Biological Evaluation of Newly Synthesized Biaryl Guanidine Derivatives to Arrest β-Secretase Enzymatic Activity Involved in Alzheimer’s Disease

Table 1

Detailed information about newly synthesized N,N-biaryl guanidine derivatives to arrest BACE1 enzymatic activity.

Code	Structure of the compound with name	Spectral detail (NMR & ESI-MS)	Miscellaneous features
1		^1H-NMR (500 MHz, CD3OD): 8.6 (2H, NH, s), 8.2 (1H, NH, s), 7.3 (2H, d,  Hz), 7.0 (2H, d,  Hz), 6.8 (2H, d,  Hz), 6.7 (2H, d,  Hz); ^13C-NMR (125 MHz, CD3OD): 165.3, 163.3, 139.5 (2C), 135.7, 132.0 (2C), 122.7 (2C), 122.6 (2C), 114.1, 113.9; ^19F-NMR (470 MHz, CD3OD): -108.06, -125.11; HR-EI MS: 247.09201; [()^+ calculated for C13H11F2N3 247.09210].	55% yield; white solid; mp 130-132°C; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-Br was used to synthesize;
2		^1H-NMR (500 MHz, CD3OD): 8.8 (2H, NH, s), 8.2 (2H, d,  Hz), 7.9 (2H, d,  Hz), 7.8 (3H, d,  Hz), 7.4 (4H, m), 6.9 (2H, d,  Hz); ^13C-NMR (125 MHz, CD3OD): 161.3, 143.2 (2C), 131.9 (2C), 131.1 (2C), 129.3 (2C), 128.7 (2C), 126.8 (2C), 126.3 (2C), 121.6 (2C), 114.5 (2C), 110.9 (2C); HR-EI MS: 466.96318; [()^+ calculated for C21H15Br2N3 466.96327].	79% yield; white solid; mp 128-130°C; ; HB_donor 4; HB_acceptor 1; rotatable bonds 3; Ar-Br was used to synthesize;
3		^1H-NMR (500 MHz, CD3OD): 8.6 (2H, NH, s), 8.3 (1H, NH, s), 7.7 (3H, m), 7.4 (3H, m), 7.0 (2H, m); ^13C-NMR (125 MHz, CD3OD): 158.5, 139.7 (2C), 132.5 (2C), 131.0 (2C), 126.4 (2C), 123.0 (2C), 111.0 (2C); HREI MS: 301.8121; [()^+ calculated for C13H11N5O4 301.8110].	92% yield; yellow solid; mp 136-138°C; ; HB_donor 5; HB_acceptor 3; rotatable bonds 6; Ar-Br was used to synthesize;
4		^1H-NMR (500 MHz, CD3OD): 8.2 (2H, s), 7.6 (3H, d,  Hz), 6.9 (3H, t,  Hz); ^13C-NMR (125 MHz, CD3OD): 160.8, 159.8 (2C), 149.2 (2C), 139.7 (2C), 119.4 (2), 111.9 (2C); HREI MS: 213.10133; [()^+ calculated for C11H11N5 213.10145].	88% yield; white solid; mp 140-142°C; ; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-Br was used to synthesize;
5		^1H-NMR (500 MHz, CD3OD): 9.8 (1H, NH, s), 8.6 (2H, d,  Hz), 8.3 (1H, NH, s), 8.1 (1H, NH, S), 8.0 (1H, s), 7.7 (1H, s), 7.5 (2H, d, ), 7.3 (6H, m). ^13C-NMR (125 MHz, CD3OD): 161.6, 146 (2C), 143.2 (2C), 138.3 (2C), 133.4 (2C), 132.6 (2C), 130.3 (2C), 124.9 (2C), 123.5 (2C), 121.7 (2C); HREI MS: 313.13265; [()^+ calculated for C19H15N5 313.13275].	90% yield; white solid; mp 133-134°C; ; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-Br was used to synthesize;
6		^1H-NMR (500 MHz, CD3OD): 9.2 (2H, NH, s), 8.2 (2H, m), 7.9 (2H, d,  Hz), 7.8 (2H, m), 7.6 (1H, NH, S), 7.5 (2H, dt,  Hz), 7.4 (1H, m), 7.2 (2H, m), 6.8 (1H, S); ^13C-NMR (125 MHz, CD3OD): 161.5, 160.4 (2C), 139.3 (2C), 134.5 (2C), 129.3 (2C), 127.6 (2C), 127.1 (2C), 124.6 (2C), 123.1 (2C), 118.0 (2C) 105.6 (2C); ^19F-NMR (470 MHz, CD3OD): -75.2; HREI MS: 347.12329; [()^+ calculated for C21H15F2N3 347.12340].	63% yield; white solid; mp 126-128°C; ; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-Br was used to synthesize;
7		^1H-NMR (500 MHz, CD3OD): 9.2 (2H, NH, s), 8.2 (4H, m), 7.94 (1H, q, , 5.5 Hz), 7.8 (2H, tt, , 7.5 Hz), 7.8 (3H, m), 7.4 (2H, q,  Hz), 6.8 (1H, NH, s); ^13C-NMR (125 MHz, CD3OD): 161.9, 137.5 (2C), 135.2 (4C), 134.5 (2C), 133.2 (2C), 132.0 (2C), 129.5 (2C), 126.1 (2C), 121.7 (2C), 116.4 (2C); HREI MS: 311.14215; [()^+ calculated for C21H17N3 311.14225].	91% yield; white solid; mp 146-148°C; ; HB_donor 3; HB_acceptor 1; rotatable bonds 4; Ar-Br was used to synthesize;
8		^1H-NMR (500 MHz, CD3OD): 8.9 (2H, NH, s), 7.3 (3H, s), 5.7 (4H, s); ^13C-NMR (125 MHz, CD3OD): 161.3, 146.3 (2C), 134.7 (4C, d, .1 Hz), 131.4 (2C), 125.8 (4C, d,  Hz), 123.7 (2C, d,  Hz), 115.7 (2C); ^19F-NMR (470 MHz, CD3OD): -61.8, -61.5; HREI MS: 483.06039; [()^+ calculated for C17H9F12N3 483.06049].	68% yield; yellowish solid; mp 76-78°C; ; HB_donor 3; HB_acceptor 13; rotatable bonds 8; Ar-I was used to synthesize;
9		^1H-NMR (500 MHz, CD3OD): 8.7 (2H, NH, s), 8.3 (2H, s), 7.4 (1H, s), 7.3 (2H, t,  Hz); ^13C-NMR (125 MHz, CD3OD): 166.9 (2C), 158.5, 146.3 (2C), 143.2 (2C), 135.7 (2C), 121.5 (2C); HREI MS: 285.06376; [()^+ calculated for C11H7F4N5 285.06386].	61% yield, whitish yellow solid; mp 128-130°C; ; HB_donor 3; HB_acceptor 7; rotatable bonds 4; Ar-Br was used to synthesize;
10		^1H-NMR (500 MHz, CD3OD): 7.5 (2H, NH, s), 7.3 (4H, d,  Hz), 7.3 (4H, d,  Hz), 6.7 (1H, NH, s); ^13C-NMR (125 MHz, CD3OD): 163.3, 153.4, 133.8 (4C), 121.1 (4C); HREI MS: 368.93187; [()^+ calculated for C13H11Br2N3 368.93197].	72% yield; white solid; mp 250-252°C; ; HB_donor 3; HB_acceptor 1; rotatable bonds 4; Ar-Br was used to synthesize;
11		^1H-NMR (500 MHz, CD3OD): 8.4 (2H, NH, s) 7.9 (2H, dd, , 10.5 Hz), 7.8 (2H, d,  Hz), 7.6 (2H, t,  Hz), 6.2 (1H, s); ^13C-NMR (125 MHz, CD3OD): 159.1 (2C), 130.3 (2C), 126.2 (2C), 121.2 (2C), HREI MS: 315.01425; [()^+ calculated for C13H9Cl2F2N3 315.01416].	69% yield; white solid; mp 160-162°C; ; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-I was used to synthesize;
12		^1H-NMR (500 MHz, CD3OD): 7.7 (2H, NH, s), 7.1 (4H, t,  Hz), 7.0 (5H, t,  Hz), ^13C-NMR (125 MHz, CD3OD) 161.3, 159.47 (2C), 127.6 (2C), 127.1 (2C), 126.7 (2C), 121.5 (2C), 116.3 (2C); ^19F-NMR (470 MHz, CD3OD): -123.4, -123.1; HREI MS: 247.11200; [()^+ calculated for C13H11F2N3 247.11210].	71% yield; white solid; mp 146-148°C; ; HB_donor 3; HB_acceptor 3; rotatable bonds 4; Ar-Br was used to synthesize;
13		^1H-NMR (500 MHz, CD3OD): 8.4 (2H, NH, s) 7.6 (2H, t,  Hz), 7.3 (3H, t,  Hz), 7.0 (2H, m); ^13C-NMR (125 MHz, CD3OD) 161.9 (2C), 158.8, 133.9 (2C), 130.1 (2C), 130.0, 126.4, 124.6, 117.1, 116.8, 108.5; ^19F-NMR (470 MHz, CD3OD): -108.0, -125.1; HR-EI MS: 283.07316; [()^+ calculated for C13H9F4N3 283.07326].	56% yield; white solid; mp150-152; ; HB_donor 3; HB_acceptor 5; rotatable bonds 4; Ar-Br was used to synthesize;

Note: NMR: nuclear magnetic resonance; ESI-MS: electrospray ionization-mass spectrometry; mp: melting point; HB: hydrogen bonding; M. Wt: molecular weight.