Table 2. SAR analysis of APJ antagonists: Kojic acid scaffold—left region R3.
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|---|---|---|---|---|
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| Entry | R1 | APJ | AT1 | SI |
| 28 | H | >79 | >79 | ND |
| 29 | 3-NO2-4-Cl | 1.75 ± 0.14 | >79 | >45 |
| 30 | 3-NO2-4-Me | 4.70 ± 0.91 (3) | >79 | >17 |
| 31 | 3-NO2 | 59.20 ±4.77 (2) | >79 | ND |
| 32 | 4-Cl | >79 | >79 | ND |
| 33 | 4-NO2 | 3.11 ± 0.68 | >79 | >25 |
| 4.32 ± 1.29 | >79 | >23 | ||
| 34 | 4-CN | 8.51 ± 1.22 | >79 | >9 |
| 11.50 ± 1.35 | >79 | >7 | ||
| 35 | 4-CF3 | 20.6 (1) | >79 | ND |
| 36 | 4-Me | >79 | >79 | ND |
| 37 | 4-OMe | >79 | >79 | ND |
| 38 | 4-F | >79 | >79 | ND |
| 39 | 4-SO2N(CH2) 4 | 39.90 ± 8.65 | >79 | ND |
| 40 | 2-NO2 -5-Cl | 58.80 ± 6.30 (2) | >79 | ND |
| 41 | 2-Cl-5-NO2 | 74.10 (1) | >79 | ND |
| 42 | 2-Cl | >59 | >79 | ND |
| 43 | 3-OMe | >79 | >79 | ND |
| 44 | 3-Me | >79 | >79 | ND |
| 45 | 3-Cl | >79 | >79 | ND |
| 46 | 2-Me | >79 | >79 | ND |
| 47 | 4-OCF3 | >79 | >79 | ND |
| 48 | 3-CN | >79 | >79 | ND |
Potency IC50 (μM), Ave. ± SEM (stdv/sqrt (n)) (n = 4) if number of replicates is different than the default it is noted in parentheses. SI = selectivity index: (IC50 AT1)/(IC50 APJ).