The above effects reveal that compounds 5h and 5m could be possible lead compounds against PI3K in malignancy therapies and are worthy of further study and optimization. ? Open in a separate window Scheme 1 Reagents and conditions: (we) HSCH2COOH, NaOH, methanol, r.t., 1 h; (ii) H2O2, acetic acid, 40C45 C, 4 h; (iii) DCC, DMAP, THF, r.t., 1 h. Supplementary Materials Supplementary materials are available on-line: the synthesis and identification of the intermediates mentioned in Plan 1; 1H-NMR and 13C-NMR spectra of all the target compounds. Click here for more data file.(2.4M, pdf) Author Contributions Conceptualization, L.W. PI3K and PI3K. Collectively, the above findings suggested that compounds 5h and 5m might be encouraging PI3K inhibitors deserving further investigation for malignancy treatment. = 30) and analyzed using < 0.01. 2.3.1. Binding Modes of Different Compounds with PI3K (3HHM) Number 4, Number 5 and Number 6 demonstrate compounds rigosertib, 5h, and 5m docking into the binding site of PI3K. Docking results showed the tested compounds created relationships with the key amino acid residues such as LYS802, VAL851, ILE932 and ILE848 at its active site. In particular, compound 5h showed the lowest binding free energy of ?8.47 kcal/mole, as compared to rigosertib and 5m (Table 4). The binding model of compound 5h into PI3K exposed several molecular relationships thought to be responsible for the observed affinity: (i) two hydrogen relationship relationships between the two oxygen atoms of the sulfonyl group and VAL851 and SER854; (ii) piCalkyl and piCsigma relationships between the benzopyrone ring and ILE932 and ILE848; and (iii) additional weak relationships, including CCH bonds, and Vehicle der Waals. Open in a separate window Number 4 A 2D model of the connection between rigosertib with the active site of PI3K. Open in a separate window Number 5 A 2D model of the connection between compound 5h with the active site of PI3K. Open in a separate window Number 6 A 2D model of the connection between compound 5m with the active site of PI3K. Table 4 Binding energies of compounds 5h and 5m with the PI3K and PI3K enzymes. ideals) were measured in hertz (Hz). Notice: Only the synthesis and characterization of target compounds are offered in this article. The intermediates described in Plan 1 are explained in the Supplementary Materials. Synthesis of THE PROSPECTIVE Compounds (5aC5o) (5a). To an ice-cold remedy of 2-[(4-methylbenzyl)sulfonyl]acetic acid (3i) (0.98 g, 4.3 mmol, 1.0 eq.) in THF was added salicylaldehyde (4a) (0.55 g, 4.5 mmol, 1.05 eq.), DCC (0.97 g, 4.7 mmol, 1.1 eq.) and DMAP (0.05 g, 0.4 mmol, 0.1 eq.). Stirring was continued at room temp for 1h, after which time TLC showed the completion of reaction. The precipitate was filtered and the filtrate was concentrated in vacuo almost to dryness, then 50 mL ethyl acetate was added. The transparent remedy was washed with dilute hydrochloric acid (20 mL 4) and saturated brine (20 mL 2) and dried with anhydrous sodium sulfate. The dried remedy was concentrated to obtain the crude product, which was recrystallized in ethyl acetate to give a white product. Yield 37%, white solid; m.p. 168C170 C; 1H-NMR (400 MHz, DMSO-= 8.0 Hz, Ar-H), 7.46 (t, 1H, = 7.2 Hz, Ar-H), 7.56 (d, 1H, = 8.4 Hz, Ar-H), 7.83 (t, 1H, = 8.4 Hz, Ar-H), 8.01 (d, 1H, = 7.8 Hz, Ar-H), 8.75 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5b). Yield 39%, white solid; m.p. 213C214 C; 1H-NMR (400 MHz, DMSO-= 8.4 Hz, Ar-H), 7.47 (t, 1H, = 7.2 Hz, Ar-H), 7.55C7.59 (m, 2H, Ar-H), 7.83 (t, 1H, = 7.6 Hz, Ar-H), 8.02 (d, 1H, = 7.8 Hz, Ar-H), 8.78 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5c). Yield 37%, pale yellow solid; m.p. 172C174 C. 1H-NMR (400 MHz, DMSO-= 7.6 Hz, Ar-H), 7.57 (d, 1H, Ar-H), 7.63 (t, 1H, = 7.2 Hz, Ar-H), 7.70-7.75 (m, 2H, Ar-H), 7.80-7.87 (m, 2H, Ar-H), 8.06 (d, 1H, = 7.8 Hz, Ar-H), 8. 87 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-= 5 Hz), 129.3, 129.6, 130.0, 131.8, 133.0, 134.9, 136.2, 149.8, 155.3, 156.3. HRMS-ESI ((5d). Yield.Moreover, 5h and 5m could significantly inhibit the migration of Hela cells. 5 and Number 6 demonstrate compounds rigosertib, 5h, and 5m docking into the binding site of PI3K. Docking results showed the tested compounds created relationships with the key amino acid residues such as LYS802, VAL851, ILE932 and ILE848 at its active site. In particular, compound 5h showed the lowest binding free energy of ?8.47 kcal/mole, as compared to rigosertib and 5m (Table 4). The binding model of compound 5h into PI3K exposed several molecular relationships thought to be responsible for the observed affinity: (i) two hydrogen relationship relationships between the two oxygen atoms of the sulfonyl group and VAL851 and SER854; (ii) piCalkyl and piCsigma relationships between the benzopyrone ring and ILE932 and ILE848; and (iii) additional weak relationships, including CCH bonds, and Vehicle der Waals. Open in a separate window Number 4 A 2D model of the connection between rigosertib with the energetic site of PI3K. Open up in another window Body 5 A 2D style of the relationship between substance 5h using the energetic site of PI3K. Open up in another window Body 6 A 2D style of the relationship between substance 5m using the energetic site of PI3K. Desk 4 Binding energies of substances 5h and 5m using the PI3K and PI3K enzymes. beliefs) were measured in hertz (Hz). Take note: Just the synthesis and characterization of focus on compounds are provided in this specific article. The intermediates talked about in System 1 are defined in the Supplementary Components. Synthesis of THE MARK Substances (5aC5o) (5a). For an ice-cold alternative of 2-[(4-methylbenzyl)sulfonyl]acetic acidity (3i) (0.98 g, 4.3 mmol, 1.0 eq.) in THF was added salicylaldehyde (4a) (0.55 g, 4.5 mmol, 1.05 eq.), DCC (0.97 g, 4.7 mmol, 1.1 eq.) and DMAP (0.05 g, 0.4 mmol, 0.1 eq.). Stirring was continuing at room heat range for 1h, and time TLC demonstrated the conclusion of response. The precipitate was filtered as well as the filtrate was focused in vacuo nearly to dryness, after that 50 mL ethyl acetate was added. The clear alternative was cleaned with dilute hydrochloric acidity (20 mL 4) and saturated brine (20 mL 2) and dried out with anhydrous sodium sulfate. The dried out alternative was focused to have the crude item, that was recrystallized in ethyl acetate to provide a white item. Produce 37%, white solid; m.p. 168C170 C; 1H-NMR (400 MHz, DMSO-= 8.0 Hz, Ar-H), 7.46 (t, 1H, = 7.2 Hz, Ar-H), 7.56 (d, 1H, = 8.4 Hz, Ar-H), 7.83 (t, 1H, = 8.4 Hz, Ar-H), 8.01 (d, 1H, = 7.8 Hz, Ar-H), 8.75 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5b). Produce 39%, white solid; m.p. 213C214 C; 1H-NMR (400 MHz, DMSO-= 8.4 Hz, Ar-H), 7.47 (t, 1H, = 7.2 Hz, Ar-H), 7.55C7.59 (m, 2H, Ar-H), 7.83 (t, 1H, = 7.6 Hz, Ar-H), 8.02 (d, 1H, = 7.8 Hz, Ar-H), 8.78 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5c). Produce 37%, pale yellow solid; m.p. 172C174 C. 1H-NMR (400 MHz, DMSO-= 7.6 Hz, Ar-H), 7.57 (d, 1H, Ar-H), 7.63 (t, 1H, = 7.2 Hz, Ar-H), 7.70-7.75 (m, 2H, Ar-H), 7.80-7.87 (m, 2H, Ar-H), 8.06 (d, 1H, = 7.8 Hz, Ar-H), 8. 87 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-= 5 Hz), 129.3, 129.6, 130.0, 131.8, 133.0, 134.9, 136.2, 149.8, 155.3, 156.3. HRMS-ESI ((5d). Produce 7%, pale yellow solid; m.p. 258.5C260 C. 1H-NMR (400 MHz, DMSO-= 2.0 Hz, Ar-H), 7.57 (d, 1H, = 2.4 Hz, Ar-H), 7.79 (d, 1H, = 8.8 Hz, Ar-H), 8.59 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-(5e). Produce 13%, yellowish solid; m.p. 252C254 C. 1H-NMR (400 MHz, DMSO-= 8.0 Hz), 7.44 (t, 1H, = 7.6 Hz, Ar-H), 7.56 (d, 1H, = 7.6 Hz, Ar-H), 7.67 (d, 1H, = 7.6 Hz, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz). 13C-NMR (125 MHz, DMSO-(5f). Produce 17%, yellowish solid; m.p. 257C259 C. 1H-NMR (400 MHz, DMSO-= 7.2 Hz, Ar-H), 7.43 (t,.Furthermore, 5h and 5m could considerably inhibit the migration of Hela cells. using < 0.01. 2.3.1. Binding Settings of Different Substances with PI3K (3HHM) Body 4, Body 5 and Body 6 demonstrate substances rigosertib, 5h, and 5m docking in to the binding site of PI3K. Docking outcomes showed the fact that tested compounds produced connections with the main element amino acidity residues such as for example LYS802, VAL851, ILE932 and ILE848 at its energetic site. Specifically, substance 5h showed the cheapest binding free of charge energy of ?8.47 kcal/mole, when compared with rigosertib and 5m (Desk 4). The binding style of substance 5h into PI3K uncovered several molecular connections regarded as in charge of the noticed affinity: (i) two hydrogen connection connections between your two air atoms from the sulfonyl group and VAL851 and SER854; (ii) piCalkyl and piCsigma connections between your benzopyrone band and ILE932 and ILE848; and (iii) various other weak connections, including CCH bonds, and Truck der Waals. Open up in another window Body 4 A 2D style of the relationship between rigosertib using the energetic site of PI3K. Open up in another window Body 5 A 2D style of the relationship between substance 5h using the energetic site of PI3K. Open up in another window Body 6 A 2D style of the relationship between substance 5m using the energetic site of PI3K. Desk 4 Binding energies of substances 5h and 5m using the PI3K and PI3K enzymes. beliefs) were measured in hertz (Hz). Take note: Just the synthesis and characterization of focus on compounds are provided in this specific article. The intermediates talked about in System 1 are defined in the Supplementary Components. Synthesis of THE MARK Substances (5aC5o) (5a). For an ice-cold alternative of 2-[(4-methylbenzyl)sulfonyl]acetic acidity (3i) (0.98 g, 4.3 mmol, 1.0 eq.) in THF was added salicylaldehyde (4a) (0.55 g, 4.5 mmol, 1.05 eq.), DCC (0.97 g, 4.7 mmol, 1.1 eq.) and DMAP (0.05 g, 0.4 mmol, 0.1 eq.). Stirring was continuing at room heat range for 1h, and time TLC demonstrated the conclusion of response. The precipitate was filtered as well as the filtrate was focused in vacuo nearly to dryness, after that 50 mL ethyl acetate was added. The clear alternative was cleaned with dilute hydrochloric acidity (20 mL 4) and saturated brine (20 mL 2) and dried out with anhydrous sodium sulfate. The dried out alternative was focused to have the crude item, that was recrystallized in ethyl acetate to provide a white item. Produce 37%, white solid; m.p. 168C170 C; 1H-NMR (400 MHz, DMSO-= 8.0 Hz, Ar-H), 7.46 (t, 1H, = 7.2 Hz, Ar-H), 7.56 (d, 1H, = 8.4 Hz, Ar-H), 7.83 (t, 1H, = 8.4 Hz, Ar-H), 8.01 (d, 1H, = 7.8 Hz, Ar-H), 8.75 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5b). Produce 39%, white solid; m.p. 213C214 C; 1H-NMR (400 MHz, DMSO-= 8.4 Hz, Ar-H), 7.47 (t, 1H, = 7.2 Hz, Ar-H), 7.55C7.59 (m, 2H, Ar-H), 7.83 (t, 1H, = 7.6 Hz, Ar-H), 8.02 (d, 1H, = 7.8 Hz, Ar-H), 8.78 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5c). Produce 37%, pale yellow solid; m.p. 172C174 C. 1H-NMR (400 MHz, DMSO-= 7.6 Hz, Ar-H), 7.57 (d, 1H, Ar-H), 7.63 (t, 1H, = 7.2 Hz, Ar-H), 7.70-7.75 (m, 2H, Ar-H), 7.80-7.87 (m, 2H, Ar-H), 8.06 (d, 1H, = 7.8 Hz, Ar-H), 8. 87 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-= 5 Hz), 129.3, 129.6, 130.0, 131.8, 133.0, 134.9, 136.2, 149.8, 155.3, 156.3. HRMS-ESI ((5d). Produce 7%, pale yellow solid; m.p. 258.5C260 C. 1H-NMR (400 MHz, DMSO-= 2.0 Hz, Ar-H), 7.57 (d, 1H, = 2.4 Hz, Ar-H), 7.79 (d, 1H, = 8.8 Hz, Ar-H), 8.59 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-(5e). Produce 13%, yellow solid; m.p. 252C254 C. 1H-NMR (400 MHz, DMSO-= 8.0 Hz), 7.44 (t, 1H, = 7.6 Hz, Ar-H), 7.56 (d, 1H, = 7.6 Hz, Ar-H), 7.67 (d, 1H, = 7.6 Hz, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz). 13C-NMR (125 MHz, DMSO-(5f). Yield 17%, yellow solid; m.p. 257C259 C. 1H-NMR (400 MHz, DMSO-= 7.2 Hz, Ar-H), 7.43 (t, 1H, Ar-H), 7.49 (t, 1H, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d,.The cells were washed thrice with 1 mL of PBS to remove the cell debris from scratches. might be promising PI3K inhibitors deserving further investigation for cancer treatment. = 30) and analyzed using < 0.01. 2.3.1. Binding Modes of Different Compounds with PI3K (3HHM) Physique 4, Physique 5 and Physique 6 demonstrate compounds rigosertib, 5h, and 5m docking into the binding site of PI3K. Docking results showed that this tested compounds formed interactions with the key amino acid residues such as LYS802, VAL851, ILE932 and ILE848 at its active site. In particular, compound 5h showed the lowest binding free energy of ?8.47 kcal/mole, as compared to rigosertib and 5m (Table 4). The binding model of compound 5h into PI3K revealed several molecular interactions thought to be responsible for the observed affinity: (i) two hydrogen bond interactions between the two oxygen atoms of the sulfonyl group and VAL851 and SER854; Rabbit Polyclonal to FPR1 (ii) piCalkyl and piCsigma interactions between the benzopyrone ring and ILE932 and ILE848; and (iii) other weak interactions, including CCH bonds, and Van der Waals. Open in a separate window Physique 4 A 2D model of the conversation between rigosertib with the active site of PI3K. Open in a separate window Physique 5 A 2D model of the conversation between compound 5h with the active site of PI3K. Open in a separate window Physique 6 A 2D model of the conversation between compound 5m with the active site of PI3K. Table 4 Binding energies of compounds 5h and 5m with the PI3K and PI3K enzymes. values) were measured in hertz (Hz). Note: Only the synthesis and characterization of target compounds are presented in this article. The intermediates mentioned in Scheme 1 are described in the Supplementary Materials. Synthesis of The Target Compounds (5aC5o) (5a). To an ice-cold solution of 2-[(4-methylbenzyl)sulfonyl]acetic acid (3i) (0.98 g, 4.3 mmol, 1.0 eq.) in THF was added salicylaldehyde (4a) (0.55 g, 4.5 mmol, 1.05 eq.), DCC (0.97 g, 4.7 mmol, 1.1 eq.) and DMAP (0.05 g, 0.4 mmol, 0.1 eq.). Stirring was continued at room temperature for 1h, after which time TLC showed the completion of reaction. The precipitate was filtered and the filtrate was concentrated in vacuo almost to dryness, then 50 mL ethyl acetate was added. The transparent solution was washed with dilute hydrochloric acid (20 mL 4) and saturated brine (20 mL 2) and dried with anhydrous sodium sulfate. The dried solution was concentrated to get the crude product, which was recrystallized in ethyl acetate to give a white product. Yield 37%, white solid; m.p. 168C170 C; 1H-NMR (400 MHz, DMSO-= 8.0 Hz, Ar-H), 7.46 (t, 1H, = 7.2 Hz, Ar-H), 7.56 (d, 1H, = 8.4 Hz, Ar-H), 7.83 (t, 1H, = 8.4 Hz, Ar-H), 8.01 (d, 1H, = 7.8 Hz, Ar-H), 8.75 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5b). Yield 39%, white solid; m.p. 213C214 C; 1H-NMR (400 MHz, DMSO-= 8.4 Hz, Ar-H), 7.47 (t, 1H, = 7.2 Hz, Ar-H), 7.55C7.59 (m, 2H, Ar-H), 7.83 (t, 1H, = (S)-Reticuline 7.6 Hz, Ar-H), 8.02 (d, 1H, = 7.8 Hz, Ar-H), 8.78 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5c). Yield 37%, pale yellow solid; m.p. 172C174 C. 1H-NMR (400 MHz, DMSO-= 7.6 Hz, Ar-H), 7.57 (d, 1H, Ar-H), 7.63 (t, 1H, = 7.2 Hz, Ar-H), 7.70-7.75 (m, 2H, Ar-H), 7.80-7.87 (m, 2H, Ar-H), 8.06 (d, 1H, = 7.8 Hz, Ar-H), 8. 87 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-= 5 Hz), 129.3, 129.6, 130.0, 131.8, 133.0, 134.9, 136.2, 149.8, 155.3, 156.3. HRMS-ESI ((5d). Yield 7%, pale yellow solid; m.p. 258.5C260 C. 1H-NMR (400 MHz, DMSO-= 2.0 Hz, Ar-H), 7.57 (d, 1H, = 2.4 Hz, Ar-H), 7.79 (d, 1H, = 8.8 Hz, Ar-H), 8.59 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-(5e). Yield 13%, yellow solid; m.p. 252C254 C. 1H-NMR (400 MHz, DMSO-= 8.0 Hz), 7.44 (t, 1H, = 7.6 Hz, Ar-H), 7.56 (d, 1H, = 7.6 Hz, Ar-H), 7.67 (d, 1H, = 7.6 Hz, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz). 13C-NMR (125 MHz, DMSO-(5f). Yield 17%, yellow solid; m.p. 257C259 C. 1H-NMR (400 MHz, DMSO-= 7.2 Hz, Ar-H), 7.43 (t, 1H, Ar-H), 7.49 (t, 1H, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-= 15 Hz), 116.1 (d, = 21 Hz), 118.2, 118.7, 125.3 (d, = 3 Hz), 127.4, 127.9, 130.2, 131.9 (d, = 8 Hz), 134.1 (d, = 3 Hz), 144.5, 149.1, 155.4, 158.7, 161.5 (d, = 246 Hz). HRMS-ESI ((5g). Yield 23%, yellow solid; m.p. 232C233 C; 1H-NMR (400 MHz, DMSO-= 9.2 Hz,.for C17H10F3NO6S [M + Na]+ 436.0079, found: 436.0076. (5j). PI3K. Collectively, the above findings suggested that compounds 5h and 5m might be promising PI3K inhibitors deserving further investigation for cancer treatment. = 30) and analyzed using < 0.01. 2.3.1. Binding Modes of Different Compounds with PI3K (3HHM) Physique 4, Physique 5 and Physique 6 demonstrate compounds rigosertib, 5h, and 5m docking into the binding site of PI3K. Docking results showed that this tested compounds formed interactions with the key (S)-Reticuline amino acid residues such as LYS802, VAL851, ILE932 and ILE848 at its active site. In particular, compound 5h showed the lowest binding free energy of ?8.47 kcal/mole, as compared to rigosertib and 5m (Table 4). The binding model of compound 5h into PI3K revealed several molecular interactions thought to be responsible for the observed affinity: (i) two hydrogen bond interactions between the two oxygen atoms of the sulfonyl group and VAL851 and SER854; (ii) piCalkyl and piCsigma interactions between the benzopyrone ring and ILE932 and ILE848; and (iii) other weak interactions, including CCH bonds, and Van der Waals. Open in a separate window Physique 4 A 2D model of the conversation between rigosertib with the active site of PI3K. Open in a separate window Physique 5 A 2D model of the conversation between compound 5h with the active site of PI3K. Open in a separate window Physique 6 A 2D model of the conversation between compound 5m with the active site of PI3K. Table 4 Binding energies of compounds 5h and 5m with the PI3K and PI3K enzymes. values) were measured in hertz (Hz). Note: Only the synthesis and characterization of target compounds are presented in this article. The intermediates mentioned in Scheme 1 are described in the Supplementary Materials. Synthesis of The Target Compounds (5aC5o) (5a). To an ice-cold solution of 2-[(4-methylbenzyl)sulfonyl]acetic acid (3i) (0.98 g, 4.3 mmol, 1.0 eq.) in THF was added salicylaldehyde (4a) (0.55 g, 4.5 mmol, 1.05 eq.), DCC (0.97 g, 4.7 mmol, 1.1 eq.) and DMAP (0.05 (S)-Reticuline g, 0.4 mmol, 0.1 eq.). Stirring was continued at room temperature for 1h, after which time TLC showed the completion of reaction. The precipitate was filtered and the filtrate was concentrated in vacuo almost to dryness, then 50 mL ethyl acetate was added. The transparent solution was washed with dilute hydrochloric acid (20 mL 4) and saturated brine (20 mL 2) and dried with anhydrous sodium sulfate. The dried solution was concentrated to get the crude product, which was recrystallized in ethyl acetate to give a white product. Yield 37%, white solid; m.p. 168C170 C; 1H-NMR (400 MHz, DMSO-= 8.0 Hz, Ar-H), 7.46 (t, 1H, = 7.2 Hz, Ar-H), 7.56 (d, 1H, = 8.4 Hz, Ar-H), 7.83 (t, 1H, = 8.4 Hz, Ar-H), 8.01 (d, 1H, = 7.8 Hz, Ar-H), 8.75 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5b). Yield 39%, white solid; m.p. 213C214 C; 1H-NMR (400 MHz, DMSO-= 8.4 Hz, Ar-H), 7.47 (t, 1H, = 7.2 Hz, Ar-H), 7.55C7.59 (m, 2H, Ar-H), 7.83 (t, 1H, = 7.6 Hz, Ar-H), 8.02 (d, 1H, = 7.8 Hz, Ar-H), 8.78 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-(5c). Yield 37%, pale yellow solid; m.p. 172C174 C. 1H-NMR (400 MHz, DMSO-= 7.6 Hz, Ar-H), 7.57 (d, 1H, Ar-H), 7.63 (t, 1H, = 7.2 Hz, Ar-H), 7.70-7.75 (m, 2H, Ar-H), 7.80-7.87 (m, 2H, Ar-H), 8.06 (d, 1H, = 7.8 Hz, Ar-H), 8. 87 (s, 1H, =CH-). 13C-NMR (125 MHz, DMSO-= 5 Hz), 129.3, 129.6, 130.0, 131.8, 133.0, 134.9, 136.2, 149.8, 155.3, 156.3. HRMS-ESI ((5d). Yield 7%, pale yellow solid; m.p. 258.5C260 C. 1H-NMR (400 MHz, DMSO-= 2.0 Hz, Ar-H), 7.57 (d, 1H, = 2.4 Hz, Ar-H), 7.79 (d, 1H, = 8.8 Hz, Ar-H), 8.59 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz, DMSO-(5e). Yield 13%, yellow solid; m.p. 252C254 C. 1H-NMR (400 MHz, DMSO-= 8.0 Hz), 7.44 (t, 1H, = 7.6 Hz, Ar-H), 7.56 (d, 1H, = 7.6 Hz, Ar-H), 7.67 (d, 1H, = 7.6 Hz, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz). 13C-NMR (125 MHz, DMSO-(5f). Yield 17%, yellow solid; m.p. 257C259 C. 1H-NMR (400 MHz, DMSO-= 7.2 Hz, Ar-H), 7.43 (t, 1H, Ar-H), 7.49 (t, 1H, Ar-H), 7.79 (d, 1H, = 9.2 Hz, Ar-H), 8.60 (d, 1H, = 2.8 Hz, Ar-H). 13C-NMR (125 MHz,.