药学学报

Compd.	R₁	R₂	R₃	R₄	Yield/%	mp/℃	Character
6a	H	H	H	H	54.5	125.9-128.1	Light yellow crystal
6b	H	H	CH₃	H	56.7	147.6-150.0	White crystal
6c	H	H	OCH₃	H	57.2	149.7-151.6	Yellow crystal
6d	H	OCH₃	OCH₃	H	55.3	141.0-142.4	Yellow crystal
6e	H	OCH₃	H	OCH₃	53.8	132.1-133.9	White crystal
6f	H	OCH₃	OCH₃	OCH₃	55.7	128.9-131.3	Yellow crystal
6g	H	H	Cl	H	54.3	163.7-165.6	White crystal
6h	H	H	Br	H	52.3	181.3-182.5	White crystal
6i	H	H	NO₂	H	53.6	152.7-154.3	Light yellow crystal
6j	Cl	H	H	H	50.7	178.9-180.1	White crystal
9a	H	H	H	H	52.2	130.3-131.7	White crystal
9b	H	H	CH₃	H	53.4	153.6-155.4	White crystal
9c	H	H	OCH₃	H	54.6	136.6-138.7	Light yellow crystal
9d	H	OCH₃	OCH₃	H	53.8	132.3-133.7	Yellow crystal
9e	H	OCH₃	H	OCH₃	52.7	127.6-129.0	Light yellow crystal
9f	H	OCH₃	OCH₃	OCH₃	55.9	113.7-115.9	Yellow crystal
9g	H	H	Cl	H	53.2	160.1-161.8	White crysta
9h	H	H	Br	H	52.1	146.6-148.3	White crystal
9i	H	H	NO₂	H	50.7	158.9-160.7	Light yellow crystal
9j	Cl	H	H	H	55.3	170.3-171.7	White crystal

Compd.	R₁	R₂	R₃	R₄	Yield/%	mp/℃	Character
6a	H	H	H	H	54.5	125.9-128.1	Light yellow crystal
6b	H	H	CH₃	H	56.7	147.6-150.0	White crystal
6c	H	H	OCH₃	H	57.2	149.7-151.6	Yellow crystal
6d	H	OCH₃	OCH₃	H	55.3	141.0-142.4	Yellow crystal
6e	H	OCH₃	H	OCH₃	53.8	132.1-133.9	White crystal
6f	H	OCH₃	OCH₃	OCH₃	55.7	128.9-131.3	Yellow crystal
6g	H	H	Cl	H	54.3	163.7-165.6	White crystal
6h	H	H	Br	H	52.3	181.3-182.5	White crystal
6i	H	H	NO₂	H	53.6	152.7-154.3	Light yellow crystal
6j	Cl	H	H	H	50.7	178.9-180.1	White crystal
9a	H	H	H	H	52.2	130.3-131.7	White crystal
9b	H	H	CH₃	H	53.4	153.6-155.4	White crystal
9c	H	H	OCH₃	H	54.6	136.6-138.7	Light yellow crystal
9d	H	OCH₃	OCH₃	H	53.8	132.3-133.7	Yellow crystal
9e	H	OCH₃	H	OCH₃	52.7	127.6-129.0	Light yellow crystal
9f	H	OCH₃	OCH₃	OCH₃	55.9	113.7-115.9	Yellow crystal
9g	H	H	Cl	H	53.2	160.1-161.8	White crysta
9h	H	H	Br	H	52.1	146.6-148.3	White crystal
9i	H	H	NO₂	H	50.7	158.9-160.7	Light yellow crystal
9j	Cl	H	H	H	55.3	170.3-171.7	White crystal

Compd.	¹H NMR (CDCl₃,300 MHz),¹³C NMR (CDCl₃,75 MHz),IR,ESI-MS
6a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.52 (d,J = 8.7 Hz,2H,ArH),7.36-7.38 (m,3H,ArH×2 and ThH),7.15 (t,J = 8.7 Hz,1H,ArH),6.79-6.88 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,127.8,125.2,124.4,123.5,116.9,61.4,45.7,43.7,42.9,40.2,25.8; IR (KBr,cm^-1) υ: 3 044.9,2 923.0,2 845.2,1 634.7,1 602.0,1 456.2,1 277.7,1 224.1,1 018.8,977.2,768.9,703.5,551.7; ESI-MS for C₂₂H₂₅N₃O₂S: m/z 396.06 [M+H]⁺
6b	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.42 (d,J = 7.8 Hz,2H,ArH),7.18 (d,J = 7.8 Hz,2H,ArH),7.09 (d,J = 5.1 Hz,1H,ThH),6.80 (d,J = 15.3 Hz,1H,COCH=),6.44 (d,J = 5.1 Hz,1H,ThH),3.64 (s,2H,Py-CH₂),3.68-3.81 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ,2.37 (s,3H,CH₃); ¹³C NMR δ: 168.5,165.8,143.5,140.2,133.1,133.0,132.2,129.6,127.8,125.1,123.0,115.3,52.9,50.5,45.6,42.0,41.9,25.4,21.4; IR (KBr,cm^-1) υ: 2 921.0,2 826.4,1 632.6,1 605.0,1 514.8,1 464.5,1 436.6,1 276.1,1 209.0,1 027.6,983.7,813.2,720.9; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.21 [M+H]⁺.
6c	¹H NMR δ: 7.66 (d,J = 15.3 Hz,1H,ArCH=),7.47 (d,J = 8.4 Hz,2H,ArH),7.08 (d,J = 4.8 Hz,ThH),6.89 (d,J = 8.4 Hz,2H,ArH),6.70-6.73 (m,1H,COCH= and ThH),3.82 (s,3H,OCH₃),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.42 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,166.0,161.0,143.2,133.2,133.0,129.4,127.7,125.1,122.9,114.3,113.9,60.8,55.4,52.9,50.6,45.7,41.9,25.4,IR (KBr,cm^-1) υ: 2 917.0,2 821.8,2 774.2,1 628.8,1 604.9,1 438.4,1 426.5,1 277.7,1 206.3,1 012.9,986.1,810.6,718.4; ESI-MS for C₂₃H₂₇N₃O₃S: m/z 426.08 [M+H]⁺.
6d	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.07-7.15 (m,2H,ArH and ThH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.69- 6.73 (m,2H,ThH and COCH=),3.92 (s,3H,OCH₃),3.90 (s,3H,OCH₃),3.65-3.79 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.9,150.7,149.1,143.6,133.1,133.0,127.9,125.1,122.9,122.1,114.1,111.1,109.8,56.0,50.5,45.6,43.4,41.9,25.4; IR (KBr,cm^-1) υ: 3 009.3,2 896.2,2 830.7,1 631.7,1 596.0,1 509.8,1 423.5,1 271.7,1 140.8,1 027.8,989.1,804.6,709.4; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.24 [M+H]⁺.
6e	¹H NMR δ: 7.52 (d,J = 15.3 Hz,1H,ArCH=),7.01 (d,J = 5.1 Hz,1H,ThH),6.73 (d,J = 15.3 Hz,1H,COCH=),6.65 (d,J = 5.1 Hz,1H,ThH),6.57 (s,2H,ArH),6.40 (s,1H,ArH),3.73 (s,6H,OCH₃×2) ,3.57-3.68 (m,8H,Pp-CH₂×4) ,3.56 (s,2H,Py-CH₂),3.35 (s,2H,COCH₂),2.81 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.6,161.0,143.5,136.9,133.1,133.0,125.1,122.9,117.1,105.9,101.9,60.7,55.5,52.9,50.6,45.6,41.9,25.4; IR (KBr,cm^-1) υ: 3 006.3,2 925.9,2 839.7,1 637.7,1 610.9,1 456.2,1 414.6,1 280.7,980.2,825.5,700.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.31 [M+H]⁺.
6f	¹H NMR δ: 7.61 (d,J = 15.3 Hz,1H,ArCH=),7.10 (d,J = 5.1 Hz,1H,ThH),6.69-6.76 (m,4H,ArH,ThH and COCH=),3.89 (s,6H,OCH₃×2) ,3.87 (s,3H,OCH₃),3.65-3.78 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.7,153.4,143.7,139.8,133.0,132.3,130.5,125.1,123.0,115.6,105.1,61.0,56.2,53.0,50.6,45.6,43.6,42.0, 25.4; IR (KBr,cm^-1) υ: 2 924.2,2 839.1,1 642.9,1 583.7,1 505.5,1 458.8,1 422.6,1 335.9,1 318.9,1 268.8,1 222.3,1 153.8,1 125.5, 1 037.7,985.7,902.9,823.4,778.9,704.9; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.11 [M+H]⁺.
6g	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.45 (d,J = 5.4 Hz,2H,ArH),7.34 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.83 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.67-3.97 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.4,142.2,135.7,133.5,133.1,133.0,129.1,129.0,125.1,123.0,117.0,53.0,50.6,45.6,42.0,25.4; IR (KBr,cm^-1) υ: 2 922.3,2 823.4,1 640.9,1 605.0,1 494.4,1 461.5,1 434.6,1 279.1,1 219.3,1 162.5,1 090.7,1 013.0,977.1,810.6,722.9; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.11 [M+H]⁺.
6h	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.41 (d,J = 5.4 Hz,2H,ArH),7.24 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.81 (d,J = 15.6 Hz,1H,COCH=),6.68 (d,J = 5.1 Hz,1H,ThH),3.71-3.99 (m,8H,Pp-CH₂×4) ,3.67 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ;¹³C NMR δ: 168.2,165.4,142.3,135.7,133.9,132.7,132.1,129.4,125.1,124.0,123.1,117.1,60.4,52.8,50.6,45.6,41.9,25.2; IR (KBr,cm^-1) υ: 2 921.0,2 733.6,1 641.9,1 468.1,1 423.4,1 286.5,1 212.8,1 068.1,981.2,821.8; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 474.32 [M+H]⁺.
6i	¹H NMR δ: 8.22 (d,J = 8.7 Hz,2H,ArH),7.73-7.68 (m,3H,ArCH= and ArH),7.10 (d,J = 5.1 Hz,ThH),5.95-7.07 (m,1H,COCH=),6.73 (d,J = 5.1 Hz,1H,ThH),3.68-3.83 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.44 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.6,164.7,148.2,141.2,140.6,133.1,133.0,128.4,125.1,124.1,122.9,120.9,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 3 098.1,2 916.6,1 839.2,1 729.3,1 637.1,1 613.3,1 515.1,1 431.7,1 339.5,1 107.4,985.4,839.6,756.3,702.7; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.17 [M+H]⁺.
6j	¹H NMR δ: 8.02 (d,J = 15.6 Hz,1H,ArCH=),7.58 (s,1H,ArH),7.36-7.44 (m,1H,ArH),7.23-7.32 (m,2H,ArH×2) ,7.09 (d,J = 5.1 Hz,1H,ThH),6.84 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.64-3.77 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.3,139.2,134.7,133.4,133.1,133.0,130.6,130.2,127.6,126.9,125.1,123.0,119.8,52.9,50.6,45.8,45.5,41.9,25.4; IR (KBr,cm^-1) υ: 2 901.7,2 812.4,2 735.1,1 654.9,1 592.4,1 467.5,1 437.7,1 220.5,988.4,747.4,696.8; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.17 [M+H]⁺.
9a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.51 (d,J = 5.1 Hz,2H,ArH),7.36 (d,J = 5.1 Hz,3H,ArH×3) ,7.15 (d,J = 4.5 Hz,1H,ThH),6.89-6.80 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.85-3.92 (m,2H,Py-CH₂),3.61-3.82 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.8 Hz,2H,COCH₂),2.81-3.00 (m,2H,Py-CH₂),2.58 (d,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,128.8,127.8,125.2,124.5,123.7,61.4,45.7,43.7,42.8,40.2,24.7; IR (KBr,cm^-1) υ: 2 920.0,2 842.6,1 637.7,1 607.9,1 456.2,1 429.4,1 227.1,1 102.2,1 006.9,763.0,697.5; ESI-MS for C₂₂H₂₅ClN₃O₂S: m/z 396.13 [M+H]⁺.
9b	¹H NMR δ: 7.47 (d,J = 15.6 Hz,1H,ArCH=),7.37 (d,J = 7.8 Hz,2H,ArH),7.15-7.27 (m,3H,ThH and ArH×2) ,6.95 (d,J = 15.6 Hz,1H,COCH=),6.79 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.88-3.95 (m,2H,Py-CH₂),3.54-3.76 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.5 Hz,2H,COCH₂),2.74-2.98 (m,2H,Py-CH₂),2.56 (d,4H,Pp-CH₂×2) ,2.23 (s,3H,CH₃); ¹³C NMR δ: 168.0,163.2,144.6,139.2,134.4,131.2,130.6,129.0,128.6,125.1,124.7,115.8,56.7,52.7,44.7,42.9,40.6,23.8,20.3; IR (KBr,cm^-1) υ: 3 018.2,2 920.0,2 512.4,1 655.5,1 610.9,1 432.4,1 274.7,1 236.0,1 122.9,983.1,786.8,703.5; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.17 [M+H]⁺.
9c	¹H NMR δ: 7.64 (d,J = 15.6 Hz,1H,ArCH=),7.46 (d,J = 8.4 Hz,ArH),7.14 (d,J = 4.8 Hz,1H,ThH),6.88 (d,J = 8.7 Hz,2H,ArH),6.81 (d,J = 4.8 Hz,1H,ThH),6.74 (d,J = 15.0 Hz,1H,COCH=),4.66 (s,2H,Py-CH₂),3.85-3.93 (m,2H,Py-CH₂),3.82 (s,3H,OCH₃),3.55-3.77 (m,4H,Pp-CH₂×2) ,3.31 (d,J = 7.5 Hz,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.56 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,160.9,142.7,134.1,132.4,132.2,131.5,129.3,127.9,125.2,123.7,61.5,55.4,45.7,43.6,42.8,40.2, 25.9; IR (KBr,cm^-1) υ: 3 065 8,2 833.7,2 812.9,1 649.6,1 631.7,1 599.0,1 512.7,1 420.5,1 280.7,1 170.6,1 003.9,831.4,703.5; ESI-MS for C₂₃H₂₇ClN₃O₃S: m/z 426.15 [M+H]⁺.
9d	¹H NMR δ: 7.62 (d,J = 15.3 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),7.11 (d,J = 8.1Hz,1H,ArH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.81 (d,J = 5.1 Hz,1H,ThH),6.72 (d,J = 15.3 Hz,1H,COCH=),4.67 (s,2H,Py-CH₂),3.84-3.92 (m,8H,OCH₃×2 and Py-CH₂),3.60-3.82 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.8 Hz,2H,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.59 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,150.6,149.1,143.0,134.1,132.3,132.2,125.2,124.5,123.7,121.9,111.1,109.9,61.5,56.0,53.2,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 902.2,2 936.7,1 643.6,1 590.1,1 509.8,1 438.4,1 262.8,1 140.8,1 000.9,804.6,703.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.35 [M+H]⁺.
9e	¹H NMR δ: 7.56 (d,J = 15.6 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),6.79-6.84 (m,2H,COCH= and ThH),6.65 (s,2H,ArH),6.47 (s,1H,ArH),4.67 (s,2H,Py-CH₂),3.85-3.94 (m,2H,Py-CH₂),3.81 (s,6H,OCH₃×2) ,3.57-3.76 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.3,160.9,142.9,137.2,132.3,132.2,125.2,123.5,117.5,105.8,101.7,61.4,55.5,45.7,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 3 101.5,2 949.8,2 833.7,1 634.7,1 575.2,1 429.4,1 325.3,1 203.3,950.4,834.4,715.4,676.7; ESI-MS for C₂₄H₂₉ClN₃O₄S: m/z 456.27 [M+H]⁺.
9f	¹H NMR δ: 7.58 (d,J = 15.3 Hz,1H,ArCH=),7.16 (d,J = 5.1 Hz,1H,ThH),6.60-6.81 (m,4H,ArH×2,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.86-3.89 (m,2H,Py-CH₂),3.82 (s,9H,OCH₃×3) ,3.57-3.74 (m,4H,Pp-CH₂×2) ,3.34 (d,J = 6.3 Hz,2H,COCH₂),2.70-3.00 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.4,153.4,143.1,139.6,132.3,132.1,130.8,125.2,123.7,116.2,104.9,61.4,60.9,56.2,53.1,45.7,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 9319,2 842.6,1 643.6,1 587.1,1 500.8,1 453.2,1 334.2,1 265.8,1 122.9,1 000.9,825.5,709.4; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.12 [M+H]⁺.
9g	¹H NMR δ: 7.63 (d,J = 15.6 Hz,1H,ArCH=),7.44 (d,J = 8.4 Hz,2H,ArH),7.33 (d,J = 8.4 Hz,2H,ArH),7.15 (d,J = 4.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.66 (s,2H,Py-CH₂),3.84-3.94 (m,2H,Py-CH₂),3.61-3.73 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,2H,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 135.4,134.1,133.7,132.3,131.4,125.2,124.4,123.7,117.5,61.4,45.7,43.6,42.8,42.1,24.7; IR (KBr,cm^-1) υ: 2 997.1,1 820.6,1 736.8,1 649.9,1 635.9,1 605.2,1 437.2,1 235.5,1 221.5,1 003.8,857.4,812.6; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.09 [M+H]⁺.
9h	¹H NMR δ: 7.60 (d,J = 15.3 Hz,1H,ArCH=),7.50 (d,J = 8.4 Hz,2H,ArH),7.38 (d,J = 8.4 Hz,2H,ArH),7.15 (t,J = 7.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.83-3.94 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.9 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 134.1,132.0,131.8,129.2,125.2,124.4,123.7,123.5,117.5,61.4,45.6,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 943.8,2 834.8,1 735.9,1 637.7,1 596.0,1 435.8,1 241.9, 1 006.9,807.6,780.8,703.5; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 476.09 [M+H]⁺.
9i	¹H NMR δ: 8.24 (d,J = 8.7 Hz,2H,ArH),7.66 (d,J = 8.4 Hz,2H,ArH),7.13-7.16 (m,1H,ArCH=),6.94 (d,J = 15.3 Hz,1H,COCH=),6.72-6.83 (m,2H,ThH×2) ,4.67 (s,2H,Py-CH₂),3.62-3.95 (m,6H,Pp-CH₂×2 and Py-CH₂),3.37 (d,J = 7.2 Hz,2H,COCH₂),2.85-3.11 (m,2H,Py-CH₂),2.65 (s,4H,Pp-CH₂×2) ,¹³C NMR δ: 168.6,165.7,148.2,141.2,140.6,133.2,133.1,128.4,126.1,122.7,120.9,118.3,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 2 812.9,1 649.6,1 631.7,1 610.9,1 515.7,1 343.1,1 221.2,1 006.9,852.2,751.1,703.5; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.12 [M+H]⁺.
9j	¹H NMR δ: 7.86 (d,J = 15.3 Hz,1H,ArCH=),7.63 (d,J = 7.5 Hz,1H,ArH),7.41 (d,J = 7.5 Hz,1H,ArH),7.25-7.33 (m,2H,ArH),7.21 (d,J = 5.1 Hz,1H,ThH),6.93 (d,J = 15.3 Hz,1H,COCH=),6.78 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.94-4.07 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.3 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 167.6,163.2,140.0,134.1,132.5,132.3,131.3,130.6,129.9,127.7,127.4,125.1,124.3,118.6,56.7,52.5,44.7,43.0,42.5,24.4; IR (KBr,cm^-1) υ: 2 962.9,2 915.5,1 634.9,1 612.4,1 475.5,1 435.9,1 270.1,1 225.4,1 051.6,880.5; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.18 [M+H]⁺.

Compd.	¹H NMR (CDCl₃,300 MHz),¹³C NMR (CDCl₃,75 MHz),IR,ESI-MS
6a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.52 (d,J = 8.7 Hz,2H,ArH),7.36-7.38 (m,3H,ArH×2 and ThH),7.15 (t,J = 8.7 Hz,1H,ArH),6.79-6.88 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,127.8,125.2,124.4,123.5,116.9,61.4,45.7,43.7,42.9,40.2,25.8; IR (KBr,cm^-1) υ: 3 044.9,2 923.0,2 845.2,1 634.7,1 602.0,1 456.2,1 277.7,1 224.1,1 018.8,977.2,768.9,703.5,551.7; ESI-MS for C₂₂H₂₅N₃O₂S: m/z 396.06 [M+H]⁺
6b	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.42 (d,J = 7.8 Hz,2H,ArH),7.18 (d,J = 7.8 Hz,2H,ArH),7.09 (d,J = 5.1 Hz,1H,ThH),6.80 (d,J = 15.3 Hz,1H,COCH=),6.44 (d,J = 5.1 Hz,1H,ThH),3.64 (s,2H,Py-CH₂),3.68-3.81 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ,2.37 (s,3H,CH₃); ¹³C NMR δ: 168.5,165.8,143.5,140.2,133.1,133.0,132.2,129.6,127.8,125.1,123.0,115.3,52.9,50.5,45.6,42.0,41.9,25.4,21.4; IR (KBr,cm^-1) υ: 2 921.0,2 826.4,1 632.6,1 605.0,1 514.8,1 464.5,1 436.6,1 276.1,1 209.0,1 027.6,983.7,813.2,720.9; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.21 [M+H]⁺.
6c	¹H NMR δ: 7.66 (d,J = 15.3 Hz,1H,ArCH=),7.47 (d,J = 8.4 Hz,2H,ArH),7.08 (d,J = 4.8 Hz,ThH),6.89 (d,J = 8.4 Hz,2H,ArH),6.70-6.73 (m,1H,COCH= and ThH),3.82 (s,3H,OCH₃),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.42 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,166.0,161.0,143.2,133.2,133.0,129.4,127.7,125.1,122.9,114.3,113.9,60.8,55.4,52.9,50.6,45.7,41.9,25.4,IR (KBr,cm^-1) υ: 2 917.0,2 821.8,2 774.2,1 628.8,1 604.9,1 438.4,1 426.5,1 277.7,1 206.3,1 012.9,986.1,810.6,718.4; ESI-MS for C₂₃H₂₇N₃O₃S: m/z 426.08 [M+H]⁺.
6d	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.07-7.15 (m,2H,ArH and ThH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.69- 6.73 (m,2H,ThH and COCH=),3.92 (s,3H,OCH₃),3.90 (s,3H,OCH₃),3.65-3.79 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.9,150.7,149.1,143.6,133.1,133.0,127.9,125.1,122.9,122.1,114.1,111.1,109.8,56.0,50.5,45.6,43.4,41.9,25.4; IR (KBr,cm^-1) υ: 3 009.3,2 896.2,2 830.7,1 631.7,1 596.0,1 509.8,1 423.5,1 271.7,1 140.8,1 027.8,989.1,804.6,709.4; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.24 [M+H]⁺.
6e	¹H NMR δ: 7.52 (d,J = 15.3 Hz,1H,ArCH=),7.01 (d,J = 5.1 Hz,1H,ThH),6.73 (d,J = 15.3 Hz,1H,COCH=),6.65 (d,J = 5.1 Hz,1H,ThH),6.57 (s,2H,ArH),6.40 (s,1H,ArH),3.73 (s,6H,OCH₃×2) ,3.57-3.68 (m,8H,Pp-CH₂×4) ,3.56 (s,2H,Py-CH₂),3.35 (s,2H,COCH₂),2.81 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.6,161.0,143.5,136.9,133.1,133.0,125.1,122.9,117.1,105.9,101.9,60.7,55.5,52.9,50.6,45.6,41.9,25.4; IR (KBr,cm^-1) υ: 3 006.3,2 925.9,2 839.7,1 637.7,1 610.9,1 456.2,1 414.6,1 280.7,980.2,825.5,700.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.31 [M+H]⁺.
6f	¹H NMR δ: 7.61 (d,J = 15.3 Hz,1H,ArCH=),7.10 (d,J = 5.1 Hz,1H,ThH),6.69-6.76 (m,4H,ArH,ThH and COCH=),3.89 (s,6H,OCH₃×2) ,3.87 (s,3H,OCH₃),3.65-3.78 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.7,153.4,143.7,139.8,133.0,132.3,130.5,125.1,123.0,115.6,105.1,61.0,56.2,53.0,50.6,45.6,43.6,42.0, 25.4; IR (KBr,cm^-1) υ: 2 924.2,2 839.1,1 642.9,1 583.7,1 505.5,1 458.8,1 422.6,1 335.9,1 318.9,1 268.8,1 222.3,1 153.8,1 125.5, 1 037.7,985.7,902.9,823.4,778.9,704.9; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.11 [M+H]⁺.
6g	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.45 (d,J = 5.4 Hz,2H,ArH),7.34 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.83 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.67-3.97 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.4,142.2,135.7,133.5,133.1,133.0,129.1,129.0,125.1,123.0,117.0,53.0,50.6,45.6,42.0,25.4; IR (KBr,cm^-1) υ: 2 922.3,2 823.4,1 640.9,1 605.0,1 494.4,1 461.5,1 434.6,1 279.1,1 219.3,1 162.5,1 090.7,1 013.0,977.1,810.6,722.9; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.11 [M+H]⁺.
6h	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.41 (d,J = 5.4 Hz,2H,ArH),7.24 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.81 (d,J = 15.6 Hz,1H,COCH=),6.68 (d,J = 5.1 Hz,1H,ThH),3.71-3.99 (m,8H,Pp-CH₂×4) ,3.67 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ;¹³C NMR δ: 168.2,165.4,142.3,135.7,133.9,132.7,132.1,129.4,125.1,124.0,123.1,117.1,60.4,52.8,50.6,45.6,41.9,25.2; IR (KBr,cm^-1) υ: 2 921.0,2 733.6,1 641.9,1 468.1,1 423.4,1 286.5,1 212.8,1 068.1,981.2,821.8; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 474.32 [M+H]⁺.
6i	¹H NMR δ: 8.22 (d,J = 8.7 Hz,2H,ArH),7.73-7.68 (m,3H,ArCH= and ArH),7.10 (d,J = 5.1 Hz,ThH),5.95-7.07 (m,1H,COCH=),6.73 (d,J = 5.1 Hz,1H,ThH),3.68-3.83 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.44 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.6,164.7,148.2,141.2,140.6,133.1,133.0,128.4,125.1,124.1,122.9,120.9,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 3 098.1,2 916.6,1 839.2,1 729.3,1 637.1,1 613.3,1 515.1,1 431.7,1 339.5,1 107.4,985.4,839.6,756.3,702.7; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.17 [M+H]⁺.
6j	¹H NMR δ: 8.02 (d,J = 15.6 Hz,1H,ArCH=),7.58 (s,1H,ArH),7.36-7.44 (m,1H,ArH),7.23-7.32 (m,2H,ArH×2) ,7.09 (d,J = 5.1 Hz,1H,ThH),6.84 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.64-3.77 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.3,139.2,134.7,133.4,133.1,133.0,130.6,130.2,127.6,126.9,125.1,123.0,119.8,52.9,50.6,45.8,45.5,41.9,25.4; IR (KBr,cm^-1) υ: 2 901.7,2 812.4,2 735.1,1 654.9,1 592.4,1 467.5,1 437.7,1 220.5,988.4,747.4,696.8; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.17 [M+H]⁺.
9a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.51 (d,J = 5.1 Hz,2H,ArH),7.36 (d,J = 5.1 Hz,3H,ArH×3) ,7.15 (d,J = 4.5 Hz,1H,ThH),6.89-6.80 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.85-3.92 (m,2H,Py-CH₂),3.61-3.82 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.8 Hz,2H,COCH₂),2.81-3.00 (m,2H,Py-CH₂),2.58 (d,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,128.8,127.8,125.2,124.5,123.7,61.4,45.7,43.7,42.8,40.2,24.7; IR (KBr,cm^-1) υ: 2 920.0,2 842.6,1 637.7,1 607.9,1 456.2,1 429.4,1 227.1,1 102.2,1 006.9,763.0,697.5; ESI-MS for C₂₂H₂₅ClN₃O₂S: m/z 396.13 [M+H]⁺.
9b	¹H NMR δ: 7.47 (d,J = 15.6 Hz,1H,ArCH=),7.37 (d,J = 7.8 Hz,2H,ArH),7.15-7.27 (m,3H,ThH and ArH×2) ,6.95 (d,J = 15.6 Hz,1H,COCH=),6.79 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.88-3.95 (m,2H,Py-CH₂),3.54-3.76 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.5 Hz,2H,COCH₂),2.74-2.98 (m,2H,Py-CH₂),2.56 (d,4H,Pp-CH₂×2) ,2.23 (s,3H,CH₃); ¹³C NMR δ: 168.0,163.2,144.6,139.2,134.4,131.2,130.6,129.0,128.6,125.1,124.7,115.8,56.7,52.7,44.7,42.9,40.6,23.8,20.3; IR (KBr,cm^-1) υ: 3 018.2,2 920.0,2 512.4,1 655.5,1 610.9,1 432.4,1 274.7,1 236.0,1 122.9,983.1,786.8,703.5; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.17 [M+H]⁺.
9c	¹H NMR δ: 7.64 (d,J = 15.6 Hz,1H,ArCH=),7.46 (d,J = 8.4 Hz,ArH),7.14 (d,J = 4.8 Hz,1H,ThH),6.88 (d,J = 8.7 Hz,2H,ArH),6.81 (d,J = 4.8 Hz,1H,ThH),6.74 (d,J = 15.0 Hz,1H,COCH=),4.66 (s,2H,Py-CH₂),3.85-3.93 (m,2H,Py-CH₂),3.82 (s,3H,OCH₃),3.55-3.77 (m,4H,Pp-CH₂×2) ,3.31 (d,J = 7.5 Hz,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.56 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,160.9,142.7,134.1,132.4,132.2,131.5,129.3,127.9,125.2,123.7,61.5,55.4,45.7,43.6,42.8,40.2, 25.9; IR (KBr,cm^-1) υ: 3 065 8,2 833.7,2 812.9,1 649.6,1 631.7,1 599.0,1 512.7,1 420.5,1 280.7,1 170.6,1 003.9,831.4,703.5; ESI-MS for C₂₃H₂₇ClN₃O₃S: m/z 426.15 [M+H]⁺.
9d	¹H NMR δ: 7.62 (d,J = 15.3 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),7.11 (d,J = 8.1Hz,1H,ArH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.81 (d,J = 5.1 Hz,1H,ThH),6.72 (d,J = 15.3 Hz,1H,COCH=),4.67 (s,2H,Py-CH₂),3.84-3.92 (m,8H,OCH₃×2 and Py-CH₂),3.60-3.82 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.8 Hz,2H,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.59 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,150.6,149.1,143.0,134.1,132.3,132.2,125.2,124.5,123.7,121.9,111.1,109.9,61.5,56.0,53.2,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 902.2,2 936.7,1 643.6,1 590.1,1 509.8,1 438.4,1 262.8,1 140.8,1 000.9,804.6,703.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.35 [M+H]⁺.
9e	¹H NMR δ: 7.56 (d,J = 15.6 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),6.79-6.84 (m,2H,COCH= and ThH),6.65 (s,2H,ArH),6.47 (s,1H,ArH),4.67 (s,2H,Py-CH₂),3.85-3.94 (m,2H,Py-CH₂),3.81 (s,6H,OCH₃×2) ,3.57-3.76 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.3,160.9,142.9,137.2,132.3,132.2,125.2,123.5,117.5,105.8,101.7,61.4,55.5,45.7,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 3 101.5,2 949.8,2 833.7,1 634.7,1 575.2,1 429.4,1 325.3,1 203.3,950.4,834.4,715.4,676.7; ESI-MS for C₂₄H₂₉ClN₃O₄S: m/z 456.27 [M+H]⁺.
9f	¹H NMR δ: 7.58 (d,J = 15.3 Hz,1H,ArCH=),7.16 (d,J = 5.1 Hz,1H,ThH),6.60-6.81 (m,4H,ArH×2,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.86-3.89 (m,2H,Py-CH₂),3.82 (s,9H,OCH₃×3) ,3.57-3.74 (m,4H,Pp-CH₂×2) ,3.34 (d,J = 6.3 Hz,2H,COCH₂),2.70-3.00 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.4,153.4,143.1,139.6,132.3,132.1,130.8,125.2,123.7,116.2,104.9,61.4,60.9,56.2,53.1,45.7,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 9319,2 842.6,1 643.6,1 587.1,1 500.8,1 453.2,1 334.2,1 265.8,1 122.9,1 000.9,825.5,709.4; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.12 [M+H]⁺.
9g	¹H NMR δ: 7.63 (d,J = 15.6 Hz,1H,ArCH=),7.44 (d,J = 8.4 Hz,2H,ArH),7.33 (d,J = 8.4 Hz,2H,ArH),7.15 (d,J = 4.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.66 (s,2H,Py-CH₂),3.84-3.94 (m,2H,Py-CH₂),3.61-3.73 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,2H,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 135.4,134.1,133.7,132.3,131.4,125.2,124.4,123.7,117.5,61.4,45.7,43.6,42.8,42.1,24.7; IR (KBr,cm^-1) υ: 2 997.1,1 820.6,1 736.8,1 649.9,1 635.9,1 605.2,1 437.2,1 235.5,1 221.5,1 003.8,857.4,812.6; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.09 [M+H]⁺.
9h	¹H NMR δ: 7.60 (d,J = 15.3 Hz,1H,ArCH=),7.50 (d,J = 8.4 Hz,2H,ArH),7.38 (d,J = 8.4 Hz,2H,ArH),7.15 (t,J = 7.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.83-3.94 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.9 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 134.1,132.0,131.8,129.2,125.2,124.4,123.7,123.5,117.5,61.4,45.6,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 943.8,2 834.8,1 735.9,1 637.7,1 596.0,1 435.8,1 241.9, 1 006.9,807.6,780.8,703.5; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 476.09 [M+H]⁺.
9i	¹H NMR δ: 8.24 (d,J = 8.7 Hz,2H,ArH),7.66 (d,J = 8.4 Hz,2H,ArH),7.13-7.16 (m,1H,ArCH=),6.94 (d,J = 15.3 Hz,1H,COCH=),6.72-6.83 (m,2H,ThH×2) ,4.67 (s,2H,Py-CH₂),3.62-3.95 (m,6H,Pp-CH₂×2 and Py-CH₂),3.37 (d,J = 7.2 Hz,2H,COCH₂),2.85-3.11 (m,2H,Py-CH₂),2.65 (s,4H,Pp-CH₂×2) ,¹³C NMR δ: 168.6,165.7,148.2,141.2,140.6,133.2,133.1,128.4,126.1,122.7,120.9,118.3,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 2 812.9,1 649.6,1 631.7,1 610.9,1 515.7,1 343.1,1 221.2,1 006.9,852.2,751.1,703.5; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.12 [M+H]⁺.
9j	¹H NMR δ: 7.86 (d,J = 15.3 Hz,1H,ArCH=),7.63 (d,J = 7.5 Hz,1H,ArH),7.41 (d,J = 7.5 Hz,1H,ArH),7.25-7.33 (m,2H,ArH),7.21 (d,J = 5.1 Hz,1H,ThH),6.93 (d,J = 15.3 Hz,1H,COCH=),6.78 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.94-4.07 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.3 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 167.6,163.2,140.0,134.1,132.5,132.3,131.3,130.6,129.9,127.7,127.4,125.1,124.3,118.6,56.7,52.5,44.7,43.0,42.5,24.4; IR (KBr,cm^-1) υ: 2 962.9,2 915.5,1 634.9,1 612.4,1 475.5,1 435.9,1 270.1,1 225.4,1 051.6,880.5; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.18 [M+H]⁺.

Compd.	IC₅₀/mmol·L^-1
6a	48.7	59.1
6b	5.2	5.8
6c	62.3	30.5
6d	9.8	5.5
6e	19.8	26.3
6f	18.4	16.2
6g	21.8	27.6
6h	13.0	8.7
6i	17.0	59.3
6j	32.5	6.1
9a	25.1	56.6
9b	2.1	4.8
9c	55.6	23.3
9d	7.4	9.2
9e	10.5	16.1
9f	15.5	25.4
9g	31.5	6.3
9h	7.2	11.3
9i	14.6	72.9
9j	28.1	19.0
Cinepazide	1.4	3.7
Aspirin	0.1	0.4

Compd.	IC₅₀/mmol·L^-1
6a	48.7	59.1
6b	5.2	5.8
6c	62.3	30.5
6d	9.8	5.5
6e	19.8	26.3
6f	18.4	16.2
6g	21.8	27.6
6h	13.0	8.7
6i	17.0	59.3
6j	32.5	6.1
9a	25.1	56.6
9b	2.1	4.8
9c	55.6	23.3
9d	7.4	9.2
9e	10.5	16.1
9f	15.5	25.4
9g	31.5	6.3
9h	7.2	11.3
9i	14.6	72.9
9j	28.1	19.0
Cinepazide	1.4	3.7
Aspirin	0.1	0.4

苯丙烯酰胺类化合物的设计、合成及抗血小板聚集活性

PDF下载

杨雨 ¹^,² , 左建 ¹^,² , 李家明 ¹^,²^,^* , 马晓东 ¹^,² , 张艳春 ¹^,² , 黄伟军 ¹^,²

药学学报 | 研究论文 2017,52(1): 120-125

收起

药学学报 | 研究论文 2017, 52(1): 120-125

苯丙烯酰胺类化合物的设计、合成及抗血小板聚集活性

全屏

杨雨¹^,², 左建¹^,², 李家明¹^,²^,^*, 马晓东¹^,², 张艳春¹^,², 黄伟军¹^,²

作者信息

1.安徽中医药大学药学院, 安徽合肥 230038

2.安徽省中医药科学院药物化学研究所, 安徽合肥 230038

通讯作者:

* Tel:86-551-68129147,Fax:86-551-65169222,E-mail:lijiaming2004@sina.com

Design, synthesis, and biological evaluation of phenylpropenamides compounds as anti-platelet aggregation

Yu YANG¹^,², Jian ZUO¹^,², Jia-ming LI¹^,²^,^*, Xiao-dong MA¹^,², Yan-chun ZHANG¹^,², Wei-jun HUANG¹^,²

Affiliations

1. College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230038, China

2. Deparment of Medicinal Chemistry, Anhui Academy of Chinese Medicine, Hefei 230038, China

出版时间: 2017-01-12 doi: 10.16438/j.0513-4870.2016-1049

文章导航

摘要

收起

依据拼合原理，设计并合成了20个具有苯丙烯酰胺类结构的化合物，其结构均经IR、¹H NMR、¹³C NMR和MS确证。采用Bron比浊法测定了所有化合物对二磷酸腺苷（adenosine diphoshate，ADP）及花生四烯酸（arachidonic acid，AA）诱导的血小板聚集的抑制活性。初步药理结果显示，化合物6b、9b、9d和9h对AA诱导的血小板聚集具有较好的抑制作用；化合物6b、6d、6j、9b和9g对ADP诱导的血小板聚集具有较好的抑制作用。

关键词

苯丙烯酰胺 / 合成 / 抗血小板聚集 / 血栓烷A₂ / 钙离子拮抗剂

Abstract

收起

Twenty phenylpropenamide analogs with structural novelty were designed and synthesized upon pharmacophore-combination strategy. The structures of target compounds were elucidated by IR, ¹H NMR, ¹³C NMR and MS, and all the target compounds were biologically evaluated for the inhibitory activities of platelet aggregation induced by adenosine diphoshate (ADP) and (AA) arachidonic acid via Bron method. As a result, compounds 6b, 9b, 9d and 9h demonstrated potent inhibitory activity against platelet aggregation induced by AA. Meanwhile, compounds 6b, 6d, 6j, 9b and 9g exhibited significant suppression of platelet aggregation induced by ADP.

Key words

phenylpropenamides / synthesis / anti-platelet aggregation / TXA₂ / Ca²⁺ inhibitor

引用本文

杨雨, 左建, 李家明, 马晓东, 张艳春, 黄伟军. 苯丙烯酰胺类化合物的设计、合成及抗血小板聚集活性. 药学学报, 2017 , 52 (1) : 120 -125 . DOI: 10.16438/j.0513-4870.2016-1049

Yu YANG, Jian ZUO, Jia-ming LI, Xiao-dong MA, Yan-chun ZHANG, Wei-jun HUANG. Design, synthesis, and biological evaluation of phenylpropenamides compounds as anti-platelet aggregation[J]. Acta Pharmaceutica Sinica, 2017 , 52 (1) : 120 -125 . DOI: 10.16438/j.0513-4870.2016-1049

正文

收起

心脑血管疾病是严重威胁人类健康的常见病和多发病。近年来,随着人口老龄化进程的加速和人们生活节奏的加快,心脑血管疾病的发病率和死亡率呈逐年上升的趋势^[1-4]。血栓的形成与心脑血管疾病的发生有着紧密的联系,而血小板在血栓的形成中起着重要的作用。因此,开发新型的抗血小板聚集的药物,抑制血栓的形成显得尤其重要^{[5, 6]}。人体内存在着多种与血小板聚集有关的受体,根据不同的作用机制可分为血栓烷A₂ (TXA₂) 受体拮抗剂、血小板糖蛋白Ⅱb/Ⅲa (GP Ⅱb/Ⅲa) 受体拮抗剂、磷酸二酯酶 (ADP) 抑制剂、凝血酶 (PAR-1) 抑制剂及5-HT受体拮抗剂等。

马来酸桂哌齐特 (cinepazide maleate,化合物1) (图 1),作为新一代哌嗪类钙离子拮抗剂,是治疗心脑血管疾病的一线药物。近年来,一些科研工作者对其结构进行改造,希望获得更加稳定和高效的抗血小板聚集药物。Ren等^[7]以桂哌齐特为模型化合物,以苯乙胺替换四氢吡咯环,设计了系列化合物,其中化合物1-(肉桂酰基)-4-(苯乙胺乙酰基) 哌嗪马来酸盐 (化合物2,图 1),采用家兔血小板体内、体外聚集试验,测定化合物2对ADP诱导的体内、体外家兔血小板最大聚集率的影响。结果表明,该化合物具有明显抑制ADP诱导的血小板聚集作用^[8]。经过对化合物1和2进行结构剖析,发现其都具有苯丙烯酰胺结构。荜茇酰胺 (piperlongumine,化合物3,图 1) 为中药荜茇的主要活性成分,近期其抗血小板聚集活性受到了科研工作者的高度关注。Masaya等^[9]研究了荜茇酰胺对家兔血小板聚集活性的影响,结果表明荜茇酰胺对由TXA₂受体激动剂引起的血小板聚集具有显著的抑制活性。Park等^[10]研究发现荜茇酰胺对胶原蛋白、花生四烯酸和血小板凝集因子等引起的血小板凝集显示出剂量依赖性的抑制作用。对桂哌齐特及其类似物以及荜茇酰胺结构进行剖析,可以看出其均具有苯丙烯酰胺结构。推断苯丙烯酰胺是具有抗血小板聚集的重要的药效片段。

噻吩并四氢吡啶母核是临床一线P₂Y₁₂受体拮抗剂氯吡格雷、普拉格雷的重要药效团。氯吡格雷具有疗效强、费用低、不良反应小等优点; 但个体差异大,对血小板抑制延迟,且易产生氯吡格雷抵抗。普拉格雷的体内抗血小板作用约是氯吡格雷的10倍,起效时间更快、个体差异小,但出血危险性增加。因此,寻找新型的抗血小板聚集药物具有非常好的医学实用价值。

本课题组以马来酸桂哌齐特为模型化合物,依据拼合原理,将苯丙烯酰胺药效片段与普拉格雷中的噻吩并吡啶药效团进行拼合,设计并合成了20个2个系列苯丙烯酰胺类化合物,希望能为治疗血小板聚集提供潜在的化合物,化合物的合成见合成路线1。

结果与讨论

收起

1 化学合成部分

在合成化合物4a～4j的步骤中,由于酰氯的活性较强,会与哌嗪形成双边取代,故需要增加哌嗪的量,以形成更多的单边取代,实验表明以5～7倍量最佳。

在制备化合物5a～5j和化合物8的反应中由于氯乙酰氯的活泼性,既会形成酰化产物,也能形成取代产物,为了下一步反应的顺利进行,此步骤需要进行纯化。如若不进行纯化,会影响后一步实验的结果,导致大量杂质产生(如形成更多的取代产物),而影响产率。

目标化合物结构经NMR、IR、ESI-MS确证,化合物的理化数据见表 1、2。

2 目标化合物的药理活性

体外抗血小板聚集实验结果 (表 3) 显示,所合成化合物均表现出一定的抗血小板聚集作用,但作用不及桂哌齐特与阿司匹林明显,原因可能由于四氢吡咯环被替换成空间体积更大的噻吩并四氢吡啶环,空间变大引起抗血小板活性降低。化合物6b、9b、9d和9h对花生四烯酸 (AA) 诱导的血小板聚集具有较好的抑制作用,化合物6b、6d、6j、9b和9g对ADP诱导的血小板聚集具有较好的抑制作用。初步构效关系显示,当R₁=R₂=R₄=H,R₃=CH₃时,无论羰基处于何位置,均对AA及ADP诱导的血小板聚集具有较好的抑制作用; 苯环R₁位置有取代基对于ADP诱导的血小板聚集强于未取代的抑制活性,详细的构效关系及机制有待进一步研究。

实验部分

收起

LCQ ADVANTAGE MAX液质连用质谱仪 (FINNIG公司) ; Nicolet Avatar 370 DTGS型红外光谱仪 (KBr压片); Bruker 300 MHz超导核磁共振仪(CDCl₃为溶剂,TMS为内标); WRS-1B数字熔点仪 (上海精密科学仪器有限公司,温度未校正); 苯甲醛、对甲氧基苯甲醛等原料购于国药集团试剂有限公司; 其他试剂均为市售分析纯; 薄层和柱色谱用硅胶均为烟台德信生物科技有限公司产品。

1 化合物的合成

1.1 肉桂酸的合成(2a)

在500 mL三颈瓶,加入1a (10.0 g,94.3 mmol)、丙二酸 (10.8 g,103.8 mmol)、吡啶25 mL、哌啶2 mL和苯150 mL,装上油水分离器,于110 ℃回流6 h,TLC [V(CHCl₃)-V(CH₃OH) = 10∶1为展开剂]检测显示反应基本完全。冷却至室温,加入25 mL饱和碳酸钠水溶液,继续搅拌30 min。分离,取水相,水相用3 mol·L^-1的盐酸调pH至4,析出大量白色固体; 抽滤,滤饼用无水乙醇重结晶,干燥得白色固体11.6 g,收率86.6%,mp 135.2～136.8 ℃。

类似方法合成化合物2b～2j。

1.2 肉桂哌嗪的合成(4a)

向装有温控磁力搅拌,尾气吸收装置的250 mL的单颈圆底烧瓶中,加入2a (2.0 g,13.5 mmol)、SOCl₂ (15 mL) 和甲苯 (45 mL),于80 ℃反应5 h。减压浓缩,并用甲苯 (20 mL) 带蒸3次,得肉桂酰氯,加入无水二氯甲烷 (15 mL) 溶解备用。

在250 mL三颈瓶中,加入哌嗪 (7.0 g,81.0 mmol)、二氯甲烷150 mL,搅拌使其完全溶解,在冰浴条件下,将肉桂酰氯缓慢滴入,继续搅拌2.5 h,TLC [V(V(CHCl₃)-V(CH₃OH) = 10∶1为展开剂]检测显示反应基本完全,用水 (100 mL×6) 洗涤,用10%的盐酸调pH ≈ 3,常温搅拌20 min,加水100 mL分液,取水层,水层用1mol·L^-1的氢氧化钠溶液调pH ≈ 9,二氯甲烷提取,无水硫酸钠干燥,浓缩,得油状物1.8 g,产率62.1%。

类似方法合成化合物4b～4j。

1.3 1-(4-(2-氯乙酰基)哌嗪-1-基)-3-苯基丙-2-烯-1-酮的合成 (5a)

将4a (1.8 g,8.3 mmol) 用60 mL二氯甲烷溶解,转移至250 mL三颈瓶中,加入3.5 mL三乙胺,冰域条件下,缓慢滴加氯乙酰氯 (1.1 g,9.1 mmol) 二氯甲烷溶液,继续搅拌1.5 h,TLC [V(CHCl₃)-V(CH₃OH) = 15∶1为展开剂]检测显示反应基本完全,分别用水 (100 mL×2) 、饱和氯化钠 (60 mL×3) 洗涤,无水硫酸钠干燥,抽滤,浓缩,得油状物粗品1.9 g,产率79.2%。

类似方法合成化合物5b～5j。

1.4 1-(4-(-2-(6,7-二氢噻吩并[3,2-c]吡啶-5(4H)-基)乙酰基)哌啶-1-基)-3-(苯基)丙-2-烯-1-酮的合成 (6a)

在250 mL三颈瓶中,依次加入5a (1.9 g,6.5 mmol)、4,5,6,7-四氢噻吩并[3,2-c]吡啶盐酸盐 (7,2.9 g,16.3 mmol)、二氯甲烷80 mL、三乙胺6.0 mL,升温至 60 ℃,反应8 h,TLC [V(CHCl₃)-V(CH₃OH) = 15∶1为展开剂]检测显示反应基本完全,冷却至室温,分别用水 (60 mL×3) 洗涤和10% 稀盐酸 (60 mL×3) 洗涤至pH = 7～8,无水硫酸钠干燥,抽滤,浓缩,经硅胶柱洗脱分离,减压浓缩,得1.4 g白色固体,收率54.5%,mp 125.9～128.1 ℃。

类似方法合成目标化合物6b～6j。

1.5 2-氯-1-(6,7-四氢噻吩并[3,2-c]吡啶-5(4H)-基)乙酮的合成 (8)

在250 mL的三颈烧瓶加入7 (3.0 g,17.1 mmol)、6 mL三乙胺和80 mL二氯甲烷,常温搅拌30 min。冰浴条件下,将氯乙酰氯 (2.1 g,18.9 mmol) 缓慢滴入,约10 min滴完。室温反应2 h,TLC [V(CHCl₃)-V(CH₃OH) = 10∶1为展开剂]检测显示反应基本完全。10% 稀盐酸调节pH ≈ 4,分别用水 (100 mL×2) 、饱和氯化钠 (60 mL×3) 洗涤,无水硫酸钠干燥,抽滤,浓缩,经硅胶柱洗脱分离,减压浓缩,得到油状液体 2.3 g,收率62.6%。

1.6 1-(4-(2-(6,7-二氢[3,2-c]吡啶-5(4H)-基)-2-氧乙基)哌嗪-1-基)-3-苯基丙-2-烯-1-酮的合成 (9a)

在250 mL三颈烧瓶中加入8 (2.3 g,10.7 mmol)、4a (2.1 g,9.7 mmol)、80 mL二氯甲烷、4 mL三乙胺和0.5 g碘化钾,在60 ℃下回流反应7 h。TLC [V(CHCl₃)-V(CH₃OH) = 10∶1为展开剂]检测显示反应基本完全。10% 稀盐酸调节pH ≈ 4,分别用水 (100 mL×2) 、饱和氯化钠溶液 (60 mL×3) 洗涤,无水硫酸钠干燥,抽滤,浓缩,得黄色油状液体,经硅胶柱分离,收集产物,减压回收溶剂,得白色固体2.0 g,产率52.2%,mp 130.3～131.7 ℃。

类似方法合成目标化合物9b～9j。

2 目标化合物抗血小板聚集活性测试

将雄性新西兰家兔 (体重1.8～2.2 kg) 用1% 盐酸普鲁卡因注射液局部麻醉,颈动脉插管放血,与枸橼酸钠溶液 (0.38 g枸橼酸钠和10 mL生理盐水配制成3.8% 的枸橼酸钠溶液) 以9∶1混合,以1 000 r·min^-1离心10 min,取富血小板血浆 (PRP),剩余部分以3 000 r·min^-1离心10 min,取贫血小板血浆 (PPP)。先取300 μL PPP加入测试杯中,然后放入测试孔,定标。然后取280 μL PRP加入测试杯中,加入10 μL不同浓度的药液,在37 ℃预温槽中预热3 min,放入测试孔后,按“开始”键时立即加入诱导剂10 μL,以测定最大聚集率,并计算IC₅₀值。按下列公式计算血小板聚集抑制率: 血小板聚集抑制率 (%) = [(空白对照组最大聚集率-给药组最大聚集率)/空白对照组最大聚集率]×100%。

基金

收起

国家创新药物孵化基地项目(2012ZX09401066)

参考文献

收起

文献

收起

参考文献引证文献

排序方式：

[1]

Mega JL, Simon T. Pharmacology of antithrombotic drugs:an assessment of oral antiplatelet and anticoagulant treatments[J]. Lancet, 2015, 386:281-291.

[2]

Wang Y, Jie W, Li J, et al. Design, synthesis and pharmacological evaluation of novel piperlongumine derivatives as potential antiplatelet aggregation candidate[J]. Chem Biol Drug Des, 2016, 87:833-840.

[3]

Lagerqvist B, Fröbert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction[J]. N Engl J Med, 2014, 371:1111-1120.

[4]

Goldstein DJ, John R, Salerno C, et al. Algorithm for the diagnosis and management of suspected pump thrombus[J]. Heart Lung Transpl, 2013, 32:667-670.

[5]

Kim TH, Kim HM, Park SW, et al. Inhibitory effects of yuzu and its components on human platelet aggregation[J]. Biomol Ther, 2015, 23:149-155.

[6]

Gregory YHL, Stephan W, Kurt H, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions[J]. Eur Heart J, 2014, 35:3155-3179.

[7]

Ren J, Niu XS, Xiong J, et al. Effects of 1-(cinnamoyl)-4-(phenylethylamine acetyl) piperazine maleate on platelet aggregation and thrombosis[J]. J China Pharm Univ (中国药科大学学报), 2011, 42:458-461.

[8]

Zhao LJ, Gao JT, Jin LY. Pharmacological effects and clinical application of cinepazide maleate[J]. J Jilin Med Coll (吉林医药学院学报), 2010, 31:296-299.

[9]

Masaya I, Nobuaki O, Satoko O, et al. Piperlongumine, a constituent of Piper longum L., inhibits rabbit platelet aggregation as a thromboxane A2 receptor antagonist[J]. Eur J Pharm, 2007, 570:38-42.

[10]

Park BS, Song DJ, Choi WS, et al. Antiplatelet activities of newly synthesized derivatives of piperlongumine[J]. Phytother Res, 2008, 22:1195-1199.

2017年第52卷第1期

PDF下载

105

引用本文

BibTeX

文章信息

doi: 10.16438/j.0513-4870.2016-1049

接收时间：2016-10-30
首发时间：2026-01-14
出版时间：2017-01-12

补充材料

相关文章

文章信息

作者

出版历史

收稿日期：2016-10-30
修回日期：2016-11-23

基金

国家创新药物孵化基地项目(2012ZX09401066)

作者信息

1.安徽中医药大学药学院, 安徽合肥 230038

2.安徽省中医药科学院药物化学研究所, 安徽合肥 230038

通讯作者:

* Tel:86-551-68129147,Fax:86-551-65169222,E-mail:lijiaming2004@sina.com

参考文献

分享链接

https://castjournals.cast.org.cn/joweb/yxxb/CN/10.16438/j.0513-4870.2016-1049

分享至

全文二维码

扫描看全文

引用本文

BibTeX

本文的引用情况

2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

关闭全屏

BibTeX
EndNote
RefWorks
TxT

Compd.	R₁	R₂	R₃	R₄	Yield/%	mp/℃	Character
6a	H	H	H	H	54.5	125.9-128.1	Light yellow crystal
6b	H	H	CH₃	H	56.7	147.6-150.0	White crystal
6c	H	H	OCH₃	H	57.2	149.7-151.6	Yellow crystal
6d	H	OCH₃	OCH₃	H	55.3	141.0-142.4	Yellow crystal
6e	H	OCH₃	H	OCH₃	53.8	132.1-133.9	White crystal
6f	H	OCH₃	OCH₃	OCH₃	55.7	128.9-131.3	Yellow crystal
6g	H	H	Cl	H	54.3	163.7-165.6	White crystal
6h	H	H	Br	H	52.3	181.3-182.5	White crystal
6i	H	H	NO₂	H	53.6	152.7-154.3	Light yellow crystal
6j	Cl	H	H	H	50.7	178.9-180.1	White crystal
9a	H	H	H	H	52.2	130.3-131.7	White crystal
9b	H	H	CH₃	H	53.4	153.6-155.4	White crystal
9c	H	H	OCH₃	H	54.6	136.6-138.7	Light yellow crystal
9d	H	OCH₃	OCH₃	H	53.8	132.3-133.7	Yellow crystal
9e	H	OCH₃	H	OCH₃	52.7	127.6-129.0	Light yellow crystal
9f	H	OCH₃	OCH₃	OCH₃	55.9	113.7-115.9	Yellow crystal
9g	H	H	Cl	H	53.2	160.1-161.8	White crysta
9h	H	H	Br	H	52.1	146.6-148.3	White crystal
9i	H	H	NO₂	H	50.7	158.9-160.7	Light yellow crystal
9j	Cl	H	H	H	55.3	170.3-171.7	White crystal

Compd.

R₁

R₂

R₃

R₄

Yield/%

mp/℃

Character

54.5

125.9-128.1

Light yellow crystal

CH₃

56.7

147.6-150.0

White crystal

OCH₃

57.2

149.7-151.6

Yellow crystal

OCH₃

55.3

141.0-142.4

Yellow crystal

OCH₃

53.8

132.1-133.9

White crystal

OCH₃

55.7

128.9-131.3

Yellow crystal

54.3

163.7-165.6

White crystal

52.3

181.3-182.5

White crystal

NO₂

53.6

152.7-154.3

Light yellow crystal

50.7

178.9-180.1

White crystal

52.2

130.3-131.7

White crystal

CH₃

53.4

153.6-155.4

White crystal

OCH₃

54.6

136.6-138.7

Light yellow crystal

OCH₃

53.8

132.3-133.7

Yellow crystal

OCH₃

52.7

127.6-129.0

Light yellow crystal

OCH₃

55.9

113.7-115.9

Yellow crystal

53.2

160.1-161.8

White crysta

52.1

146.6-148.3

White crystal

NO₂

50.7

158.9-160.7

Light yellow crystal

55.3

170.3-171.7

White crystal

Compd.	¹H NMR (CDCl₃,300 MHz),¹³C NMR (CDCl₃,75 MHz),IR,ESI-MS
6a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.52 (d,J = 8.7 Hz,2H,ArH),7.36-7.38 (m,3H,ArH×2 and ThH),7.15 (t,J = 8.7 Hz,1H,ArH),6.79-6.88 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,127.8,125.2,124.4,123.5,116.9,61.4,45.7,43.7,42.9,40.2,25.8; IR (KBr,cm^-1) υ: 3 044.9,2 923.0,2 845.2,1 634.7,1 602.0,1 456.2,1 277.7,1 224.1,1 018.8,977.2,768.9,703.5,551.7; ESI-MS for C₂₂H₂₅N₃O₂S: m/z 396.06 [M+H]⁺
6b	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.42 (d,J = 7.8 Hz,2H,ArH),7.18 (d,J = 7.8 Hz,2H,ArH),7.09 (d,J = 5.1 Hz,1H,ThH),6.80 (d,J = 15.3 Hz,1H,COCH=),6.44 (d,J = 5.1 Hz,1H,ThH),3.64 (s,2H,Py-CH₂),3.68-3.81 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ,2.37 (s,3H,CH₃); ¹³C NMR δ: 168.5,165.8,143.5,140.2,133.1,133.0,132.2,129.6,127.8,125.1,123.0,115.3,52.9,50.5,45.6,42.0,41.9,25.4,21.4; IR (KBr,cm^-1) υ: 2 921.0,2 826.4,1 632.6,1 605.0,1 514.8,1 464.5,1 436.6,1 276.1,1 209.0,1 027.6,983.7,813.2,720.9; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.21 [M+H]⁺.
6c	¹H NMR δ: 7.66 (d,J = 15.3 Hz,1H,ArCH=),7.47 (d,J = 8.4 Hz,2H,ArH),7.08 (d,J = 4.8 Hz,ThH),6.89 (d,J = 8.4 Hz,2H,ArH),6.70-6.73 (m,1H,COCH= and ThH),3.82 (s,3H,OCH₃),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.42 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,166.0,161.0,143.2,133.2,133.0,129.4,127.7,125.1,122.9,114.3,113.9,60.8,55.4,52.9,50.6,45.7,41.9,25.4,IR (KBr,cm^-1) υ: 2 917.0,2 821.8,2 774.2,1 628.8,1 604.9,1 438.4,1 426.5,1 277.7,1 206.3,1 012.9,986.1,810.6,718.4; ESI-MS for C₂₃H₂₇N₃O₃S: m/z 426.08 [M+H]⁺.
6d	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.07-7.15 (m,2H,ArH and ThH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.69- 6.73 (m,2H,ThH and COCH=),3.92 (s,3H,OCH₃),3.90 (s,3H,OCH₃),3.65-3.79 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.9,150.7,149.1,143.6,133.1,133.0,127.9,125.1,122.9,122.1,114.1,111.1,109.8,56.0,50.5,45.6,43.4,41.9,25.4; IR (KBr,cm^-1) υ: 3 009.3,2 896.2,2 830.7,1 631.7,1 596.0,1 509.8,1 423.5,1 271.7,1 140.8,1 027.8,989.1,804.6,709.4; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.24 [M+H]⁺.
6e	¹H NMR δ: 7.52 (d,J = 15.3 Hz,1H,ArCH=),7.01 (d,J = 5.1 Hz,1H,ThH),6.73 (d,J = 15.3 Hz,1H,COCH=),6.65 (d,J = 5.1 Hz,1H,ThH),6.57 (s,2H,ArH),6.40 (s,1H,ArH),3.73 (s,6H,OCH₃×2) ,3.57-3.68 (m,8H,Pp-CH₂×4) ,3.56 (s,2H,Py-CH₂),3.35 (s,2H,COCH₂),2.81 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.6,161.0,143.5,136.9,133.1,133.0,125.1,122.9,117.1,105.9,101.9,60.7,55.5,52.9,50.6,45.6,41.9,25.4; IR (KBr,cm^-1) υ: 3 006.3,2 925.9,2 839.7,1 637.7,1 610.9,1 456.2,1 414.6,1 280.7,980.2,825.5,700.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.31 [M+H]⁺.
6f	¹H NMR δ: 7.61 (d,J = 15.3 Hz,1H,ArCH=),7.10 (d,J = 5.1 Hz,1H,ThH),6.69-6.76 (m,4H,ArH,ThH and COCH=),3.89 (s,6H,OCH₃×2) ,3.87 (s,3H,OCH₃),3.65-3.78 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.7,153.4,143.7,139.8,133.0,132.3,130.5,125.1,123.0,115.6,105.1,61.0,56.2,53.0,50.6,45.6,43.6,42.0, 25.4; IR (KBr,cm^-1) υ: 2 924.2,2 839.1,1 642.9,1 583.7,1 505.5,1 458.8,1 422.6,1 335.9,1 318.9,1 268.8,1 222.3,1 153.8,1 125.5, 1 037.7,985.7,902.9,823.4,778.9,704.9; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.11 [M+H]⁺.
6g	¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.45 (d,J = 5.4 Hz,2H,ArH),7.34 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.83 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.67-3.97 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.4,142.2,135.7,133.5,133.1,133.0,129.1,129.0,125.1,123.0,117.0,53.0,50.6,45.6,42.0,25.4; IR (KBr,cm^-1) υ: 2 922.3,2 823.4,1 640.9,1 605.0,1 494.4,1 461.5,1 434.6,1 279.1,1 219.3,1 162.5,1 090.7,1 013.0,977.1,810.6,722.9; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.11 [M+H]⁺.
6h	¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.41 (d,J = 5.4 Hz,2H,ArH),7.24 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.81 (d,J = 15.6 Hz,1H,COCH=),6.68 (d,J = 5.1 Hz,1H,ThH),3.71-3.99 (m,8H,Pp-CH₂×4) ,3.67 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ;¹³C NMR δ: 168.2,165.4,142.3,135.7,133.9,132.7,132.1,129.4,125.1,124.0,123.1,117.1,60.4,52.8,50.6,45.6,41.9,25.2; IR (KBr,cm^-1) υ: 2 921.0,2 733.6,1 641.9,1 468.1,1 423.4,1 286.5,1 212.8,1 068.1,981.2,821.8; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 474.32 [M+H]⁺.
6i	¹H NMR δ: 8.22 (d,J = 8.7 Hz,2H,ArH),7.73-7.68 (m,3H,ArCH= and ArH),7.10 (d,J = 5.1 Hz,ThH),5.95-7.07 (m,1H,COCH=),6.73 (d,J = 5.1 Hz,1H,ThH),3.68-3.83 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.44 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.6,164.7,148.2,141.2,140.6,133.1,133.0,128.4,125.1,124.1,122.9,120.9,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 3 098.1,2 916.6,1 839.2,1 729.3,1 637.1,1 613.3,1 515.1,1 431.7,1 339.5,1 107.4,985.4,839.6,756.3,702.7; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.17 [M+H]⁺.
6j	¹H NMR δ: 8.02 (d,J = 15.6 Hz,1H,ArCH=),7.58 (s,1H,ArH),7.36-7.44 (m,1H,ArH),7.23-7.32 (m,2H,ArH×2) ,7.09 (d,J = 5.1 Hz,1H,ThH),6.84 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.64-3.77 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.3,139.2,134.7,133.4,133.1,133.0,130.6,130.2,127.6,126.9,125.1,123.0,119.8,52.9,50.6,45.8,45.5,41.9,25.4; IR (KBr,cm^-1) υ: 2 901.7,2 812.4,2 735.1,1 654.9,1 592.4,1 467.5,1 437.7,1 220.5,988.4,747.4,696.8; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.17 [M+H]⁺.
9a	¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.51 (d,J = 5.1 Hz,2H,ArH),7.36 (d,J = 5.1 Hz,3H,ArH×3) ,7.15 (d,J = 4.5 Hz,1H,ThH),6.89-6.80 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.85-3.92 (m,2H,Py-CH₂),3.61-3.82 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.8 Hz,2H,COCH₂),2.81-3.00 (m,2H,Py-CH₂),2.58 (d,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,128.8,127.8,125.2,124.5,123.7,61.4,45.7,43.7,42.8,40.2,24.7; IR (KBr,cm^-1) υ: 2 920.0,2 842.6,1 637.7,1 607.9,1 456.2,1 429.4,1 227.1,1 102.2,1 006.9,763.0,697.5; ESI-MS for C₂₂H₂₅ClN₃O₂S: m/z 396.13 [M+H]⁺.
9b	¹H NMR δ: 7.47 (d,J = 15.6 Hz,1H,ArCH=),7.37 (d,J = 7.8 Hz,2H,ArH),7.15-7.27 (m,3H,ThH and ArH×2) ,6.95 (d,J = 15.6 Hz,1H,COCH=),6.79 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.88-3.95 (m,2H,Py-CH₂),3.54-3.76 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.5 Hz,2H,COCH₂),2.74-2.98 (m,2H,Py-CH₂),2.56 (d,4H,Pp-CH₂×2) ,2.23 (s,3H,CH₃); ¹³C NMR δ: 168.0,163.2,144.6,139.2,134.4,131.2,130.6,129.0,128.6,125.1,124.7,115.8,56.7,52.7,44.7,42.9,40.6,23.8,20.3; IR (KBr,cm^-1) υ: 3 018.2,2 920.0,2 512.4,1 655.5,1 610.9,1 432.4,1 274.7,1 236.0,1 122.9,983.1,786.8,703.5; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.17 [M+H]⁺.
9c	¹H NMR δ: 7.64 (d,J = 15.6 Hz,1H,ArCH=),7.46 (d,J = 8.4 Hz,ArH),7.14 (d,J = 4.8 Hz,1H,ThH),6.88 (d,J = 8.7 Hz,2H,ArH),6.81 (d,J = 4.8 Hz,1H,ThH),6.74 (d,J = 15.0 Hz,1H,COCH=),4.66 (s,2H,Py-CH₂),3.85-3.93 (m,2H,Py-CH₂),3.82 (s,3H,OCH₃),3.55-3.77 (m,4H,Pp-CH₂×2) ,3.31 (d,J = 7.5 Hz,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.56 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,160.9,142.7,134.1,132.4,132.2,131.5,129.3,127.9,125.2,123.7,61.5,55.4,45.7,43.6,42.8,40.2, 25.9; IR (KBr,cm^-1) υ: 3 065 8,2 833.7,2 812.9,1 649.6,1 631.7,1 599.0,1 512.7,1 420.5,1 280.7,1 170.6,1 003.9,831.4,703.5; ESI-MS for C₂₃H₂₇ClN₃O₃S: m/z 426.15 [M+H]⁺.
9d	¹H NMR δ: 7.62 (d,J = 15.3 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),7.11 (d,J = 8.1Hz,1H,ArH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.81 (d,J = 5.1 Hz,1H,ThH),6.72 (d,J = 15.3 Hz,1H,COCH=),4.67 (s,2H,Py-CH₂),3.84-3.92 (m,8H,OCH₃×2 and Py-CH₂),3.60-3.82 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.8 Hz,2H,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.59 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,150.6,149.1,143.0,134.1,132.3,132.2,125.2,124.5,123.7,121.9,111.1,109.9,61.5,56.0,53.2,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 902.2,2 936.7,1 643.6,1 590.1,1 509.8,1 438.4,1 262.8,1 140.8,1 000.9,804.6,703.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.35 [M+H]⁺.
9e	¹H NMR δ: 7.56 (d,J = 15.6 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),6.79-6.84 (m,2H,COCH= and ThH),6.65 (s,2H,ArH),6.47 (s,1H,ArH),4.67 (s,2H,Py-CH₂),3.85-3.94 (m,2H,Py-CH₂),3.81 (s,6H,OCH₃×2) ,3.57-3.76 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.3,160.9,142.9,137.2,132.3,132.2,125.2,123.5,117.5,105.8,101.7,61.4,55.5,45.7,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 3 101.5,2 949.8,2 833.7,1 634.7,1 575.2,1 429.4,1 325.3,1 203.3,950.4,834.4,715.4,676.7; ESI-MS for C₂₄H₂₉ClN₃O₄S: m/z 456.27 [M+H]⁺.
9f	¹H NMR δ: 7.58 (d,J = 15.3 Hz,1H,ArCH=),7.16 (d,J = 5.1 Hz,1H,ThH),6.60-6.81 (m,4H,ArH×2,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.86-3.89 (m,2H,Py-CH₂),3.82 (s,9H,OCH₃×3) ,3.57-3.74 (m,4H,Pp-CH₂×2) ,3.34 (d,J = 6.3 Hz,2H,COCH₂),2.70-3.00 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.4,153.4,143.1,139.6,132.3,132.1,130.8,125.2,123.7,116.2,104.9,61.4,60.9,56.2,53.1,45.7,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 9319,2 842.6,1 643.6,1 587.1,1 500.8,1 453.2,1 334.2,1 265.8,1 122.9,1 000.9,825.5,709.4; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.12 [M+H]⁺.
9g	¹H NMR δ: 7.63 (d,J = 15.6 Hz,1H,ArCH=),7.44 (d,J = 8.4 Hz,2H,ArH),7.33 (d,J = 8.4 Hz,2H,ArH),7.15 (d,J = 4.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.66 (s,2H,Py-CH₂),3.84-3.94 (m,2H,Py-CH₂),3.61-3.73 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,2H,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 135.4,134.1,133.7,132.3,131.4,125.2,124.4,123.7,117.5,61.4,45.7,43.6,42.8,42.1,24.7; IR (KBr,cm^-1) υ: 2 997.1,1 820.6,1 736.8,1 649.9,1 635.9,1 605.2,1 437.2,1 235.5,1 221.5,1 003.8,857.4,812.6; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.09 [M+H]⁺.
9h	¹H NMR δ: 7.60 (d,J = 15.3 Hz,1H,ArCH=),7.50 (d,J = 8.4 Hz,2H,ArH),7.38 (d,J = 8.4 Hz,2H,ArH),7.15 (t,J = 7.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.83-3.94 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.9 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 134.1,132.0,131.8,129.2,125.2,124.4,123.7,123.5,117.5,61.4,45.6,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 943.8,2 834.8,1 735.9,1 637.7,1 596.0,1 435.8,1 241.9, 1 006.9,807.6,780.8,703.5; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 476.09 [M+H]⁺.
9i	¹H NMR δ: 8.24 (d,J = 8.7 Hz,2H,ArH),7.66 (d,J = 8.4 Hz,2H,ArH),7.13-7.16 (m,1H,ArCH=),6.94 (d,J = 15.3 Hz,1H,COCH=),6.72-6.83 (m,2H,ThH×2) ,4.67 (s,2H,Py-CH₂),3.62-3.95 (m,6H,Pp-CH₂×2 and Py-CH₂),3.37 (d,J = 7.2 Hz,2H,COCH₂),2.85-3.11 (m,2H,Py-CH₂),2.65 (s,4H,Pp-CH₂×2) ,¹³C NMR δ: 168.6,165.7,148.2,141.2,140.6,133.2,133.1,128.4,126.1,122.7,120.9,118.3,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 2 812.9,1 649.6,1 631.7,1 610.9,1 515.7,1 343.1,1 221.2,1 006.9,852.2,751.1,703.5; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.12 [M+H]⁺.
9j	¹H NMR δ: 7.86 (d,J = 15.3 Hz,1H,ArCH=),7.63 (d,J = 7.5 Hz,1H,ArH),7.41 (d,J = 7.5 Hz,1H,ArH),7.25-7.33 (m,2H,ArH),7.21 (d,J = 5.1 Hz,1H,ThH),6.93 (d,J = 15.3 Hz,1H,COCH=),6.78 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.94-4.07 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.3 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 167.6,163.2,140.0,134.1,132.5,132.3,131.3,130.6,129.9,127.7,127.4,125.1,124.3,118.6,56.7,52.5,44.7,43.0,42.5,24.4; IR (KBr,cm^-1) υ: 2 962.9,2 915.5,1 634.9,1 612.4,1 475.5,1 435.9,1 270.1,1 225.4,1 051.6,880.5; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.18 [M+H]⁺.

Compd.

¹H NMR (CDCl₃,300 MHz),¹³C NMR (CDCl₃,75 MHz),IR,ESI-MS

¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.52 (d,J = 8.7 Hz,2H,ArH),7.36-7.38 (m,3H,ArH×2 and ThH),7.15 (t,J = 8.7 Hz,1H,ArH),6.79-6.88 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,127.8,125.2,124.4,123.5,116.9,61.4,45.7,43.7,42.9,40.2,25.8; IR (KBr,cm^-1) υ: 3 044.9,2 923.0,2 845.2,1 634.7,1 602.0,1 456.2,1 277.7,1 224.1,1 018.8,977.2,768.9,703.5,551.7; ESI-MS for C₂₂H₂₅N₃O₂S: m/z 396.06 [M+H]⁺

¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.42 (d,J = 7.8 Hz,2H,ArH),7.18 (d,J = 7.8 Hz,2H,ArH),7.09 (d,J = 5.1 Hz,1H,ThH),6.80 (d,J = 15.3 Hz,1H,COCH=),6.44 (d,J = 5.1 Hz,1H,ThH),3.64 (s,2H,Py-CH₂),3.68-3.81 (m,8H,Pp-CH₂×4) ,3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ,2.37 (s,3H,CH₃); ¹³C NMR δ: 168.5,165.8,143.5,140.2,133.1,133.0,132.2,129.6,127.8,125.1,123.0,115.3,52.9,50.5,45.6,42.0,41.9,25.4,21.4; IR (KBr,cm^-1) υ: 2 921.0,2 826.4,1 632.6,1 605.0,1 514.8,1 464.5,1 436.6,1 276.1,1 209.0,1 027.6,983.7,813.2,720.9; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.21 [M+H]⁺.

¹H NMR δ: 7.66 (d,J = 15.3 Hz,1H,ArCH=),7.47 (d,J = 8.4 Hz,2H,ArH),7.08 (d,J = 4.8 Hz,ThH),6.89 (d,J = 8.4 Hz,2H,ArH),6.70-6.73 (m,1H,COCH= and ThH),3.82 (s,3H,OCH₃),3.64-3.78 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.42 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,166.0,161.0,143.2,133.2,133.0,129.4,127.7,125.1,122.9,114.3,113.9,60.8,55.4,52.9,50.6,45.7,41.9,25.4,IR (KBr,cm^-1) υ: 2 917.0,2 821.8,2 774.2,1 628.8,1 604.9,1 438.4,1 426.5,1 277.7,1 206.3,1 012.9,986.1,810.6,718.4; ESI-MS for C₂₃H₂₇N₃O₃S: m/z 426.08 [M+H]⁺.

¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.07-7.15 (m,2H,ArH and ThH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.69- 6.73 (m,2H,ThH and COCH=),3.92 (s,3H,OCH₃),3.90 (s,3H,OCH₃),3.65-3.79 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.9,150.7,149.1,143.6,133.1,133.0,127.9,125.1,122.9,122.1,114.1,111.1,109.8,56.0,50.5,45.6,43.4,41.9,25.4; IR (KBr,cm^-1) υ: 3 009.3,2 896.2,2 830.7,1 631.7,1 596.0,1 509.8,1 423.5,1 271.7,1 140.8,1 027.8,989.1,804.6,709.4; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.24 [M+H]⁺.

¹H NMR δ: 7.52 (d,J = 15.3 Hz,1H,ArCH=),7.01 (d,J = 5.1 Hz,1H,ThH),6.73 (d,J = 15.3 Hz,1H,COCH=),6.65 (d,J = 5.1 Hz,1H,ThH),6.57 (s,2H,ArH),6.40 (s,1H,ArH),3.73 (s,6H,OCH₃×2) ,3.57-3.68 (m,8H,Pp-CH₂×4) ,3.56 (s,2H,Py-CH₂),3.35 (s,2H,COCH₂),2.81 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.6,161.0,143.5,136.9,133.1,133.0,125.1,122.9,117.1,105.9,101.9,60.7,55.5,52.9,50.6,45.6,41.9,25.4; IR (KBr,cm^-1) υ: 3 006.3,2 925.9,2 839.7,1 637.7,1 610.9,1 456.2,1 414.6,1 280.7,980.2,825.5,700.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.31 [M+H]⁺.

¹H NMR δ: 7.61 (d,J = 15.3 Hz,1H,ArCH=),7.10 (d,J = 5.1 Hz,1H,ThH),6.69-6.76 (m,4H,ArH,ThH and COCH=),3.89 (s,6H,OCH₃×2) ,3.87 (s,3H,OCH₃),3.65-3.78 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ;
¹³C NMR δ: 168.5,165.7,153.4,143.7,139.8,133.0,132.3,130.5,125.1,123.0,115.6,105.1,61.0,56.2,53.0,50.6,45.6,43.6,42.0,
25.4; IR (KBr,cm^-1) υ: 2 924.2,2 839.1,1 642.9,1 583.7,1 505.5,1 458.8,1 422.6,1 335.9,1 318.9,1 268.8,1 222.3,1 153.8,1 125.5,
1 037.7,985.7,902.9,823.4,778.9,704.9; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.11 [M+H]⁺.

¹H NMR δ: 7.64 (d,J = 15.3 Hz,1H,ArCH=),7.45 (d,J = 5.4 Hz,2H,ArH),7.34 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.83 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.67-3.97 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.4,142.2,135.7,133.5,133.1,133.0,129.1,129.0,125.1,123.0,117.0,53.0,50.6,45.6,42.0,25.4; IR (KBr,cm^-1) υ: 2 922.3,2 823.4,1 640.9,1 605.0,1 494.4,1 461.5,1 434.6,1 279.1,1 219.3,1 162.5,1 090.7,1 013.0,977.1,810.6,722.9; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.11 [M+H]⁺.

¹H NMR δ: 7.67 (d,J = 15.3 Hz,1H,ArCH=),7.41 (d,J = 5.4 Hz,2H,ArH),7.24 (d,J = 8.4 Hz,2H,ArH),7.10 (d,J = 5.1 Hz,1H,ThH),6.81 (d,J = 15.6 Hz,1H,COCH=),6.68 (d,J = 5.1 Hz,1H,ThH),3.71-3.99 (m,8H,Pp-CH₂×4) ,3.67 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ;¹³C NMR δ: 168.2,165.4,142.3,135.7,133.9,132.7,132.1,129.4,125.1,124.0,123.1,117.1,60.4,52.8,50.6,45.6,41.9,25.2; IR (KBr,cm^-1) υ: 2 921.0,2 733.6,1 641.9,1 468.1,1 423.4,1 286.5,1 212.8,1 068.1,981.2,821.8; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 474.32 [M+H]⁺.

¹H NMR δ: 8.22 (d,J = 8.7 Hz,2H,ArH),7.73-7.68 (m,3H,ArCH= and ArH),7.10 (d,J = 5.1 Hz,ThH),5.95-7.07 (m,1H,COCH=),6.73 (d,J = 5.1 Hz,1H,ThH),3.68-3.83 (m,8H,Pp-CH₂×4) ,3.64 (s,2H,Py-CH₂),3.44 (s,2H,COCH₂),2.89 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.6,164.7,148.2,141.2,140.6,133.1,133.0,128.4,125.1,124.1,122.9,120.9,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 3 098.1,2 916.6,1 839.2,1 729.3,1 637.1,1 613.3,1 515.1,1 431.7,1 339.5,1 107.4,985.4,839.6,756.3,702.7; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.17 [M+H]⁺.

¹H NMR δ: 8.02 (d,J = 15.6 Hz,1H,ArCH=),7.58 (s,1H,ArH),7.36-7.44 (m,1H,ArH),7.23-7.32 (m,2H,ArH×2) ,7.09 (d,J = 5.1 Hz,1H,ThH),6.84 (d,J = 15.6 Hz,1H,COCH=),6.72 (d,J = 5.1 Hz,1H,ThH),3.64-3.77 (m,8H,Pp-CH₂×4) ,3.63 (s,2H,Py-CH₂),3.43 (s,2H,COCH₂),2.88 (s,4H,Py-CH₂×2) ; ¹³C NMR δ: 168.5,165.3,139.2,134.7,133.4,133.1,133.0,130.6,130.2,127.6,126.9,125.1,123.0,119.8,52.9,50.6,45.8,45.5,41.9,25.4; IR (KBr,cm^-1) υ: 2 901.7,2 812.4,2 735.1,1 654.9,1 592.4,1 467.5,1 437.7,1 220.5,988.4,747.4,696.8; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.17 [M+H]⁺.

¹H NMR δ: 7.67 (d,J = 15.6 Hz,1H,ArCH=),7.51 (d,J = 5.1 Hz,2H,ArH),7.36 (d,J = 5.1 Hz,3H,ArH×3) ,7.15 (d,J = 4.5 Hz,1H,ThH),6.89-6.80 (m,2H,COCH= and ThH),4.67 (s,2H,Py-CH₂),3.85-3.92 (m,2H,Py-CH₂),3.61-3.82 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.8 Hz,2H,COCH₂),2.81-3.00 (m,2H,Py-CH₂),2.58 (d,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.5,143.0,135.2,132.3,132.2,129.7,128.8,127.8,125.2,124.5,123.7,61.4,45.7,43.7,42.8,40.2,24.7; IR (KBr,cm^-1) υ: 2 920.0,2 842.6,1 637.7,1 607.9,1 456.2,1 429.4,1 227.1,1 102.2,1 006.9,763.0,697.5; ESI-MS for C₂₂H₂₅ClN₃O₂S: m/z 396.13 [M+H]⁺.

¹H NMR δ: 7.47 (d,J = 15.6 Hz,1H,ArCH=),7.37 (d,J = 7.8 Hz,2H,ArH),7.15-7.27 (m,3H,ThH and ArH×2) ,6.95 (d,J = 15.6 Hz,1H,COCH=),6.79 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.88-3.95 (m,2H,Py-CH₂),3.54-3.76 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.5 Hz,2H,COCH₂),2.74-2.98 (m,2H,Py-CH₂),2.56 (d,4H,Pp-CH₂×2) ,2.23 (s,3H,CH₃); ¹³C NMR δ: 168.0,163.2,144.6,139.2,134.4,131.2,130.6,129.0,128.6,125.1,124.7,115.8,56.7,52.7,44.7,42.9,40.6,23.8,20.3; IR (KBr,cm^-1) υ: 3 018.2,2 920.0,2 512.4,1 655.5,1 610.9,1 432.4,1 274.7,1 236.0,1 122.9,983.1,786.8,703.5; ESI-MS for C₂₃H₂₇N₃O₂S: m/z 410.17 [M+H]⁺.

¹H NMR δ: 7.64 (d,J = 15.6 Hz,1H,ArCH=),7.46 (d,J = 8.4 Hz,ArH),7.14 (d,J = 4.8 Hz,1H,ThH),6.88 (d,J = 8.7 Hz,2H,ArH),6.81 (d,J = 4.8 Hz,1H,ThH),6.74 (d,J = 15.0 Hz,1H,COCH=),4.66 (s,2H,Py-CH₂),3.85-3.93 (m,2H,Py-CH₂),3.82 (s,3H,OCH₃),3.55-3.77 (m,4H,Pp-CH₂×2) ,3.31 (d,J = 7.5 Hz,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.56 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,160.9,142.7,134.1,132.4,132.2,131.5,129.3,127.9,125.2,123.7,61.5,55.4,45.7,43.6,42.8,40.2, 25.9; IR (KBr,cm^-1) υ: 3 065 8,2 833.7,2 812.9,1 649.6,1 631.7,1 599.0,1 512.7,1 420.5,1 280.7,1 170.6,1 003.9,831.4,703.5; ESI-MS for C₂₃H₂₇ClN₃O₃S: m/z
426.15 [M+H]⁺.

¹H NMR δ: 7.62 (d,J = 15.3 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),7.11 (d,J = 8.1Hz,1H,ArH),7.03 (s,1H,ArH),6.86 (d,J = 8.4 Hz,1H,ArH),6.81 (d,J = 5.1 Hz,1H,ThH),6.72 (d,J = 15.3 Hz,1H,COCH=),4.67 (s,2H,Py-CH₂),3.84-3.92 (m,8H,OCH₃×2 and Py-CH₂),3.60-3.82 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 7.8 Hz,2H,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.59 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.7,150.6,149.1,143.0,134.1,132.3,132.2,125.2,124.5,123.7,121.9,111.1,109.9,61.5,56.0,53.2,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 902.2,2 936.7,1 643.6,1 590.1,1 509.8,1 438.4,1 262.8,1 140.8,1 000.9,804.6,703.5; ESI-MS for C₂₄H₂₉N₃O₄S: m/z 456.35 [M+H]⁺.

¹H NMR δ: 7.56 (d,J = 15.6 Hz,1H,ArCH=),7.15 (d,J = 4.5 Hz,1H,ThH),6.79-6.84 (m,2H,COCH= and ThH),6.65 (s,2H,ArH),6.47 (s,1H,ArH),4.67 (s,2H,Py-CH₂),3.85-3.94 (m,2H,Py-CH₂),3.81 (s,6H,OCH₃×2) ,3.57-3.76 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,COCH₂),2.87-2.96 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.2,165.3,160.9,142.9,137.2,132.3,132.2,125.2,123.5,117.5,105.8,101.7,61.4,55.5,45.7,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 3 101.5,2 949.8,2 833.7,1 634.7,1 575.2,1 429.4,1 325.3,1 203.3,950.4,834.4,715.4,676.7; ESI-MS for C₂₄H₂₉ClN₃O₄S: m/z 456.27 [M+H]⁺.

¹H NMR δ: 7.58 (d,J = 15.3 Hz,1H,ArCH=),7.16 (d,J = 5.1 Hz,1H,ThH),6.60-6.81 (m,4H,ArH×2,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.86-3.89 (m,2H,Py-CH₂),3.82 (s,9H,OCH₃×3) ,3.57-3.74 (m,4H,Pp-CH₂×2) ,3.34 (d,J = 6.3 Hz,2H,COCH₂),2.70-3.00 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.4,153.4,143.1,139.6,132.3,132.1,130.8,125.2,123.7,116.2,104.9,61.4,60.9,56.2,53.1,45.7,43.7,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 9319,2 842.6,1 643.6,1 587.1,1 500.8,1 453.2,1 334.2,1 265.8,1 122.9,1 000.9,825.5,709.4; ESI-MS for C₂₅H₃₁N₃O₅S: m/z 486.12 [M+H]⁺.

¹H NMR δ: 7.63 (d,J = 15.6 Hz,1H,ArCH=),7.44 (d,J = 8.4 Hz,2H,ArH),7.33 (d,J = 8.4 Hz,2H,ArH),7.15 (d,J = 4.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.66 (s,2H,Py-CH₂),3.84-3.94 (m,2H,Py-CH₂),3.61-3.73 (m,4H,Pp-CH₂×2) ,3.32 (d,J = 7.2 Hz,2H,COCH₂),2.85-2.95 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 135.4,134.1,133.7,132.3,131.4,125.2,124.4,123.7,117.5,61.4,45.7,43.6,42.8,42.1,24.7; IR (KBr,cm^-1) υ: 2 997.1,1 820.6,1 736.8,1 649.9,1 635.9,1 605.2,1 437.2,1 235.5,1 221.5,1 003.8,857.4,812.6; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.09 [M+H]⁺.

¹H NMR δ: 7.60 (d,J = 15.3 Hz,1H,ArCH=),7.50 (d,J = 8.4 Hz,2H,ArH),7.38 (d,J = 8.4 Hz,2H,ArH),7.15 (t,J = 7.8 Hz,1H,ThH),6.79-6.87 (m,2H,ThH and COCH=),4.67 (s,2H,Py-CH₂),3.83-3.94 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.9 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.60 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 168.1,165.1,141.6, 134.1,132.0,131.8,129.2,125.2,124.4,123.7,123.5,117.5,61.4,45.6,43.6,42.8,40.2,25.9; IR (KBr,cm^-1) υ: 2 943.8,2 834.8,1 735.9,1 637.7,1 596.0,1 435.8,1 241.9,
1 006.9,807.6,780.8,703.5; ESI-MS for C₂₂H₂₄BrN₃O₂S: m/z 476.09 [M+H]⁺.

¹H NMR δ: 8.24 (d,J = 8.7 Hz,2H,ArH),7.66 (d,J = 8.4 Hz,2H,ArH),7.13-7.16 (m,1H,ArCH=),6.94 (d,J = 15.3 Hz,1H,COCH=),6.72-6.83 (m,2H,ThH×2) ,4.67 (s,2H,Py-CH₂),3.62-3.95 (m,6H,Pp-CH₂×2 and Py-CH₂),3.37 (d,J = 7.2 Hz,2H,COCH₂),2.85-3.11 (m,2H,Py-CH₂),2.65 (s,4H,Pp-CH₂×2) ,¹³C NMR δ: 168.6,165.7,148.2,141.2,140.6,133.2,133.1,128.4,126.1,122.7,120.9,118.3,60.7,53.0,50.6,45.7,42.0,25.4; IR (KBr,cm^-1) υ: 2 812.9,1 649.6,1 631.7,1 610.9,1 515.7,1 343.1,1 221.2,1 006.9,852.2,751.1,703.5; ESI-MS for C₂₂H₂₄N₄O₄S: m/z 441.12 [M+H]⁺.

¹H NMR δ: 7.86 (d,J = 15.3 Hz,1H,ArCH=),7.63 (d,J = 7.5 Hz,1H,ArH),7.41 (d,J = 7.5 Hz,1H,ArH),7.25-7.33 (m,2H,ArH),7.21 (d,J = 5.1 Hz,1H,ThH),6.93 (d,J = 15.3 Hz,1H,COCH=),6.78 (d,J = 5.1 Hz,1H,ThH),4.70 (s,2H,Py-CH₂),3.94-4.07 (m,2H,Py-CH₂),3.62-3.75 (m,4H,Pp-CH₂×2) ,3.33 (d,J = 6.3 Hz,2H,COCH₂),2.86-2.97 (m,2H,Py-CH₂),2.58 (s,4H,Pp-CH₂×2) ; ¹³C NMR δ: 167.6,163.2,140.0,134.1,132.5,132.3,131.3,130.6,129.9,127.7,127.4,125.1,124.3,118.6,56.7,52.5,44.7,43.0,42.5,24.4; IR (KBr,cm^-1) υ: 2 962.9,2 915.5,1 634.9,1 612.4,1 475.5,1 435.9,1 270.1,1 225.4,1 051.6,880.5; ESI-MS for C₂₂H₂₄ClN₃O₂S: m/z 430.18 [M+H]⁺.

Compd.	IC₅₀/mmol·L^-1
6a	48.7	59.1
6b	5.2	5.8
6c	62.3	30.5
6d	9.8	5.5
6e	19.8	26.3
6f	18.4	16.2
6g	21.8	27.6
6h	13.0	8.7
6i	17.0	59.3
6j	32.5	6.1
9a	25.1	56.6
9b	2.1	4.8
9c	55.6	23.3
9d	7.4	9.2
9e	10.5	16.1
9f	15.5	25.4
9g	31.5	6.3
9h	7.2	11.3
9i	14.6	72.9
9j	28.1	19.0
Cinepazide	1.4	3.7
Aspirin	0.1	0.4

Compd.

IC₅₀/mmol·L^-1

ADP

48.7

59.1

5.2

5.8

62.3

30.5

9.8

5.5

19.8

26.3

18.4

16.2

21.8

27.6

13.0

8.7

17.0

59.3

32.5

6.1

25.1

56.6

2.1

4.8

55.6

23.3

7.4

9.2

10.5

16.1

15.5

25.4

31.5

6.3

7.2

11.3

14.6

72.9

28.1

19.0

Cinepazide

1.4

3.7

Aspirin

0.1

0.4