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[ CAS No. 13161-30-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 13161-30-3
Chemical Structure| 13161-30-3
Chemical Structure| 13161-30-3
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Product Details of [ 13161-30-3 ]

CAS No. :13161-30-3 MDL No. :MFCD00006195
Formula : C5H5NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :SNUSZUYTMHKCPM-UHFFFAOYSA-N
M.W : 111.10 Pubchem ID :69975
Synonyms :

Calculated chemistry of [ 13161-30-3 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 29.63
TPSA : 45.69 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.09 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.78
Log Po/w (XLOGP3) : -0.16
Log Po/w (WLOGP) : 0.03
Log Po/w (MLOGP) : 0.36
Log Po/w (SILICOS-IT) : -0.33
Consensus Log Po/w : 0.13

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.98
Solubility : 11.6 mg/ml ; 0.104 mol/l
Class : Very soluble
Log S (Ali) : -0.34
Solubility : 50.2 mg/ml ; 0.452 mol/l
Class : Very soluble
Log S (SILICOS-IT) : 0.01
Solubility : 113.0 mg/ml ; 1.02 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.66

Safety of [ 13161-30-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 13161-30-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 13161-30-3 ]

[ 13161-30-3 ] Synthesis Path-Downstream   1~85

  • 1
  • [ 694-59-7 ]
  • [ 6602-28-4 ]
  • [ 6890-62-6 ]
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  • 4
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  • [ 81415-92-1 ]
  • [ 81416-09-3 ]
  • 5
  • [ 13161-30-3 ]
  • [ 74405-13-3 ]
  • [ 81416-07-1 ]
  • 6
  • [ 13161-30-3 ]
  • [ 74405-11-1 ]
  • [ 81416-05-9 ]
  • 7
  • [ 13161-30-3 ]
  • [ 74405-14-4 ]
  • [ 81416-08-2 ]
  • 8
  • [ 13161-30-3 ]
  • [ 74405-12-2 ]
  • [ 81416-06-0 ]
  • 9
  • [ 74405-16-6 ]
  • [ 13161-30-3 ]
  • [ 65-45-2 ]
  • 10
  • [ 65332-95-8 ]
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  • [ 80738-10-9 ]
  • 11
  • [ 65332-95-8 ]
  • [ 513-81-5 ]
  • [ 13161-30-3 ]
  • [ 80738-10-9 ]
  • 16
  • [ 13161-30-3 ]
  • [ 174265-77-1 ]
  • (2R,3R)-3-Cyclopentylmethyl-4-oxo-4-piperidin-1-yl-2-(3,4,4-trimethyl-2,5-dioxo-imidazolidin-1-ylmethyl)-butyric acid; compound with pyridin-2-ol [ No CAS ]
  • 17
  • [ 13161-30-3 ]
  • [ 219614-25-2 ]
  • (2S,3R)-2-Isobutyl-3-((E)-3-phenyl-allyl)-succinic acid 4-tert-butyl ester; compound with pyridin-2-ol [ No CAS ]
  • 18
  • [ 13161-30-3 ]
  • [ 380302-94-3 ]
  • C22H34N2O5S*C5H5NO [ No CAS ]
  • 19
  • [ 13161-30-3 ]
  • 5-aminopentanal hydrochloride [ No CAS ]
  • 20
  • [ 13161-30-3 ]
  • [ 13139-15-6 ]
  • 2-<i>tert</i>-butoxycarbonylamino-4-methyl-pentanoic acid 2-oxo-2<i>H</i>-pyridin-1-yl ester [ No CAS ]
  • 21
  • [ 13161-30-3 ]
  • [ 25952-53-8 ]
  • 1-(3-dimethylamino-propyl)-3-ethyl-2-(2-oxo-2<i>H</i>-pyridin-1-yl)-isourea; hydrochloride [ No CAS ]
  • 22
  • [ 13161-30-3 ]
  • [ 116-16-5 ]
  • 1,1'-carbonyldioxydi[2(1H)-pyridone] [ No CAS ]
  • 23
  • [ 13161-30-3 ]
  • [ 51439-58-8 ]
  • [ 390755-07-4 ]
  • 24
  • [ 13161-30-3 ]
  • [ 723-62-6 ]
  • 1-(9-anthroyloxy)-2-pyridone [ No CAS ]
  • 25
  • [ 13161-30-3 ]
  • [ 607-42-1 ]
  • [ 487010-81-1 ]
  • 26
  • [ 13161-30-3 ]
  • [ 613-08-1 ]
  • [ 487010-91-3 ]
  • 27
  • [ 13161-30-3 ]
  • [ 58601-32-4 ]
  • [ 390755-11-0 ]
  • 28
  • [ 13161-30-3 ]
  • [ 51439-63-5 ]
  • [ 390755-09-6 ]
  • 29
  • [ 13161-30-3 ]
  • [ 58778-69-1 ]
  • [ 390755-10-9 ]
  • 30
  • [ 13161-30-3 ]
  • [ 70696-57-0 ]
  • [ 390755-08-5 ]
  • 31
  • [ 13161-30-3 ]
  • [ 879-18-5 ]
  • [ 390755-05-2 ]
  • 32
  • [ 13161-30-3 ]
  • [ 2243-83-6 ]
  • [ 390755-06-3 ]
  • 33
  • [ 13161-30-3 ]
  • [ 188975-33-9 ]
  • 3-[4-(3,6-dihydro-2<i>H</i>-pyran-4-yl)-3-fluoro-phenyl]-5-(1-oxy-pyridin-2-yloxymethyl)-oxazolidin-2-one [ No CAS ]
  • 34
  • [ 1628-89-3 ]
  • [ 13161-30-3 ]
  • 36
  • [ 109-09-1 ]
  • [ 13161-30-3 ]
  • 37
  • [ 2402-95-1 ]
  • [ 13161-30-3 ]
  • 38
  • [ 13161-30-3 ]
  • [ 900139-09-5 ]
  • [ 14396-03-3 ]
YieldReaction ConditionsOperation in experiment
68% With nitric acid; In acetic acid; Example 22 5-amino-2-hydroxypyridine-N-oxide was prepared as follows. One hundred grams of the 2-hydroxypyridine-N-oxide were dissolved in 500 mL of acetic acid with warming. The solution was cooled to approximately 10 C., and 65 mL of 70% nitric acid was added slowly to keep the temperature below 35 C. The mixture was stirred for an additional 30 min and the product was collected by filtration. After washing with acetic acid, and then water, the product was dried under vacuum at 70 C., to give 5-nitro-2-hydroxypyridine-N-oxide (95.9 g, 68% yield). 1H-NMR data for this compound (dmso) was as follows: delta 9.2 (d, 1H), 8.1 (dd, 1H), 6.6 (d, 1H).
  • 39
  • [ 13161-30-3 ]
  • 5-amino-2-hydroxypyridine-N-oxide, sodium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
With nitric acid; In acetic acid; Example 70 First Colorant The sodium salt of 5-amino-2-hydroxypyridine-N-oxide was prepared as follows. <strong>[13161-30-3]2-Hydroxypyridine-N-oxide</strong> (100 g) was dissolved in 500 mL of acetic acid with warming. The solution was cooled to approximately 10 C., and 65 mL of 70% nitric acid was added slowly to keep the temperature below 35 C. The mixture was stirred for an additional 30 min and the product (5-nitro-2-hydroxypyridine-N-oxide) was collected by filtration. After washing with acetic acid, and then water, the product was dried under vacuum at 70 C. 1H-NMR data for this compound (dmso) was as follows: 9.2 (d, 1H), 8.1 (dd, 1H), 6.6 (d, 1H).
  • 40
  • [ 13161-30-3 ]
  • thorium(IV) nitrate pentahydrate [ No CAS ]
  • Th(4+)*4C5H4NO2(1-)*2H2O=Th(C5H4NO2)4*2H2O [ No CAS ]
  • 41
  • [ 13161-30-3 ]
  • uranyl nirate hexahydrate [ No CAS ]
  • UO2(C5H4NO2)2*H2O [ No CAS ]
  • aquabis(1,2-dioxo-pyridinato)dioxouranium(VI) monohydrate [ No CAS ]
  • 42
  • [ 13161-30-3 ]
  • [ 14637-34-4 ]
  • 2,2-diphenyl-1,3-dioxa-3a-azonia-2-borataindan [ No CAS ]
  • 43
  • [ 13161-30-3 ]
  • thorium(IV) nitrate pentahydrate [ No CAS ]
  • Th(C5H4NOO)4(CH3OH) [ No CAS ]
  • Th(4+)*3OC5H4NO(1-)*OH(1-)=Th(OC5H4NO)3OH [ No CAS ]
  • 44
  • zinc(II) sulfate heptahydrate [ No CAS ]
  • [ 13161-30-3 ]
  • di(2-hydroxypyridine-N-oxidato)zinc(II) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With barium hydroxide octahydrate; In water; at 20℃; An aqueous solution of ZnSO4?7H2O (431 mg, 1.5 mM) was addedto an aqueous solution of 2-HPO (333 mg, 3.0 mM) and Ba(OH)2?8H2O(475 mg, 1.5 mM), and the solution was stirred at room temperature.After filtering out precipitated BaSO4 and removing the solvent, the residuewas washed with water.
  • 45
  • [ 13161-30-3 ]
  • nickel(II) chloride hexahydrate [ No CAS ]
  • Ni(2+)*C5H4NO2(1-)*Cl(1-)*1.5H2O=Ni(C5H4NO2)Cl*1.5H2O [ No CAS ]
  • 46
  • [ 13161-30-3 ]
  • copper(II) choride dihydrate [ No CAS ]
  • Cu(2+)*C5H4NO2(1-)*Cl(1-)=Cu(C5H4NO2)Cl [ No CAS ]
  • 47
  • [ 13161-30-3 ]
  • copper(II) nitrate trihydrate [ No CAS ]
  • Cu(2+)*C5H4NO2(1-)*NO3(1-)*H2O=Cu(C5H4NO2)NO3*H2O [ No CAS ]
  • 48
  • [ 13161-30-3 ]
  • [ 7705-08-0 ]
  • Fe(C5H4NO2)3*H2O [ No CAS ]
  • 49
  • [ 13161-30-3 ]
  • [ 6046-93-1 ]
  • 1-hydroxy-1<i>H</i>-pyridin-2-one; copper (II)-salt [ No CAS ]
  • 50
  • [ 13161-30-3 ]
  • [ 7789-45-9 ]
  • Cu(2+)*C5H4NO2(1-)*Br(1-)*0.5CH3OH=Cu(C5H4NO2)Br*0.5CH3OH [ No CAS ]
  • 51
  • potassium hydridotris(3-phenylpyrazol-1-yl)borate [ No CAS ]
  • [ 13161-30-3 ]
  • copper(II) choride dihydrate [ No CAS ]
  • [Cu2(μ-Cl)2(2-hydroxypyridine-N-oxide(-H))2(3-phenylpyrazolyl)2] [ No CAS ]
  • 52
  • [ 13161-30-3 ]
  • [Cu2(2,6-bis[bis(2-pyridylmethyl)aminomethyl]-4-methylphenolato)(hydroxo)](ClO4)2 [ No CAS ]
  • (Cu2(CH3C6H2O(CH2N(CH2C5H4N)2)2)(O2NC5H4)(H2O)2)(2+)*2ClO4(1-)=(Cu2(CH3C6H2O(CH2N(CH2C5H4N)2)2)(O2NC5H4)(H2O)2)(ClO4)2 [ No CAS ]
  • 53
  • [ 13161-30-3 ]
  • [Cu2(N2,N2,N2',N2'-tetrakis[2-(2-pyridyl)ethyl][1-1'-biphenyl]-2,2'-dimethylamine)(H2O)2(CF3SO3)2](CF3SO3)2 [ No CAS ]
  • (Cu2(C6H4CH2N(CH2CH2C5H4N)2)2(O2NC5H4)2)(2+)*2CF3SO3(1-)=(Cu2(C6H4CH2N(CH2CH2C5H4N)2)2(O2NC5H4)2)(CF3SO3)2 [ No CAS ]
  • 54
  • [ 13161-30-3 ]
  • ammonium vanadate(V) [ No CAS ]
  • [ 7732-18-5 ]
  • NH4[VO2(2-hydroxypyridine-N-oxide(-1H))2]*3H2O [ No CAS ]
  • 55
  • [ 13161-30-3 ]
  • [ 100-39-0 ]
  • [ 5280-02-4 ]
YieldReaction ConditionsOperation in experiment
84% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16.0h; <strong>[13161-30-3]2-hydroxypyridine-1-oxide</strong> (0.50 g, 4.5 mmol) was reacted with benzyl bromide (0.64 mL, 5.4 mmol) in DMF (10 mL) in the presence of K2CO3 (1.8 g, 13.5 mmol) at 80 C. for 16 h. After cooling to room temperature, the solvent was removed by rotary evaporation. The crude product was redissolved in DCM and washed twice with water. The organic layer was then dried over MgSO4, filtered, and concentrated resulting in 7 as a white solid in 84% yield (0.78 g, 3.8 mmol) without the need for further purification. 1H NMR (400 MHz, CDCl3) delta=7.41-7.36 (m, 5H), 7.25 (td, J1=6.8 Hz, J2=2.0 Hz, 1H), 7.10 (dd, J1=7.2 Hz, J2=2.0 Hz, 1H), 6.68 (dd, J1=9.2 Hz, J2=1.6 Hz, 1H), 5.91 (td, J1=6.8 Hz, J2=1.6 Hz, 1H), 5.28 (s, 2H). 13C NMR (100 MHz, CDCl3) delta=159.2, 138.9, 136.9, 133.9, 130.3, 129.6, 128.9, 122.9, 104.7, 78.6. ESI-MS(+): m/z 202.19 [M+H]+, 224.29 [M+Na]+.
  • 56
  • [ 13161-30-3 ]
  • [ 10130-89-9 ]
  • [ 1259401-64-3 ]
  • 57
  • [ 13161-30-3 ]
  • [ 98-74-8 ]
  • [ 1259401-62-1 ]
  • 58
  • [ 13161-30-3 ]
  • [ 98-59-9 ]
  • [ 5087-06-9 ]
  • 59
  • [ 13161-30-3 ]
  • [ 1656-44-6 ]
  • [ 1259401-63-2 ]
  • 60
  • [ 1259401-62-1 ]
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  • 61
  • [ 1259401-63-2 ]
  • [ 13161-30-3 ]
  • 62
  • [ 1259401-64-3 ]
  • [ 13161-30-3 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide; at 20℃;pH 7.5;HEPES buffer;Kinetics; Building on the strategy of glycosidic protecting groups, we first focused our attention on the development of glucose-protected non-hydroxamate zinc-binding groups (ZBGs)32,33 that can be activated by enzymatic cleavage of the protecting group with beta-glucosidase to release the ZBG and glucose (FIG. 1). The synthesis of the protected ZBGs (2, 4, and 6) was accomplished following a literature procedure used by Orvig and coworkers for enzyme-activated metal-binding chelators (Scheme 1 following).9,34. The ZBG was protected with acetobromo-alpha-D-glucose in a 1:1 solution of 1.0 M NaOH and CH2Cl2 in the presence of (nBu)4NBr. The desired products were obtained by cleavage of the glucose acetate groups using NaOMe in MeOH. The conditions for Scheme 1 are the following: (i) acetobromo-alpha-D-glucose, tetrabutylammonium bromide, CH2Cl2:1.0 M NaOH (1:1), 3 h, room temp; (ii) NaOMe, MeOH, 2-3 h, room temp; (iii) P4S10, HMDO, benzene, 100 C., 45 min.To evaluate the ability of these compounds to be enzymatically activated, cleavage of the protected ZBGs in the presence of beta-glucosidase (from almond extract, Fluka) was followed using electronic spectroscopy. To a solution of the protected ZBG in HEPES buffer was added beta-glucosidase and the change in absorbance was monitored over time. As can be seen in FIG. 2 for compound 2, the absorbance over time shows a decrease at 292 nm while a band at 312 nm emerges, indicative of the deprotected ZBG 1-hydroxy-2-pyridin-2(1H)-one (1). Similar spectra were observed for the hydroxypyrone derivatives 4 and 6 (FIGS. 3-4). In addition, cleavage of the protected ZBGs was confirmed by HPLC analysis (FIGS. 5-7). These studies demonstrate that in aqueous buffer at room temperature, the glucose-protected ZBGs can be readily activated in the presence of beta-glucosidase providing compelling evidence that hydroxypyridinone and hydroxypyrone ZBGs are well suited for the development of enzyme-activated MMP proinhibitors.Having demonstrated the use of glucose as an effective protecting group for the aforementioned ZBGs, we aimed to incorporate a glucose protecting group into a full-length MMPi (matrix metalloprotease inhibitor) to develop an MMP proinhibitor. We selected the full-length inhibitor 1,2-HOPO-2 (7), a potent non-hydroxamate inhibitor of MMPs that uses a 1-hydroxy-2-pyridin-2(1H)-one (1) ZBG.35 Synthesis of the MMP proinhibitor was achieved by addition of acetobromo-alpha-D-glucose and Cs2CO3 to 7 in DMF at room temperature to give 8a in high yields (>80%, Scheme 2). These reaction conditions were a vast improvement in yield over the aqueous reaction conditions used to protect the ZBGs. Surprisingly, these high-yield reaction conditions did not produce the desired products with the ZBGs (1, 3, and 5). The final proinhibitor (8) was obtained by deprotection of the glucose acetate groups with NaOMe in MeOH at 0 C. for one hour. The MMP proinhibitor 8 was first evaluated for activation by beta-glucosidase using electronic spectroscopy and HPLC analysis (FIGS. 8-9). Results from these studies indicate that while cleavage of 8 to produce the active MMPi 1,2-HOPO-2 (7) goes to completion, the kinetics of the reaction are noticeably slower than that observed for the protected ZBGs. Complete conversion of 8 to 7 required 4 h at 37 C.; a Km value of 210 muM was determined (FIG. 10). Notably, compound 8 was not cleaved under acidic conditions (0.1 M HCl) over 24 h (FIG. 11). Overall, this is the first example of a glucosidase proinhibitor that can be enzymatically cleaved to yield the active MMPi.The ability of the protected compounds to inhibit MMP-9 (gelatinase-B) in the presence of beta-glucosidase was evaluated using a fluorescence-based assay.36. Compounds 1-8 were evaluated at a concentration close to their reported IC50 values in the presence and absence of beta-glucosidase (FIG. 12). The percent inhibition of MMP-9 with the ZBGs (1, 3, and 5) is close to 50% when tested with and without beta-glucosidase indicating that the presence of low concentrations of beta-glucosidase in the assay has little effect on MMP inhibition. The protected ZBGs (2, 4, and 6) show attenuated inhibition when evaluated without the activating enzyme and complete restoration of inhibition when exposed to beta-glucosidase. Compounds 2, 4, and 6 do show some inhibition of MMP-9 which is likely due to non-specific binding at the high concentrations of the ZBGs (0.125-4 mM) used in these experiments.In the absence of beta-glucosidase, the complete MMPi 8 (16 muM) displays very little inhibition of MMP-9, but upon activation, MMP-9 activity is inhibited by 73%, which is essentially identical to an authentic sample of inhibitor 7. Even greater potency was observed against MMP-8, where MMPi 8 could be activated with beta-glucosidase to obtain 33% inhibition at only 150 nM (FIG. 11), representing a >1000-fold increase in activity upon enzymatic activation. The factor of 1000 difference in the quotient IC5...
  • 63
  • [ 13161-30-3 ]
  • [ 98-09-9 ]
  • [ 5033-19-2 ]
YieldReaction ConditionsOperation in experiment
77% With pyridine; at 20℃;Cooling with ice; Inert atmosphere; General Procedure for the Synthesis of Sulfonate Ester ZBGs. The ZBG compound was dissolved in pyridine on ice. To this was added the desired sulfonyl chloride. The reaction flask was removed from the ice bath and left stirring overnight under nitrogen while warming to room temperature. The pyridine was removed by rotary evaporation and the resulting oil was re-dissolved in dichloromethane and washed with 1 M HCl (30 mL), water, and brine. The organic layer was dried over MgSO4, filtered, and then concentrated via rotary evaporation. The product was purified on a silica gel column eluting with 1% MeOH in CH2Cl2 unless otherwise noted.2-Oxopyridin-1(2H)-yl benzenesulfonate(PZBG-1a). 2-Hydroxypyridine-1-oxide (1.0 g, 9.1 mmol) was reacted with benzenesulfonyl chloride (1.27 mL, 10.0 mmol) in 75 mL of pyridine to afford PZBG-1a in 77% yield (1.75 g, 7.0 mmol). 1H NMR (500 MHz, CDCl3) delta=8.02 (d, J=8.0 Hz, 2H), 7.75 (t, J=8.0 Hz, 1H), 7.59 (m, 3H), 7.28 (dt, J1=6.9 Hz, J2=2.3 Hz, 1H), 6.52 (d, J=9.8 Hz, 1H), 6.15 (t, J=7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3) delta=157.0, 139.7, 137.1, 136.0, 133.8, 130.0, 129.5, 123.4, 105.4. ESI-MS(+): m/z 252.01 [M+H]+, 273.95 [M+Na]+. Anal. calcd for C11H9NO4S: C, 52.58; H, 3.61; N, 5.57. Found: C, 52.21; H, 3.99; N, 5.44.
  • 64
  • [ 5033-19-2 ]
  • [ 13161-30-3 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide; at 20℃;pH 7.5;HEPES buffer;Kinetics; Building on the strategy of glycosidic protecting groups, we first focused our attention on the development of glucose-protected non-hydroxamate zinc-binding groups (ZBGs)32,33 that can be activated by enzymatic cleavage of the protecting group with beta-glucosidase to release the ZBG and glucose (FIG. 1). The synthesis of the protected ZBGs (2, 4, and 6) was accomplished following a literature procedure used by Orvig and coworkers for enzyme-activated metal-binding chelators (Scheme 1 following).9,34. The ZBG was protected with acetobromo-alpha-D-glucose in a 1:1 solution of 1.0 M NaOH and CH2Cl2 in the presence of (nBu)4NBr. The desired products were obtained by cleavage of the glucose acetate groups using NaOMe in MeOH. The conditions for Scheme 1 are the following: (i) acetobromo-alpha-D-glucose, tetrabutylammonium bromide, CH2Cl2:1.0 M NaOH (1:1), 3 h, room temp; (ii) NaOMe, MeOH, 2-3 h, room temp; (iii) P4S10, HMDO, benzene, 100 C., 45 min.To evaluate the ability of these compounds to be enzymatically activated, cleavage of the protected ZBGs in the presence of beta-glucosidase (from almond extract, Fluka) was followed using electronic spectroscopy. To a solution of the protected ZBG in HEPES buffer was added beta-glucosidase and the change in absorbance was monitored over time. As can be seen in FIG. 2 for compound 2, the absorbance over time shows a decrease at 292 nm while a band at 312 nm emerges, indicative of the deprotected ZBG 1-hydroxy-2-pyridin-2(1H)-one (1). Similar spectra were observed for the hydroxypyrone derivatives 4 and 6 (FIGS. 3-4). In addition, cleavage of the protected ZBGs was confirmed by HPLC analysis (FIGS. 5-7). These studies demonstrate that in aqueous buffer at room temperature, the glucose-protected ZBGs can be readily activated in the presence of beta-glucosidase providing compelling evidence that hydroxypyridinone and hydroxypyrone ZBGs are well suited for the development of enzyme-activated MMP proinhibitors.Having demonstrated the use of glucose as an effective protecting group for the aforementioned ZBGs, we aimed to incorporate a glucose protecting group into a full-length MMPi (matrix metalloprotease inhibitor) to develop an MMP proinhibitor. We selected the full-length inhibitor 1,2-HOPO-2 (7), a potent non-hydroxamate inhibitor of MMPs that uses a 1-hydroxy-2-pyridin-2(1H)-one (1) ZBG.35 Synthesis of the MMP proinhibitor was achieved by addition of acetobromo-alpha-D-glucose and Cs2CO3 to 7 in DMF at room temperature to give 8a in high yields (>80%, Scheme 2). These reaction conditions were a vast improvement in yield over the aqueous reaction conditions used to protect the ZBGs. Surprisingly, these high-yield reaction conditions did not produce the desired products with the ZBGs (1, 3, and 5). The final proinhibitor (8) was obtained by deprotection of the glucose acetate groups with NaOMe in MeOH at 0 C. for one hour. The MMP proinhibitor 8 was first evaluated for activation by beta-glucosidase using electronic spectroscopy and HPLC analysis (FIGS. 8-9). Results from these studies indicate that while cleavage of 8 to produce the active MMPi 1,2-HOPO-2 (7) goes to completion, the kinetics of the reaction are noticeably slower than that observed for the protected ZBGs. Complete conversion of 8 to 7 required 4 h at 37 C.; a Km value of 210 muM was determined (FIG. 10). Notably, compound 8 was not cleaved under acidic conditions (0.1 M HCl) over 24 h (FIG. 11). Overall, this is the first example of a glucosidase proinhibitor that can be enzymatically cleaved to yield the active MMPi.The ability of the protected compounds to inhibit MMP-9 (gelatinase-B) in the presence of beta-glucosidase was evaluated using a fluorescence-based assay.36. Compounds 1-8 were evaluated at a concentration close to their reported IC50 values in the presence and absence of beta-glucosidase (FIG. 12). The percent inhibition of MMP-9 with the ZBGs (1, 3, and 5) is close to 50% when tested with and without beta-glucosidase indicating that the presence of low concentrations of beta-glucosidase in the assay has little effect on MMP inhibition. The protected ZBGs (2, 4, and 6) show attenuated inhibition when evaluated without the activating enzyme and complete restoration of inhibition when exposed to beta-glucosidase. Compounds 2, 4, and 6 do show some inhibition of MMP-9 which is likely due to non-specific binding at the high concentrations of the ZBGs (0.125-4 mM) used in these experiments.In the absence of beta-glucosidase, the complete MMPi 8 (16 muM) displays very little inhibition of MMP-9, but upon activation, MMP-9 activity is inhibited by 73%, which is essentially identical to an authentic sample of inhibitor 7. Even greater potency was observed against MMP-8, where MMPi 8 could be activated with beta-glucosidase to obtain 33% inhibition at only 150 nM (FIG. 11), representing a >1000-fold increase in activity upon enzymatic activation. The factor of 1000 difference in the quotient IC5...
  • 65
  • [ 5087-06-9 ]
  • [ 13161-30-3 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide; at 20℃;pH 7.5;HEPES buffer;Kinetics; Building on the strategy of glycosidic protecting groups, we first focused our attention on the development of glucose-protected non-hydroxamate zinc-binding groups (ZBGs)32,33 that can be activated by enzymatic cleavage of the protecting group with beta-glucosidase to release the ZBG and glucose (FIG. 1). The synthesis of the protected ZBGs (2, 4, and 6) was accomplished following a literature procedure used by Orvig and coworkers for enzyme-activated metal-binding chelators (Scheme 1 following).9,34. The ZBG was protected with acetobromo-alpha-D-glucose in a 1:1 solution of 1.0 M NaOH and CH2Cl2 in the presence of (nBu)4NBr. The desired products were obtained by cleavage of the glucose acetate groups using NaOMe in MeOH. The conditions for Scheme 1 are the following: (i) acetobromo-alpha-D-glucose, tetrabutylammonium bromide, CH2Cl2:1.0 M NaOH (1:1), 3 h, room temp; (ii) NaOMe, MeOH, 2-3 h, room temp; (iii) P4S10, HMDO, benzene, 100 C., 45 min.To evaluate the ability of these compounds to be enzymatically activated, cleavage of the protected ZBGs in the presence of beta-glucosidase (from almond extract, Fluka) was followed using electronic spectroscopy. To a solution of the protected ZBG in HEPES buffer was added beta-glucosidase and the change in absorbance was monitored over time. As can be seen in FIG. 2 for compound 2, the absorbance over time shows a decrease at 292 nm while a band at 312 nm emerges, indicative of the deprotected ZBG 1-hydroxy-2-pyridin-2(1H)-one (1). Similar spectra were observed for the hydroxypyrone derivatives 4 and 6 (FIGS. 3-4). In addition, cleavage of the protected ZBGs was confirmed by HPLC analysis (FIGS. 5-7). These studies demonstrate that in aqueous buffer at room temperature, the glucose-protected ZBGs can be readily activated in the presence of beta-glucosidase providing compelling evidence that hydroxypyridinone and hydroxypyrone ZBGs are well suited for the development of enzyme-activated MMP proinhibitors.Having demonstrated the use of glucose as an effective protecting group for the aforementioned ZBGs, we aimed to incorporate a glucose protecting group into a full-length MMPi (matrix metalloprotease inhibitor) to develop an MMP proinhibitor. We selected the full-length inhibitor 1,2-HOPO-2 (7), a potent non-hydroxamate inhibitor of MMPs that uses a 1-hydroxy-2-pyridin-2(1H)-one (1) ZBG.35 Synthesis of the MMP proinhibitor was achieved by addition of acetobromo-alpha-D-glucose and Cs2CO3 to 7 in DMF at room temperature to give 8a in high yields (>80%, Scheme 2). These reaction conditions were a vast improvement in yield over the aqueous reaction conditions used to protect the ZBGs. Surprisingly, these high-yield reaction conditions did not produce the desired products with the ZBGs (1, 3, and 5). The final proinhibitor (8) was obtained by deprotection of the glucose acetate groups with NaOMe in MeOH at 0 C. for one hour. The MMP proinhibitor 8 was first evaluated for activation by beta-glucosidase using electronic spectroscopy and HPLC analysis (FIGS. 8-9). Results from these studies indicate that while cleavage of 8 to produce the active MMPi 1,2-HOPO-2 (7) goes to completion, the kinetics of the reaction are noticeably slower than that observed for the protected ZBGs. Complete conversion of 8 to 7 required 4 h at 37 C.; a Km value of 210 muM was determined (FIG. 10). Notably, compound 8 was not cleaved under acidic conditions (0.1 M HCl) over 24 h (FIG. 11). Overall, this is the first example of a glucosidase proinhibitor that can be enzymatically cleaved to yield the active MMPi.The ability of the protected compounds to inhibit MMP-9 (gelatinase-B) in the presence of beta-glucosidase was evaluated using a fluorescence-based assay.36. Compounds 1-8 were evaluated at a concentration close to their reported IC50 values in the presence and absence of beta-glucosidase (FIG. 12). The percent inhibition of MMP-9 with the ZBGs (1, 3, and 5) is close to 50% when tested with and without beta-glucosidase indicating that the presence of low concentrations of beta-glucosidase in the assay has little effect on MMP inhibition. The protected ZBGs (2, 4, and 6) show attenuated inhibition when evaluated without the activating enzyme and complete restoration of inhibition when exposed to beta-glucosidase. Compounds 2, 4, and 6 do show some inhibition of MMP-9 which is likely due to non-specific binding at the high concentrations of the ZBGs (0.125-4 mM) used in these experiments.In the absence of beta-glucosidase, the complete MMPi 8 (16 muM) displays very little inhibition of MMP-9, but upon activation, MMP-9 activity is inhibited by 73%, which is essentially identical to an authentic sample of inhibitor 7. Even greater potency was observed against MMP-8, where MMPi 8 could be activated with beta-glucosidase to obtain 33% inhibition at only 150 nM (FIG. 11), representing a >1000-fold increase in activity upon enzymatic activation. The factor of 1000 difference in the quotient IC5...
  • 66
  • [ 13161-30-3 ]
  • [ 138500-85-3 ]
  • [ 1254765-78-0 ]
YieldReaction ConditionsOperation in experiment
87% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere; <strong>[13161-30-3]2-hydroxypyridine-1-oxide</strong> (0.04 g, 0.34 mmol) was dissolved in 5 mL of anhydrous DMF. To this was added K2CO3 (0.14 g, 1.02 mmol) and 4-bromomethylphenyl boronic acid pinacol ester (0.10 g, 0.34 mmol). The reaction was heated to 80 C. and allowed to stir under nitrogen overnight. After cooling to room temperature, the solvent was evaporated and the resulting residue was brought up in dichloromethane and washed twice with water. The organic layer was dried over MgSO4, filtered and concentrated for purification via silica gel chromatography eluting with 2% MeOH in DCM. The protected B19 was collected as an off-white solid in 87% yield (98 mg, 0.3 mmol). 1H NMR (400 MHz, CDCl3) delta=7.79 (d, J=8.0 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.24 (td, J=7.2 Hz, J2=2.0 Hz, 1H), 7.05 (dd, J=7.2 Hz, J2=2.0 Hz, 1H), 6.67 (dd, J=9.2 Hz, J2=1.2 Hz, 1H), 5.89 (td, J=6.8 Hz, J2=1.6 Hz, 1H), 5.29 (s, 2H), 1.35 (s, 12H). 13C NMR (100 MHz, CDCl3) delta=159.2, 138.9, 137.0, 136.8, 135.3, 129.5, 122.9, 104.7, 84.3, 78.4, 25.1. ESI-MS(+): m/z 328.18 [M+H]+. Anal. calcd. for C18H22BNO4. 0.4 CH3OH: C, 65.26; H, 6.94; N, 4.16. Found: C, 65.54; H, 7.20; N, 3.76.
  • 67
  • [ 1325206-84-5 ]
  • [ 13161-30-3 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide; at 20℃;pH 7.5;HEPES buffer;Kinetics; In the development of ROS-activated proMMPi, we employed a relatively underutilized self-immolative protecting group with several apparent advantages over previously described systems. The use of self-immolative linkers has become increasingly popular in drug development, molecular sensors, and polymeric delivery systems.1, 19-21 Linkers that undergo self-immolative elimination upon removal of the protecting group can release an active species through a 1,6-benzyl elimination (FIG. 19). This reaction is thermodynamically driven by the release of CO2 when a carbonate or carbamate ester linkage is employed.21-23 However, in the development of proMMPi, it was found that the use of an ether linkage between the activating group and the inhibitor was preferred over the more commonly used carbonate ester linkage (compare compound B1 vs. B2 in FIG. 19) due to better synthetic accessibility, superior hydrolytic stability, and comparably fast cleavage kinetics. Recently, this ether linkage was utilized in studies on ROS-sensitive luciferase probes24 and protease-sensitive fluorophores.22 Nonetheless, there are essentially no studies on the generality and utility of this promising linking strategy. This report investigates the scope of this ether-connected, self-immolative proinhibitor strategy with a variety of functional groups and MBGs.Here we further investigate the behavior of different activation strategies using related, but distinct self-immolative linkers for coupling to the MBGs. All of the strategies studied here use boronic ester protecting groups that can be selectively removed by H2O2. A series of methyl salicylate derivatives containing phenol, thiophenol, aniline, and benzylamine leaving groups were investigated using either an ether linkage, a carbonate/carbamate ester linker, or no linker to the boronic ester protecting group (FIG. 19 and FIG. 20). In addition, we looked at a variety of MBGs protected with a boronic ester self-immolative leaving group to expand our inventory of MBGs for use in novel metalloprotein prodrugs.Compounds B1-B3 were designed to release methyl salicylate in the presence of H2O2 using a self-immolative ether linkage (B1), a carbonate ester linkage (B2), or no self-immolative linker (B3) to directly compare three possible designs of a prodrug scaffold. The syntheses of these compounds are described in Example 3. Compounds B1-B3 were first examined for activation in the presence of H2O2 using UV-Vis spectroscopy. To a solution of the boronic ester derivative in HEPES buffer (50 mM, pH 7.5) was added H2O2 and the change in absorbance was monitored over time. As shown in FIG. 20 for compound B1, the absorbance over time shows an increase at 302 nm indicative of the emergence of methyl salicylate with a clear isobestic point at 293 nm. Similar results were obtained with compounds B2 and B3. While compounds B1 and B2 achieved >90% cleavage within 45 min using an 18-fold excess of H2O2 (FIG. 24-25), deprotection of compound B3 required a 180-fold excess of H2O2 to realize cleavage in a comparable time frame. Release of methyl salicylate for all three compounds was confirmed by HPLC (FIG. 26-27).The rates of conversion to methyl salicylate were determined by monitoring the change in absorbance under pseudo first-order reaction conditions with an excess of H2O2. The calculated rate constants are presented in Table 2. Consistent with earlier reports, the carbonate ester derivative B2 displayed the fastest rate of conversion, but B2 also underwent spontaneous hydrolytic cleavage in buffer, whereas compound B1 was stable in buffer over a 4 h period (data not shown). Introduction of the carbonate group into the self-immolative linker of B2 leads to hydrolytic instability facilitated by nucleophilic attack of water at the carbonyl position which is not possible in compound B1.25 Interestingly, while the hydrolytic stability of B3 was comparable to the ether linkage used in B1, the rate of conversion for B3 was about two orders of magnitude slower than either B1 or B2, suggesting that use of self-immolative linker facilitates conversion to the desired active compound. TABLE 2 Pseudo first-order rate constants calculated with an excess of H2O2. Compoundk (M-1s-1) B1 1.12 +/- 0.04 B2 2.7 +/- 0.1 B3 0.031 +/- 0.002 B10 3.1 +/- 0.5 B11 5.9 +/- 0.2 B12 3.5 +/- 0.3 B13 2.9 +/- 0.1 B14 4.1 +/- 0.2 Based on the behavior of compounds B1-B3, the most promising linking strategy is the benzyl ether linkage seen in compound B1. The benzyl ether linkage shows excellent stability in buffer while maintaining rapid cleavage kinetics upon activation. Therefore, we investigated the use of this motif with other leaving groups. Compounds B4-B7 were synthesized to study the effects of using sulfur (B4), aniline (B5-B6), or benzyl amine (B7) leaving groups. Evaluation with UV-Vis absorption spectroscopy of B4-B7 in the presence of H2O2 showed no cleavage of the protecting group (FIG. 29-32). Further evaluation w...
  • 68
  • [ 1254765-78-0 ]
  • [ 13161-30-3 ]
YieldReaction ConditionsOperation in experiment
With dihydrogen peroxide; at 20℃;pH 7.5;HEPES buffer;Kinetics; A promising strategy in MMPi is through the development of MMP prodrugs or ?proinhibitors? that offer the ability to selectively control inhibitory activity. Metalloenzyme inhibitors such as MMPi are particularly suitable to the proinhibitor approach because such compounds generally contain a metal-binding group that can be blocked, which strongly attenuates their inhibitory activity. In the presence of the appropriate stimuli, the protecting group can be removed from the metal-binding group to release the MMPi at the site of activation, and thereby avoiding systemic inhibition of MMPs (which are necessary for normal physiological processes).[8,9] However, metalloenzyme proinhibitors have not been widely investigated, especially in the case of MMP proinhibitors. MMP proinhibitors are shown to be activated by H2O2 for use as protective therapeutics following ischemia and reperfusion injury during stroke (FIG. 43). As described below, the proinhibitors reported can protect the blood brain barrier (BBB) in two ways, taking advantage of both the triggering mechanism and the resulting MMPi. First, the proinhibitors will consume damaging ROS (e.g. H2O2), which would otherwise directly attack the BBB and also activate pathogenic MMPs. Second, the resulting active MMPi serves to inhibit any remaining MMP activity that might damage the BBB. Thus, this unprecedented class of proinhibitors has a dual mode of action: reducing the amount of ROS available to activate MMPs, while also generating an active MMPi.Two MMPi, the pyridinone-based molecule 1,2-HOPO-2 and the pyrone-based molecule PY-2, were selected for this study. Both compounds are potent, semi-selective MMPi that have been previously described.[11] The hydroxyl group of the zinc-binding group (ZBG) of each inhibitor was protected with a self-immolative protecting group containing a boronic ester as the ROS-sensitive trigger (FIG. 44). In the presence of H2O2, the boronic ester is cleaved by nucleophilic attack of H2O2, facilitating a spontaneous reaction to release the active MMPi through a 1,6-benzyl elimination (FIG. 43). Boronic esters as H2O2-reactive protecting groups has been well documented in the literature for H2O2-activated fluorophores[12, 13] and in the generation of triggered Fe(III) and Cu(II) chelates.[14, 15] The ROS-triggered self-immolative protecting group can be attached to the MMPi by using either an ether (B19, B20) or carbonate ester (B21) linkage at the hydroxyl group of the ZBG (FIG. 44). To determine which linker strategy provided the best overall approach, both the cleavage kinetics and solution stability of protected B19, B20, B21 were examined. The ability of these compounds to be activated by H2O2 was evaluated by using electronic spectroscopy. A sample of each compound in HEPES buffer (50 mM, pH 7.5) was activated with an excess (18 equiv)[12-15] of H2O2 and the change in absorbance was monitored over time. In all cases, the spectra of the protected ZBG compounds decreased over time while the spectra of the free ZBG appeared, demonstrating the expected cleavage reaction. To confirm that the boronic ester moiety was necessary for H2O2 cleavage, the ZBGs were prepared with benzyl protecting groups without the boronic ester. For these compounds, no change in absorbance was observed over time in the presence of H2O2. Additionally, the selectivity of the boronic ester towards H2O2 was confirmed by examining cleavage in the presence of KO2 and catalase. As expected,[12, 20] the superoxide anion was unable to activate the protected ZBGs.The rates of conversion of compounds B19-B21 their respective activated ZBGs were then determined by monitoring the change in absorption using pseudo-first order reaction conditions with an excess of H2O2. The calculated rate constants indicated that the carbonate ester linkage in compound B21 provided the fastest conversion with a rate constant of 6.7 M-1s-1, while rate constants of 4.0 M-1s-1 and 2.9 M-1s-1 were found for compounds B19 and B20, respectively. Upon examination of the solution stability of these compounds, B19 and B20 were stable in buffer over a 24 h time period, while B21 showed >50% hydrolysis. Although the use of carbonate and carbamate ester linkages in self-immolative systems are more common (due to the additional thermodynamic driving force from the release of CO2 in the cascade reaction).After establishing a strategy for the addition of H2O2 activated protecting groups to the appropriate ZBGs, the full-length inhibitors 1,2-HOPO-2 and PY-2 were protected with 4-bromomethylphenyl boronic acid pinacol ester in the presence of K2CO3 in DMF to yield compounds B17 and B18, respectively. Activation of B17 and B18 by H2O2 to release 1,2-HOPO-2 and PY-2 was confirmed by absorption spectroscopy. Similar spectra were obtained under the same reaction conditions as those used for compounds B19 and B20 indicating that the cleavage rates for the proinhibitors B17 and B18 would have comparable ...
  • 69
  • [ 13161-30-3 ]
  • cis-[VO(2-hydroxypyridine-N-oxide(-1H))2(1-methylimidazole)] [ No CAS ]
  • 70
  • [ 13161-30-3 ]
  • cis-[VO(2-hydroxypyridine-N-oxide(-1H))2(DMF)] [ No CAS ]
  • 71
  • [ 13161-30-3 ]
  • cis-[VO(2-hydroxypyridine-N-oxide(-1H))2(DMSO)] [ No CAS ]
  • 72
  • vanadyl sulfate trihydrate [ No CAS ]
  • [ 13161-30-3 ]
  • [VO(2-hydroxypyridine-N-oxide(-1H))2] [ No CAS ]
  • 73
  • vanadyl sulfate trihydrate [ No CAS ]
  • [ 13161-30-3 ]
  • [V(2-hydroxypyridine-N-oxide(-1H))3](3+) [ No CAS ]
  • 74
  • [ 13161-30-3 ]
  • C35H38Cu2N6O2(2+)*2ClO4(1-) [ No CAS ]
  • C40H41Cu2N7O3(2+)*2ClO4(1-) [ No CAS ]
  • 75
  • [ 13161-30-3 ]
  • [ 14396-03-3 ]
YieldReaction ConditionsOperation in experiment
68% With nitric acid; acetic acid; In water; at 10 - 35℃; for 0.5h; 5-amino-2-hydroxypyridine-N-oxide was prepared as follows. One hundred grams of the 2-hydroxypyridine-N-oxide were dissolved in 500 mL of acetic acid with warming. The solution was cooled to approximately 10 C., and 65 mL of 70% nitric acid was added slowly to keep the temperature below 35 C. The mixture was stirred for an additional 30 min and the product was collected by filtration. After washing with acetic acid, and then water, the product was dried under vacuum at 70 C., to give 5-nitro-2-hydroxypyridine-N-oxide (95.9 g, 68% yield). 1HNMR data for this compound (dmso) was as follows: delta 9.2 (d, 1H), 8.1 (dd, 1H), 6.6 (d, 1H).; 5-nitro-2-hydroxypyridine-N-oxide (8.52 g) was dissolved in 151 g of a 0.34M NaOH solution and hydrogenated with 5% Pd/carbon (5.2 g) at about 45 psi for 75 minutes. The catalyst was removed by filtration to give an aqueous solution of the sodium salt of 5-amino-2-hydroxypyridine-N-oxide. 1HNMR data for this compound (dmso) was as follows: delta 7.3 (s, 1H), 6.4 (d, 1H), 6.0 (d, 1H). This material was used without further purification.
  • 76
  • [ 13161-30-3 ]
  • nickel(II) chloride hexahydrate [ No CAS ]
  • Ni(2+)*2C5H4NO2(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% In ethanol; at 20℃; for 72.0h;Heating; A solution of 0.24 g (1 mmol) of NiCl2.6H2O in 10 ml ofEtOH was slowly added to the mixture of 0.11 g (1 mmol)of HOPO in 10 ml of EtOH under rigorous stirring at roomtemperature. The suspension was stirred and slowly heatedfor 10 min. The reaction mixture was cooled and left atroom temperature for 72 h. The resulting yellow crystalswere then filtered off, washed several times with EtOHfollowed by Et2O, recrystallized from H2O and finally airdried,yield is about 83 %.
  • 77
  • [ 13161-30-3 ]
  • [ 52462-29-0 ]
  • C15H18ClNO2Ru [ No CAS ]
  • 78
  • [ 13161-30-3 ]
  • [(9aneS3)Ru(dmso)3](PF6)2 [ No CAS ]
  • C13H22NO3RuS4(1+)*F6P(1-) [ No CAS ]
  • 79
  • zinc(II) sulfate heptahydrate [ No CAS ]
  • sodium azide [ No CAS ]
  • [ 13161-30-3 ]
  • C5H4NO2(1-)*N3(1-)*Zn(2+)*H2O [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% In water; at 20℃; A mixture of ZnSO4·7H2O (2.59g, 9mmol), 2-hydroxypyridine-N-oxide (0.33g, 3mmol) and NaN3 (1.17g, 18mmol) were dissolved in H2O (14mL) and the resulting solution was allowed to crystallize at room temperature. In the following day, the colorless crystals which separated were collected by filtration and dried in air (yield: 0.45g, 64%). Anal. Calc. for C5H6N4O3Zn (235.53g/mol): C, 25.5; H, 2.6; N, 23.8. Found: C, 25.3; H, 2.5; N, 23.7%. Selected IR bands (ATR-IR, cm-1): 3213 (s,br), 2563 (w), 2112 (vs), 2064 (vs), 1621 (s), 1549 (w), 1512 (vs), 1446 (m), 1363 (m), 1285(m), 1230 (w), 1180 (s), 1148 (w), 1109 (m), 924 (w), 884 (m), 846 (w), 783 (w), 741 (m), 690 (w), 609 (m), 545 (m), 448 (w).
  • 80
  • [ 13161-30-3 ]
  • gallium(III) nitrate hydrate [ No CAS ]
  • Ga(3+)*3C5H4NO2(1-) [ No CAS ]
  • 81
  • [ 13161-30-3 ]
  • [ 4834-98-4 ]
  • C22H28N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With triethylamine; In chloroform; at 0 - 20℃; for 1.0h; <strong>[13161-30-3]2-Hydroxypyridine N-oxide</strong> (11 g) was added to a solution of bis(acid chloride) (20) (12 g) in chloroform, and was then cooled to 0 C. Triethylamine (10 g) was further added dropwise at the same temperature as above, and the resulting mixture was then stirred at room temperature for 1 hour. The reaction was quenched with an aqueous solution of saturated sodium hydrogen carbonate, and extraction with chloroform, washing with brine, drying with Na2SO4, and distillation off of the solvent under reduced pressure were performed. The resulting crude product was recrystallized with ethyl acetate/hexane to obtain a compound represented by the above formula (4) (6.6 g, yield: 37%) as a white solid. 1H-NMR (CDCl3, 400 MHz) delta ppm: 1.29-1.45 (12H, m), 1.57-1.63 (4H, m), 2.65 (4H, t, J=7.6 Hz), 6.18 (2H, ddd, J=6.8 Hz, 6.8 Hz, 1.7 Hz), 6.71-6.74 (2H, m), 7.31-7.39 (4H, m)
  • 82
  • [ 13161-30-3 ]
  • Mo7O24(6-)*6H(1+)*6H3N*2H2O [ No CAS ]
  • C10H8MoN2O6 [ No CAS ]
  • 83
  • [ 13161-30-3 ]
  • [ 3068-32-4 ]
  • oxypyrion-β-D-galactopyranoside tetraacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% With tetrabutylammomium bromide; sodium hydroxide; In dichloromethane; water; for 6.0h;Reflux; To a solution of oxypyrion (47 g, 423 mmol), tetra-butylammonium bromide (38 g, 1 18 mmol) and 2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl bromide (90 g, 219 mmol) in 1 .25 I dichloromethane were added water (1 .25 I) and 10 N sodium hydroxide solution (100 ml) and the reaction mixture was vigorously stirred for 6 hours at reflux temperature. pH was kept constant at 12 to 13 by adding 10 N sodium hydroxide solution. The reaction mixture was cooled to room temperature and diluted with dichloromethane (150ml). The organic layer was separated, washed with water (200 ml) and concentrated in vacuum. Purification via flash chromatography [toluene/ ethyl acetate (1 :1 )] afforded 4b (28 g, 29 %, 63.4 mmol) as a white foam,1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1 .99 (s, 3 H) 2.01 (s, 3 H) 2.18 (s, 3 H) 2.22 (s, 3 H) 3.89 (t, J=6.6 Hz, 1 H) 4.07 (dd, J=1 1 .3, 6.6 Hz, 1 H) 4.22 (dd, J=1 1 .3, 6.7 Hz, 1 H) 5.1 1 (dd, J=10.4, 3.4 Hz, 1 H) 5.19 (d, J=8.2 Hz, 1 H) 5.37 (dd, J=8.4, 10.4 Hz, 1 H) 5.43 (d, J=3.2 Hz, 1 H) 6.05 (t, J=6.8 Hz, 1 H) 6.63 (d, J=9.3 Hz, 1 H) 7.27 - 7.33 (m, 1 H) 7.56 (d, J=7.0 Hz, 1 H)
  • 84
  • [ 13161-30-3 ]
  • [ 3068-32-4 ]
  • oxypyrion-beta-D-galactopyranoside [ No CAS ]
  • 85
  • [ 13161-30-3 ]
  • [ 116965-29-8 ]
  • C13H12N2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
66.6% With triethylamine; In acetonitrile; at 20℃; for 2.0h; S2, 2-hydroxypyridine-N-oxide (24.4 g, 0.22 mol), triethylamine (30.66 g, 0.3 mmol) was dissolved in 160 mL of acetonitrile solution, and the crude maleimidobutyryl chloride in acetonitrile (100 mL) solution was added dropwise thereto. The temperature control of ice water cooling is less than 20 C, and the system is stirred at room temperature for 2 h. The reaction solution is concentrated to remove acetonitrile, dissolved in 200 mL of dichloromethane, and the organic phase is washed with 100 mL of water to remove triethylamine hydrochloride.1 mol/L hydrochloric acid 50 mL was washed to remove excess triethylamine, and 100 mL of saturated brine was washed, dried over anhydrous sodium sulfate, and concentrated to give a white solid, 45 g, and recrystallized from ethyl acetate and petroleum ether.Obtaining 36.8 g of a white solid of the compound N-maleimidobutyric acid pyridine-N-oxide ester in a yield of 66.6%.
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