Chan–Lam–Evans Coupling of Cbz‐Protected Histidines
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Abstract Direct functionalization of protected histidines with arylboronic acids is described under Chan–Lam–Evans conditions to give the corresponding N (τ)‐arylhistidines in moderate to good yields (12 examples, up to 83 % yield) under mild conditions.Keywords:
Evans Blue
Surface Modification
Abstract The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C−H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal‐catalyzed C−H functionalization of a “programmed” 4‐hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity‐oriented functionalization, of which four were targeted. The C‐2 and C‐8 decorations were directed by an N ‐oxide, before taking benefit of an O ‐carbamoyl protection at C‐4 to perform a Fries rearrangement and install a carboxamide at C‐3. This also released the carbonyl group of 4‐quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C−H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.
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Objective:To search new markers that can quantify sensitively the degree of blood-brain barrier injury and to make better the method that quantifies the Evans Blue in cerebral tissue. [WT5HZ]Methods: Cerebral ischemia and reperfusion model that can result in damaging the blood-brain barrier (BBB) was induced in SD rat. Immunohistochemistry staining and semi-quantitation analysis were performed to detect the cerebral ZO-1. Life vital signs, the Evans Blue that permeated BBB was quantified by the two new methods. [WT5HZ] Results:① ZO-1 expression decreased quickly on the injured side of cerebrum, and it reached the lowest point at 24 h post-ischemia and reperfusion. Then it increased slowly, and went back to normal till Day 7. ② Evans Blue that permeated blood-brain barrier reached the highest at 24 h post-reperfusion with the two new methods, their change trends were same to the change of ZO-1 depression in rat brain. [WT5HZ]Conclusion:The permeability of BBB to Evans Blue and the changes of ZO-1 depression in brain are the markers of degree of BBB injury. The method, quantifying the permeability of BBB to Evans Blue by fluorescence microscope, can reflect simply and sensitively the degree of BBB injury. [WT5HZ]
Evans Blue
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Evans Blue
Extravasation
Convulsion
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Evans Blue
Vascular permeability
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The Programmed Multiple C–H Bond Functionalization of 4-Hydroxyquinoline and Its Medicinal Potential
The introduction of substituents on bare heterocyclic scaffolds can selectively be achieved by directed C–H functionalization. However, such methods have only occasionally been used, in an iterative manner, to decorate various positions of a medicinal scaffold to build chemical libraries. We herein report the multiple, site selective, metal-catalyzed C–H functionalization of a "programmed" 4-hydroxyquinoline. This medicinally privileged template indeed possesses multiple reactive sites for diversity-oriented functionalization, of which four were targeted. The C-2 and C-8 decorations were directed by an N -oxide, before taking benefit of an O -carbamoyl protection at C-4 to perform a Fries rearrangement and install a carboxamide at C-3. This also released the carbonyl group of 4-quinolones, the ultimate directing group to functionalize position 5. Our study highlights the power of multiple C–H functionalization to generate diversity in a biologically relevant library, after showing its strong antimalarial potential.
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Evans Blue
Extravasation
Vascular permeability
Serum Albumin
Paracellular transport
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To investigate the impact of high-dose microbubbles induced by high mechanical index myocardial contrast echocardiography (MCE) on vascular permeability and its recovery time in rats.Thirty male Wistar rats were randomized into 4 MCE groups (groups A-D) and a control group. In the MCE groups, Evans blue was injected at 10 s before MCE (A), immediately after the end of MCE (B), and at 5 min (C) and 20 min after the end of MCE (D). In the control group, the microbubbles and Evans blue were injected at the end of a 5-min ultrasound exposure. All the rats were sacrificed 5 min after Evans blue injection, and the content of Evans blue in the myocardium and the percentage of Evans blue leakage area were determined.The percentage of Evans blue leakage area in groups A, B and C were significantly higher than that in the control group (P<0.05), while the percentage was similar between group D and the control group (P>0.05). Evans blue contents in groups A and B were significantly higher than that in the control group (P<0.05), but groups C and D showed comparable contents with the control group E (P>0.05). No significant changes of the heart rates and premature beat number were observed during and after MCE in these groups (P>0.05).High mechanical index MCE and a high contrast dose may induce increased microvascular leakage in rats, and the vascular permeability can recover in 20 min after MCE.
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Vascular permeability
Mechanical index
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Mongolian gerbils were used to evaluate brain edema during restoration of flow following bilateral carotid occlusion for 1 h. We have modified the method for fluorometric measurement of Evans blue to monitor vascular protein leakage (vasogenic edema). The extraction of extravasated Evans blue was performed by homogenizing the whole brain in 50% trichloroacetic acid. The supernatant was diluted fourfold with ethanol and the Evans blue fluorescence was measured. The tissue blank was negligible. Evans blue content of the plasma was similarly determined and the ratio of tissue to plasma Evans blue content was calculated. Furthermore, Evans blue fluorescence was used for microscopic investigation. It is suggested that Evans blue fluorescence can be applied for quantification of protein leakage with much more sensitivity and accuracy than the colorimetric absorbance method, as well as for tissue localization of protein leakage.
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Gerbil
Vascular permeability
Trichloroacetic acid
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