JP2020519321A - 腎機能測定方法 - Google Patents
腎機能測定方法 Download PDFInfo
- Publication number
- JP2020519321A JP2020519321A JP2019555615A JP2019555615A JP2020519321A JP 2020519321 A JP2020519321 A JP 2020519321A JP 2019555615 A JP2019555615 A JP 2019555615A JP 2019555615 A JP2019555615 A JP 2019555615A JP 2020519321 A JP2020519321 A JP 2020519321A
- Authority
- JP
- Japan
- Prior art keywords
- patient
- gfr
- hours
- administration
- pyrazine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003907 kidney function Effects 0.000 title claims abstract description 49
- 238000000691 measurement method Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 179
- 230000005670 electromagnetic radiation Effects 0.000 claims abstract description 27
- 210000003734 kidney Anatomy 0.000 claims abstract description 17
- 230000024924 glomerular filtration Effects 0.000 claims abstract description 13
- 238000005259 measurement Methods 0.000 claims description 144
- 239000003795 chemical substances by application Substances 0.000 claims description 72
- 230000003595 spectral effect Effects 0.000 claims description 46
- 208000020832 chronic kidney disease Diseases 0.000 claims description 45
- 150000001875 compounds Chemical class 0.000 claims description 29
- 229940024606 amino acid Drugs 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 16
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 14
- 229930195711 D-Serine Natural products 0.000 claims description 12
- 150000004676 glycans Polymers 0.000 claims description 12
- 239000002953 phosphate buffered saline Substances 0.000 claims description 12
- 150000004804 polysaccharides Polymers 0.000 claims description 12
- 239000007850 fluorescent dye Substances 0.000 claims description 11
- 229920001184 polypeptide Polymers 0.000 claims description 11
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 11
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 10
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 238000001990 intravenous administration Methods 0.000 claims description 9
- 238000007911 parenteral administration Methods 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 claims description 6
- 230000029142 excretion Effects 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 5
- 230000003204 osmotic effect Effects 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000007920 subcutaneous administration Methods 0.000 claims description 5
- 230000002485 urinary effect Effects 0.000 claims description 5
- DCXYFEDJOCDNAF-UWTATZPHSA-N D-Asparagine Chemical compound OC(=O)[C@H](N)CC(N)=O DCXYFEDJOCDNAF-UWTATZPHSA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 4
- ODKSFYDXXFIFQN-SCSAIBSYSA-N D-arginine Chemical compound OC(=O)[C@H](N)CCCNC(N)=N ODKSFYDXXFIFQN-SCSAIBSYSA-N 0.000 claims description 4
- 229930028154 D-arginine Natural products 0.000 claims description 4
- 229930182846 D-asparagine Natural products 0.000 claims description 4
- 229930182847 D-glutamic acid Natural products 0.000 claims description 4
- ZDXPYRJPNDTMRX-GSVOUGTGSA-N D-glutamine Chemical compound OC(=O)[C@H](N)CCC(N)=O ZDXPYRJPNDTMRX-GSVOUGTGSA-N 0.000 claims description 4
- 229930195715 D-glutamine Natural products 0.000 claims description 4
- HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 4
- 229930195721 D-histidine Natural products 0.000 claims description 4
- UKAUYVFTDYCKQA-GSVOUGTGSA-N D-homoserine Chemical compound OC(=O)[C@H](N)CCO UKAUYVFTDYCKQA-GSVOUGTGSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 150000007650 D alpha amino acids Chemical class 0.000 claims description 3
- OUYCCCASQSFEME-MRVPVSSYSA-N D-tyrosine Chemical compound OC(=O)[C@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-MRVPVSSYSA-N 0.000 claims description 3
- 229930195709 D-tyrosine Natural products 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical group P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 102000009027 Albumins Human genes 0.000 claims description 2
- 108010088751 Albumins Proteins 0.000 claims description 2
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims description 2
- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims description 2
- 229930182819 D-leucine Natural products 0.000 claims description 2
- FFEARJCKVFRZRR-SCSAIBSYSA-N D-methionine Chemical compound CSCC[C@@H](N)C(O)=O FFEARJCKVFRZRR-SCSAIBSYSA-N 0.000 claims description 2
- 229930182818 D-methionine Natural products 0.000 claims description 2
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 claims description 2
- 229930182832 D-phenylalanine Natural products 0.000 claims description 2
- 229930182820 D-proline Natural products 0.000 claims description 2
- AYFVYJQAPQTCCC-STHAYSLISA-N D-threonine Chemical compound C[C@H](O)[C@@H](N)C(O)=O AYFVYJQAPQTCCC-STHAYSLISA-N 0.000 claims description 2
- 229930182822 D-threonine Natural products 0.000 claims description 2
- 229930182827 D-tryptophan Natural products 0.000 claims description 2
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 claims description 2
- 229930182831 D-valine Natural products 0.000 claims description 2
- 229930195710 D‐cysteine Natural products 0.000 claims description 2
- 239000003002 pH adjusting agent Substances 0.000 claims description 2
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 2
- 108060006698 EGF receptor Proteins 0.000 claims 4
- 125000001483 monosaccharide substituent group Chemical group 0.000 claims 2
- AGPKZVBTJJNPAG-RFZPGFLSSA-N D-Isoleucine Chemical compound CC[C@@H](C)[C@@H](N)C(O)=O AGPKZVBTJJNPAG-RFZPGFLSSA-N 0.000 claims 1
- 229930182845 D-isoleucine Natural products 0.000 claims 1
- 230000003078 antioxidant effect Effects 0.000 claims 1
- 229940021746 d- serine Drugs 0.000 claims 1
- 230000002335 preservative effect Effects 0.000 claims 1
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 abstract description 89
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 abstract description 51
- -1 pyrazine compound Chemical class 0.000 abstract description 37
- 150000003216 pyrazines Chemical class 0.000 abstract description 37
- 238000012544 monitoring process Methods 0.000 abstract description 18
- 238000010586 diagram Methods 0.000 abstract description 2
- 230000001839 systemic circulation Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 94
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 78
- 239000000203 mixture Substances 0.000 description 74
- 239000000700 radioactive tracer Substances 0.000 description 59
- XHNJXRDGTITISI-QWWZWVQMSA-N (2r)-2-[[3,6-diamino-5-[[(1r)-1-carboxy-2-hydroxyethyl]carbamoyl]pyrazine-2-carbonyl]amino]-3-hydroxypropanoic acid Chemical compound NC1=NC(C(=O)N[C@H](CO)C(O)=O)=C(N)N=C1C(=O)N[C@H](CO)C(O)=O XHNJXRDGTITISI-QWWZWVQMSA-N 0.000 description 45
- 238000002347 injection Methods 0.000 description 38
- 239000007924 injection Substances 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000007787 solid Substances 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 29
- 239000000047 product Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 26
- 230000007717 exclusion Effects 0.000 description 26
- 210000003128 head Anatomy 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 23
- 235000002639 sodium chloride Nutrition 0.000 description 23
- 235000001014 amino acid Nutrition 0.000 description 22
- 230000014759 maintenance of location Effects 0.000 description 22
- 239000011734 sodium Substances 0.000 description 21
- 210000003491 skin Anatomy 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000013442 quality metrics Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 14
- 150000002772 monosaccharides Chemical group 0.000 description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 13
- 235000008206 alpha-amino acids Nutrition 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000012267 brine Substances 0.000 description 12
- 101150026055 Ngfr gene Proteins 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 238000004128 high performance liquid chromatography Methods 0.000 description 11
- 230000000670 limiting effect Effects 0.000 description 11
- 210000002700 urine Anatomy 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 150000001371 alpha-amino acids Chemical class 0.000 description 10
- 238000011067 equilibration Methods 0.000 description 10
- 238000010606 normalization Methods 0.000 description 10
- 238000012545 processing Methods 0.000 description 10
- VELGYJCKWFALBF-UHFFFAOYSA-N 3,6-diaminopyrazine-2,5-dicarboxylic acid Chemical compound NC1=NC(C(O)=O)=C(N)N=C1C(O)=O VELGYJCKWFALBF-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000009826 distribution Methods 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 230000008085 renal dysfunction Effects 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 229910004298 SiO 2 Inorganic materials 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000002872 contrast media Substances 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 8
- 208000009304 Acute Kidney Injury Diseases 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 229940109239 creatinine Drugs 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 230000008030 elimination Effects 0.000 description 7
- 238000003379 elimination reaction Methods 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 239000006260 foam Substances 0.000 description 7
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 208000033626 Renal failure acute Diseases 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 201000011040 acute kidney failure Diseases 0.000 description 6
- 208000012998 acute renal failure Diseases 0.000 description 6
- 238000004364 calculation method Methods 0.000 description 6
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 210000001147 pulmonary artery Anatomy 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 210000001562 sternum Anatomy 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 208000034486 Multi-organ failure Diseases 0.000 description 5
- 208000010718 Multiple Organ Failure Diseases 0.000 description 5
- 208000012641 Pigmentation disease Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 229960001025 iohexol Drugs 0.000 description 5
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 5
- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000007704 transition Effects 0.000 description 5
- 239000003039 volatile agent Substances 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- QCHPKSFMDHPSNR-UHFFFAOYSA-N 3-aminoisobutyric acid Chemical compound NCC(C)C(O)=O QCHPKSFMDHPSNR-UHFFFAOYSA-N 0.000 description 4
- ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical compound OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 description 4
- 208000028399 Critical Illness Diseases 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 4
- 210000001217 buttock Anatomy 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000013016 damping Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 4
- CLLHVSIBXXMHJI-UHFFFAOYSA-N pyrazine-2,5-dicarboxamide Chemical compound NC(=O)C1=CN=C(C(N)=O)C=N1 CLLHVSIBXXMHJI-UHFFFAOYSA-N 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 3
- OQEBBZSWEGYTPG-UHFFFAOYSA-N 3-aminobutanoic acid Chemical compound CC(N)CC(O)=O OQEBBZSWEGYTPG-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- 206010062237 Renal impairment Diseases 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 108010055917 Technetium Tc 99m Mertiatide Proteins 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- PMZXXNPJQYDFJX-UHFFFAOYSA-N acetonitrile;2,2,2-trifluoroacetic acid Chemical compound CC#N.OC(=O)C(F)(F)F PMZXXNPJQYDFJX-UHFFFAOYSA-N 0.000 description 3
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 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 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 210000001723 extracellular space Anatomy 0.000 description 3
- 238000001506 fluorescence spectroscopy Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000000155 isotopic effect Effects 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 210000000062 pectoralis major Anatomy 0.000 description 3
- 235000021317 phosphate Nutrition 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 238000013441 quality evaluation Methods 0.000 description 3
- 238000004088 simulation Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- SBWXTSBZXYNCOJ-QWWZWVQMSA-N (2R)-2-[[3,6-diamino-5-[[(1R)-1-carboxyethyl]carbamoyl]pyrazine-2-carbonyl]amino]propanoic acid Chemical compound NC=1C(=NC(=C(N=1)C(=O)N[C@@H](C(=O)O)C)N)C(=O)N[C@@H](C(=O)O)C SBWXTSBZXYNCOJ-QWWZWVQMSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- SBWXTSBZXYNCOJ-IMJSIDKUSA-N (2S)-2-[[3,6-diamino-5-[[(1S)-1-carboxyethyl]carbamoyl]pyrazine-2-carbonyl]amino]propanoic acid Chemical compound NC=1C(=NC(=C(N=1)C(=O)N[C@H](C(=O)O)C)N)C(=O)N[C@H](C(=O)O)C SBWXTSBZXYNCOJ-IMJSIDKUSA-N 0.000 description 2
- IDNSGZOFDGAHTI-BYPYZUCNSA-N (3s)-3,6-diamino-6-oxohexanoic acid Chemical compound OC(=O)C[C@@H](N)CCC(N)=O IDNSGZOFDGAHTI-BYPYZUCNSA-N 0.000 description 2
- UJOYFRCOTPUKAK-MRVPVSSYSA-N (R)-3-ammonio-3-phenylpropanoate Chemical compound OC(=O)C[C@@H](N)C1=CC=CC=C1 UJOYFRCOTPUKAK-MRVPVSSYSA-N 0.000 description 2
- UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 2
- SXRSWYYRRUAGAG-PPVZQFBESA-N 2-N,5-N-bis[(1R,2S,3R,4R)-1,2,3,4,5-pentahydroxypentyl]pyrazine-2,5-dicarboxamide Chemical compound N1=C(C=NC(=C1)C(=O)N[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O)C(=O)N[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O SXRSWYYRRUAGAG-PPVZQFBESA-N 0.000 description 2
- KZHOCYBKZBVZBI-UHFFFAOYSA-N 2-[[3,6-diamino-5-(2-carboxypropan-2-ylcarbamoyl)pyrazine-2-carbonyl]amino]-2-methylpropanoic acid Chemical compound NC=1C(=NC(=C(N=1)C(=O)NC(C(=O)O)(C)C)N)C(=O)NC(C(=O)O)(C)C KZHOCYBKZBVZBI-UHFFFAOYSA-N 0.000 description 2
- ODUOWWQCPGDMJB-UHFFFAOYSA-N 2-[[3,6-diamino-5-(carboxymethylcarbamoyl)pyrazine-2-carbonyl]amino]acetic acid Chemical compound NC=1C(=NC(=C(N=1)C(=O)NCC(=O)O)N)C(=O)NCC(=O)O ODUOWWQCPGDMJB-UHFFFAOYSA-N 0.000 description 2
- UVKNREAAHQRBKA-IEOVAKBOSA-I 2-[bis[2-[bis(carboxylatomethyl)amino]ethyl]amino]acetate;technetium-99(4+) Chemical compound [99Tc+4].[O-]C(=O)CN(CC([O-])=O)CCN(CC(=O)[O-])CCN(CC([O-])=O)CC([O-])=O UVKNREAAHQRBKA-IEOVAKBOSA-I 0.000 description 2
- AUCAOJOWDGGBMH-UHFFFAOYSA-N 2-n,2-n,5-n,5-n-tetrakis(2-methoxyethyl)pyrazine-2,5-dicarboxamide Chemical compound COCCN(CCOC)C(=O)C1=CN=C(C(=O)N(CCOC)CCOC)C=N1 AUCAOJOWDGGBMH-UHFFFAOYSA-N 0.000 description 2
- RQRIPQYTFAYYMX-UHFFFAOYSA-N 3,6-dibromopyrazine-2,5-dicarboxylic acid Chemical compound OC(=O)C1=NC(Br)=C(C(O)=O)N=C1Br RQRIPQYTFAYYMX-UHFFFAOYSA-N 0.000 description 2
- PGRYIDPCVQRGJY-UHFFFAOYSA-N 3-[[3,6-diamino-5-(2-carboxyethylcarbamoyl)pyrazine-2-carbonyl]amino]propanoic acid Chemical compound NC=1C(=NC(=C(N=1)C(=O)NCCC(=O)O)N)C(=O)NCCC(=O)O PGRYIDPCVQRGJY-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- LRCYAJZPDFSJPQ-UHFFFAOYSA-N 3-azaniumyl-2-phenylpropanoate Chemical compound NCC(C(O)=O)C1=CC=CC=C1 LRCYAJZPDFSJPQ-UHFFFAOYSA-N 0.000 description 2
- WSVMIVFELRCSPA-UHFFFAOYSA-N 3-azaniumyl-4-naphthalen-2-ylbutanoate Chemical compound C1=CC=CC2=CC(CC(CC(O)=O)N)=CC=C21 WSVMIVFELRCSPA-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 0 COC[C@](COCc1ccccc1)NC(c1nc(N)c(C(N[C@@](COCc2ccccc2)C(*)=O)=O)nc1N)=O Chemical compound COC[C@](COCc1ccccc1)NC(c1nc(N)c(C(N[C@@](COCc2ccccc2)C(*)=O)=O)nc1N)=O 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 206010069351 acute lung injury Diseases 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
- 125000000129 anionic group Chemical group 0.000 description 2
- HJJPJSXJAXAIPN-UHFFFAOYSA-N arecoline Chemical compound COC(=O)C1=CCCN(C)C1 HJJPJSXJAXAIPN-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229940000635 beta-alanine Drugs 0.000 description 2
- 150000001576 beta-amino acids Chemical class 0.000 description 2
- 238000009534 blood test Methods 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 238000011018 current good manufacturing practice Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 210000001061 forehead Anatomy 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 229940050410 gluconate Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 229940049906 glutamate Drugs 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- BBJIPMIXTXKYLZ-UHFFFAOYSA-N isoglutamic acid Chemical compound OC(=O)CC(N)CC(O)=O BBJIPMIXTXKYLZ-UHFFFAOYSA-N 0.000 description 2
- 208000017169 kidney disease Diseases 0.000 description 2
- 238000012933 kinetic analysis Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229940001447 lactate Drugs 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 229960003194 meglumine Drugs 0.000 description 2
- 230000036564 melanin content Effects 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 238000011169 microbiological contamination Methods 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000013307 optical fiber Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 230000019612 pigmentation Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 210000005227 renal system Anatomy 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 230000010248 tubular secretion Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- NLCBWTXCWRLPIR-RFZPGFLSSA-N (1R,2R)-2-aminocyclopent-3-ene-1-carboxylic acid Chemical compound N[C@H]1[C@@H](CC=C1)C(=O)O NLCBWTXCWRLPIR-RFZPGFLSSA-N 0.000 description 1
- CKTUXQBZPWBFDX-RITPCOANSA-N (1r,3s)-3-aminocyclohexane-1-carboxylic acid Chemical compound N[C@H]1CCC[C@@H](C(O)=O)C1 CKTUXQBZPWBFDX-RITPCOANSA-N 0.000 description 1
- CKTUXQBZPWBFDX-WDSKDSINSA-N (1s,3s)-3-azaniumylcyclohexane-1-carboxylate Chemical compound [NH3+][C@H]1CCC[C@H](C([O-])=O)C1 CKTUXQBZPWBFDX-WDSKDSINSA-N 0.000 description 1
- HXOYWCSTHVTLOW-UHFFFAOYSA-N (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine Chemical compound CC1(C)OCC(CN)O1 HXOYWCSTHVTLOW-UHFFFAOYSA-N 0.000 description 1
- IBZNTYBFTKFSMU-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-[2-[2-[2-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoate Chemical compound COCCOCCOCCOCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O IBZNTYBFTKFSMU-UHFFFAOYSA-N 0.000 description 1
- XHNJXRDGTITISI-IMJSIDKUSA-N (2s)-2-[[3,6-diamino-5-[[(1s)-1-carboxy-2-hydroxyethyl]carbamoyl]pyrazine-2-carbonyl]amino]-3-hydroxypropanoic acid Chemical compound NC1=NC(C(=O)N[C@@H](CO)C(O)=O)=C(N)N=C1C(=O)N[C@@H](CO)C(O)=O XHNJXRDGTITISI-IMJSIDKUSA-N 0.000 description 1
- YGZNUMKUTITNGO-DKWTVANSSA-N (2s)-2-aminopropanoic acid;chloroethane Chemical compound CCCl.C[C@H](N)C(O)=O YGZNUMKUTITNGO-DKWTVANSSA-N 0.000 description 1
- BUZICZZQJDLXJN-GSVOUGTGSA-N (3R)-3-amino-4-hydroxybutanoic acid Chemical compound OC[C@H](N)CC(O)=O BUZICZZQJDLXJN-GSVOUGTGSA-N 0.000 description 1
- DUVVFMLAHWNDJD-VIFPVBQESA-N (3S)-3-Amino-4-(1H-indol-3-yl)butanoic acid Chemical compound C1=CC=C2C(C[C@@H](CC(O)=O)N)=CNC2=C1 DUVVFMLAHWNDJD-VIFPVBQESA-N 0.000 description 1
- OFVBLKINTLPEGH-VIFPVBQESA-N (3S)-3-Amino-4-phenylbutanoic acid Chemical compound OC(=O)C[C@@H](N)CC1=CC=CC=C1 OFVBLKINTLPEGH-VIFPVBQESA-N 0.000 description 1
- NIVRJEWVLMOZNV-QWWZWVQMSA-N (3r,4r)-3-amino-4-hydroxypentanoic acid Chemical compound C[C@@H](O)[C@H](N)CC(O)=O NIVRJEWVLMOZNV-QWWZWVQMSA-N 0.000 description 1
- JHEDYGILOIBOTL-NTSWFWBYSA-N (3r,4s)-3-azaniumyl-4-methylhexanoate Chemical compound CC[C@H](C)[C@H]([NH3+])CC([O-])=O JHEDYGILOIBOTL-NTSWFWBYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- MLYMSIKVLAPCAK-LURJTMIESA-N (S)-3-Amino-5-methylhexanoic acid Chemical compound CC(C)C[C@H](N)CC(O)=O MLYMSIKVLAPCAK-LURJTMIESA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- JHTPBGFVWWSHDL-UHFFFAOYSA-N 1,4-dichloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=C(Cl)C(N=C=S)=C1 JHTPBGFVWWSHDL-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- GIUTUZDGHNZVIA-UHFFFAOYSA-N 2-(ethylamino)acetic acid;hydrochloride Chemical compound Cl.CCNCC(O)=O GIUTUZDGHNZVIA-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- HEUWVFJLYQNYMK-CRCLSJGQSA-N 2-[(2s,4r)-4-hydroxypyrrolidin-1-ium-2-yl]acetate Chemical compound O[C@H]1CN[C@H](CC(O)=O)C1 HEUWVFJLYQNYMK-CRCLSJGQSA-N 0.000 description 1
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 1
- VLOIVYPDUSVCLZ-UHFFFAOYSA-N 2-[2-(azaniumylmethyl)phenyl]acetate Chemical compound NCC1=CC=CC=C1CC(O)=O VLOIVYPDUSVCLZ-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- JTPXVCKCLBROOJ-UHFFFAOYSA-N 2-amino-6-chloropyrazine Chemical compound NC1=CN=CC(Cl)=N1 JTPXVCKCLBROOJ-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- GRJKRZJFMZEFPZ-UHFFFAOYSA-N 2-n,5-n-bis(2,3-dihydroxypropyl)pyrazine-2,5-dicarboxamide Chemical compound OCC(O)CNC(=O)C1=CN=C(C(=O)NCC(O)CO)C=N1 GRJKRZJFMZEFPZ-UHFFFAOYSA-N 0.000 description 1
- JJLAHRWIQXYXBT-UHFFFAOYSA-N 3-[bis(2-methoxyethyl)amino]-5-bromo-6-chloropyrazine-2-carbonitrile Chemical compound COCCN(CCOC)C1=NC(Br)=C(Cl)N=C1C#N JJLAHRWIQXYXBT-UHFFFAOYSA-N 0.000 description 1
- VHKORUZVIHTHQO-UHFFFAOYSA-N 3-[bis(2-methoxyethyl)amino]-6-chloro-5-(furan-2-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C#N)C(N(CCOC)CCOC)=NC(C=2OC=CC=2)=C1Cl VHKORUZVIHTHQO-UHFFFAOYSA-N 0.000 description 1
- RLYAXKJHJUXZOT-UHFFFAOYSA-N 3-amino-3-(3-bromophenyl)propanoic acid Chemical compound OC(=O)CC(N)C1=CC=CC(Br)=C1 RLYAXKJHJUXZOT-UHFFFAOYSA-N 0.000 description 1
- MLLSSTJTARJLHK-UHFFFAOYSA-N 3-aminocyclopentane-1-carboxylic acid Chemical compound NC1CCC(C(O)=O)C1 MLLSSTJTARJLHK-UHFFFAOYSA-N 0.000 description 1
- LDSJMFGYNFIFRK-UHFFFAOYSA-N 3-azaniumyl-2-hydroxy-4-phenylbutanoate Chemical compound OC(=O)C(O)C(N)CC1=CC=CC=C1 LDSJMFGYNFIFRK-UHFFFAOYSA-N 0.000 description 1
- IHXITIQUZBCIHA-UHFFFAOYSA-N 3-azaniumyl-4-(4-phenylphenyl)butanoate Chemical compound C1=CC(CC(CC(O)=O)N)=CC=C1C1=CC=CC=C1 IHXITIQUZBCIHA-UHFFFAOYSA-N 0.000 description 1
- CJJYCYZKUNRKFP-UHFFFAOYSA-N 3-azaniumyl-5-phenylpentanoate Chemical compound OC(=O)CC(N)CCC1=CC=CC=C1 CJJYCYZKUNRKFP-UHFFFAOYSA-N 0.000 description 1
- UEMNCMYSSFWTCS-UHFFFAOYSA-N 3-azaniumylhex-5-enoate Chemical compound C=CCC(N)CC(O)=O UEMNCMYSSFWTCS-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- OZGUGVRKYBSDBN-UHFFFAOYSA-N 3-phenylmethoxypropanoic acid Chemical compound OC(=O)CCOCC1=CC=CC=C1 OZGUGVRKYBSDBN-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- IMXOPSRIUPQKAZ-UHFFFAOYSA-N 5-amino-3,6-dichloropyrazine-2-carbonitrile Chemical compound NC1=NC(Cl)=C(C#N)N=C1Cl IMXOPSRIUPQKAZ-UHFFFAOYSA-N 0.000 description 1
- ADBJFSVGVOWWBE-UHFFFAOYSA-N 5-amino-3-[bis(2-methoxyethyl)amino]-6-chloropyrazine-2-carbonitrile Chemical compound COCCN(CCOC)C1=NC(N)=C(Cl)N=C1C#N ADBJFSVGVOWWBE-UHFFFAOYSA-N 0.000 description 1
- XNMDHWGZTPXFNH-UHFFFAOYSA-N 5-bromo-3,6-dichloropyrazin-2-amine Chemical compound NC1=NC(Cl)=C(Br)N=C1Cl XNMDHWGZTPXFNH-UHFFFAOYSA-N 0.000 description 1
- AYHFEOBBBLAEMA-UHFFFAOYSA-N 6-[bis(2-methoxyethyl)amino]-3-chloro-5-cyanopyrazine-2-carboxylic acid Chemical compound COCCN(CCOC)C1=NC(C(O)=O)=C(Cl)N=C1C#N AYHFEOBBBLAEMA-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- FKIPQNCEJZNNDC-ROUUACIJSA-N C([C@H](NC(=O)C=1N=C(C(=NC=1N)C(=O)N[C@@H](COCC=1C=CC=CC=1)C(O)=O)N)C(O)=O)OCC1=CC=CC=C1 Chemical compound C([C@H](NC(=O)C=1N=C(C(=NC=1N)C(=O)N[C@@H](COCC=1C=CC=CC=1)C(O)=O)N)C(O)=O)OCC1=CC=CC=C1 FKIPQNCEJZNNDC-ROUUACIJSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 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
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 229920000869 Homopolysaccharide Polymers 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 206010020674 Hypermetabolism Diseases 0.000 description 1
- 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 1
- 150000007649 L alpha amino acids Chemical class 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical class C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- VUNPIAMEJXBAFP-QMMMGPOBSA-N L-beta-Homotyrosine Chemical compound OC(=O)C[C@@H](N)CC1=CC=C(O)C=C1 VUNPIAMEJXBAFP-QMMMGPOBSA-N 0.000 description 1
- QWVNCDVONVDGDV-YFKPBYRVSA-N L-beta-homomethionine Chemical compound CSCC[C@H](N)CC(O)=O QWVNCDVONVDGDV-YFKPBYRVSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012901 Milli-Q water Substances 0.000 description 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical class CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- RMCVWOSEYPWPMX-UHFFFAOYSA-N OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.N1=C(C=NC(=C1)C(=O)N(CCOC)CCOC)C(=O)N(CCOC)CCOC Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.N1=C(C=NC(=C1)C(=O)N(CCOC)CCOC)C(=O)N(CCOC)CCOC RMCVWOSEYPWPMX-UHFFFAOYSA-N 0.000 description 1
- HMFVJBMUMIUJIW-UHFFFAOYSA-N OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.N1=C(C=NC(=C1)C(=O)NCCN)C(=O)NCCN Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.N1=C(C=NC(=C1)C(=O)NCCN)C(=O)NCCN HMFVJBMUMIUJIW-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 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
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009056 active transport Effects 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 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
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229960004909 aminosalicylic acid Drugs 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- NYKUZBVJIFJLLO-UHFFFAOYSA-N benzoic acid;4-methylbenzenesulfonic acid Chemical compound OC(=O)C1=CC=CC=C1.CC1=CC=C(S(O)(=O)=O)C=C1 NYKUZBVJIFJLLO-UHFFFAOYSA-N 0.000 description 1
- MGZWCDQAKCHOBX-SBSPUUFOSA-N benzyl (2r)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.OC[C@@H](N)C(=O)OCC1=CC=CC=C1 MGZWCDQAKCHOBX-SBSPUUFOSA-N 0.000 description 1
- AMUBGQXJKQNCRK-UHFFFAOYSA-N benzyl 3-[[3,6-diamino-5-[(3-oxo-3-phenylmethoxypropyl)carbamoyl]pyrazine-2-carbonyl]amino]propanoate Chemical compound Nc1nc(C(=O)NCCC(=O)OCc2ccccc2)c(N)nc1C(=O)NCCC(=O)OCc1ccccc1 AMUBGQXJKQNCRK-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- ADSALMJPJUKESW-UHFFFAOYSA-N beta-Homoproline Chemical compound OC(=O)CC1CCCN1 ADSALMJPJUKESW-UHFFFAOYSA-N 0.000 description 1
- GLUJNGJDHCTUJY-UHFFFAOYSA-N beta-leucine Chemical compound CC(C)C(N)CC(O)=O GLUJNGJDHCTUJY-UHFFFAOYSA-N 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000011449 brick Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FGZBFIYFJUAETR-UHFFFAOYSA-N calcium;magnesium;silicate Chemical compound [Mg+2].[Ca+2].[O-][Si]([O-])([O-])[O-] FGZBFIYFJUAETR-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical group 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- CJXAEXPPLWQRFR-UHFFFAOYSA-N clemizole Chemical compound C1=CC(Cl)=CC=C1CN1C2=CC=CC=C2N=C1CN1CCCC1 CJXAEXPPLWQRFR-UHFFFAOYSA-N 0.000 description 1
- 229950002020 clemizole Drugs 0.000 description 1
- 238000009535 clinical urine test Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 230000002596 correlated effect Effects 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
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N d-arabitol Chemical compound OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- XCZGJTBEXSLSNT-UHFFFAOYSA-L disodium;3,6-diaminopyrazine-2,5-dicarboxylate Chemical compound [Na+].[Na+].NC1=NC(C([O-])=O)=C(N)N=C1C([O-])=O XCZGJTBEXSLSNT-UHFFFAOYSA-L 0.000 description 1
- QNDQILQPPKQROV-UHFFFAOYSA-N dizinc Chemical compound [Zn]=[Zn] QNDQILQPPKQROV-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000000624 ear auricle Anatomy 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- JCXLZWMDXJFOOI-PGMHMLKASA-N ethyl (2r)-2-aminopropanoate;hydrochloride Chemical compound Cl.CCOC(=O)[C@@H](C)N JCXLZWMDXJFOOI-PGMHMLKASA-N 0.000 description 1
- LABJTCLBFBHCBB-UHFFFAOYSA-N ethyl 2-[[3,6-diamino-5-[(2-ethoxy-2-oxoethyl)carbamoyl]pyrazine-2-carbonyl]amino]acetate Chemical compound NC=1C(=NC(=C(N=1)C(=O)NCC(=O)OCC)N)C(=O)NCC(=O)OCC LABJTCLBFBHCBB-UHFFFAOYSA-N 0.000 description 1
- HCTJHQFFNDLDPF-UHFFFAOYSA-N ethyl 3-(benzylamino)propanoate Chemical compound CCOC(=O)CCNCC1=CC=CC=C1 HCTJHQFFNDLDPF-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 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
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 235000004554 glutamine Nutrition 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 208000019622 heart disease Diseases 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
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 235000014304 histidine Nutrition 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical class OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010339 medical test Methods 0.000 description 1
- KCUNTYMNJVXYKZ-JTQLQIEISA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 KCUNTYMNJVXYKZ-JTQLQIEISA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical group 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 1
- 231100001019 reduced numbers of red blood cells Toxicity 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 230000007756 renal tubular secretion Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000005316 response function Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000024053 secondary metabolic process Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000036555 skin type Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- BBQLWSWFTUQJQG-UHFFFAOYSA-N tert-butyl N-[2-[(5-carbamoylpyrazine-2-carbonyl)amino]ethyl]carbamate Chemical compound N1=C(C=NC(=C1)C(=O)N)C(=O)NCCNC(=O)OC(C)(C)C BBQLWSWFTUQJQG-UHFFFAOYSA-N 0.000 description 1
- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 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
- 230000008733 trauma Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 230000009723 vascular congestion Effects 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/20—Measuring for diagnostic purposes; Identification of persons for measuring urological functions restricted to the evaluation of the urinary system
- A61B5/201—Assessing renal or kidney functions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/007—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests for contrast media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B57/00—Other synthetic dyes of known constitution
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1074—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms
- C09K2211/1077—Heterocyclic compounds characterised by ligands containing more than three nitrogen atoms as heteroatoms with oxygen
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pathology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biophysics (AREA)
- Surgery (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Physics & Mathematics (AREA)
- Physiology (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Anesthesiology (AREA)
- Materials Engineering (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
X1及びX2は、互いに独立して、-CO2R1、−CONR1R2、−CO(AA)、及び−CONH(PS)からなる群から選択され、
Y1及びY2は、互いに独立して、NR1R2、及び
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、
AAは、ペプチド結合またはアミド結合によって互いに結合された1以上の天然または非天然のアミノ酸を含むポリペプチド鎖であり、AAの各々は、互いに同一であってもよいし異なっていてもよく、
PSは、グリコシド結合によって互いに結合された1以上の単糖単位を含む硫化多糖鎖または非硫化多糖鎖であり、
aは、1〜10の範囲の数であり、
cは、1〜100の範囲の数であり、
m及びnは、互いに独立して、1〜3の範囲の数である。
X1及びX2は、互いに独立して、-CO2R1、−CONR1R2、−CO(AA)、及び−CONH(PS)からなる群から選択され、
Y1及びY2は、互いに独立して、NR1R2、及び
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、
AAは、ペプチド結合またはアミド結合によって互いに結合された1以上の天然または非天然のアミノ酸を含むポリペプチド鎖であり、AAの各々は、互いに同一であってもよいし、異なっていてもよく、
PSは、グリコシド結合によって互いに結合された1以上の単糖単位を含む硫化多糖鎖または非硫化多糖鎖であり、
aは、1〜10の範囲の数であり、
cは、1〜100の範囲の数であり、
m及びnは、互いに独立して、1〜3の範囲の数である。
X1及びX2は、互いに独立して、-CO2R1、−CONR1R2、−CO(AA)、及び−CONH(PS)からなる群から選択され、
Y1及びY2は、互いに独立して、NR1R2、及び
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、
AAは、ペプチド結合またはアミド結合によって互いに結合された1以上の天然または非天然のアミノ酸を含むポリペプチド鎖であり、AAの各々は、互いに同一であってもよいし異なっていてもよく、
PSは、グリコシド結合によって互いに結合された1以上の単糖単位を含む硫化多糖鎖または非硫化多糖鎖であり、
aは、0〜10の範囲の数であり、
cは、1〜100の範囲の数であり、
m及びnは、互いに独立して、1〜3の範囲の数である。
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、a、c、m及びnは、上述した通りである。
Claims (35)
- 糸球体濾過率(GFR)の測定を必要とする患者のGFRを測定する方法であって、
下記の化学式Iで表される化合物またはその薬学的に許容可能な塩を前記患者に投与するステップと、
前記患者の体内の前記化学式Iの化合物の濃度を測定時間ウィンドウにわたって測定するステップと、
前記患者のGFRを測定するステップと、を含むことを特徴とする方法。
X1及びX2は、互いに独立して、-CO2R1、−CONR1R2、−CO(AA)、及び−CONH(PS)からなる群から選択され、
Y1及びY2は、互いに独立して、NR1R2、及び
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、
AAは、ペプチド結合またはアミド結合によって互いに結合された1以上の天然または非天然のアミノ酸を含むポリペプチド鎖であり、AAの各々は、互いに同一であってもよいし異なっていてもよく、
PSは、グリコシド結合によって互いに結合された1以上の単糖単位を含む硫化多糖鎖または非硫化多糖鎖であり、
aは、1〜10の範囲の数であり、
cは、1〜100の範囲の数であり、
m及びnは、互いに独立して、1〜3の範囲の数である。 - 請求項1に記載の方法であって、
前記測定時間ウィンドウは、約48時間であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記化学式Iの化合物は、抗菌剤、酸化防止剤、緩衝剤、浸透圧調節剤、pH調節剤、防腐剤、溶媒、安定化剤、界面活性剤、張度調節剤、粘度調節剤、及びそれらの任意の組み合わせからなる群より選択される少なくとも1つの薬学的に許容可能な賦形剤と組み合わされることを特徴とする方法。 - 請求項3に記載の方法であって、
前記少なくとも1つの薬学的に許容可能な賦形剤のうちの1つが、リン酸緩衝生理食塩水であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記化学式Iの化合物は、経腸投与、静脈投与、経口投与、非経口投与、皮下投与、または経皮投与によって前記患者に投与されることを特徴とする方法。 - 請求項1に記載の方法であって、
前記患者は、以前の測定で測定されたGFRが90未満であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記患者は、高い尿中タンパク質濃度を有することを特徴とする方法。 - 請求項7に記載の方法であって、
前記高い尿中タンパク質濃度は、前記患者の高い尿中アルブミン濃度に起因することを特徴とする方法。 - 請求項1に記載の方法であって、
前記X1及び前記X2の少なくとも一方は、−CO(PS)または−CO(AA)であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記X1及び前記X2の両方は、−CO(AA)であることを特徴とする方法。 - 請求項10に記載の方法であって、
前記AAの各々は、1または複数のD−α−アミノ酸であることを特徴とする方法。 - 請求項10に記載の方法であって、
前記AAの各々は、単一のD−α−アミノ酸であることを特徴とする方法。 - 請求項10に記載の方法であって、
前記AAは、D−アラニン、D−アルギニン、D−アスパラギン、D−アスパラギン酸、D−システイン、D−グルタミン酸、D−グルタミン、グリシン、D−ヒスチジン、D−ホモセリン、D−イソロイシン、D−ロイシン、D−リジン、D−メチオニン、D−フェニルアラニン、D−プロリン、D−セリン、D−トレオニン、D−トリプトファン、D−チロシン、及びD−バリンからなる群から選択されることを特徴とする方法。 - 請求項10に記載の方法であって、
前記AAは、D−アルギニン、D−アスパラギン、D−アスパラギン酸、D−グルタミン酸、D−グルタミン、グリシン、D−ヒスチジン、D−ホモセリン、D−リジン、及びD−セリンからなる群から選択されることを特徴とする方法。 - 請求項10に記載の方法であって、
前記AAは、D−アスパラギン酸及びD−セリンからなる群から選択されることを特徴とする方法。 - 請求項12に記載の方法であって、
前記AAは、D−セリンであることを特徴とする方法。 - 請求項12に記載の方法であって、
前記AAはD−セリンであり、前記Y1及び前記Y2はそれぞれ−NR1R2及びR1=R2=Hであることを特徴とする方法。 - 患者の腎機能を評価する方法であって、
蛍光化合物またはその薬学的に許容可能な塩を前記患者に投与するステップと、
前記蛍光化合物を電磁放射線に暴露させて、前記蛍光化合物からスペクトルエネルギーを放出させるステップと、
前記蛍光化合物から放出された前記スペクトルエネルギーを検出するステップと、
検出された前記スペクトルエネルギーに基づいて前記患者の腎機能を評価するステップと、を含む方法。 - 請求項18に記載の方法であって、
前記蛍光化合物は、下記の化学式Iで表される化合物であることを特徴とする方法。
X1及びX2は、互いに独立して、-CO2R1、−CONR1R2、−CO(AA)、及び−CONH(PS)からなる群から選択され、
Y1及びY2は、互いに独立して、NR1R2、及び
Z1は、単結合、−CR1R2−、−O−、−NR1−、−NCOR1−、−S−、−SO−、及び−SO2−からなる群から選択され、
R1及びR2は、互いに独立して、H、−CH2(CHOH)aH、−CH2(CHOH)aCH3、−CH2(CHOH)aCO2H、−(CHCO2H)aCO2H、−(CH2CH2O)cH、−(CH2CH2O)cCH3、−(CH2)aSO3H、−(CH2)aSO3 −、−(CH2)aSO2H、−(CH2)aSO2 −、−(CH2)aNHSO3H、−(CH2)aNHSO3 −、−(CH2)aNHSO2H、−(CH2)aNHSO2 −、−(CH2)aPO4H3、−(CH2)aPO4H2 −、−(CH2)aPO4H2−、−(CH2)aPO4 3−、−(CH2)aPO3H2、−(CH2)aPO3H−、及び−(CH2)aPO3 2−からなる群から選択され、
AAは、ペプチド結合またはアミド結合によって互いに結合された1以上の天然または非天然のアミノ酸を含むポリペプチド鎖であり、AAの各々は、互いに同一であってもよいし異なっていてもよく、
PSは、グリコシド結合によって互いに結合された1以上の単糖単位を含む硫化多糖鎖または非硫化多糖鎖であり、
aは、1〜10の範囲の数であり、
cは、1〜100の範囲の数であり、
m及びnは、互いに独立して、1〜3の範囲の数である。 - 請求項18に記載の方法であって、
前記患者は、110未満のGFRまたはeGFRを有していることを特徴とする方法。 - 請求項18に記載の方法であって、
前記患者は、90未満のGFRまたはeGFRを有していることを特徴とする方法。 - 請求項18に記載の方法であって、
前記患者は、60未満のGFRまたはeGFRを有していることを特徴とする方法。 - 請求項18に記載の方法であって、
前記患者は、30未満のGFRまたはeGFRを有していることを特徴とする方法。 - 請求項18に記載の方法であって、
前記投与は、経腸投与、静脈投与、経口投与、非経口投与、皮下投与、または経皮投与によって行われることを特徴とする方法。 - 請求項18に記載の方法であって、
前記投与は、静脈内投与または経皮投与によって行われることを特徴とする方法。 - 請求項18に記載の方法であって、
前記患者は、慢性腎臓病(CKD)に関する1以上の危険因子を有していることを特徴とする方法。 - 請求項27に記載の方法であって、
前記患者は、ステージ1のCKDと以前に診断されていることを特徴とする方法。 - 請求項27に記載の方法であって、
前記患者は、ステージ2のCKDと以前に診断されていることを特徴とする方法。 - 請求項27に記載の方法であって、
前記患者は、ステージ3のCKDと以前に診断されていることを特徴とする方法。 - 請求項27に記載の方法であって、
前記患者は、ステージ4のCKDと以前に診断されていることを特徴とする方法。 - 請求項18に記載の方法であって、
前記電磁放射線は、赤外線、紫外線、及び/または可視光のうちの少なくとも1つであることを特徴とする方法。 - 請求項18に記載の方法であって、
前記蛍光化合物の少なくとも98%が、前記患者による腎排泄の前に代謝されないことを特徴とする方法。 - 請求項18に記載の方法であって、
前記蛍光化合物が、予め定められた期間内に前記患者の腎臓から排泄されることによって完全に除去されることを特徴とする方法 - 請求項34に記載の方法であって、
前記予め定められた期間が48時間であることを特徴とする方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2021193972A JP2022051729A (ja) | 2017-10-27 | 2021-11-30 | 腎臓機能測定のための化合物 |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201762577951P | 2017-10-27 | 2017-10-27 | |
US62/577,951 | 2017-10-27 | ||
PCT/US2018/057743 WO2019084425A1 (en) | 2017-10-27 | 2018-10-26 | METHODS FOR EVALUATING RENAL FUNCTION |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021193972A Division JP2022051729A (ja) | 2017-10-27 | 2021-11-30 | 腎臓機能測定のための化合物 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2020519321A true JP2020519321A (ja) | 2020-07-02 |
Family
ID=66245826
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019555615A Pending JP2020519321A (ja) | 2017-10-27 | 2018-10-26 | 腎機能測定方法 |
JP2021193972A Pending JP2022051729A (ja) | 2017-10-27 | 2021-11-30 | 腎臓機能測定のための化合物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021193972A Pending JP2022051729A (ja) | 2017-10-27 | 2021-11-30 | 腎臓機能測定のための化合物 |
Country Status (15)
Country | Link |
---|---|
US (2) | US11590244B2 (ja) |
EP (1) | EP3700579A4 (ja) |
JP (2) | JP2020519321A (ja) |
KR (1) | KR102438880B1 (ja) |
CN (1) | CN110545854A (ja) |
AU (2) | AU2018354391C1 (ja) |
BR (1) | BR112019021040A2 (ja) |
CA (1) | CA3058767C (ja) |
IL (1) | IL269613B2 (ja) |
MX (1) | MX2019011902A (ja) |
MY (1) | MY197490A (ja) |
PH (1) | PH12019502374A1 (ja) |
RU (1) | RU2734776C1 (ja) |
SG (1) | SG11201909367VA (ja) |
WO (1) | WO2019084425A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020516680A (ja) * | 2017-10-27 | 2020-06-11 | メディビーコン,インク. | 腎機能測定のための組成物及びシステム |
Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10548521B2 (en) | 2017-01-30 | 2020-02-04 | Medibeacon Inc. | Method for non-invasive monitoring of fluorescent tracer agent with diffuse reflection corrections |
CN111033637B (zh) | 2017-08-08 | 2023-12-05 | 费森尤斯医疗保健控股公司 | 用于治疗和评估慢性肾脏疾病的进程的系统和方法 |
KR20210102371A (ko) * | 2018-12-12 | 2021-08-19 | 메디비콘 아이엔씨. | 지속적 신장 대체 요법에서 경피 사구체 여과율 측정의 용도 |
CN111436947B (zh) | 2019-01-16 | 2022-12-23 | 麦迪贝肯有限公司 | 两件式传感器组件及其使用方法 |
CN115334977A (zh) * | 2020-03-27 | 2022-11-11 | 泰尔茂株式会社 | 生物体功能推定装置及生物体功能推定方法 |
KR102410292B1 (ko) * | 2020-05-27 | 2022-06-17 | 주식회사 스파이더코어 | 신장 기능 이상을 검출하는 심층 신경망 기반 망막 영상 분석 방법 및 장치 |
WO2022145542A1 (ko) * | 2020-12-30 | 2022-07-07 | 주식회사 메디웨일 | 심혈관 질병 진단 보조 방법 및 장치 |
TW202321203A (zh) * | 2021-08-11 | 2023-06-01 | 中國大陸商杭州中美華東製藥有限公司 | 製備作為螢光示蹤劑的吡嗪羧酸類衍生物的方法 |
CN117881665A (zh) * | 2021-08-27 | 2024-04-12 | 杭州中美华东制药有限公司 | 吡嗪类衍生物的晶型及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008525487A (ja) * | 2004-12-23 | 2008-07-17 | マリンクロッド・インコーポレイテッド | 蛍光ピラジン誘導体および腎機能評価におけるその使用方法 |
JP2009534396A (ja) * | 2006-06-22 | 2009-09-24 | マリンクロッド・インコーポレイテッド | ピラジン誘導体および腎臓の監視におけるその使用 |
JP2012512258A (ja) * | 2008-12-17 | 2012-05-31 | マリンクロッド エルエルシー | 修飾ピラジン誘導体およびその使用 |
JP2017502706A (ja) * | 2013-10-22 | 2017-01-26 | ハインリッヒ,ラルフ | 改善された経皮臓器機能測定 |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6909912B2 (en) | 2002-06-20 | 2005-06-21 | University Of Florida | Non-invasive perfusion monitor and system, specially configured oximeter probes, methods of using same, and covers for probes |
WO2004096082A2 (en) | 2003-04-24 | 2004-11-11 | The Board Of Regents Of The University Of Texas System | Noninvasive blood analysis by optical probing of the veins under the tongue |
US20060095102A1 (en) | 2003-09-17 | 2006-05-04 | Thomas Perez | Method and apparatus for sublingual application of light to blood |
US8664392B2 (en) | 2004-12-23 | 2014-03-04 | Medibeacon, LLC | Pyrazine derivatives for bioconjugation |
AU2006340061A1 (en) | 2006-02-24 | 2007-09-20 | Mallinckrodt Llc | Process for using optical agents |
AU2007261397A1 (en) | 2006-06-22 | 2007-12-27 | Mallinckrodt Llc | Pyrazine derivatives with extended conjugation and uses thereof |
CN101687040A (zh) | 2007-03-01 | 2010-03-31 | 马林克罗特公司 | 整合光活性的小分子及其用途 |
CA2641297A1 (en) | 2008-07-11 | 2010-01-11 | Richard B. Dorshow | Pyrazine derivatives, methods of use, and methods for preparing same |
KR20100007666A (ko) * | 2008-07-11 | 2010-01-22 | 말린크로트, 인코포레이티드 | 피라진 유도체, 사용 방법 및 그의 제조 방법 |
US20120172679A1 (en) | 2010-12-30 | 2012-07-05 | Logan Robert J | Systems and methods for monitoring and processing biometric data |
WO2012149227A2 (en) | 2011-04-26 | 2012-11-01 | Incube Labs, Llc | Mouthpiece for measurement of biometric data of a diver and underwater communication |
US11077211B2 (en) | 2013-11-11 | 2021-08-03 | Medibeacon Inc. | Compositions and methods for assessing gut function |
US9270623B2 (en) * | 2014-07-22 | 2016-02-23 | Verizon Patent And Licensing Inc. | Network and device solution on sponsored data application |
US10525149B2 (en) | 2015-05-12 | 2020-01-07 | Medibeacon Inc. | Compositions and methods for assessing eye vasculature |
-
2018
- 2018-10-26 CA CA3058767A patent/CA3058767C/en active Active
- 2018-10-26 US US16/171,695 patent/US11590244B2/en active Active
- 2018-10-26 EP EP18871229.3A patent/EP3700579A4/en active Pending
- 2018-10-26 AU AU2018354391A patent/AU2018354391C1/en active Active
- 2018-10-26 SG SG11201909367V patent/SG11201909367VA/en unknown
- 2018-10-26 IL IL269613A patent/IL269613B2/en unknown
- 2018-10-26 KR KR1020197030755A patent/KR102438880B1/ko active IP Right Grant
- 2018-10-26 MX MX2019011902A patent/MX2019011902A/es unknown
- 2018-10-26 RU RU2019132949A patent/RU2734776C1/ru active
- 2018-10-26 MY MYPI2019006127A patent/MY197490A/en unknown
- 2018-10-26 CN CN201880013822.XA patent/CN110545854A/zh active Pending
- 2018-10-26 JP JP2019555615A patent/JP2020519321A/ja active Pending
- 2018-10-26 BR BR112019021040-7A patent/BR112019021040A2/pt unknown
- 2018-10-26 WO PCT/US2018/057743 patent/WO2019084425A1/en unknown
-
2019
- 2019-10-18 PH PH12019502374A patent/PH12019502374A1/en unknown
-
2020
- 2020-12-14 AU AU2020289719A patent/AU2020289719B2/en active Active
-
2021
- 2021-11-30 JP JP2021193972A patent/JP2022051729A/ja active Pending
-
2023
- 2023-01-25 US US18/159,253 patent/US20230158175A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008525487A (ja) * | 2004-12-23 | 2008-07-17 | マリンクロッド・インコーポレイテッド | 蛍光ピラジン誘導体および腎機能評価におけるその使用方法 |
JP2009534396A (ja) * | 2006-06-22 | 2009-09-24 | マリンクロッド・インコーポレイテッド | ピラジン誘導体および腎臓の監視におけるその使用 |
JP2012512258A (ja) * | 2008-12-17 | 2012-05-31 | マリンクロッド エルエルシー | 修飾ピラジン誘導体およびその使用 |
JP2017502706A (ja) * | 2013-10-22 | 2017-01-26 | ハインリッヒ,ラルフ | 改善された経皮臓器機能測定 |
Non-Patent Citations (1)
Title |
---|
RAGHAVAN RAJAGOPALAN ET AL.: "Hydrophilic Pyrazine Dyes as Exogenous Fluorescent Tracer Agents for Real-Time Point-of-Care Measure", JOURNAL OF MEDICINAL CHEMISTRY, vol. 54, JPN6020033999, 13 June 2011 (2011-06-13), pages 5048 - 5058, ISSN: 0004366627 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020516680A (ja) * | 2017-10-27 | 2020-06-11 | メディビーコン,インク. | 腎機能測定のための組成物及びシステム |
Also Published As
Publication number | Publication date |
---|---|
AU2020289719B2 (en) | 2022-05-12 |
WO2019084425A1 (en) | 2019-05-02 |
RU2734776C1 (ru) | 2020-10-23 |
AU2020289719A1 (en) | 2021-01-21 |
PH12019502374A1 (en) | 2020-09-14 |
CA3058767C (en) | 2022-03-15 |
MX2019011902A (es) | 2019-12-05 |
IL269613A (en) | 2019-11-28 |
US20230158175A1 (en) | 2023-05-25 |
CA3058767A1 (en) | 2019-05-02 |
BR112019021040A2 (pt) | 2020-05-12 |
KR20200011033A (ko) | 2020-01-31 |
IL269613B2 (en) | 2023-12-01 |
AU2018354391B2 (en) | 2020-09-17 |
MY197490A (en) | 2023-06-19 |
SG11201909367VA (en) | 2019-11-28 |
US20190125902A1 (en) | 2019-05-02 |
CN110545854A (zh) | 2019-12-06 |
AU2018354391C1 (en) | 2021-01-21 |
JP2022051729A (ja) | 2022-04-01 |
US11590244B2 (en) | 2023-02-28 |
EP3700579A1 (en) | 2020-09-02 |
IL269613B1 (en) | 2023-08-01 |
KR102438880B1 (ko) | 2022-09-01 |
AU2018354391A1 (en) | 2019-10-17 |
EP3700579A4 (en) | 2021-07-21 |
NZ757959A (en) | 2023-11-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102438880B1 (ko) | 신장 기능 측정 방법 | |
JP7362869B2 (ja) | 腎機能測定のための組成物及びシステム | |
EP2145879B1 (en) | Pyrazine derivatives, methods of use, and methods for preparing same | |
JP2009534396A (ja) | ピラジン誘導体および腎臓の監視におけるその使用 | |
JP2023548017A (ja) | ピラジン化合物の皮下及び筋肉内投与 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A525 Effective date: 20191010 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20191010 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20201020 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20201023 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210119 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210316 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210615 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20210803 |