4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid → Nadide (JAN/USAN/INN)

HRID 626087

Reaktionsgleichung

Reaktionsgleichung von HRID 626087
C1N(CCO)CCN(CCS(O)(=O)=O)C1.[CH:16]1[N:17]=[C:18]([NH2:59])[C:19]2[N:24]=[CH:23][N:22]([C@@H:25]3[O:29][C@H:28]([CH2:30][O:31][P:32]([O:35][P:36]([O:39][CH2:40][C@H:41]4[O:45][C@@H:44]([N:46]5[CH:51]=[C:50]([C:52]([NH2:54])=[O:53])[CH2:49][CH:48]=[CH:47]5)[C@H:43]([OH:55])[C@@H:42]4[OH:56])([OH:38])=[O:37])([OH:34])=[O:33])[C@@H:27]([OH:57])[C@H:26]3[OH:58])[C:20]=2[N:21]=1.[CH:60]1[CH:65]=[N+:64]([C@@H:66]2[O:70][C@H:69]([CH2:71][O:72][P:73]([O:76][P:77]([O:80][CH2:81][C@H:82]3[O:86][C@@H:85]([N:87]4[C:91]5[N:92]=[CH:93][N:94]=[C:95]([NH2:96])[C:90]=5[N:89]=[CH:88]4)[C@H:84]([OH:97])[C@@H:83]3[OH:98])([OH:79])=[O:78])([OH:75])=[O:74])[C@@H:68]([OH:99])[C@H:67]2[OH:100])[CH:63]=[C:62]([C:101]([NH2:103])=[O:102])[CH:61]=1.[C:104]([S:109][CH2:110][CH2:111][NH:112][C:113](=[O:156])[CH2:114][CH2:115][NH:116][C:117](=[O:155])[C@H:118]([OH:154])[C:119]([CH3:153])([CH3:152])[CH2:120][O:121][P:122]([OH:151])(=[O:150])[O:123][P:124]([OH:149])(=[O:148])[O:125][CH2:126][C@H:127]1[O:131][C@@H:130]([N:132]2[C:141]3[N:140]=[CH:139][N:138]=[C:136]([NH2:137])[C:135]=3[N:134]=[CH:133]2)[C@H:129]([OH:142])[C@@H:128]1[O:143][P:144]([OH:147])([OH:146])=[O:145])(=[O:108])/[CH:105]=[CH:106]/[CH3:107]>CS(C)=O>[CH:16]1[N:17]=[C:18]([NH2:59])[C:19]2[N:24]=[CH:23][N:22]([C@@H:25]3[O:29][C@H:28]([CH2:30][O:31][P:32]([O:35][P:36]([O:39][CH2:40][C@H:41]4[O:45][C@@H:44]([N:46]5[CH:51]=[C:50]([C:52]([NH2:54])=[O:53])[CH2:49][CH:48]=[CH:47]5)[C@H:43]([OH:55])[C@@H:42]4[OH:56])([OH:38])=[O:37])([OH:34])=[O:33])[C@@H:27]([OH:57])[C@H:26]3[OH:58])[C:20]=2[N:21]=1.[CH:60]1[CH:65]=[N+:64]([C@@H:66]2[O:70][C@H:69]([CH2:71][O:72][P:73]([O:76][P:77]([O:80][CH2:81][C@H:82]3[O:86][C@@H:85]([N:87]4[C:91]5[N:92]=[CH:93][N:94]=[C:95]([NH2:96])[C:90]=5[N:89]=[CH:88]4)[C@H:84]([OH:97])[C@@H:83]3[OH:98])([OH:79])=[O:78])([OH:75])=[O:74])[C@@H:68]([OH:99])[C@H:67]2[OH:100])[CH:63]=[C:62]([C:101]([NH2:103])=[O:102])[CH:61]=1.[C:104]([S:109][CH2:110][CH2:111][NH:112][C:113](=[O:156])[CH2:114][CH2:115][NH:116][C:117](=[O:155])[C@H:118]([OH:154])[C:119]([CH3:152])([CH3:153])[CH2:120][O:121][P:122]([OH:151])(=[O:150])[O:123][P:124]([OH:149])(=[O:148])[O:125][CH2:126][C@H:127]1[O:131][C@@H:130]([N:132]2[C:141]3[N:140]=[CH:139][N:138]=[C:136]([NH2:137])[C:135]=3[N:134]=[CH:133]2)[C@H:129]([OH:142])[C@@H:128]1[O:143][P:144]([OH:147])([OH:146])=[O:145])(=[O:108])/[CH:105]=[CH:106]/[CH3:107]

Komponenten

7

Edukt 3

HCID 238314-(2-Hydroxyethyl)-1-piperazineethanesulfonic acidHCID 5497143crotonoyl-CoAHCID 86639099Nadh nad+

Produkt 3

HCID 5893Nadide (JAN/USAN/INN)HCID 439153NadhHCID 5497143crotonoyl-CoA

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel2×

Versuchsvorschrift

The assay buffer “AB” contains 50 mM Hepes pH7.5, 100 μM Dithiothreitol, 0.006% Triton-X100. The following components are added in a black polystyrene Costar plate up to a final volume of 55 μL: 1.5 μL DMSO, or inhibitor dissolved in DMSO and 53.5 μL of a FabI/NADH/NAD+ mixture in AB. After 60 min of pre-incubation at room temperature, the reaction is started by addition of 5 μL of Crotonoyl-CoA to a final volume of 60 μL. This reaction mixture is then composed of 40 nM FabI (produced in house from E. coli, C-terminal 6-His tagged), 20 μM NADH (Biochemika), 10 μM NAD+ (Biochemika), 50 μM Crotonoyl-CoA (Biochemika) and compound at defined concentration. Fluorescence intensity of NADH (lex=360 nm, lem=520 nm) is measured immediately after Crotonoyl-CoA addition, and 2 hours later by a Fluostar Optima (BMG). Enzyme activity is proportional to the signal decrease from which inhibition percentages are derived. For IC50 determinations, the inhibitor is tested at 6 to 10 different concentrations, and the related inhibitions are fitted to a classical langmuir equilibrium model using XLFIT (IDBS).

Quellen und Nachweise

ORD-Eintrag
ord-52bd2822a5454a239c69c54faf56b86d
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309179B2

Verknüpfte Notizen

Wird geladen…