(C)(=O)OC.C(C(=C)C)(=O)O ZKAISLGYPWGEAE-UHFFFAOYSA-N 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 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
• 206010008803 Chromoblastomycosis Diseases 0.000 description 1
• 208000015116 Chromomycosis Diseases 0.000 description 1
• 240000000560 Citrus x paradisi Species 0.000 description 1
• 241000223203 Coccidioides Species 0.000 description 1
• 206010052360 Colorectal adenocarcinoma Diseases 0.000 description 1
• 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 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
• 241000235555 Cunninghamella Species 0.000 description 1
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
• 238000005361 D2 NMR spectroscopy Methods 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 101710088194 Dehydrogenase Proteins 0.000 description 1
• QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 108010049047 Echinocandins Proteins 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
• 108010010803 Gelatin Proteins 0.000 description 1
• 229920002148 Gellan gum Polymers 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 239000012981 Hank's balanced salt solution Substances 0.000 description 1
• 241000592938 Helminthosporium solani Species 0.000 description 1
• 241000228402 Histoplasma Species 0.000 description 1
• 101000971171 Homo sapiens Apoptosis regulator Bcl-2 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
• 208000026350 Inborn Genetic disease 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 244000062730 Melissa officinalis Species 0.000 description 1
• 235000010654 Melissa officinalis Nutrition 0.000 description 1
• 201000009906 Meningitis 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
• 241000160608 Mimus gilvus Species 0.000 description 1
• HGINADPHJQTSKN-UHFFFAOYSA-N Monoethyl malonic acid Chemical compound CCOC(=O)CC(O)=O HGINADPHJQTSKN-UHFFFAOYSA-N 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
• 241000475481 Nebula Species 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• 102000007999 Nuclear Proteins Human genes 0.000 description 1
• 108010089610 Nuclear Proteins Proteins 0.000 description 1
• 208000007027 Oral Candidiasis Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 102000035195 Peptidases Human genes 0.000 description 1
• 108091005804 Peptidases Proteins 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
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 239000004365 Protease Substances 0.000 description 1
• 241000223596 Pseudallescheria Species 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
• 241000235070 Saccharomyces Species 0.000 description 1
• 206010039491 Sarcoma Diseases 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
• 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
• 241000972623 Streptomyces albulus Species 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 208000000389 T-cell leukemia Diseases 0.000 description 1
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 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 1
• 206010043870 Tinea infections Diseases 0.000 description 1
• 101710183280 Topoisomerase Proteins 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
• 229940122429 Tubulin inhibitor Drugs 0.000 description 1
• 241000287411 Turdidae Species 0.000 description 1
• 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
• 108010046308 Type II DNA Topoisomerases Proteins 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
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 201000007096 Vulvovaginal Candidiasis Diseases 0.000 description 1
• JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 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
• 239000013543 active substance Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 125000004423 acyloxy group Chemical group 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
• 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
• 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical group 0.000 description 1
• 125000000033 alkoxyamino group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
• 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 238000000540 analysis of variance Methods 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 239000002259 anti human immunodeficiency virus agent Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 239000012871 anti-fungal composition Substances 0.000 description 1
• 229940124411 anti-hiv antiviral agent Drugs 0.000 description 1
• 230000002924 anti-infective effect Effects 0.000 description 1
• 230000000845 anti-microbial effect Effects 0.000 description 1
• 230000001946 anti-microtubular Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 239000002519 antifouling agent Substances 0.000 description 1
• 238000002827 antifungal susceptibility testing Methods 0.000 description 1
• 229960005475 antiinfective agent Drugs 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 238000003782 apoptosis assay Methods 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
• 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
• 230000008901 benefit Effects 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
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-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
• 239000003124 biologic agent Substances 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
• 210000000481 breast Anatomy 0.000 description 1
• 201000008275 breast carcinoma Diseases 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 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
• 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
• 230000006369 cell cycle progression 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
• 230000003833 cell viability Effects 0.000 description 1
• 159000000006 cesium salts Chemical class 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 150000001793 charged compounds Chemical class 0.000 description 1
• 230000001886 ciliary effect Effects 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 229960004022 clotrimazole 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
• 230000000112 colonic effect Effects 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 229960005537 combretastatin A-4 Drugs 0.000 description 1
• 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 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
• JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical class N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 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
• 230000008602 contraction Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 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
• 239000013078 crystal Substances 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000003436 cytoskeletal effect Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 238000006356 dehydrogenation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000000151 deposition Methods 0.000 description 1
• 230000003831 deregulation Effects 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
• 238000010586 diagram Methods 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 230000009699 differential effect Effects 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
• GMVIQOCPXTZUFJ-UHFFFAOYSA-L dipotassium;2-ethylpropanedioate Chemical compound [K+].[K+].CCC(C([O-])=O)C([O-])=O GMVIQOCPXTZUFJ-UHFFFAOYSA-L 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
• 239000000975 dye Substances 0.000 description 1
• 238000004043 dyeing Methods 0.000 description 1
• 229960003913 econazole Drugs 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 210000002889 endothelial cell Anatomy 0.000 description 1
• 230000007613 environmental effect Effects 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
• 239000003797 essential amino acid Substances 0.000 description 1
• 235000020776 essential amino acid Nutrition 0.000 description 1
• 229940011871 estrogen Drugs 0.000 description 1
• 239000000262 estrogen Substances 0.000 description 1
• 150000002170 ethers Chemical class 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
• KQWWVLVLVYYYDT-UHFFFAOYSA-N ethyl 3-oxohexanoate Chemical compound CCCC(=O)CC(=O)OCC KQWWVLVLVYYYDT-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
• YVBVIJQMJDNVFD-UHFFFAOYSA-N ethyl 5-tert-butyl-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C=1N=COC=1C(C)(C)C YVBVIJQMJDNVFD-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
• 125000004494 ethyl ester group Chemical group 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
• UKFXDFUAPNAMPJ-UHFFFAOYSA-N ethylmalonic acid Chemical compound CCC(C(O)=O)C(O)=O UKFXDFUAPNAMPJ-UHFFFAOYSA-N 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
• 230000007717 exclusion Effects 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
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000001215 fluorescent labelling Methods 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
• 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
• 229940014259 gelatin Drugs 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
• 208000016361 genetic disease Diseases 0.000 description 1
• 231100000025 genetic toxicology Toxicity 0.000 description 1
• 230000001738 genotoxic effect Effects 0.000 description 1
• 239000010651 grapefruit oil Substances 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 239000003966 growth inhibitor Substances 0.000 description 1
• 229920000591 gum Polymers 0.000 description 1
• 239000001307 helium Substances 0.000 description 1
• 229910052734 helium Inorganic materials 0.000 description 1
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 230000010224 hepatic metabolism Effects 0.000 description 1
• 125000005553 heteroaryloxy group Chemical group 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
• 239000004030 hiv protease inhibitor Substances 0.000 description 1
• 210000005260 human cell Anatomy 0.000 description 1
• 238000013415 human tumor xenograft model Methods 0.000 description 1
• 239000003906 humectant Substances 0.000 description 1
• 150000004678 hydrides Chemical class 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 239000000852 hydrogen donor Substances 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([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
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000001861 immunosuppressant effect Effects 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000010874 in vitro model Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000011261 inert gas Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 230000010189 intracellular transport Effects 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
• 238000011835 investigation Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 229960000779 irinotecan hydrochloride Drugs 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• WDAXFOBOLVPGLV-UHFFFAOYSA-N isobutyric acid ethyl ester Natural products CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-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
• 239000010410 layer Substances 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000000865 liniment Substances 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000003120 macrolide antibiotic agent Substances 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 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
• 230000014759 maintenance of location Effects 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 231100000682 maximum tolerated dose Toxicity 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-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
• 210000003632 microfilament Anatomy 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 210000001589 microsome Anatomy 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• 230000025090 microtubule depolymerization Effects 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
• 230000011278 mitosis Effects 0.000 description 1
• 230000004660 morphological change Effects 0.000 description 1
• 238000010172 mouse model Methods 0.000 description 1
• 230000036457 multidrug resistance Effects 0.000 description 1
• 108010066052 multidrug resistance-associated protein 1 Proteins 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
• CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
• 239000004311 natamycin Substances 0.000 description 1
• 235000010298 natamycin Nutrition 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 230000007935 neutral effect Effects 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
• 239000002997 ophthalmic solution Substances 0.000 description 1
• 230000004768 organ dysfunction Effects 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 230000000399 orthopedic effect 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
• 238000012856 packing Methods 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 231100000435 percutaneous penetration Toxicity 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 239000012466 permeate Substances 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 150000002994 phenylalanines Chemical class 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• JTHRRMFZHSDGNJ-UHFFFAOYSA-N piperazine-2,3-dione Chemical compound O=C1NCCNC1=O JTHRRMFZHSDGNJ-UHFFFAOYSA-N 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
• 229920000642 polymer Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920001282 polysaccharide Polymers 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
• 229940116317 potato starch Drugs 0.000 description 1
• 238000002203 pretreatment Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000005522 programmed cell death Effects 0.000 description 1
• 238000007430 reference method Methods 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 230000008439 repair process 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
• 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
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate 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
• 229960003885 sodium benzoate Drugs 0.000 description 1
• 235000017550 sodium carbonate Nutrition 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000012439 solid excipient Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000007619 statistical method Methods 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
• 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
• 239000011593 sulfur Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000024891 symptom 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
• 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
• 150000003573 thiols Chemical class 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• OHHDIOKRWWOXMT-UHFFFAOYSA-N trazodone hydrochloride Chemical compound [H+].[Cl-].ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 OHHDIOKRWWOXMT-UHFFFAOYSA-N 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
• 210000003954 umbilical cord Anatomy 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 208000037965 uterine sarcoma Diseases 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 210000005167 vascular cell Anatomy 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 239000004066 vascular targeting agent Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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