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Over the years, the energy efficiency of the North American housing stock has significantly improved mainly due to higher insulation levels, more efficient windows and, more importantly, adoption of various energy efficiency measures by building codes. The increased insulation levels of building envelopes for homes leads to a multitude of opportunities as well as challenges. A major opportunity is to reduce heat losses and thereby significantly reducing the space heating loads. However, there are many challenges that necessitate changes in the current construction process, durability of products, and more importantly, the effect of higher insulation levels on the overall moisture performance and expected long-term performance of the building envelope. A major barrier to the uptake of highly insulated homes is the lack of proven evidence of reliable thermal and moisture performance of these homes as might be achieved in various climates of Canada. Following a survey of current construction practices, a set of six wall assemblies with different types of exterior insulation systems were chosen for field monitoring study undertaken in two separate Phases over a two year period in a test facility located in Ottawa, Canada. These wall assemblies ranged from total insulation value of RSI-4.8 to RSI 7.9 (R-27 to R-45). Full scale testing included year-round performance monitoring. These wall specimens were installed in a side-by-side test bay and were subjected to local climate conditions of Ottawa, Canada; on the interior of the specimens conditions were nominally maintained at 20°C and 50% RH. This paper provides results of field trials of the six wall assemblies in terms of their hygrothermal performance and risk for condensation over a two year period of operation., International Conference on Thermal Performance of the Exterior Envelopes of Whole Buildings XIII, 4-8 December, 2016, Clearwater Beach, FL, US

Derivatives of the title ring system of type 10 were obtained in good yield by fusion of the intermediates 12. Attempt to cyclize the acetylamino derivative 9 under Bischler-Napieralski conditions failed because of the insufficient electronic density in the position 4 of the pyrazole ring created by the adjacent carbonyl moiety. The derivatives of the new ring system, assayed as anxiolytic agents, showed no significant activity.

11th Canadian Building Science and Technology Conference: 22 March 2007, Banff, Alberta

Inadequate detailing practice and defective installation of windows has accounted for a significant number of premature failures of the building envelope. This has spurred the development of alternative construction details to manage water intrusion at the wall-window interface. Laboratory investigations focused on assessing the effectiveness of wall-window interface details to manage rainwater intrusion in the wall assembly have provided an effective way to obtain useful information on the varying performance of different interface details. Previous studies undertaken to investigate the effectiveness of details typically used in wood frame low-rise wall assemblies have shown the degree to which different details manage rainwater intrusion and the extent of fault tolerance of these systems. This paper offers a report on more selected results obtained from evaluating the watertightness of a series of four wall-window interface details representative of construction practice across Canada. A brief overview of four sets of wallwindow interface details and variations on their implementation are described in general and details for a set, comprised of two specific wall-window interface details evaluated in the study are provided. The set of two variations of interface details described were configured for a fixed PVC window incorporating mounting flanges and installed in a rainscreen wall. The results of water penetration tests are provided in terms of water entry through deficiencies in the cladding, water collection within the assembly and the severity of the simulated wind-driven rain loads. The effectiveness of the two approaches to window installation in managing rainwater entry is discussed., 11th Canadian Building Science and Technology Conference: 22 March 2007, Banff, Alberta

Recent computer simulation studies at the Institute for Research in Construction (IRC) of the National Research Council (NRC) Canada have indicated that the combined wetting and drying potential of the wood-frame face sealed stucco clad wall is significantly influenced by the water vapour permeability and liquid diffusivity of the stucco material. Lower liquid diffusivity and higher water vapour permeability of the stucco material can positively influence the overall moisture management capacity of the wood-frame face sealed stucco clad wall. This paper presents preliminary experimental results from a pilot research project that aims to use the lessons learned from the simulation studies for the development of new materials or modify existing materials. The results from the experimental study show that it is possible to reduce the water absorption coefficient (a measure of liquid diffusivity) of the stucco material without reducing water vapour permeability through appropriate mix design., 11th Canadian Building Science and Technology Conference: 22 March 2007, Banff, Canada

Inadequate detailing and defective installation of windows has accounted for a significant number of premature failures of the building envelope. This has spurred the development of alternative construction details to control water intrusion at the wall-window interface. However, it is not known how effective these construction details may be over the life expectancy of the wall assembly. Laboratory investigations can provide an effective way to obtain reliable, insightful information regarding the effectiveness of specific wall-window interface details on their ability to influence rainwater entry to the wall assembly. A study was undertaken to investigate the effectiveness of such details typically used in wood frame low-rise wall assemblies to manage rainwater. An overview of the experimental approach and test protocol is given and includes a description of the test apparatus and the basis for estimating the effects on specimenssubjected to simulated climate loads. The test specimen configuration is described and details of specific wall-window interfaces evaluated in the study are provided. Results on water entry for the different wallwindow interface configurations are provided and the effectiveness of different details is discussed., 10th Canadian Conference on Building Science & Technology (10BS&T), May 12, 2005, Ottawa, Ontario, Canada

Following our previous research on anti-inflammatory drugs (NSAIDs), we report on the design and synthesis of 4-(aryloyl)phenyl methyl sulfones. These substances were characterized for their capacity to inhibit cyclooxygenase (COX-1 and COX-2) isoenzymes. Molecular modeling studies showed that the methylsulfone group of these compounds was inserted deep in the pocket of the human COX-2 binding site, in an orientation that precludes hydrogen bonding with Arg120, Ser353, and Tyr355 through their oxygen atoms. The N-arylindole 33 was the most potent inhibitor of COX-2 and also the most selective (COX-1/COX-2 IC(50) ratio was 262). The indole derivative 33 was further tested in vivo for its anti-inflammatory activity in rats. This compound showed greater inhibitory activity than ibuprofen. Other compounds (20, 26, 9, and 30) showed strong activity against carrageenan-induced inflammation. The latter compounds showed a weak capacity to inhibit the proliferation of human cell lines K562, NCI-H460, and HT-29 in vitro.

A series of substituted derivatives containing the 1,4-benzodioxine or pyrrole nucleus are described. All the newly synthesized compounds were examined for their in vitro and in vivo anti-inflammatory activity. Several derivatives, including (S)-2, 14 and 17, showed more anti-inflammatory activity in vivo in these assays (rat paw oedema induced by carrageenan) than the known classical anti-inflammatory agent ibuprofen, whereas other compounds like 1 were equipotent to ibuprofen. Compound 17 was the most outstanding derivative because of its remarkable in vivo anti-inflammatory activity. In this paper, we examine and discuss the structure-activity relationships and anti-inflammatory activities of these compounds.

The diazonium salt derived from 4-amino-N,1,3-trimethyl-N-(3-methyl-1-phenyl-1H-pyrazol-5-yl)-1H-pyrazole-5-carboxamide (14) was reacted with a mixture of CuSO4 and NaCl, with ascorbic acid as an initiator to afford the planar derivative 4,6-dihydro-1,4,6,8-tetramethyl-3-phenyldipyrazolo[3,4-b:4′,3′-d]pyridin-5(3H)-one (16) and its unexpected isomer 4,6-dihydro-3,4,6,8-tetramethyl-1-phenyldipyrazolo[4,3-b:4′,3′-d]pyridin-5(1H)-one (17), as well as the epimers (3S,4S)- (or (3S,4R)-) and (3S,4R)- (or (3S,4S)-) 4-chloro-2,4-dihydro-1′,3′,5,5′-tetramethyl-2-phenylspiro[pyrazole-3,4′(1′H)-pyrrolo[3,4-c]pyrazol]-6′(5′H)-one (18a and b, respectively). Epimers 18a and b were converted under basic conditions to 4′-chloro-N,1,3,3′-tetramethyl-1′-phenyl-[4,5′-bi-1H-pyrazole]-5-carboxamide (19). The structures of isomers 16 and 17 determined by single-crystal X-ray analysis are also reported. Linear dichroism (LD) measurements for the above isomers suggest that 17 intercalates into DNA, and 17 exhibited antiproliferation activity against human NCI-H460 pulmonary carcinoma cells.

Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observed difference among Dacarbazine and the active 4-triazenopyrazoles migth be explained admiting that these last compounds, differently by Dacarbazine, did not follow a mechanism of action based on the cytochrome P-450 induced demethylation. The most active compound 2d showed growth inhibition values of 97.8 and 99.4% against K562 and Raji cell lines respectively. Methotrexate inhibition values at 0.2 microM against the above cell lines were 86.7 and 75.1% respectively.

In order to study the influence of 3-substitution on the cytotoxic activity of 2-styrylquinazolinones, new 6-chloro-2-styryl-3-(heteroaryl)-4(3H)-quinazolinones were synthesized by refluxing equimolar amounts of 6-chloro-2-methyl-3-(heteroaryl)-4(3H)-quinazolinones and benzaldehyde in glacial acetic acid. At 1 microg ml(-1) concentration, almost all 2-styrylquinazolinones showed some cytotoxic activity against the L1210 and K562 leukemia cell lines. However, only 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone inhibited the growth of these cells by over 50%. This last compound was also the only member of the series that inhibited tubulin polymerization, with an IC(50) value of 5.8 versus 3.2 microM for colchicine. It was also examined for effects on the growth of human MCF7 breast carcinoma cells and Burkitt lymphoma CA46 cells, which had IC(50) values of 0.34 and 1.0 microM, respectively. At 10 microM 6-chloro-2-styryl-3-(pyrimidin-2yl)-4(3H)-quinazolinone induced G2/M arrest (66%) in Burkitt cells, with a mitotic index of 20%. At 3.4 microM, it caused disruption of the cellular microtubule system of the MCF7 cells. Both these cellular effects are consistent with its mechanism of action resulting from its inhibitory effect on tubulin assembly.

Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a–s and 17t–v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c–k and 11t–v with the appropriate anthranilamide derivatives 10a–c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents.

Recently our research group has reported the synthesis of some 3-amino-N-phenyl-1H-indazole-1-carboxamides able to inhibit at low micromolar concentrations the cell growth of many neoplastic cell lines. The above compounds are unsubstituted in the indazole nucleus and this gives the hope to obtain more active compounds if appropriate substituents are beared by the above nucleus. So, several new N-phenyl-1H-indazole-1-carboxamides 1c-h and 4l,m were prepared by reacting phenyl isocyanates 3a,b with 3-amino-1H-indazoles 2c,e,g, or 1H-indazole 2l respectively. Chemical trasformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamides 5a,b, and 3,5-diamino-N-phenyl-1H-indazole-1-carboxamides 4i,j respectively. Finally, 3,5-diacetamido-N-phenyl-1H-indazole-1-carboxamides 6a,b were prepared by acethylation of 4i,j. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against 60 human tumoral cell lines derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). Compound 1c, the most active of the series, was able to inhibit cell growth showing GI50 values in the 0.041-33.6 μM range, being very effective against colon and melanoma cell lines. Compound 1c induced an increase of cells in G0-G1 peak and a decrease of cells in S and G2-M phases when used at a concentration of or higher than 40µM which is the TGI calculated after 24 h of 1c exposure. This could be due to a block of G1-S transition as indicated by the ability of 1c to increase the hypophosphorylate pRb/ total pRb ratio.

Many infections such as otitis media, sinusitis, cholesteatoma, tonsillitis and adenoiditis are caused by biofilm forming mucosal pathogens (P. aeruginosa, S. aureus, S. peneomoniae, H. influenzae and M. catarrhalis). Moreover, the role of biofilms in the chronic otolaryngologic infections has been recognized for otitis media, tonsillitis and rhinosinusitis. Finally, bacterial biofilms of S. aureus, S. epidermis and E. faecalis are the leading cause of medical device-related infections. Pathogens growing as biofilms are intrinsically resistant to conventional antibiotics and therefore the discovery of new compounds able to act against biofilm aggregated micro organisms is an urgent task. Previously, we reported the study on the antibiofilm activity of 4-diazopyrazole derivatives of type 1 against S. aureus ATCC 29213, methycillin-resistant S. aureus ATCC 43866 and methycillin-resistant S. epidermis RP626 preformed biofilms. The compounds were active at the maximum tested concentration of 25 microg/ml. On the basis of these results, we have prepared a new series of 4-diazopyrazole derivatives 2a-i and 3 which take the phenylureido or phenylacetamido moiety at 5-position of the pyrazole nucleus. The compounds has been tested preliminarly against planktonic (single cells) strains of S. aureus (ATCC 25923), S. aureus (ATCC 29213), E. coli (ATCC 25922) and P. aeruginosa (ATCC 9027), showing MIC’s values in the range 50-0.097 microg/ml. Experimental work aimed to verify the effect of the above compounds on the corresponding microbial biofilms are in progress.

The pyrazolo[3,4-d]pyrimidine system shows a multitude of interesting pharmacological properties. Owing to the potential anti-inflammatory activity of 5-benzamido-pyrazolo[3,4-d]pyrimidin- 4-one derivatives and considering the easy synthesis of this class of compounds, a set of new 5- benzamido-1H-pyrazolo[3,4-d]pyrimidin-4-ones has been prepared in 42-80% yields by reacting 5- aminopyrazole-4(N-benzoyl)carbohydrazide derivatives and the opportune triethylorthoesters. Compounds 8a, b, 10a–d, and 11a, b revealed a superior inhibitory profile against COX-2, when compared to that of reference standards NS398 and indomethacin. Molecular modelling studies confirmed the obtained biological results.

A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1 μM (0.0153 μM in SR leukemia) causing a block in G0–G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.

A series of N-1H-indazole-1-carboxamides has been synthesized and their effects on both CDK1/cyclin B and the K-562 (human chronic myelogenus leukemia) cell line were evaluated. Using a computational model, we have observed that all the most active compounds 9e, f, i-n exhibited the same binding mode of purvanalol A in the ATP-binding cleft. Although they were able to moderately inhibit the leukemic cell line K-562 and to show inhibitory activity against the Cdc2-Cyclin B kinase in the low micromolar range, they turned out to be non-cytotoxic against HuDe (IZSL) primary cell cultures from human derm. These preliminary results are quite encouraging in view of the low toxicity demonstrated by the above-mentioned compounds.

The diazonium tetrafluoroborate 11 obtained from 2-amino-N-methyl-N-(1-phenyl-3- methylpyrazol-5-yl)benzamide was transformed in dry acetonitrile via an ionic or radical pathway. Differences were observed with respect to ionic or radical transformations in aqueous media of the analogous diazonium hydrogen sulfate 1 derived from the same amine. In acetonitrile solution, the ionic pathway was characterized by an increased yield of 1,4-dimethyl- 3-phenyl-pyrazolo(3,4-c)isoquinolin-5-one 4 and by the formation of its isomer, the new derivative 7,9-dimethyldibenzo(e,g)pyrazolo(1,5-a)(1,3)diazocin-10(9H)-one 12. When the reaction followed a radical pathway, the pyrazolo(3,4-c)isoquinoline derivative 4 and N-methyl- 2-(1-phenyl-3-methylpyrazol-5-yl)benzamide 17, the latter due to a 1,4-pyrazolyl transfer process, were isolated in low yields. Decomposition of the solid diazonium tetrafluoroborate at its melting point gave compounds 4, 12 and the N-(1-phenyl-3-methylpyrazol-5-yl)-2- fluorobenzamide 17. The crystal structure of compound 12 was also determined.