Table 1.
Structure, Nln Activation Activity, and In Silico Physicochemical Property Predictions of Monocyclic Aromatic-Containing Histidine Peptidomimetics
| Compound | Structure | A50a (μM; 95% Cl) | Amaxb {%; 95% CI) | MPOc Score | LLEd |
|---|---|---|---|---|---|
| 1 |
|
85.5 (65.1 to 112.2) |
465.2 (440.2 to 492.3) |
4 | 7.39 |
| 2 |
|
126.5 (108 to 148.3) |
498.1 (481 to 516.5) |
4 | 8.95 |
| 3 |
|
74.5 (56.2 to 98.8) |
442.3 (418.8 to 467.6) |
4.1 | 6.78 |
| 4 |
|
39.4 (27 to 57.4) |
430.3 (402.9 to 459.6) |
4.0 | 7.07 |
| 4a |
|
Inactive | Inactive | N/A | N/Ad |
| 4b |
|
Inactive | Inactive | N/A | N/A |
| 4c |
|
20.7 (10.5 to 40.8) |
337.2 (302 to 378.6) |
5 | 4.86 |
| 4d |
|
24.6 (17.3 to 35) |
294.6 (278.0 to 313) |
5 | 4.79 |
| 4e |
|
46 (31.5 to 68) |
339.4 (314.2 to 369.3) |
5 | 4.60 |
| 4f |
|
66.4 (48.1 to 92.7) |
378.3 (350.5 to 411.9) |
5 | 4.44 |
| 4g |
|
31.8 (21 to 48.7) |
319 (296.1 to 345.4) |
5 | 4.76 |
| 4h |
|
30 (24 to 37.5) |
328 (315.4 to 342) |
5 | 4.78 |
| 4i |
|
29.6 (22.7 to 38.8) |
367 (349.7 to 387.1) |
5 | 4.79 |
| 4j |
|
19.8 (9,5 to 40.6) |
255.3 (230.5 to 284.8) |
5 | 4.97 |
| 4k |
|
15.7 (11.6 to 22.4) |
299.4 (283.9 to 316.2) |
5 | 4.10 |
| 4l |
|
24 (17.9 to 32.2) |
330.1 (313.9 to 347.7) |
5 | 3.92 |
| 4m |
|
11.6 (5.7 to 23) |
253.8 (231.2 to 278.9) |
5 | 4.97 |
| 4n |
|
35.7 (29.3 to 43.6) |
353.8 (340.6 to 368.1) |
5 | 4.49 |
| 4o |
|
9.8 (6.3 to 15.15) |
282.4 (266.5 to 299.5) |
4 | 5.45 |
| 4p |
|
25.5 (16.7 to 38.8) |
267.5 (250.1 to 287.1) |
4 | 5.03 |
| 4q |
|
9.5 (6.12 to 14.6) |
258.2 (244 to 273.4) |
5 | 3.32 |
| 4r |
|
11.7 (8.26 to 16.7) |
269.7 (256.8 to 283.4) |
5 | 3.22 |
| 5a |
|
24.25 (7.85 to 71.4) |
152.2 (137.3 to 171.5) |
5 | 5.01 |
| 5b |
|
221 (149 to 354) |
428.8 (373 to 523.5) |
5 | 4.13 |
| 5c |
|
226.8 (146 to 392.4) |
703.5 (588.9 to 915.6) |
5 | 4.12 |
| 5d |
|
42.31 (32.1 to 55.6) |
385.8 (363.8 to 410.5) |
5 | 4.85 |
| 5e |
|
43.4 (30.9 to 61.5) |
324.9 (304 to 349) |
5 | 4.84 |
| 5f |
|
66.8 (51.6 to 87.1) |
327.5 (309.7 to 348.2) |
5 | 4.65 |
| 5g |
|
61.83 (46.5 to 83) |
477.1 (444 to 516) |
5 | 4.68 |
| 5h |
|
25.8 (19.5 to 34.19) |
287.7 (274.7 to 301.8) |
5 | 4.10 |
| 5i |
|
29.3 (17.1 to 48.9) |
319.1 (296.3 to 344.3) |
5 | 4.04 |
| 5j |
|
48.6 (31.4 to 76.7) |
362.2 (331.6 to 400.1) |
5 | 3.83 |
| 5k |
|
27.1 (17.1 to 43.3) |
345.8 (317.5 to 378.3) |
5 | 4.08 |
| 5l |
|
8.6 (4.9 to 14.9) |
270.2 (251.4 to 290.7) |
5 | 4.58 |
| 5m |
|
19.95 (11.1 to 35.4) |
282 (258.4 to 309.1) |
5 | 4.21 |
| 5n |
|
14.9 (10–22) |
293 (276.5–310.7) |
5 | 5.08 |
| 5o |
|
29.8 (20.8 to 42.9) |
320.5 (299.7 to 343.9) |
5 | 4.78 |
| 5p |
|
27.4 (17.6 to 42.81) |
310 (287.2 to 336.1) |
5 | 4.07 |
| 5q |
|
26.7 (14.9 to 46.4) |
337.1 (312 to 364.9) |
5 | 4.09 |
| 5r |
|
28.16 (22.67 to 35.03) |
287.5 (277.4 to 298.4) |
5 | 3.28 |
| 5s |
|
16.1 (9.5 to 27.1) |
251.5 (233.7 to 271.3) |
5 | 3.52 |
| 6a |
|
252 (170.6 to 406.6) |
466.6 (402.3 to 579.7) |
5 | 4.02 |
| 6b |
|
113.6 (92.8 to 140.5) |
440.3 (414.9 to 470.4) |
5 | 4.37 |
| 7a |
|
20.6 (14.91 to 28.4) |
288.1 (273.6 to 303.8) |
5 | 4.49 |
| 7b |
|
21 (16 to 27.7) |
281.8 (269.9 to 294.5) |
5 | 4.48 |
| 8a |
|
126 (101 to 159) |
328 (309 to 351) |
5 | 3.17 |
| 8b |
|
27.4 (16.9 to 46.8) |
233.8 (215.9 to 254.8) |
5 | 3.84 |
a
Half maximal activation concentration. Values are presented as the mean of n = 4 experiments with 95% confidence intervals (CIs) in parentheses.
b
Maximum % activation achieved. Values are presented as the mean of n = 4 experiments with 95% confidence intervals (CIs) in parentheses.
c
Multiparameter optimization.
d
Ligand-lipophilicity efficiency.
e
Not applicable.