**7. Pyrano-pyrimidines**

Pyrano[2,3-*d*]pyrimidine derivatives could be synthesized *via* a multicomponent domini Knoevenagel/hetero Diels-Alder reaction of 1,3-dimethyl barbituric acid with an aromatic aldehyde and ethyl vinyl ether or 2,3-dihydrofuran in presence of 1 mol % of indium (III) chloride. The reaction also proceeds in aqueous media without using any catalyst, but the yield is comparatively less (65–75%). Preparation of naturally occurring complex molecules containing a uracil ring possesses significant synthetic challenges. The development of clinically useful anticancer (5-fluorouracil)

**Figure 8.** *Pyrano-pyrimidines.*

and antiviral drugs (AZT, DDC, DDI, BVDV) has renewed interest in the synthetic manipulation of uracils.

Ahluwalia *et al*. [39] reported the synthesis of pyrano[2,3-*d*] pyrimidines **16** by reacting thiobarbturic acids, **1** with mesityl oxide in the presence of pyridine (**Figure 8)**. The products were identical with the products obtained by the reaction of appropriate thiobarbituric acids with acetone in presence of triethylamine. The reaction of thiobarbituric acids with mesityl oxide in the absence of any base gave the corresponding open chain compounds **17** which on heating with glacial acetic acids and phosphorus pentoxide gave the corresponding cyclic compounds **18** [39].

Although a variety of routes for the synthesis of these compounds have been appeared in the literature, the majority of them involve a number of steps, drastic conditions, long reaction time and low yields [40–44]. Moreover, very few methods are reported for the synthesis of 2-thioxo-pyrano[2,3-d]pyrimidine-4-ones, as most of the methods reported are of pyrano[2,3-*d*]pyrimidines. In search of an efficient method and in continuation to our studies on fused pyrimidine derivatives, we report the full details of the work and studies related to the synthesis of 7-amino-1,3-diaryl-5-phenyl-2-thioxo-pyrano[2,3-d]pyrimidin-4(1*H*)-ones (**19**) from DTBA by reacting with various arylidenes, such as, phenylmethylenemalononitrile, ethyl phenylmethylene-cyanoacetate and phenylmethylenecyanoacetamide in presence of sodium methoxide and methanol [45]. Thus, the reaction of DTBA with arylidenes and sodium methoxide in presence of methanol by refluxing for 6 hr. afforded the compounds **19** in 70–82% overall yields (**Figure 9**).

Compounds containing dihydro-5H-pyrano[2,3-*d*]pyrimidines moiety have interesting biological properties [46]. In addition, compounds having a chalcone

**Figure 9.** *2-Thioxo-pyrano[2,3-d]pyrimidine-4-ones.* *Construction of Biologically Active Five- and Six-Membered Fused Ring Pyrimidine Derivatives… DOI: http://dx.doi.org/10.5772/intechopen.108842*

unit attached to the pyranopyrimidine ring are efficient herbicides [47]. The antifungal screening of the synthesized compounds (**19**) were done *in vitro* at 100 and 300 μg/ml solution against the two types of fungi, namely, *Fusarium oxysporum* and *Helminthosporium oryzae* using acetone as solvent. The zones of inhibition were measured in mm. The result showed that most of the compounds exhibit moderate to high activity against both fungi. Incorporation of chlorine increased the activity of high order [48]. The synthesized compounds, **19** were also screened against gram negative bacteria *Escherichia coli* (MTCC 739) and gram positive bacterium *Bacillus subtilis* (MTCC 121). The agar cup-plate method was used and nutrient agar was culture medium for the antibacterial activity. The solvent acetone served as a control. The zone of inhibition frame was measured in mm. The result of antibacterial activity showed that compounds **19b** and **19e** showed the most active compound against *B. subtilis* only, while **19a** and **19c** do not show any zone of inhibition against these bacteria [48].


**4. Current data**

*Advanced Concepts in Endocarditis - 2021*

**152**

**3.5 Indications**

*AngioVac placement and configuration.*

**Figure 4.**

The surgical indications for TVE are less clear than that of endocarditis involving the left side of the heart. Current indications for surgery include vegetations >2 cm, evidence of septic pulmonary emboli, methicillin resistant organism, fungal infections and structural deterioration causing severe tricuspid valve regurgitation and heart failure [21]. However, given the repeat IVDU in these patients a surgical treatment is less likely to last for long due to repeat episodes of TVE. More concerning is the potential of prosthetic valve endocarditis which almost always necessitates a reoperation. Surgeons often find themselves in an ethical dilemma when patients represent needing a reoperation, especially when they have failed a second or third time. The risk of reoperation steadily increases and at some point, the risks outweigh the benefits.


**2.7 Surface processing for bio-medical application**

In the case of implant materials, the interaction between the biological environment and the implanted materials occurs on the biomaterial surface. Clinical

**57**

**Figure 4.**

*Processing of Beta Titanium Alloys for Aerospace and Biomedical Applications*

biomedical beta titanium alloys is schematically shown in **Figure 4**.

wear resistance through the formation of the titanium carbide [37].

*Overview of surface modification of beta titanium alloys for biomedical application [33].*

**2.8 Powder metallurgy**

success of implant materials is greatly dependent on various surface characteristics viz. chemical inertness, texture, corrosion resistance and surface energy [31] . In the case of orthopaedic implants, the surface should possess more bone forming ability and for blood contacting devices, it should not initiate any blood clot formation. Hence surface modification of biomedical grade beta titanium alloys is very significant. Oxide layer formation will occur spontaneously on the surface of titanium on exposure to air. This TiO2 film possesses a thickness of about 1.5 to 10 nm at room temperature. Chemical stability and structural characteristics of this oxide film greatly influence the biocompatibility of titanium implant materials. Some of the potential methods to enhance the properties of native TiO2 film are anodisation, sol–gel methods, acidic and alkaline treatments [32]. In addition to these, specific surface topographies and roughness induced by mechanical surface modifications (sandblasting, grit blasting, peening) have improved the clinical success of implant materials. An overview of the various surface modification techniques employed for

In dental applications, Laser Nitriding has proved to be an effective process in enhancing the surface hardness, the coefficient of friction and corrosion resistance of the Ti-20Nb-13Zr and wear and corrosion resistance of Ti-13Nb-13Zr biomedical-beta alloys [34, 35]. Plasma nitrided beta 21S (Ti-15Mo-3Nb-3Al-0.2Si) alloy showed higher hardness but inferior corrosion resistance compared to the untreated alloy [36]. In line with the Nitriding, carburising of Ti-13Nb-13Zr (a biomedical beta alloy used for artificial joints) improved the surface hardness and

As mentioned in the introduction (Section 1), a major limiting factor for the titanium application is its high production cost. In addition to the high raw

*DOI: http://dx.doi.org/10.5772/intechopen.81899*

### *Processing of Beta Titanium Alloys for Aerospace and Biomedical Applications DOI: http://dx.doi.org/10.5772/intechopen.81899*

success of implant materials is greatly dependent on various surface characteristics viz. chemical inertness, texture, corrosion resistance and surface energy [31] . In the case of orthopaedic implants, the surface should possess more bone forming ability and for blood contacting devices, it should not initiate any blood clot formation. Hence surface modification of biomedical grade beta titanium alloys is very significant. Oxide layer formation will occur spontaneously on the surface of titanium on exposure to air. This TiO2 film possesses a thickness of about 1.5 to 10 nm at room temperature. Chemical stability and structural characteristics of this oxide film greatly influence the biocompatibility of titanium implant materials. Some of the potential methods to enhance the properties of native TiO2 film are anodisation, sol–gel methods, acidic and alkaline treatments [32]. In addition to these, specific surface topographies and roughness induced by mechanical surface modifications (sandblasting, grit blasting, peening) have improved the clinical success of implant materials. An overview of the various surface modification techniques employed for biomedical beta titanium alloys is schematically shown in **Figure 4**.

In dental applications, Laser Nitriding has proved to be an effective process in enhancing the surface hardness, the coefficient of friction and corrosion resistance of the Ti-20Nb-13Zr and wear and corrosion resistance of Ti-13Nb-13Zr biomedical-beta alloys [34, 35]. Plasma nitrided beta 21S (Ti-15Mo-3Nb-3Al-0.2Si) alloy showed higher hardness but inferior corrosion resistance compared to the untreated alloy [36]. In line with the Nitriding, carburising of Ti-13Nb-13Zr (a biomedical beta alloy used for artificial joints) improved the surface hardness and wear resistance through the formation of the titanium carbide [37].


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**Author details**

Mehwish Naseer and Kashif Rashid\*

\*Address all correspondence to<EMAIL_ADDRESS>
Department of Management Sciences, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, Pakistan