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Highlights • The treatment paradigm for aortic dissection is complex and dependent on acuity of presentation with clinical and anatomical considerations. • Endovascular treatment of supraceliac IAADs represents a feasible and safe. • The long-term outcome data suggest that endovascular repair., Aortic dissection originates from isolated tear in the abdominal aorta is rare but potentially life or limb-threatening condition particularly if misdiagnosed. It may have a number of clinical presentations with potentially serious adverse effects and should be considered in the differential diagnosis of any patient with an acute onset of abdominal pain radiating to the back and the buttocks together with presence or absence of a pulsatile abdominal mass, signs of limb ischemia, or discernible risk factors. Surgical and endovascular treatments are two valid options for these cases according to their clinical and anatomical considerations with acceptable results. We present a quite unusual case of a spontaneous supraceliac isolated abdominal aortic dissection with contained peri-aortic hematoma and manifesting as acute persistent abdominal pain. Better illustration of the natural history of this ill-defined pathology is needed to understand and improve patient care.

Digital technologies reflected on the designer's awareness of the morphology of the Modeling structure of the interior spaces and its design elements. Thus, the ultimate goal of the designer is to achieve environmental quality to raise the functional efficiency of all types of the interior design. Despite the importance of that goal, but many of the design and architectural works lack the mechanisms to thoughtful and application achievement. As a result, the Orientation towards mechanical techniques with their negative physiological effects to achieve part of the quality of the interior environment and here lies the research problem.The research seeks to take advantage of morphology as a functional determinant to find the design treatment to achieve the quality of the natural interior environment and reduce dependence on mechanical devices for their negatives. Therefore, the structural structure of the research is directed to the study of morphology; the functional determinants of content and form building, techniques of morphological construction of shapes, and the quality of the interior environment; and its relationship to the functional determinants of the morphology and the design analysis of morphological structure in its forms and content to enrich the interior environment Hygienically in form and substance under the codification of morphology. The research follows the descriptive analytical approach.

Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl-thiophene-carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties.

Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described.

A new class of Aurora-A inhibitors have been identified based on the 2-amino-pyrrolo[2,3-d]pyrimidine scaffold. Here, we describe the synthesis and SAR of this novel series. We report compounds which exhibit nanomolar activity in the Aurora-A biochemical assay and are able to inhibit tumor cell proliferation. This study culminates in compound 30, an inhibitor with potent activity against Aurora A (IC50=0.008 microM), anti-proliferative activity against several tumor cell lines and induces polyploidy in H460 cells.

Activation of the classical pathway of complement has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury and acute transplant rejection. The trypsin-like serine protease C1s represents a pivotal upstream point of control in the classical pathway of complement activation and is therefore likely to be a useful target in the therapeutic intervention of these disease states. A series of thiopheneamidine-based inhibitors of C1s has been optimized to give a 70 nM inhibitor that inhibits the classical pathway of complement activation in vitro.

6-Substituted bicyclic thiazolidine lactam peptidomimetics of Pro-Leu-Gly-NH(2) (1) were synthesized to test the hypothesis that incorporation of a hydrophobic side chain into the bicyclic thiazolidine lactam scaffold would further enhance the dopamine receptor modulating activity of such peptidomimetics. The substituents employed were the isobutyl, butyl, and benzyl groups to give peptidomimetics 3-5, respectively. These peptidomimetics were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism and were compared with the unsubstituted bicyclic thiazolidine lactam Pro-Leu-Gly-NH(2) peptidomimetic 2. Peptidomimetics 3-5 each affected rotational behavior in a bell-shaped dose-response relationship producing maximal increases of 44% (1 microgram/kg,ip), 56% (0.1 microgram/kg,ip), and 30% (1 microgram/kg, ip), respectively. In comparison, unsubstituted peptidomimetic 2 increased rotational behavior by only 23% at a dose of 0.1 microgram/kg, ip.

Bicyclic thiazolidine lactam 1 was used as a model system for developing synthetic methodology into β-turn mimics that would contain side chain functionality. treatment of a mixture of 1 and a non-enolizable aldehyde at −100 °C with LDA resulted in a good yield of the aldol adduct when aromatic aldehydes were used. Radical dehydroxylation of the pentafluorophenylcarbonate derivative of the aldol adduct with ( n -Bu) 3 SnH and AIBN gave a single isomer of the C-2 alkylated bicyclic 5,5-thiazolidine lactam. This methodology was applied to the synthesis of the 2-substituted spiro bicyclic thiazolidine lactam type II' β-turn mimic 14 .

An improved method for the N - tert -butoxycarbonyl protection of the amino functionality of α-alkylated prolines and other sterically hindered α,α-disubstituted amino acids has been developed in which the lipophilic base tetramethylammonium hydroxide is used to solubilize the otherwise insoluble zwitterionic amino acid in acetonitrile, thereby obviating the need for an aqueous medium.

An improved method for the N - tert -butoxycarbonyl protection of the amino functionality of α-alkylated prolines and other sterically hindered α,α-disubstituted amino acids has been developed in which the lipophilic base tetramethylammonium hydroxide is used to solubilize the otherwise insoluble zwitterionic amino acid in acetonitrile, thereby obviating the need for an aqueous medium.

Bicyclic thiazolidine lactam 1 was used as a model system for developing synthetic methodology into β-turn mimics that would contain side chain functionality. treatment of a mixture of 1 and a non-enolizable aldehyde at −100 °C with LDA resulted in a good yield of the aldol adduct when aromatic aldehydes were used. Radical dehydroxylation of the pentafluorophenylcarbonate derivative of the aldol adduct with ( n -Bu) 3 SnH and AIBN gave a single isomer of the C-2 alkylated bicyclic 5,5-thiazolidine lactam. This methodology was applied to the synthesis of the 2-substituted spiro bicyclic thiazolidine lactam type II' β-turn mimic 14 .

Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboxamidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a Ki of 10nM and >1000-fold selectivity over uPA, tPA, FX(a), thrombin, and plasmin.

In the present study, the synthesis of the 5.5.6. and 5.6.5. spiro bicyclic lactam PLG peptidomimetics, compounds 3 and 4, respectively, was undertaken. These peptidomimetics were designed to examine the following: (1) the effect that changing the size of the thiazolidine and lactam ring systems would have on the ability of these systems to mimic the type-II beta-turn and (2) the effect that these structural perturbations would have on the ability of the peptidomimetics to modulate dopamine receptors. Through the use of the [3H]spiroperidol/N-propylnorapomorphine (NPA) dopamine D2 receptor competitive binding assay, 3 and 4, at a concentration of 100 nM, decreased the dissociation constant of the high-affinity state of the dopamine receptor for the agonist. These effects were observed when either Gpp(NH)p was absent or present and they were comparable to those produced by PLG at a concentration of 1 microM. Peptidomimetics 3 and 4 also increased the percentage of D2 receptors that existed in the high-affinity state. Even with Gpp(NH)p present, 3 and 4 were able to return the RH/RL ratios to values observed in the respective controls where Gpp(NH)p was absent. Furthermore, both peptidomimetics were able to attenuate the Gpp(NH)p-induced shift to the low-affinity state to a greater extent than PLG. Peptidomimetics 3 and 4 were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism, and each affected the rotational behavior in a bell-shaped dose-response relationship producing increases of 95 +/- 31% (0.01 mg/kg, ip) and 88 +/- 14% (0.001 mg/kg, ip), respectively. In comparison, the previously reported 5.5.5. spiro bicyclic lactam 2 increased rotational behavior by 25 +/- 11% (0.01 mg/kg, ip).