AMIDE DERIVATIVES OF N-UREA SUBSTITUTED AMINO ACIDS AS FORMYL PEPTIDE RECEPTOR LIKE-1 (FPRL-1) RECEPTOR MODULATORS

Abstract

The present invention relates to novel amide derivatives of N-urea substituted amino acids, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of the N-formyl peptide receptor like-1 (FPRL-1) receptor.

Claims

1. A pharmaceutical composition comprising a therapeutically effective amount of a compound having the following structure: ##STR00173## or a pharmaceutically acceptable salt thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0253] It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention claimed. As used herein, the use of the singular includes the plural unless specifically stated otherwise.

[0254] It will be readily apparent to those skilled in the art that some of the compounds of the invention may contain one or more asymmetric centers, such that the compounds may exist in enantiomeric as well as in diastereomeric forms. Unless it is specifically noted otherwise, the scope of the present invention includes all enantiomers, diastereomers and racemic mixtures.

[0255] Some of the compounds of the invention may form salts with pharmaceutically acceptable acids or bases, and such pharmaceutically acceptable salts of the compounds described herein are also within the scope of the invention.

[0256] The present invention includes all pharmaceutically acceptable isotopically enriched compounds. Any compound of the invention may contain one or more isotopic atoms enriched or different than the natural ratio such as deuterium .sup.2H (or D) in place of hydrogen .sup.1H (or H) or use of .sup.13C enriched material in place of .sup.12C and the like. Similar substitutions can be employed for N, O and S. The use of isotopes may assist in analytical as well as therapeutic aspects of the invention. For example, use of deuterium may increase the in vivo half-life by altering the metabolism (rate) of the compounds of the invention. These compounds can be prepared in accord with the preparations described by use of isotopically enriched reagents.

[0257] The following examples are for illustrative purposes only and are not intended, nor should they be construed as limiting the invention in any manner. Those skilled in the art will appreciate that variations and modifications of the following examples can be made without exceeding the spirit or scope of the invention.

[0258] As will be evident to those skilled in the art, individual isomeric forms can be obtained by separation of mixtures thereof in conventional manner. For example, in the case of diastereoisomeric isomers, chromatographic separation may be employed.

[0259] Compound names were generated with ACD version 12.5. In general, characterization of the compounds is performed according to the following methods, NMR spectra are recorded on 300 or 600 MHz Varian and acquired at room temperature. Chemical shifts are given in ppm referenced either to internal TMS or to the solvent signal.

[0260] All the reagents, solvents, catalysts for which the synthesis is not described are purchased from chemical vendors such as Sigma Aldrich, Fluka, Bio-Blocks, Combi-blocks, TCI, VWR, Lancaster, Oakwood, Trans World Chemical, Alfa, Fisher, Maybridge, Frontier, Matrix, Ukrorgsynth, Toronto, Ryan Scientific, SiliCycle, Anaspec, Syn Chem, Chem-Impex, MIC-scientific, Ltd; however some known intermediates, were prepared according to published procedures.

[0261] Usually the compounds of the invention were purified by medium pressure liquid chromatography, unless noted otherwise.

[0262] The following abbreviations are used in the examples:

Et.sub.3N triethylamine
CH.sub.2Cl.sub.2 dichloromethane
CDCl.sub.3 deuterated chloroform
MeOH methanol
CD.sub.3OD deuterated methanol
Na.sub.2SO.sub.4 sodium sulfate
DMF N,N dimethylformamide
EDCI 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide

HOBt Hydroxybenzotriazole

[0263] THF tetrahydrofuran
ClCO.sub.2Et ethylchloroformate
NH.sub.3 ammonia

[0264] The following synthetic schemes illustrate how compounds according to the invention can be made. Those skilled in the art will be routinely able to modify and/or adapt the following schemes to synthesize any compound of the invention covered by Formula II.

Example 1

Intermediate 1

tert-Butyl (2S)-2-{[(4-Bromophenyl)carbamoyl]amino}-3-phenylpropanoate

[0265] ##STR00045##

[0266] To a solution of L-phenyl-alanine tert-butyl ester hydrochloride (100 mg, 0.41 mmol) and 6 mL of methylene chloride at 25° C. was added 4-bromo-phenyl isocyanate (81 mg, 0.41 mmol) and triethylamine (62 mg, 0.62 mmol). The resulting mixture was stirred at 25° C. for 30 minutes. The mixture was concentrated and the residue was purified by medium pressure liquid chromatography on silica gel using ethyl acetate:hexane (20:80) to yield Intermediate 1, as a white solid.

[0267] .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.20-7.35 (m, 5H), 7.13-7.20 (m, 2H), 7.01-7.10 (m, 2H), 6.79 (br. s., NH), 5.52 (br. s., NH), 4.70 (t, J=6.2 Hz, 1H), 2.91 (ddd, J=19.0 Hz, J=6.0 Hz, 2H), 1.47 (in, 9H).

[0268] Intermediates 2, 3 and 4 were prepared from the corresponding amino acid in a similar manner to the procedure described in Example 1 for Intermediate 1, starting with the appropriate amino acid. The results are described below in Table 1.

TABLE-US-00001 TABLE 1 Interm. IUPAC name No. Structure .sup.1H NMR δ (ppm) 2 tert-Butyl (2S,3S)-2-{[(4-bromo .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.29- phenyl)carbamoyl]amino}-3- 7.39 (m, 2H), 7.10-7.22 (m, 2H), methylpentanoate   [00046] 6.83 (br. s., 1H), 4.44 (d, J = 4.4 Hz, 1H), 1.81-1.99 (m, 1H), 1.36-1.46 (m, 1H), 1.08-1.31 (m, 1H), 0.86- 1.02 (m, 6H). 3 tert-Butyl (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.26- carbamoyl]amino}-pentanoate   [00047] 7.36 (m, 2H), 7.09-7.18 (m, 2H), 6.95 (br. s., NH), 4.40-4.50 (m, 1H), 1.73-1.89 (m, 1H), 1.52-1.72 (m, 1H), 1.25-1.46 (m, 2H), 0.95 (t, 2H). 4 tert-butyl (2S)-2-{[(4-bromo phenyl) .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.20- carbamoyl]amino}-4- 7.33 (m, 2H), 7.04-7.15 (m, 2H), methylpentanoate   [00048] 4.44 (dd, J = 9.1, 5.3 Hz, 1H), 1.74 (dd, J = 12.9, 6.4 Hz, 1H), 1.54-1.68 (m, 1H), 1.50 (s, 9H), 1.40-1.47 (m, 1H), 0.97 (d, J = 3.5 Hz, 3H), 0.95 (d, 3H).

Example 2

Intermediate 5

(2S)-2-{[(4-Bromophenyl)carbamoyl]amino}-3-phenylpropanoic Acid

[0269] ##STR00049##

[0270] A solution of Intermediate 1 (60 mg, 0.15 mmol) and 0.5 mL of formic acid was stirred at 25° C. for 3 hours. The resulting mixture was quenched with water (1 mL) then extracted with ethyl acetate. The organic layer was washed with water, brine, dried over Na.sub.2SO.sub.4, filtered, and the filtrate was concentrated under reduced pressure. The residue was rinsed 4 times with methylene chloride:hexane (1:1) to yield Intermediate 5 as a white solid.

[0271] .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.29 (s, NH), 7.40-7.50 (m, 2H), 7.32-7.40 (m, 2H), 7.18-7.31 (m, 5H), 5.98 (d, J=7.9 Hz, NH), 4.67 (m, 1H), 3.02 (ddd, J=19.0 Hz, J=6.0 Hz, 2H).

[0272] Intermediates 6, 7 and 8 and Compounds 1 through 6 were prepared from the corresponding urea derivative in a similar manner to the procedure described in Example 2 for Intermediate 5. The results are described below in Table 2.

TABLE-US-00002 TABLE 2 Interm. IUPAC name No. Structure .sup.1H NMR δ (ppm) 6 (2S,3S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.24 carbamoyl]amino}-3- (br. s., 1H), 7.44-7.53 (m, 2H), 7.32- methylpentanoic acid 7.42 (m, 2H), 6.08 (d, J = 8.8 Hz, 1H), [00050] 4.44 (dd, J = 8.6, 4.8 Hz, 1H), 1.86-2.00 (m, J = 9.1, 6.9, 4.6, 4.6 Hz, 1H), 1.43- 1.61 (m, 1H), 1.15-1.33 (m, 1H), 0.88- 1.04 (m, 6H). 7 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.20 carbamoyl]amino}-pentanoic (s, NH), 7.43-7.52 (m, 2H), 7.33-7.41 acid (m, 2H), 6.08 (d, J = 9.1 Hz, NH), 4.38- [00051] 4.50 (m, 1H), 1.77-1.92 (m, 1H), 1.61- 1.76 (m, 1H), 1.36-1.53 (m, 2H), 0.89- 1.00 (m, 3H). 8 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.17 (s, carbamoyl]amino}-4- NH), 7.43-7.51 (m, 2H), 7.35-7.41 (m, methylpentanoic acid 2H), 6.04 (d, J = 9.1 Hz, NH), 4.42-4.53 [00052] (m, 1H), 1.73-1.88 (m, 1H), 1.53-1.73 (m, 2H), 0.97 (d, J = 2.1 Hz, 3H), 0.95 (d, 3H). Comp. IUPAC name No. Structure .sup.1H NMR δ (ppm) 1 {[(2S)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.26 (s, bromophenyl)carbamoyl]amino}- NH), 7.71 (br. s., NH), 7.32-7.46 (m, 3-phenylpropanoyl] 4H), 7.13-7.31 (m, 5H), 6.03 (d, J = 8.5 amino}acetic Hz, NH), 4.71 (td, J = 7.7, 5.4 Hz, 1H), acid 3.98 (d, J = 5.9 Hz, 2H), 3.14-3.26 (m, [00053] 1H), 3.01 (dd, 1H). 2 3-{[(2S)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.27 (s, bromophenyl)carbamoyl] NH), 7.44 (s, NH), 7.33-7.43 (m, 4H), amino}-3- 7.15-7.30 (m, 5H), 6.03 (d, J = 7.9 Hz, phenylpropanoyl]amino} NH), 4.53-4.65 (m, 1H), 3.34-3.51 (m, propanoic acid 2H), 2.93-3.15 (m, 2H), 2.47 (td, 2H). [00054] 3 {[(2S,3S)-2-{[(4-bromo-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.28 (t, fluorophenyl)carbamoyl] J = 8.9 Hz, 1H), 8.16 (br. s., NH), 7.67 (br. amino}-3- s., NH), 7.34 (dd, J = 11.0, 2.2 Hz, 1H), methylpentanoyl]amino}acetic 7.23-7.30 (m, 1H), 6.57 (d, J = 9.4 Hz, acid NH), 4.37 (dd, J = 8.6, 5.7 Hz, 1H), 3.89- [00055] 4.08 (m, 2H), 1.86-1.98 (m, 1H), 1.53- 1.67 (m, 1H), 1.10-1.27 (m, 1H), 0.98 (d, J = 6.7 Hz, 3H), 0.85-0.94 (m, 3H). 4 {[(2S,3S)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.27 (s, bromophenyl)carbamoyl] NH), 7.66 (br. s., NH), 7.42-7.51 (m, amino}-3- 2H), 7.32-7.41 (m, 2H), 6.08 (d, J = 8.2 methylpentanoyl]amino} Hz, NH), 4.34 (dd, J = 8.6, 5.7 Hz, 1H), acetic acid 3.88-4.09 (m, 2H), 1.81-1.96 (m, 1H), [00056] 1.49-1.67 (m, 1H), 1.06-1.27 (m, 1H), 0.97 (d, J = 6.7 Hz, 3H), 0.86-0.93 (m, 3H). 5 {[(2S)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.25 (s, bromophenyl)carbamoyl]amino} NH), 7.67 (br. s., NH), 7.41-7.51 (m, pentanoyl]amino}acetic 2H), 7.34-7.41 (m, 2H), 6.13 (d, J = 7.9 acid Hz, NH), 4.42 (td, J = 7.7, 5.4 Hz, 1H), [00057] 3.89-4.08 (m, 2H), 1.73-1.89 (m, 1H), 1.54-1.69 (m, 1H), 1.34-1.51 (m, 2H), 0.91 (t J = 7.3 Hz, 3H). 6 {[(2S)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.19 (s, bromophenyl)carbamoyl] NH), 7.70 (br. s., NH), 7.42-7.51 (m, amino}-4- 2H), 7.33-7.41 (m, 2H), 6.07 (d, J = 7.6 methylpentanoyl]amino} Hz, NH), 4.46 (ddd, J = 9.6, 8.3, 5.0 Hz, acetic acid 1H), 3.87-4.07 (m, 2H), 1.72-1.86 (m, [00058] 1H), 1.61-1.72 (m, 1H), 1.46-1.59 (m, 1H), 0.95 (s, 3H), 0.93 (s, 3H).

Example 3

Compound 7

tert-Butyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-phenylpropanoyl]amino}acetate

[0273] ##STR00059##

[0274] To a solution of Intermediate 5 (80 mg, 0.22 mmol) and 2 mL of anhydrous DMF at 25° C. was added EDCI (64 mg, 0.33 mmol), HOBt (45 mg, 0.33 mmol), glycine tert-butyl ester (44 mg, 0.33 mmol) and N-methylmorpholine (44 mg, 0.44 mmol). The resulting mixture was stirred at 25° C. for 12 hours. The mixture was quenched with water (1 mL), and the product was extracted with ethyl acetate (20 mL). The layers were separated, and the organic layer was washed with water, brine, dried over Na.sub.2SO.sub.4, filtered, and the filtrate was concentrated under reduced pressure. The resulting product was purified by medium pressure liquid chromatography on silica gel using ethyl acetate:hexane (40:60) to yield Compound 7 as a white solid.

[0275] .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.18-7.35 (m, 7H), 7.03 (d, J=8.5 Hz, 2H), 6.85 (br. s., 1H), 4.69 (t, J=7.5 Hz, 1H), 3.74-3.96 (min, 2H), 2.98-3.19 (m, 2H), 1.42 (s, 9H).

[0276] Compounds 8 through 27 and Intermediate 9 were prepared from the corresponding urea derivative in a similar manner to the procedure described in Example 3 for Compound 7. The results are described below in Table 3.

TABLE-US-00003 TABLE 3 Comp. IUPAC name No. Structure .sup.1H NMR δ (ppm) 8 tert-butyl 3-{[(2S)-2-{[(4- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.18- bromophenyl)carbamoyl]amino}- 7.35 (m, 7H), 7.08-7.17 (m, 2H), 3-phenylpropanoyl] 4.54-4.64 (m, 1H), 3.28-3.52 (m, amino}propanoate 2H), 2.94-3.17 (m, 2H), 2.18-2.40 [00060] (m, 2H), 1.41 (s, 9H). 9 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.30- carbamoyl]amino}-N-(2- 7.37 (m, 2H), 7.17-7.30 (m, 7H), hydroxyethyl)-3-phenylpropanamide 4.50 (dd, J = 7.8, 6.3 Hz, 1H), 3.44- [00061] 3.59 (m, 2H), 3.23-3.30 (m, 2H), 3.05-3.15 (m, 1H), 2.90-3.01 (m, 1H). 10 tert-butyl {[(2S,3S)-2-{[(4-bromo-2- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.92- fluorophenyl) carbamoyl]amino}-3- 7.99 (t, J = 8.9 Hz, 1H), 7.40 (br. s., methylpentanoyl]amino}acetate NH), 7.07-7.16 (m, 2H), 6.67 (s, [00062] NH), 6.54 (br. s., NH), 4.21-4.27 (m, 1H), 4.05-4.15 (m, 1H), 3.83- 3.92 (m, 1H), 1.79-1.88 (m, 1H), 1.57-1.64 (m, 1H), 1.47 (s, 9H), 1.19-1.24 (m, 1H), 1.00 (d, J = 6.7 Hz, 3H), 0.92 (t, 3H). 11 tert-butyl {[(2S,3S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.55 bromophenyl) carbamoyl]amino}-3- (s, NH), 8.36 (br. s., NH), 7.33-7.40 methylpentanoyl]amino}acetate (m, 2H), 7.26-7.33 (m, 2H), 6.28 [00063] (d, J = 8.5 Hz, NH), 4.20 (dd, J = 8.6, 6.3 Hz, 1H), 3.72-3.97 (m, 2H), 1.80-1.94 (m, 1H), 1.56-1.70 (m, 1H), 1.45 (s, 9H), 1.13-1.31 (m, 1H), 1.01 (d, J = 6.7 Hz, 3H), 0.92- 0.98 (m, 3H). 12 (2S,3S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.34- carbamoyl]amino}-3-methyl-N-(2- 7.41 (m, 2H), 7.26-7.34 (m, 2H), oxopropyl)pentanamide 4.22 (d, J = 6.2 Hz, 1H), 4.05 (d, J = [00064] 8.2 Hz, 2H), 2.14 (s, 3H), 1.80-1.94 (m, 1H), 1.53-1.68 (m, 1H), 1.14- 1.26 (m, 1H), 0.81-1.07 (m, 6H). 13 (2S,3S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.99 carbamoyl]amino}-3-methyl-N-(2- (t, J = 8.8 Hz, 1H), 7.31 (dd, J = oxopropyl)pentanamide 10.7, 2.2 Hz, 1H), 7.16-7.27 (m, [00065] 1H), 4.22 (d, J = 5.9 Hz, 1H), 3.94- 4.14 (m, 2H), 2.14 (s, 3H), 1.84- 1.96 (m, 1H), 1.52-1.67 (m, 1H), 1.14-1.32 (m, 1H), 1.01 (d, J = 7.0 Hz, 3H), 0.92-0.98 (m, 3H). 14 (2S,3S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: carbamoyl]amino}-N-(2- 7.33-7.42 (m, 2H), 7.26-7.33 (m, hydroxyethyl)-3-methylpentanamide 2H), 4.12 (d, J = 6.4 Hz, 1H), 3.55- [00066] 3.65 (m, 2H), 3.32-3.37 (m, 1H), 1.76-1.91 (m, 1H), 1.48-1.63 (m, 1H), 1.09-1.31 (m, 2H), 0.90-0.99 (m, 6H). 15 (2S,3S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: carbamoyl]amino}-N-(2- 7.99 (t, J = 8.6 Hz, 1H), 7.31 (dd, J = hydroxyethyl)-3-methylpentanamide 10.8, 2.3 Hz, 1H), 7.18-7.27 (m, [00067] 1H), 4.13 (d, J = 6.4 Hz, 1H), 3.56- 3.65 (m, 2H), 3.31-3.37 (m, 1H), 1.77-1.89 (m, 1H), 1.50-1.61 (m, 1H), 1.10-1.26 (m, 1H), 0.88-1.01 (m, 6H). 16 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-N-(2-oxopropyl)-3- 8.23 (s, NH), 7.59 (br. s., NH), 7.32- phenylpropanamide 7.47 (m, 4H), 7.15-7.29 (m, 5H), [00068] 6.01 (d, J = 8.2 Hz, NH), 4.70 (td, J = 7.7, 5.7 Hz, 1H), 4.05 (d, J = 5.3 Hz, 2H), 3.12-3.24 (m, 1H), 2.95- 3.06 (m, 1H), 2.10 (s, 3H). 17 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-N-(2-oxopropyl)-3- 8.22 (t, J = 8.9 Hz, 1H), 8.12 (br. s., phenylpropanamide NH), 7.61 (br. s., NH), 7.32 (dd, J = [00069] 11.0, 2.2 Hz, 1H), 7.15-7.29 (m, 6H), 6.51 (d, J = 7.3 Hz, NH), 4.72 (td, J = 7.9, 5.6 Hz, 1H), 4.05 (dd, J = 5.6, 1.2 Hz, 2H), 3.14-3.24 (m, 1H), 2.95-3.05 (m, 1H), 2.10 (s, 3H). 18 tert-butyl {[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-pentanoyl]amino} 8.20 (s, NH), 7.60 (br. s., NH), 7.42- acetate 7.51 (m, 2H), 7.32-7.41 (m, 2H), [00070] 6.07 (d, J = 7.6 Hz, NH), 4.41 (td, J = 7.9, 5.3 Hz, 1H), 3.75-3.99 (m, 2H), 1.73-1.89 (m, 1H), 1.53-1.70 (m, 1H), 1.43 (s, 9H), 1.37-1.48 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H). 19 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: carbamoyl]amino}-N-(2- 7.91 (t, J = 8.6 Hz, 1H), 7.17-7.34 hydroxyethyl)-3-phenylpropanamide (m, 7H), 4.50 (dd, J = 8.2, 6.2 Hz, [00071] 1H), 3.44-3.59 (m, 2H), 3.23-3.27 (m, 2H), 3.05-3.17 (m, 1H), 2.87- 2.99 (m, 1H). 20 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- carbamoyl]amino}-N-(2- 7.41 (m, 2H), 7.25-7.33 (m, 2H), hydroxyethyl)pentanamide 4.23 (dd, J = 8.2, 5.6 Hz, 1H), 3.56- [00072] 3.63 (m, 2H), 1.69-1.84 (m, 1H), 1.54-1.68 (m, 1H), 1.29-1.51 (m, 2H), 0.91-1.02 (m, 3H). 21 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.97 carbamoyl]amino}-N-(2- (t, J = 8.6 Hz, 1H), 7.31 (dd, J = hydroxyethyl) pentanamide 10.7, 2.2 Hz, 1H), 7.19-7.27 (m, [00073] 1H), 4.23 (dd, J = 8.1, 5.4 Hz, 1H), 3.56-3.66 (m, 2H), 1.68-1.83 (m, 1H), 1.54-1.68 (m, 1H), 1.34-1.51 (m, 2H), 0.91-1.03 (m, 3H). 22 methyl {[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}- 8.19 (s, NH), 7.71 (br. s., NH), 7.42- pentanoyl]amino}acetate 7.52 (m, 2H), 7.31-7.42 (m, 2H), [00074] 6.07 (d, J = 8.2 Hz, NH), 4.34-4.47 (m, 1H), 3.86-4.10 (m, 2H), 3.66 (s, 3H), 1.73-1.87 (m, 1H), 1.55-1.71 (m, 1H), 1.35-1.51 (m, 2H), 0.92 (t, 3H). 23 ethyl {[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}- 8.19 (s, NH), 7.69 (br. s., NH), 7.42- pentanoyl]amino}acetate 7.50 (m, 2H), 7.32-7.40 (m, 2H), [00075] 6.07 (d, J = 8.2 Hz, NH), 4.42 (td, J = 7.9, 5.6 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 3.85-4.06 (m, 2H), 1.73- 1.88 (m, 1H), 1.55-1.69 (m, 1H), 1.34-1.51 (m, 2H), 1.20 (t, J = 7.3, 3H), 0.92 (t, J = 7.3, 3H). 24 isopropyl {[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-pentanoyl]amino} 8.20 (s, NH), 7.67 (br. s., NH), 7.43- acetate 7.51 (m, 2H), 7.33-7.42 (m, 2H), [00076] 6.07 (d, J = 9.7 Hz, NH), 4.97 (dt, J = 12.5, 6.2 Hz, 1H), 4.41 (td, J = 7.8, 5.4 Hz, 1H), 3.82-4.04 (m, 2H), 1.73-1.89 (m, 1H), 1.55-1.70 (m, 1H), 1.34-1.50 (m, 2H), 1.22 (s, 3H), 1.20 (s, 3H), 0.92 (t, J = 7.3, 3H). 25 tert-butyl {[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-4- 8.16 (s, NH), 7.62 (br. s., NH), 7.42- methylpentanoyl]amino}acetate 7.49 (m, 2H), 7.33-7.40 (m, 2H), [00077] 6.03 (d, J = 8.8 Hz, NH), 4.40-4.51 (m, 1H), 3.76-3.95 (m, 2H), 1.72- 1.84 (m, 1H), 1.60-1.73 (m, 1H), 1.45-1.58 (m, 1H), 0.95 (s, 3H), 0.93 (s, 3H). 26 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3 OD, 300 MHz) δ: carbamoyl]amino}-N-(2- 7.34-7.41 (m, 2H), 7.26-7.33 (m, hydroxyethyl)-4- 2H), 4.24-4.33 (m, 1H), 3.55-3.64 methylpentanamide (m, 2H), 3.32-3.35 (m, 2H), 1.64- [00078] 1.79 (m, 1H), 1.48-1.62 (m, 2H), 0.98 (d, J = 4.1 Hz, 3H), 0.96 (d, J = 3.8 Hz, 3H). 27 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-4-methyl-N-(2- 8.17 (s, NH), 7.61 (br. s., NH), 7.42- oxopropyl)pentanamide 7.50 (m, 2H), 7.32-7.42 (m, 2H), [00079] 6.06 (d, J = 8.5 Hz, NH), 4.45 (ddd, J = 9.7, 8.1, 5.0 Hz, 1H), 4.04 (d, J = 5.6 Hz, 2H), 2.12 (s, 3H), 1.72-1.84 (m, 1H), 1.60-1.72 (m, 1H), 1.45- 1.58 (m, 1H), 0.95 (s, 3H), 0.93 (s, 3H). Interm. IUPAC name No. Structure .sup.1H NMR δ (ppm) 9 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: carbamoyl]amino}-N- 10.27 (br. s., OH), 8.18 (br. s., NH), hydroxypentanamide 8.03 (s, NH), 7.42-7.50 (m, 2H), [00080] 7.32-7.41 (m, 2H), 6.11 (d, J = 9.1 Hz, NH), 4.23-4.34 (m, 1H), 1.52- 1.80 (m, 2H), 1.27-1.49 (m, 2H), 0.87-0.95 (t, J = 7.3 Hz, 3H).

Example 4

Compound 28

(2S,3S)—N-(2-amino-2-oxoethyl)-2-{[(4-bromophenyl) carbamoyl]amino}-3-methylpentanamide

[0277] ##STR00081##

[0278] To a solution of Compound 11 (50 mg, 0.13 mmol) and 5 mL of anhydrous tetrahydrofuran under argon at −78° C. was added triethylamine (24 mg, 0.17 mmol) and ethyl chloroformate (17 mg, 0.16 mmol). The mixture was stirred at −78° C. for 30 minutes, and then ammonia gas was bubbled into reaction flask for 1 minute. The resulting mixture was stirred at 25° C. for 2 hours. The reaction was quenched with water (1 mL), and the residue was extracted with ethyl acetate (20 mL). The layers were separated, and the organic layer was washed with water, brine, dried over Na.sub.2SO.sub.4, filtered, and the filtrate was concentrated under reduced pressure. The resulting product was purified by medium pressure chromatography on silica gel using an eluent of methanol:dichloromethane (10:90) to yield to yield Compound 28 as a white solid.

[0279] .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33-7.40 (i, 2H), 7.26-7.33 (8, 2H), 4.05 (d, J=6.7 Hz, 1H), 3.85 (q, J=17.0 Hz, 2H), 1.78-1.91 (m, 1H), 1.54-1.69 (n, TH), 1.16-1.33 (n, TH), 0.99 (d, J=6.7 Hz, 3H), 0.92-0.98 (n, 3H).

[0280] Compounds 29 through 85 as well as Intermediates 10 through 35 were prepared from the corresponding acid derivative in a similar manner to the procedure described in Example 4 for Compound 28.

TABLE-US-00004 TABLE 4 Comp. IUPAC name No. Structure .sup.1H NMR δ (ppm) 29 (2S,3S)-N-(2-amino-2-oxoethyl)-2- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.00 {[(4-bromo-2-fluorophenyl) (t, J = 8.6 Hz, 1H), 7.32 (dd, J = 10.7, carbamoyl]amino}-3- 2.2 Hz, 1H), 7.18-7.26 (m, 1H), 4.05 methylpentanamide (d, J = 6.4 Hz, 1H), 3.74-3.95 (m, 2H), [00082] 1.80-1.91 (m, 1H), 1.51-1.69 (m, 1H), 1.18-1.32 (m, 1H), 1.00 (d, J = 7.0 Hz, 3H), 0.92-0.98 (m, 3H). 30 (2S)-N-(2-amino-2-oxoethyl)-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.27 {[(4-bromophenyl) (s, NH), 7.70 (br. s., NH), 7.41-7.48 carbamoyl]amino}-pentanamide (m, 2H), 7.33-7.41 (m, 2H), 7.02 (s, [00083] NH), 6.30 (s, NH), 6.22 (d, J = 5.3 Hz, NH), 4.22-4.32 (m, 1H), 3.72-3.91 (m, 2H), 1.73-1.88 (m, 1H), 1.56- 1.71 (m, 1H), 1.37-1.53 (m, 2H), 0.88- 0.97 (m, 3H). 31 (2S)-N-(2-amino-2-oxoethyl)-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.23 {[(4-bromo-2-fluorophenyl] (t, J = 8.8 Hz, 1H), 8.13 (br. s., NH), carbamoyl}amino)pentanamide 7.72 (s, NH), 7.35 (dd, J = 10.8, 2.3 Hz, [00084] 1H), 7.26 (dt, J = 8.9, 1.9 Hz, 1H), 7.00 (s, NH), 6.66 (d, J = 6.7 Hz, NH), 6.34 (s, NH), 4.29 (dd, J = 12.2, 8.1 Hz, 1H), 3.82 (dd, J = 5.9, 1.8 Hz, 2H), 1.75- 1.90 (m, 1H), 1.58-1.73 (m, 1H), 1.37- 1.53 (m, 2H), 0.89-0.98 (m, 3H). 32 (2S)-N-(2-amino-2-oxoethyl)-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.20 {[(4-bromophenyl) (s, NH), 7.77 (br. s., NH), 7.40-7.47 carbamoyl]amino}-4- (m, 2H), 7.32-7.39 (m, 2H), 7.04 (br. methylpentanamide s., NH), 6.38 (br. s., NH), 6.18 (d, J = [00085] 7.3 Hz, NH), 4.31 (ddd, J = 9.4, 7.0, 5.3 Hz, 1H), 3.71-3.93 (m, 2H), 1.69- 1.85 (m, 1H), 1.49-1.69 (m, 2H), 0.96 (d, J = 3.2 Hz, 3H), 0.93 (d, J = 3.2 Hz, 3H). 33 tert-butyl {[(2S)-2-{[(4-bromo-2- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.89 (t, fluorophenyl) carbamoyl] amino}- J = 8.8 Hz, 1H), 7.55 (br. s., NH), 7.07 4-methylpentanoyl] amino}acetate (dd, J = 10.7, 2.2 Hz, 1H), 6.95-7.04 [00086] (m, 1H), 6.84 (br. s., NH), 4.43 (br. s., NH), 4.00-4.16 (m, 1H), 3.81-3.92 (m, 1H), 1.69-1.88 (m, 1H), 1.56- 1.70 (m, 2H), 1.47 (s, 9H), 0.97 (d, J = 4.7 Hz, 3H), 0.95 (d, 3H). 34 {[(2S)-2-{[(4-bromo-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.27 fluorophenyl) carbamoyl]amino}-4- (t, J = 8.8 Hz, 1H), 8.07 (br. s., NH), methylpentanoyl]amino}acetic acid 7.71 (br. s., NH), 7.34 (dd, J = 10.8, 2.1 [00087] Hz, 1H), 7.27 (dt, J = 8.8, 1.8 Hz, 1H), 6.54 (d, J = 8.8 Hz, NH), 4.42-4.53 (m, 1H), 3.93-4.01 (m, 2H), 1.72- 1.86 (m, 1H), 1.63-1.74 (m, 1H), 1.46- 1.60 (m, 1H), 0.96 (s, 3H), 0.93 (s, 3H). 35 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.30 carbamoyl]amino}-4-methyl-N-(2- (t, J = 8.8 Hz, 1H), 8.06 (br. s., NH), oxopropyl)pentanamide 7.62 (br. s., NH), 7.31-7.38 (m, 2H), [00088] 7.24-7.30 (m, 2H), 6.52 (d, J = 8.2 Hz, NH), 4.39-4.53 (m, 1H), 4.04 (d, J = 5.6 Hz, 2H), 2.10-2.15 (m, 3H), 1.70- 1.86 (m, 1H), 1.61-1.71 (m, 1H), 1.47- 1.62 (m, 1H), 0.96 (s, 3H), 0.93 (s, 3H). 36 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.97 (t, carbamoyl]amino}-N-(2- J = 8.8 Hz, 1H), 7.31 (dd, J = 10.8, 2.3 hydroxyethyl)-4- Hz, 1H), 7.18-7.27 (m, 1H), 4.28 (dd, methylpentanamide J = 9.2, 5.4 Hz, 1H), 3.56-3.64 (m, [00089] 2H), 3.32-3.37 (m, 2H), 1.64-1.80 (m, 1H), 1.50-1.62 (m, 2H), 0.98 (d, J = 4.4 Hz, 3H), 0.96 (d, 3H). 37 (2S)-N-(2-amino-2-oxoethyl)-2-{[(4- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.22 bromo-2-fluorophenyl) (t, J = 8.8 Hz, 1H), 8.09 (br. s., NH), carbamoyl]amino}-4- 7.77 (br. s., NH), 7.34 (dd, J = 11.0, 2.2 methylpentanamide Hz, 1H), 7.25 (dt, J = 8.9, 1.7 Hz, 1H), [00090] 6.99 (br. s., NH), 6.62 (d, J = 7.0 Hz, NH), 6.37 (br. s., NH), 4.33 (ddd, J = 9.6, 7.0, 5.1 Hz, 1H), 3.72-3.92 (m, 2H), 1.68-1.86 (m, 1H), 1.49-1.70 (m, 2H), 0.96 (d, J = 3.5 Hz, 3H), 0.94 (d, 3H). 38 tert-butyl (2S)-2-{[(2S)-2-{[(4- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.90 (t, bromo-2-fluorophenyl) J = 8.8 Hz, 1H), 7.45 (br. s., NH), 7.02- carbamoyl]amino}-4- 7.15 (m, 2H), 6.92 (s, NH), 6.61 (br. methylpentanoyl]amino} s., NH), 4.37-4.54 (m, 2H), 1.79 (dt, propanoate J = 13.2, 6.9 Hz, 1H), 1.56-1.69 (m, [00091] 2H), 1.46 (s, 9H), 1.40 (d, J = 7.3 Hz, 3H), 0.97 (s, 3H), 0.95 (s, 3H). 39 (2S)-2-{[(2S)-2-{[(4-bromo-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.26 fluorophenyl) carbamoyl]amino}-4- (t, J = 8.9 Hz, 1H), 8.08 (br. s., NH), methylpentanoyl]amino}propanoic 7.67 (d, J = 7.0 Hz, NH), 7.33 (dd, J = acid 10.8, 2.3 Hz, 1H), 7.27 (dt, J = 8.8, 1.8 [00092] Hz, 1H), 6.52 (d, J = 9.1 Hz, NH), 4.40- 4.54 (m, 2H), 1.72-1.87 (m, 1H), 1.59-1.72 (m, 1H), 1.45-1.57 (m, 1H), 1.39 (d, J = 7.3 Hz, 3H), 0.95 (s, 3H), 0.93 (s, 3H). 40 (2S)-N-[(1S)-2-amino-1-methyl-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.25 oxoethyl]-2-{[(4-bromo-2- (t, J = 8.8 Hz, 1H), 8.09 (br. s., NH), fluorophenyl) carbamoyl]amino}-4- 7.57 (d, J = 5.6 Hz, NH), 7.35 (dd, J = methylpentanamide 11.0, 2.2 Hz, 1H), 7.22-7.31 (m, 1H), [00093] 6.92 (br. s., NH), 6.54 (d, J = 7.3 Hz, NH), 6.29 (br. s., NH), 4.30-4.44 (m, 2H), 1.73-1.90 (m, 1H), 1.47-1.72 (m, 2H), 1.30 (d, J = 7.0 Hz, 3H), 0.95 (d, J = 1.5 Hz, 3H), 0.93 (d, 3H). 41 tert-butyl (2S)-2-{[(2S)-2-{[(4- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.62 (br. bromophenyl) carbamoyl}amino)- s., NH), 7.21-7.29 (m, 2H), 7.08-7.16 4-methylpentanoyl] (m, 2H), 6.90 (br. s., NH), 4.39-4.50 amino}propanoate (m, 1H), 4.35 (t, J = 7.0 Hz, 1H), 1.73- [00094] 1.86 (m, 1H), 1.54-1.67 (m, 2H), 1.45 (s, 9H), 1.38 (d, 3H), 0.97 (d, J = 2.9 Hz, 3H), 0.95 (d, J = 2.9 Hz, 3H). 42 tert-butyl (2S)-2-{[(2S)-2-{[(4- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.45 (br. bromophenyl) carbamoyl]amino}- s., NH), 7.21-7.30 (m, 2H), 7.10-7.18 4-methylpentanoyl]amino}-3- (m, 2H), 4.45 (t, J = 7.2 Hz, 1H), 4.32 methylbutanoate (dd, J = 8.5, 5.0 Hz, 1H), 2.07-2.20 [00095] (m, 1H), 1.77 (dt, J = 13.3, 6.8 Hz, 1H), 1.56-1.67 (m, 2H), 1.47 (s, 9H), 0.98 (d, J = 2.3 Hz, 3H), 0.96 (d, 3H), 0.93 (s, 3H), 0.91 (s, 3H). 43 (2S)-2-{[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.22 carbamoyl]amino}-4- (s, NH), 7.66 (d, J = 6.4 Hz, NH), 7.43- methylpentanoyl]amino}propanoic 7.50 (m, 2H), 7.34-7.41 (m, 2H), 6.05 acid (d, J = 7.9 Hz, NH), 4.39-4.52 (m, [00096] 2H), 2.81 (br. s., 4H), 1.71-1.86 (m, 1H), 1.57-1.71 (m, 1H), 1.43-1.57 (m, 1H), 1.39 (d, J = 7.3 Hz, 3H), 0.94 (s, 3H), 0.92 (s, 3H). 44 (2S)-2-{[(2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 7.45 carbamoyl]amino}-4- (br. s., NH), 7.21-7.30 (m, 2H), 7.10- methylpentanoyl]amino}-3- 7.18 (m, 2H), 4.45 (t, J = 7.2 Hz, 1H), methylbutanoic acid 4.32 (dd, J = 8.5, 5.0 Hz, 1H), 2.07- [00097] 2.20 (m, 1H), 1.77 (dt, J = 13.3, 6.8 Hz, 1H), 1.56-1.67 (m, 2H), 1.47 (s, 9H), 0.98 (d, J = 2.3 Hz, 3H), 0.96 (d, 3H), 0.93 (s, 3H), 0.91 (s, 3H). 45 (2S)-N-[(1S)-2-amino-1-methyl-2- .sup.1H NMR (acetone-d.sub.6, 300 MHz) δ: 8.21 oxoethyl]-2-{[(4-bromophenyl) (s, NH), 7.56 (s, NH), 7.42-7.49 (m, carbamoyl]amino}-4- 2H), 7.33-7.40 (m, 2H), 6.06-6.12 (s, methylpentanamide NH), 4.28-4.44 (m, 2H), 1.70-1.89 [00098] (m, 1H), 1.59-1.70 (m, 1H), 1.47- 1.59 (m, 1H), 1.30 (d, J = 7.3 Hz, 3H), 0.95 (s, 3H), 0.92 (s, 3H). 46 (2S)-N-[(1S)-1-(amino-3-methyl-1- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.34- oxobutan-2-yl]-2-{[(4- 7.40 (m, 2H), 7.26-7.33 (m, 2H), 4.34 bromophenyl) carbamoyl]amino}- (dd, J = 9.5, 5.4 Hz, 1H), 4.21 (d, J = 4-methylpentanamide 7.0 Hz, 1H), 2.02-2.16 (m, 1H), 1.67- [00099] 1.79 (m, 1H), 1.51-1.65 (m, 1H), 0.94- 1.00 (m, 9H). 47 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.93 carbamoyl]amino}-N-(2-hydroxy- (s, NH), 7.33-7.40 (m, 2H), 7.26- 2-methylpropyl)-4- 7.33 (m, 2H), 6.28 (br. s., NH), 4.25- methylpentanamide 4.36 (m, 1H), 3.15-3.27 (m, 2H), 1.67- [00100] 1.81 (m, 1H), 1.50-1.67 (m, 2H), 1.17 (s, 6H), 0.99 (d, J = 4.7 Hz, 3H), 0.97 (d, 3H). 48 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- carbamoyl]amino}-N-[2-hydroxy- 7.41 (m, 2H), 7.26-7.33 (m, 2H), 4.30 1-(hydroxymethyl)ethyl]-4- (dd, J = 9.4, 5.6 Hz, 1H), 3.86-3.96 methylpentanamide (m, 1H), 3.62 (t, J = 5.6 Hz, 4H), 1.67- [00101] 1.81 (m, 1H), 1.52-1.67 (m, 2H), 0.98 (d, J = 3.8 Hz, 3H), 0.96 (d, 3H). 47 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- carbamoyl]amino}-N-(2,3- 7.41 (m, 2H), 7.27-7.34 (m, 2H), 4.28 dihydroxypropyl)-4- (dd, J = 8.9, 5.1 Hz, 1H), 3.64-3.76 methylpentanamide (m, 1H), 3.46-3.52 (m, 2H), 3.33- [00102] 3.42 (m, 1H), 3.15-3.27 (m, 1H), 1.67- 1.80 (m, 1H), 1.48-1.67 (m, 2H), 0.98 (d, J = 4.7 Hz, 3H), 0.96 (d, 3H). 48 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- carbamoyl]amino}-N-[(1R)-2- 7.40 (m, 2H), 7.26-7.32 (m, 2H), 4.26 hydroxy-1-methylethyl]-4- (dd, J = 8.2, 6.7 Hz, 1H), 3.88-3.99 methylpentanamide (m, 1H), 3.49 (dd, J = 5.4, 1.3 Hz, 2H), [00103] 1.72 (dt, J = 13.3, 6.8 Hz, 1H), 1.50- 1.60 (m, 2H), 1.14 (d, J = 6.7 Hz, 3H), 0.98 (d, J = 3.8 Hz, 3H), 0.96 (d, 3H). 49 tert-butyl (2S)-2-{[(2S)-2-{[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-4- 7.39 (m, 2H), 7.27-7.32 (m, 2H), 4.36 methyl pentanoyl] (dd, J = 9.5, 5.4 Hz, 1H), 4.26 (dd, J = amino}propanoate 8.6, 5.4 Hz, 1H), 1.49-1.84 (m, 6H), [00104] 1.45 (s, 9H), 1.36-1.43 (m, 1H), 0.99 (d, J = 4.4 Hz, 3H), 0.97 (d, J = 4.1 Hz, 3H), 0.90-0.96 (m, 3H). 50 tert-butyl (2S)-{[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.32- bromophenyl)carbamoyl]amino}-4- 7.43 (m, 6H), 7.25-7.31 (m, 2H), 4.41 methylpentanoyl]amino}(phenyl) (dd, J = 9.4, 5.3 Hz, 1H), 1.72-1.81 ethanoate (m, 1H), 1.49-1.70 (m, 2H), 1.40 (s, [00105] 9H), 1.17-1.19 (m, 0H), 0.99 (t, J = 6.7 Hz, 6H). 51 (2S)-2-{[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-4- 7.40 (m, 2H), 7.25-7.33 (m, 2H), 4.32- methylpentanoyl]amino}pentanoic 4.44 (m, 2H), 1.35-1.90 (m, 7H), acid 0.99 (d, J = 3.8 Hz, 3H), 0.97 (d, J = 3.8 [00106] Hz, 3H), 0.91-0.96 (m, 3H). 52 (2S)-{[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.40- bromophenyl)carbamoyl]amino}-4- 7.47 (m, 2H), 7.23-7.39 (m, 7H), 4.41 methylpentanoyl]amino}(phenyl) (dd, J = 9.4, 5.3 Hz, 1H), 1.70-1.84 ethanoic acid (m, 1H), 1.48-1.69 (m, 2H), 0.98 (t, [00107] 6H). 53 (2S)-N-[(2S)-1-amino-1-oxopentan- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- 2-yl]-2-{[(4- 7.41 (m, 2H), 7.26-7.33 (m, 2H), 4.30 bromophenyl)carbamoyl]amino}-4- (ddd, J = 16.0, 9.4, 5.1 Hz, 1H), 1.50- methylpentanamide 1.86 (m, 5H), 1.33-1.48 (m, 2H), 0.95- [00108] 1.01 (m, 6H), 0.89-0.96 (m, 3H). 54 (2S)-N-[(1S)-2-amino-2-oxo-1- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.41- phenylethyl]-2-{[(4- 7.48 (m, 2H), 7.24-7.42 (m, 7H), 4.36 bromophenyl)carbamoyl]amino}-4- (dd, J = 9.7, 5.0 Hz, 1H), 1.52-1.82 methylpentanamide (m, 3H), 0.92-1.02 (m, 6H). [00109] 55 tert-butyl {[2-{[(4-bromophenyl) .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.30- carbamoyl]amino}-2,4- 7.39 (m, 2H), 7.15-7.23 (m, 2H), 6.82 dimethylpentanoyl]amino}acetate (br. s., 1H), 2.15-2.32 (m, 1H), 1.68- [00110] 1.79 (m, 2H), 1.63 (s, 3H), 1.48 (s, 9H), 0.93 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.2 Hz, 3H). 56 {[2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.31 carbamoyl]amino}-2,4- (d, J = 14.4 Hz, 2H), 3.92 (d, J = 1.2 dimethylpentanoyl] amino}acetic Hz, 2H), 2.03-2.15 (m, 1H), 1.70- acid 1.86 (m, 2H), 1.58 (s, 3H), 0.95 (d, J = [00111] 6.4 Hz, 3H), 0.91 (d, J = 6.4 Hz, 3H). 57 tert-butyl {[2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: carbamoyl]amino}-2- 7.247.39 (m, 2H), 7.24 (m, 2H), 6.50 (s, ethylbutanoyl] amino}acetate NH), 3.85 (s, 2H), 2.21-2.40 (m, 2H), [00112] 1.82 (dq, J = 14.2, 7.3 Hz, 2H), 1.45 (s, 9H), 0.85 (t, J = 7.3 Hz, 6H). 58 {[2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 600 MHz) δ: 7.35 carbamoyl]amino}-2- (d, J = 8.8 Hz, 2H), 7.26-7.30 (m, 2H), ethylbutanoyl]amino}acetic acid 3.92 (s, 2H), 2.23-2.34 (m, 2H), 1.78- [00113] 1.89 (m, 2H), 0.85 (t, J = 7.5 Hz, 6H). 59 tert-butyl {[2-{[(4-bromophenyl) .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.23 carbamoyl]amino}-2- (m, 2H), 7.39 (m, 2H), 3.81 (s, 2H), methylpropanoyl]amino}acetate 1.52 (s, 6H), 1.45 (s, 9H). [00114] 60 {[2-{[(4-bromophenyl) .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.23- carbamoyl]amino}-2- 7.40 (m, 4H), 3.81 (s, 2H), 1.51 (s, 6H). methylpropanoyl] amino}acetic acid [00115] 61 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.34- carbamoyl]amino}-N-[2- 7.39 (m, 2H), 7.28-7.33 (m, 2H), 4.36 (dimethylamino)-2-oxoethyl]-4- (dd, J = 10.0, 4.7 Hz, 1H), 3.97-4.13 methylpentanamide (m, 2H), 3.03 (s, 3H), 2.94 (s, 3H), 1.51- [00116] 1.83 (m, 3H), 0.94-1.03 (m, 6H). 62 tert-butyl {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.49- (trifluoromethyl)phenyl]carbamoyl} 7.56 (m, 4H), 4.36 (dd, J = 9.7, 5.3 Hz, amino)pentanoyl]amino}acetate 1H), 3.70-3.95 (m, 2H), 1.69-1.86 [00117] (m, 1H), 1.51-1.68 (m, 2H), 1.43- 1.46 (m, 9H), 0.99 (dd, J = 6.4, 4.1 Hz, 6H). 63 {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.50- (trifluoromethyl)phenyl]carbamoyl} 7.56 (m, 4H), 6.37 (d, J = 7.6 Hz, NH), amino)pentanoyl]amino}acetic 4.38 (dd, J = 9.7, 5.0 Hz, 1H), 3.79- acid 4.04 (m, 2H), 1.69-1.87 (m, 1H), 1.50- [00118] 1.70 (m, 2H), 0.99 (dd, J = 6.4, 3.8 Hz, 6H). 64 tert-butyl {[(2R,3R)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-3- 7.39 (m, 2H), 7.26-7.32 (m, 2H), 6.29 methylpentanoyl]amino}acetate (s, NH), 4.17-4.24 (m, 0H), 3.73- [00119] 3.95 (m, 2H), 1.87 (dtd, J = 9.8, 6.5, 3.2 Hz, 0H) 1.61 (ddt, J = 17.0, 7.4, 3.6 Hz, 0H), 1.43-1.47 (m, 9H), 1.11- 1.27 (m, 0H), 0.90-1.03 (m, 6H). 65 {[(2R,3R)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-3- 7.39 (m, 2H), 7.27-7.32 (m, 2H), 6.29 methylpentanoyl]amino}acetic (s, NH), 4.19-4.26 (m, 1H), 3.81- acid 4.00 (m, 2H), 1.84-1.94 (m, 1H), 1.60 [00120] (ddd, J = 13.2, 7.6, 3.5 Hz, 1H), 1.13- 1.30 (m, 2H), 1.13-1.30 (m, 2H), 0.96 (d, J = 17.6 Hz, 3H). 66 tert-butyl {[(2R)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 600 MHz) δ: 7.35- bromophenyl)carbamoyl]amino}-4- 7.38 (m, 2H), 7.28-7.31 (m, 2H), 4.34 methylpentanoyl]amino}acetate (dd, J = 10.0, 5.0 Hz, 1H), 3.75-3.91 [00121] (m, 2H), 1.73-1.80 (m, 1H), 1.63- 1.68 (m, 1H), 1.53-1.59 (m, 1H), 1.44- 1.47 (m, 9H), 0.99 (d, J = 6.7 Hz, 3H), 0.97 (d, J = 6.7 Hz, 3H). 67 {[(2R)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 600 MHz) δ: 7.34- bromophenyl)carbamoyl]amino}-4- 7.39 (m, 2H), 7.26-7.32 (m, 2H), 4.32- methylpentanoyl]amino}acetic 4.38 (m, 1H), 3.84-4.00 (m, 2H), acid 1.72-1.81 (m, 1H), 1.63-1.70 (m, [00122] 1H), 1.52-1.60 (m, 1H), 0.99 (d, J = 6.7 Hz, 3H), 0.97 (d, J = 6.7 Hz, 3H). 68 tert-butyl {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.27- (methylsulfanyl)phenyl]carbamoyl} 7.34 (m, 2H), 7.17-7.24 (m, 2H), 6.24 amino)pentanoyl]amino}acetate (d, J = 7.9 Hz, NH), 4.30-4.40 (m, [00123] 1H), 3.72-3.95 (m, 2H), 2.40-2.43 (m, 3H), 1.69-1.84 (m, 1H), 1.50- 1.68 (m, 2H), 1.44-1.47 (m, 9H), 0.99 (dd, J = 6.4, 4.7 Hz, 6H). 69 2-methyl-2-{[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.27 (trifluoromethyl)phenyl]carbamoyl} (s, NH), 7.52 (d, J = 19.9 Hz, 4H), 6.29 amino)pentanoyl]amino} (d, J = 8.5 Hz, NH), 4.27-4.43 (m, propanoic acid 1H), 1.70-1.85 (m, 1H), 1.45-1.67 [00124] (m, 8H), 0.98 (dd, J = 6.4, 2.9 Hz, 6H). 70 {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.26- (methylsulfanyl)phenyl]carbamoyl} 7.34 (m, 2H), 7.17-7.24 (m, 2H), 4.30- amino)pentanoyl]amino}acetic 4.41 (m, 1H), 3.80-4.03 (m, 2H), acid 2.39-2.43 (m, 3H), 1.49-1.84 (m, [00125] 3H), 0.98 (dd, J = 6.4, 4.1 Hz, 6H). 71 tert-butyl ({(2S)-4-methyl-2-[({4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.52- [(trifluoromethyl)sulfanyl]phenyl} 7.57 (m, 2H), 7.47-7.52 (m, 2H), 4.32- carbamoyl)amino]pentanoyl}amino) 4.40 (m, 1H), 3.72-3.95 (m, 2H), acetate 1.69-1.84 (m, 1H), 1.50-1.68 (m, [00126] 2H), 1.42-1.47 (m, 9H), 0.99 (dd, J = 6.3, 4.2 Hz, 6H). 72 ({(2S)-4-methyl-2-[({4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.47- [(trifluoromethyl)sulfanyl]phenyl} 7.57 (m, 4H), 4.37 (dd, J = 9.5, 5.1 Hz, carbamoyl)amino]pentanoyl}amino) 1H), 3.83-4.02 (m, 2H), 1.70-1.83 acetic acid (m, 1H), 1.51-1.68 (m, 2H), 0.99 (d, [00127] J = 3.8 Hz, 3H), 0.97 (d, J = 3.8 Hz, 3H). 73 tert-butyl 2-{[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-4- 7.38 (m, 2H), 7.26-7.32 (m, 2H), 4.31 methylpentanoyl]amino}-2- (dd, J = 9.1, 5.6 Hz, 1H), 1.67-1.80 methylpropanoate (m, 1H), 1.45-1.63 (m, 2H), 1.39- [00128] 1.44 (m, 15H), 0.97 (dd, J = 6.6, 3.1 Hz, 6H). 74 2-{[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.46 bromophenyl)carbamoyl]amino}-4- (s, NH), 8.26 (s, NH), 7.33-7.38 (m, methylpentanoyl]amino}-2- 2H), 7.25-7.31 (m, 2H), 4.32 (dd, J = methylpropanoic acid 9.2, 5.4 Hz, 1H), 1.68-1.80 (m, 1H), [00129] 1.51-1.65 (m, 2H), 1.49 (s, 3H), 1.48 (s, 3H), 0.98 (d, J = 3.5 Hz, 3H), 0.96 (d, J = 3.5 Hz, 3H). 75 tert-butyl {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.61 (methylsulfinyl)phenyl]carbamoyl} (s, 4H), 4.37 (dd, J = 9.8, 5.1 Hz, 1H), amino)pentanoyl]amino}acetate 3.72-3.96 (m, 2H), 2.77 (s, 3H), 1.69- [00130] 1.85 (m, 1H), 1.51-1.69 (m, 2H), 1.45 (s, 9H), 0.94-1.05 (m, 6H). 76 tert-butyl {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.77- (methylsulfonyl)phenyl]carbamoyl} 7.86 (m, 2H), 7.57-7.67 (m, 2H), 4.37 amino)pentanoyl]amino}acetate (dd, J = 9.7, 5.0 Hz, 1H), 3.71-3.96 [00131] (m, 2H), 3.07 (s, 3H), 1.69-1.83 (m, 1H), 1.51-1.70 (m, 2H), 1.40-1.49 (m, 9H), 0.94-1.03 (m, 6H). 77 {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.57- (methylsulfinyl)phenyl]carbamoyl} 7.66 (m, 4H), 4.38 (dd, J = 9.7, 5.0 Hz, amino)pentanoyl]amino}acetic 1H), 3.81-4.03 (m, 2H), 2.77 (s, 3H), acid 1.69-1.85 (m, 1H), 1.48-1.68 (m, [00132] 2H), 0.92-1.03 (m, 6H). 78 {[(2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.76- (methylsulfonyl)phenyl]carbamoyl} 7.87 (m, 2H), 7.57-7.68 (m, 2H), 6.43 amino)pentanoyl]amino}acetic (d, J = 8.5 Hz, NH), 4.32-4.45 (m, acid 1H), 3.81-4.04 (m, 2H), 3.07 (s, 3H), [00133] 1.71-1.83 (m, 1H), 1.49-1.70 (m, 2H), 0.98 (dd, J = 6.4, 3.5 Hz, 6H). 79 tert-butyl 2-methyl-2-{[(2S)-4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.46- methyl-2-({[4- 7.58 (m, 2H), 4.33 (dd, J = 9.2, 5.7 Hz, (trifluoromethyl)phenyl]carbamoyl} 1H), 1.69-1.86 (m, 1H), 1.46-1.66 amino)pentanoyl]amino} (m, 2H), 1.36-1.46 (m, 15H), 0.94- propanoate 1.04 (m, 6H). [00134] 80 tert-butyl {[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.24- bromophenyl)carbamoyl]amino}-4- 7.41 (m, 4H), 4.44 (dd, J = 7.8, 5.4 Hz, (methylsulfanyl)butanoyl]amino} 1H), 3.70-3.99 (m, 2H), 2.54-2.68 acetate (m, 2H), 2.12-2.18 (m, 1H), 2.11 (s, [00135] 3H), 1.85-2.02 (m, 1H), 1.41-1.50 (m, 9H). [α]D = −21.8 (c = 1.00, MeOH) 81 tert-butyl {[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.26- bromophenyl)carbamoyl]amino}-4- 7.43 (m, 4H), 4.43-4.57 (m, 1H), 3.70- (methylsulfonyl)butanoyl]amino} 4.03 (m, 2H), 3.24 (s, 2H), 2.99 (s, acetate 4H), 2.28-2.42 (m, 1H), 2.11-2.26 [00136] (m, 1H), 1.47 (s, 9H). 82 {[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.25- bromophenyl)carbamoyl]amino}-4- 7.44 (m, 4H), 6.55 (d, J = 7.3 Hz, NH), (methylsulfanyl)butanoyl]amino} 4.53 (m, 1H), 3.79-4.10 (m, 2H), 3.26 acetic acid (m., 2H), 2.98 (s, 3H), 2.26-2.42 (m, [00137] 1H), 2.20 (m, 1H). 83 {[(2S)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.26- bromophenyl)carbamoyl]amino}-4- 7.42 (m, 4H), 6.55 (d, J = 7.3 Hz, NH), (methylsulfonyl)butanoyl]amino} 4.47-4.58 (m, 1H), 3.80-4.11 (m, acetic acid 2H), 3.25 (m, 2H), 2.98 (s, 3H), 2.28- [00138] 2.43 (m, 1H), 2.11-2.27 (m, 1H). 84 tert-butyl {[2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.61 bromophenyl)carbamoyl]amino}-3- (s, 1H), 7.21-7.41 (m, 4H), 6.94 (s, (1H-imidazol-4- 1H), 4.51-4.64 (m, 1H), 3.75-3.96 yl)propanoyl]amino}acetate (m, 2H), 3.07-3.22 (m, 1H), 2.93- [00139] 3.06 (m, 1H), 1.49 (s, 9H). 85 {[2-{[(4- .sup.1H NMR (DMSO-D.sub.6, 300 MHz) δ: 8.93 bromophenyl)carbamoyl]amino}-3- (NH, 1H), 8.42 (br. s., NH), 7.67 (s, (1H-imidazol-4- 1H), 7.34 (d, J = 4.1 Hz, 4H), 6.88 (s, yl)propanoyl]amino}acetic 1H), 6.28 (d, J = 7.3 Hz, NH), 4.44 (m., acid 1H), 3.55-3.90 (m, 2H), 2.93 (m., 2H). [00140] 86 tert-butyl 2-{[(2R)-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- bromophenyl)carbamoyl]amino}-4- 7.38 (m, 2H), 7.26-7.32 (m, 2H), 4.31 methylpentanoyl]amino}-2- (dd, J = 9.1, 5.6 Hz, 1H), 1.67-1.80 methylpropanoate (m, 1H), 1.45-1.63 (m, 2H), 1.39- [00141] 1.44 (m, 15H), 0.97 (dd, J = 6.6, 3.1 Hz, 6H). 87 2-{[(2R)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.46 carbamoyl]amino}-4- (s, NH), 8.23 (s, 2NH), 7.33-7.39 (m, methylpentanoyl] amino}-2- 2H), 7.26-7.31 (m, 2H), 6.19 (d, J = methylpropanoic acid 8.2 Hz, NH), 4.31 (m 1H), 1.73 (m, [00142] 1H), 1.51-1.65 (m, 2H), 1.49 (s, 3H), 1.48 (s, 3H), 0.98 (d, J = 3.8 Hz, 6H), 0.96 (d, J = 3.5 Hz, 6H). 88 tert-butyl {[4-amino-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.27- bromophenyl) carbamoyl]amino}- 7.42 (m, 4H), 4.69 (t, J = 6.0 Hz, 1H), 4-oxobutanoyl]amino}acetate 3.75-3.94 (m, 2H), 2.70-2.78 (m, [00143] 2H), 1.45 (s, 9H). 89 4-amino-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.26- carbamoyl]amino}-4-oxobutanoic 7.44 (m, 4H), 4.62 (t, J = 5.3 Hz, 1H), acid 2.70-2.94 (m, 2H). [00144] 90 tert-butyl {[2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.56- carbamoyl]amino}-3-(1H-indol-3- 7.61 (m, 1H), 7.30-7.36 (m, 3H), 7.23- yl) propanoyl]amino}acetate 7.26 (m, 2H), 7.16 (s, NH), 7.08 (td, [00145] J = 7.6, 1.2 Hz, 1H), 6.95-7.02 (m, 1H), 6.13 (d, J = 7.3 Hz, NH), 4.60-4.68 (m, 1H), 3.80 (s, 2H), 3.32-3.38 (m, 1H), 3.11-3.23 (m, 1H), 1.43-1.47 (m, 9H). 91 tert-butyl {[4-amino-2-{[(4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.27- bromophenyl) carbamoyl]amino}- 7.42 (m, 4H), 4.69 (t, J = 6.0 Hz, 1H), 4-oxobutanoyl]amino}acetate 3.75-3.94 (m, 2H), 2.70-2.78 (m, [00146] 2H), 1.45 (s, 9H). Interm. IUPAC name No. Structure .sup.1H NMR δ (ppm) 10 (2S,3S)-2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.33- carbamoyl]amino}-3- 7.41 (m, 2H), 7.26-7.33 (m, 2H), 4.18 methylpentanamide (d, J = 6.2 Hz, 1H), 1.74-1.91 (m, 1H), [00147] 1.50-1.66 (m, 1H), 1.11-1.33 (m, 1H), 0.99 (d, J = 7.0 Hz, 3H), 0.91- 0.97 (m, 3H). 11 (2S,3S)-2-{[(4-bromo-2- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.99 fluorophenyl) carbamoyl]amino}-3- (t, J = 8.8 Hz, 1H), 7.31 (dd, J = 10.7, methylpentanamide 2.2 Hz, 1H), 7.19-7.27 (m, 1H), 4.18 [00148] (d, J = 6.2 Hz, 1H), 1.78-1.95 (m, 1H), 1.49-1.65 (m, 1H), 1.10-1.27 (m, 1H), 1.00 (d, J = 6.7 Hz, 3H), 0.91- 0.98 (m, 3H). 12 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (acetone-d6, 300 MHz) δ: carbamoyl]amino}-pentanamide 8.28 (t, J = 8.8 Hz, 1H), 8.12 (br. s., [00149] NH), 7.33 (dd, J = 11.0, 2.2 Hz, 1H), 7.26 (dt, J = 8.9, 1.9 Hz, 1H), 7.07 (br. s., NH), 6.55 (d, J = 7.0 Hz, NH), 6.40 (br. s., NH), 4.38 (td, J = 7.8, 5.3 Hz, 1H), 1.73-1.89 (m, 1H), 1.54-1.70 (m, 1H), 1.24-1.49 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H). 13 (2S)-2-{[(4-bromophenyl) .sup.1H NMR (acetone-d6, 300 MHz) δ: carbamoyl]amino}-4- 8.17 (s, NH), 7.41-7.50 (m, 2H), 7.33- methylpentanamide 7.40 (m, 2H), 6.03 (d, J = 8.2 Hz, [00150] NH), 4.39 (ddd, J = 9.4, 8.2, 5.0 Hz, 1H), 3.58 (q, J = 5.6 Hz, 2H), 3.26- 3.37 (m, 2H), 1.66-1.81 (m, 1H), 1.44- 1.67 (m, 2H), 0.94 (d, J = 1.5 Hz, 3H), 0.92 (d, J = 1.4 Hz, 3H). 14 (2S)-2({[(4-bromo-2-fluorophenyl) .sup.1H NMR (acetone-d6, 300 MHz) δ: 8.27 carbamoyl]amino}-4- (t, J = 8.9 Hz, 1H), 8.06 (br. s., NH), methylpentanoate 7.34 (dd, J = 10.8, 2.3 Hz, 1H), 7.25- [00151] 7.31 (m, 1H), 6.53 (d, J = 7.0 Hz, NH), 4.43-4.55 (m, 1H), 1.73-1.87 (m, 1H), 1.53-1.71 (m, 2H), 0.98 (d, J = 1.5 Hz, 3H), 0.96 (d, J = 1.5 Hz, 3H). 15 (2S)-2-{[(4-bromo-2-fluorophenyl) .sup.1H NMR (acetone-d6, 300 MHz) δ: 8.28 carbamoyl]amino}-4- (t, J = 8.9 Hz, 1H), 8.07 (br. s., NH), methylpentanamide 7.33 (dd, J = 10.8, 2.3 Hz, 1H), 7.23- [00152] 7.30 (m, 1H), 7.10 (br. s., NH), 6.50 (d, J = 8.2 Hz, NH), 6.38 (br. s., NH), 4.42 (ddd, J = 9.6, 8.3, 5.0 Hz, 1H), 1.70- 1.87 (m, 1H), 1.59-1.70 (m, 1H), 1.44- 1.59 (m, 1H), 0.95 (d, J = 1.5 Hz, 3H), 0.93 (d, 3H). 16 tert-butyl (2S)-2-{[(4-bromo-2- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.89 (t, fluorophenyl) carbamoyl]amino}-4- J = 8.8 Hz, 1H), 7.14 (dd, J = 10.4, 2.2 methylpentanoate Hz, 1H), 7.06 (d, J = 9.1 Hz, 1H), 6.80 [00153] (d, J = 2.6 Hz, NH), 5.79 (br. s., NH), 4.45 (dd, J = 8.8, 5.0 Hz, 1H), 1.69- 1.85 (m, 1H), 1.57-1.69 (m, 1H), 1.52 (s, 9H), 1.41-1.48 (m, 1H), 0.97 (d, J = 3.5 Hz, 3H), 0.95 (d, 3H). 17 2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.31- carbamoyl]amino}-2,4- 7.39 (m, 2H), 7.22-7.30 (m, 2H), 1.80- dimethylpentanoic acid 1.92 (m, 2H), 1.71-1.82 (m, 1H), [00154] 1.56-1.67 (m, 2H), 1.44 (s, 3H), 0.98 (d, J = 1.2 Hz, 3H), 0.95 (d, J = 1.2 Hz, 3H). 18 tert-butyl {[2-{[(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 9.29 carbamoyl]amino}-2- (br. s., NH), 8.58-8.75 (m, 4H), 7.33 methylpropanoate (br. s., NH), 2.65-2.75 (m, 9H). [00155] 19 2-{[(4-bromophenyl) .sup.1H NMR (CD3OD, 300 MHz) δ: 7.32- carbamoyl]amino}-2- 7.37 (m, 2H), 7.24-7.29 (m, 2H), 1.52 methylpropanoic acid (s, 6H). [00156] 20 2-{[(4-bromophenyl) .sup.1H NMR (acetone-d6, 300 MHz) δ: carbamoyl]amino}-2-ethylbutanoic 8.76 (br. s., 1H), 7.44-7.52 (m, 2H), acid 7.31-7.40 (m, 2H), 6.30 (br. s., 1H), [00157] 2.29-2.48 (m, 2H), 1.75-1.92 (m, 2H), 0.76-0.86 (m, 6H). 21 tert-butyl (2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.50 (trifluoromethyl)phenyl]carbamoyl} (s, 4H), 4.27 (dd, J = 9.1, 5.6 Hz, 1H), amino)pentanoate 1.68-1.86 (m, 1H), 1.52-1.66 (m, [00158] 2H), 1.45-1.50 (s, 9H), 0.95 (t, J = 6.9 Hz, 6H). 22 (2S)-4-methyl-2-({[4- .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.49- (trifluoromethyl)phenyl]carbamoyl} 7.57 (m, 4H), 4.38 (dd, J = 9.4, 5.0 Hz, amino)pentanoic acid 1H), 1.69-1.87 (m, 1H), 1.51-1.69 [00159] (m, 2H), 0.92-1.01 (m, 6H). 23 tert-butyl (2S)-2-({(4-chlorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.30- carbamoyl}amino)4- 7.39 (m, 2H), 7.17-7.28 (m, 1H), 4.25 methylpentanoate (dd, J = 8.9, 5.7 Hz, 1H), 1.74 (dd, J = [00160] 13.6, 7.5 Hz, 1H), 1.51-1.67 (m, 2H), 1.47 (s, 9H), 0.97 (t, J = 6.9 Hz, 6H). 24 (2S)-2-({(4-chlorophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.29- carbamoyl}amino)4- 7.38 (m, 2H), 7.17-7.27 (m, 2H), 4.36 methylpentanoic acid (dd, J = 9.4, 5.0 Hz, 1H), 1.73 (dd, J = [00161] 18.3, 5.7 Hz, 1H), 1.51-1.68 (m, 2H), 0.98 (dd, J = 6.4, 3.5 Hz, 6H). 25 tert-butyl (2S)-2-({(4-iodophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.50- carbamoyl}amino)4- 7.59 (m, 2H), 7.12-7.23 (m, 2H), 4.25 methylpentanoate (m, 1H), 1.73 (m, 1H), 1.49-1.63 (m, [00162] 2H), 1.47 (s, 9H), 0.91-1.03 (m, 6H). 26 (2S)-2-({(4-iodophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.50- carbamoyl}amino)4- 7.58 (m, 2H), 7.13-7.21 (m, 2H), 4.35 methylpentanoic acid (dd, J = 9.4, 5.0 Hz, 1H), 1.50-1.86 [00163] (m, 2H), 1.01 (m, 6H). 27 (2R,3R)-2-({(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.35- carbamoyl}amino)3- 7.39 (m, 2H), 7.28-7.32 (m, 2H), 4.32 methylpentanoic acid (d, J = 4.7 Hz, 1H), 1.92 (dq, J = 6.8, [00164] 4.6 Hz, 1H), 1.46-1.60 (m, 1H), 1.16- 1.33 (m, 1H), 0.93-1.02 (m, 6H). 28 tert-butyl (2R)-2-({(4- .sup.1H NMR (CDCl.sub.3, 300 MHz) δ: 7.33 (d, bromophenyl) carbamoyl}amino)4- J = 8.5 Hz, 2H), 7.17 (s, 2H), 4.43 (dd, methylpentanoate J = 9.1, 5.3 Hz, 1H), 1.68-1.79 (m, [00165] 1H), 1.56-1.67 (m, 1H), 1.48 (s, 9H), 1.44 (s, 1H), 0.97 (d, J = 4.1 Hz, 3H), 0.95 (d, J = 4.4 Hz, 3H). 29 (2R)-2-({(4-bromophenyl) .sup.1H NMR (acetone-D6, 300 MHz) δ: carbamoyl}amino)4- 8.17 (s, NH), 7.43-7.50 (m, 2H), 7.33- methylpentanoic acid 7.41 (m, 2H), 6.04 (d, J = 7.9 Hz, [00166] NH), 4.42-4.52 (m, 1H), 1.71-1.87 (m, 1H), 1.52-1.69 (m, 2H), 0.97 (d, J = 2.1 Hz, 3H), 0.95 (d, J = 2.3 Hz, 3H). 30 tert-butyl (2S)-4-methyl-2-({[4- .sup.1H NMR (CD3OD, 300 MHz) δ: 7.27- (methylthio)phenyl] 7.32 (m, 2H), 7.18-7.23 (m, 2H), 4.22- carbamoyl}amino)pentanoate 4.29 (m, 1H), 2.42 (s, 3H), 1.70-1.79 [00167] (m, 1H), 1.51-1.61 (m, 2H), 1.47 (s, 9H), 0.97 (t, J = 6.7 Hz, 6H). 31 (2S)-4-methyl-2-({[4- .sup.1H NMR (CD3OD, 300 MHz) δ: 7.25- (methylthio)phenyl] 7.31 (m, 2H), 7.14-7.20 (m, 2H), 4.37 carbamoyl}amino)pentanoic acid (dd, J = 9.2, 5.1 Hz, 1H), 2.39 (s, 3H), [00168] 1.68- 1.83 (m, 1H), 1.51-1.67 (m, 2H), 0.96 (dd, J = 6.2, 2.3 Hz, 6H). 32 (2S)-4-methyl-2-{({4- .sup.1H NMR (CD3OD, 300 MHz) δ: 7.52- [(trifluoromethyl)thio]phenyl} 7.58 (m, 2H), 7.47-7.52 (m, 2H), 4.37 carbamoyl}amino)pentanoic acid (dd, J = 9.4, 5.0 Hz, 1H), 1.70-1.82 [00169] (m, 1H), 1.53-1.69 (m, 2H), 0.99 (d, J = 3.2 Hz, 3H), 0.97 (d, J = 3.2 Hz, 3H). 33 tert-butyl (2S)-4-methyl-2-{({4- .sup.1H NMR (CD3OD, 300 MHz) δ: 7.53- [(trifluoromethyl)thio]phenyl} 7.57 (m, 2H), 7.47-7.51 (m, 2H), 4.26 carbamoyl}amino)pentanoate (dd, J = 8.9, 5.7 Hz, 1H), 1.74 (td, J = [00170] 13.6, 6.7 Hz, 1H), 1.51-1.65 (m, 2H), 1.47 (s, 9H), 0.97 (t, J = 6.7 Hz, 6H). 34 (2S)-2-({(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 7.23- carbamoyl}amino)4- 7.41 (m, 4H), 4.31-4.42 (m, 1H), 2.56 (methylthio)butanoic acid (d, J = 15.5 Hz, 2H), 2.12-2.23 (m, [00171] 1H), 2.08 (s, 3H), 1.98 (dt, J = 14.0, 7.2 Hz, 1H). 35 2-({(4-bromophenyl) .sup.1H NMR (CD.sub.3OD, 300 MHz) δ: 8.76 carbamoyl}amino)3-(1H-imidazol- (s, 1H), 7.23-7.40 (m, 6H), 4.65 (m, 4-yl)propanoic acid 1H), 3.03-3.27 (m, 2H). [00172]

Biological Data

[0281] Biological activity of compounds according to Formula II is set forth in Table 5 below. CHO-Gα16 cells stably expressing FPRL1 were cultured in (F12, 10% FBS, 1% PSA, 400 μg/ml geneticin and 50 μg/ml hygromycin) and HEK-Gqi5 cells stable expressing FPR1 were cultured in (DMEM high glucose, (0% FBS, 1% PSA, 400 μg/ml geneticin and 50 μg/ml hygromycin). In general, the day before the experiment, 18,000 cells/well were plated in a 384-well clear bottom poly-d-lysine coated plate. The following day the screening compound-induced calcium activity was assayed on the FLIPR.sup.Tetra. The drug plates were prepared in 384-well microplates using the EP3 and the MultiPROBE robotic liquid handling systems. Compounds were tested at concentrations ranging from 0.61 to 10,000 nM. Results are expressed as EC.sub.50 (nM) and efficacy values.

TABLE-US-00005 TABLE 5 FPRL-1 Ga16-CHO EC.sub.50 (nM) IUPAC Name Compound (Rel. eff.) {[2-{[(4-bromophenyl)carbamoyl]amino}-3-(1H-imidazol-4- 10.0 (0.95) yl)propanoyl]amino}acetic acid tert-butyl {[2-{[(4-bromophenyl)carbamoyl]amino}-3-(1H- 263 (0.95) imidazol-4-yl)propanoyl]amino}acetate {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 247 (1.01) (methylsulfonyl)butanoyl]amino}acetic acid tert-butyl{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 1238 (0.97) (methylsulfonyl)butanoyl]amino}acetate {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 7 (1.03) (methylsulfanyl)butanoyl]amino}acetic acid tert-butyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 127 (0.98) (methylsulfanyl)butanoyl]amino}acetate 2-methyl-2-{[(2S)-4-methyl-2-({[4- 2.3 (0.92) (trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}propanoic acid tert-butyl2-methyl-2-{[(2S)-4-methyl-2-({[4- 1016 (1.07) (trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}propanoate {[(2S)-4-methyl-2-({[4- 459 (1.12) (methylsulfonyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid tert-butyl{[(2S)-4-methyl-2-({[4- 1083 (0.90) (methylsulfonyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetate {[(2S)-4-methyl-2-({[4- 358 (1.21) (methylsulfinyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid tert-butyl {[(2S)-4-methyl-2-({[4- 668 (0.97) (methylsulfinyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetate 2-{[(2S)-2-({[(4-bromophenyl)amino]carbamoyl}amino)-4- 1 (0.96) methylpentanoyl] amino}-2-methylpropanoic acid tert-butyl 2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}- 133 (1.16) 4-methylpentanoyl]amino}-2-methylpropanoate ({(2S)-4-methyl-2-[({4- 560 (1.07) [(trifluoromethyl)sulfanyl]phenyl}carbamoyl)amino]pentanoyl}amino)acetic acid tert-butyl ({(2S)-4-methyl-2-[({4- 3103 (0.78) [(trifluoromethyl)sulfanyl]phenyl}carbamoyl)amino]pentanoyl}amino)acetate {[(2S)-4-methyl-2-({[4- 2.95 (1.05) (methylsulfanyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid tert-butyl {[(2S)-4-methyl-2-({[4- 116 (0.98) (methylsulfanyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetate {[(2R)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 1229 (0.97) methylpentanoyl]amino}acetic acid tert-butyl {[(2R)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 3657 (0.92) methylpentanoyl]amino}acetate {[(2R,3R)-2-{[(4-bromophenyl)carbamoyl]amino}-3- 19315 (0.45) methylpentanoyl]amino}acetic acid tert-butyl {[(2R,3R)-2-{[(4-bromophenyl)carbamoyl]amino}- 3974 (0.44) 3-methylpentanoyl]amino}acetate {[(2S)-4-methyl-2-({[4- 1.8 (0.99) (trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetic acid tert-butyl {[(2S)-4-methyl-2-({[4- 309 (0.81) (trifluoromethyl)phenyl]carbamoyl}amino)pentanoyl]amino}acetate {[(2R)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4- 1489 (0.87) methylpentanoyl]amino}acetic acid (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-[2- 1.4 (0.90) (dimethylamino)-2-oxoethyl]-4-methylpentanamide [(2-{[(4-bromophenyl)carbamoyl]amino}-2- 480 (0.99) methylpropanoyl)amino]acetic acid tert-butyl [(2-{[(4-bromophenyl)carbamoyl]amino}-2- 114 (1.02) methylpropanoyl)amino]acetate [(2-{[(4-bromophenyl)carbamoyl]amino}-2- 19 (1.04) ethylbutanoyl)amino]acetic acid tert-butyl [(2-{[(4-bromophenyl)carbamoyl]amino}-2- 31 (1.03) ethylbutanoyl)amino]acetate [(2-{[(4-bromophenyl)carbamoyl]amino}-2,4- 22 (0.98) dimethylpentanoyl)amino]acetic acid tert-butyl [(2-{[(4-bromophenyl)carbamoyl]amino}-2,4- 58 (0.98) dimethylpentanoyl)amino]acetate (2S)-N-[(1S)-2-amino-2-oxo-1-phenylethyl]-2-{[(4- 84 (0.99) bromophenyl)carbamoyl]amino}-4-methylpentanamide (2S)-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 9.1 (1.08) methylpentanoyl]amino}(phenyl)ethanoic acid tert-butyl (2S)-{[(2S)-2-{[(4- 122 (1.02) bromophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}(phenyl)ethanoate (2S)-N-[(2S)-1-amino-1-oxopentan-2-yl]-2-{[(4- 6.4 (1.03) bromophenyl)carbamoyl]amino}-4-methylpentanamide (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 1.0 (0.89) methylpentanoyl]amino}pentanoic acid tert-butyl (2S)-2-{[(2S)-2-{[(4- 13 (1.06) bromophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}pentanoate (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-[(2R)-1- 3.0 (1.00) hydroxypropan-2-yl]-4-methylpentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2,3- 5.1 (0.98) dihydroxypropyl)-4-methylpentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(1,3- 7.4 (0.96) dihydroxypropan-2-yl)-4-methylpentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2-hydroxy- 2.1 (1.01) 2-methylpropyl)-4-methylpentanamide (2S)-N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-2-{[(4- 1.3 (1.03) bromophenyl)carbamoyl]amino}-4-methylpentanamide (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 1.83 (1.13) methylpentanoyl|amino}-3-methylbutanoic acid tert-butyl (2S)-2-{[(2S)-2-{[(4- 68 (0.98) bromophenyl)carbamoyl]amino}-4-methylpentanoyl]amino}- 3-methylbutanoate (2S)-N-[(2S)-1-amino-1-oxopropan-2-yl]-2-{[(4- 24 (0.96) bromophenyl)carbamoyl]amino}-4-methylpentanamide (2S)-2-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 11 (1.05) methylpentanoyl]amino}propanoic acid tert-butyl (2S)-2-{[(2S)-2-{[(4- 147 (0.96) bromophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}propanoate (2S)-N-[(2S)-1-amino-1-oxopropan-2-yl]-2-{[(4-bromo-2- 31 (1.05) fluorophenyl)carbamoyl]amino}-4-methylpentanamide (2S)-2-{[(2S)-2-{[(4-bromo-2- 12 (0.95) fluorophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}propanoic acid tert-butyl (2S)-2-{[(2S)-2-{[(4-bromo-2- 174 (1.00) fluorophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}propanoate (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2- 77 (1.05) hydroxyethyl)-4-methylpentanamide (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4- 20 (0.99) methyl-N-(2-oxopropyl)pentanamide (2S)-N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2- 4.5 (0.95) fluorophenyl)carbamoyl]amino}-4-methylpentanamide {[(2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-4- 3.6 (1.10) methylpentanoyl]amino}acetic acid tert-butyl {[(2S)-2-{[(4-bromo-2- 134 (1.19) fluorophenyl)carbamoyl]amino}-4- methylpentanoyl]amino}acetate (2S)-N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2- 5.2 (0.98) fluorophenyl)carbamoyl]amino}pentanamide (2S)-N-(2-amino-2-oxoethyl)-2-{[(4- 2.5 (0.97) bromophenyl)carbamoyl]amino}pentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4-methyl-N-(2- 4.7 (0.82) oxopropyl)pentanamide (2S)-N-(2-amino-2-oxoethyl)-2-{[(4- 1.05 (1.08) bromophenyl)carbamoyl]amino}-4-methylpentanamide {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 0.88 (0.91) methylpentanoyl]amino}acetic acid (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 11 (0.92) hydroxyethyl)-4-methylpentanamide tert-butyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 140 (0.85) methylpentanoyl]amino}acetate {[(2S)-2-{[(4-bromo-2- 4.8 (0.92) fluorophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid tert-butyl {[(2S)-2-{[(4-bromo-2- 83 (0.95) fluorophenyl)carbamoyl]amino}pentanoyl]amino}acetate (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2- 92 (0.92) oxopropyl)pentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 35 (1.05) oxopropyl)pentanamide propan-2-yl {[(2S)-2-{[(4- 14 (1.04) bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate ethyl {[(2S)-2-{[(4- 57 (1.18) bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate methyl {[(2S)-2-{[(4- 17 (0.88) bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2- 105 (0.87) hydroxyethyl)pentanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 38 (0.92) hydroxyethyl)pentanamide (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2- 16 (0.98) hydroxyethyl)-3-phenylpropanamide {[(2S)-2-{[(4- 3.2 (0.91) bromophenyl)carbamoyl]amino}pentanoyl]amino}acetic acid tert-butyl {[(2S)-2-{[(4- 31 (0.95) bromophenyl)carbamoyl]amino}pentanoyl]amino}acetate (2S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N-(2- 12 (0.94) oxopropyl)-3-phenylpropanamide (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 29 (0.96) oxopropyl)-3-phenylpropanamide (2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-N- 62 (1.00) (2-hydroxyethyl)-3-methylpentanamide (2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 24 (1.00) hydroxyethyl)-3-methylpentanamide (2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}-3- 36 (1.01) methyl-N-(2-oxopropyl)pentanamide (2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3-methyl-N- 10 (0.97) (2-oxopropyl)pentanamide (2S,3S)-N-(2-amino-2-oxoethyl)-2-{[(4-bromo-2- 10 (1.00) fluorophenyl)carbamoyl]amino}-3-methylpentanamide (2S,3S)-N-(2-amino-2-oxoethyl)-2-{[(4- 4.6 (0.81) bromophenyl)carbamoyl]amino}-3-methylpentanamide {[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- 2.7 (1.00) methylpentanoyl]amino}acetic acid tert-butyl {[(2S,3S)-2-{[(4-bromophenyl)carbamoyl]amino}- 280 (0.85) 3-methylpentanoyl]amino}acetate {[(2S,3S)-2-{[(4-bromo-2-fluorophenyl)carbamoyl]amino}- 5.5 (0.95) 3-methylpentanoyl]amino}acetic acid tert-butyl {[(2S,3S)-2-{[(4-bromo-2- 757 (0.86) fluorophenyl)carbamoyl]amino}-3- methylpentanoyl]amino}acetate (2S)-2-{[(4-bromophenyl)carbamoyl]amino}-N-(2- 6 (0.92) hydroxyethyl)-3-phenylpropanamide 3-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- 18 (0.98) phenylpropanoyl]amino}propanoic acid tert-butyl 3-{[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}- 255 (1.00) 3-phenylpropanoyl]amino}propanoate {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- 7.7 (0.99) phenylpropanoyl]amino}acetic acid tert-butyl {[(2S)-2-{[(4-bromophenyl)carbamoyl]amino}-3- 118 (0.91) phenylpropanoyl]amino}acetate tert-butyl 2-{[(2R)-2-{[(4-bromophenyl)carbamoyl]amino}- 2725 (0.74) 4-methylpentanoyl]amino}-2-methylpropanoate 2-{[(2R)-2-{[(4-bromophenyl)carbamoyl]amino}-4- 490 (0.74) methylpentanoyl]amino}-2-methylpropanoic acid {[2-{[(4-bromophenyl)carbamoyl]amino}-3-(1H-indol-3- 0.73 (0.97) yl)propanoyl]amino}acetic acid tert-butyl {[2-{[(4-bromophenyl)carbamoyl]amino}-3-(1H- 305 (1.03) indol-3-yl)propanoyl]amino}acetate [(4-amino-2-{[(4-bromophenyl)carbamoyl]amino}-4- 2938 (0.81) oxobutanoyl)amino]acetic acid tert-butyl [(4-amino-2-{[(4-bromophenyl)carbamoyl]amino}- 2306 (0.90) 4-oxobutanoyl)amino]acetate