# US 7,408,025 B2 · Lipopeptides as antibacterial agents

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- Number: US 7,408,025 B2
- Document ID: US7408025B2
- Status: Granted
- Kind: B2
- Application number: 09/737,908
- Filed: 2000-12-15
- Published: 2004-04-08
- Granted: 2008-08-05
- Earliest claimed: 1999-12-15
- Assignees: Cubist Pharmaceuticals, Inc.
- Inventors: Jason Hill; Ian Parr; Michael Morytko; Jim Siedlecki; Xiang Yang Yu; Jared Silverman; Dennis Keith; John Finn; Dale Christensen; Tsvetelina Lazarova; Alan D. Watson; Yan Zhang
- Web page: https://patentgrep.com/patent/US7408025B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61P 31/04: Antibacterial agents
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to novel lipopeptide compounds. The invention also relates to pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The invention also relates to methods of producing these novel lipopeptide compounds and intermediates used in producing these compounds.

## Claims

### Claim 1

A compound having the formula (I):
and salts thereof;
wherein R is:
wherein X′ and X″ are independently C═O, C═S, C═NH, C═NRX, S═O or SO2;
wherein n is 0 or 1;
wherein RX is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
wherein B is X″RY, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
wherein RY is hydrido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or hydroxyl;
wherein A is H, NH2, NHRA, NRARB, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl or heterocyclyl;
wherein RA and RB are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or carboalkoxy;
wherein when n is 0, then A is additionally:
wherein each of R50-R53 is independently C1-C15 alkyl;
alternatively, wherein B and A together form a 5-7 membered heterocyclic or heteroaryl ring;
wherein R1 is
wherein X′ and X′″ are independently C═O, C═S, C═NH, C═NRX′, S═O or SO2;
wherein m is 0 or 1;
wherein RX′ is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heteorcyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
wherein B′ is X′″RY′, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
wherein RY′ is hydrido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or hydroxyl;
wherein A′ is unsubstituted alkyl, alkenyl, alkynyl, alkoxy, aryloxy; or alkyl wherein one or more hydrogen atoms is replaced by a substituent group selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino, and formyl;
provided that when B′ is H then (X′)m-A′ is other than
(a) —C(O)(C1-C16 unsubstituted alkyl)-NH2;
(b) —C(O)(C1-C10 unsubstituted alkyl)-NHC(O)RD, wherein RD is —C1-C18 unsubstituted alkyl, or —C1-C18 selected substituted alkyl wherein one proton is replaced by a hydroxyl, carboxyl or C1-C3 alkoxy, or one to three protons is replaced by a halo substituent;
(c) —C(O)C1-C18 unsubstituted alkyl;
(d) —C(O)C4-C18 unsubstituted alkenyl;
wherein R54 is selected from C1-C17-unsubstituted alkyl or C2-C17-unsubstituted alkenyl; wherein R55 is selected from hyroxyethyl, hydroxymethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indolemthyl, phenyl optionally substituted with a group selected from halo, nitro, C1-C3-unsubstituted alkyl, hydroxy, C1-C3-unsubstituted alkoxy, C1-C3-unsubstituted alkylthio, carbamyl or C1-C3 unsubstituted alkylcarbamyl; or benzyl optionally substituted with a group selected from halo, nitro, C1-C3-unsubstituted alkyl, hydroxy, C1-C3-unsubstituted alkoxy, C1-C3-unsubstituted alkylthio, carbamyl or C1-C3 unsubstituted alkylcarbamyl; wherein t is 0 or 1 and wherein u is an integer from 1-3;
(f) —C(O)C1-C18 selected unsubstituted alkyl wherein one proton is replaced by a hydroxyl, carboxyl or C1-C3 alkoxy, or one to three protons is replaced by a halo substituent; and
(g) an amino protecting group; and
wherein when B′ is H and m is 0, then A′ is other than C4-C14 unsubstituted alkyl;
wherein R2 is
wherein K and K′ together form a C3-C7 cycloalkyl or heterocyclyl ring or a C5-C10 aryl or heteroaryl ring;
wherein J is hydrido, amino, NHRJ, NRJRK, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, alkylamino, hydroxyl, thio, alkylthio, alkenylthio, sulfinyl, sulfonyl, azido, cyano, halo,
wherein each of R24, R25, and R26 is independently alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; or R24 and R25 together form a 5-8 membered heterocyclyl ring;
wherein RJ and RK are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; or
alternatively, wherein J together with R17, forms a 5-8 membered heterocyclyl or cycloalkyl ring; or
alternatively, wherein J, together with both R17 and R18, forms a 5-8 membered aryl, cycloalkyl, heterocyclyl or heteroaryl ring; and
wherein each of R17 and R18 is independently hydrido, halo, hydroxyl, alkoxy, amino, thio, sulfinyl, sulfonyl or
wherein R17 and R18 taken together can form a ketal, thioketal,
wherein each of R22 and R23 is independently hydrido or alkyl.

### Claim 2

A compound having the formula (I):
and salts thereof;
wherein R is:
wherein X and X′ are independently C═O, C═S, C═NH, C═NRX, S═O or SO2;
wherein n is 0 or 1;
wherein RX is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
wherein B is X″RY, H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl;
wherein RY is hydrido, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or hydroxyl;
wherein A is H, NH2, NHRA, NRARB, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl or heterocyclyl;
wherein RA and RB are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or carboalkoxy;
wherein when n is 0, then A is additionally:
wherein each of R50-R53 is independently C1-C15 alkyl;
alternatively, wherein B and A together form a 5-7 membered heterocyclic or heteroaryl ring;
wherein R1 is
wherein X′ and X″′ are independently C═O, C═S, C═NH, C═NRX′S═O or SO2;
wherein m is 0 or 1;
wherein RX′ is alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heteorcyclyl, hydroxyl, alkoxy, carboxy or carboalkoxy;
wherein B′ and A′ together form a 5-7 membered heterocyclic or heteroaryl ring;
wherein RA′ and RB′ are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl or carboalkoxy;
wherein R2 is
wherein K and K′ together form a C3-C7 cycloalkyl or heterocyclyl ring or a C5-C10 aryl or heteroaryl ring;
wherein J is hydrido, amino, NHRJ, NRJRK, alkyl, alkenyl, alkynyl, alkoxy, aryloxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, alkylamino, hydroxyl, thio, alkylthio, alkenylthio, sulfinyl, sulfonyl, azido, cyano, halo,
wherein each of R24, R25, and R26 is independently alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl; or R24 and R25 together form a 5-8 membered heterocyclyl ring;
wherein RJ and RK are independently alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl or heterocyclyl; or
alternatively, wherein J, together with R17, forms a 5-8 membered heterocyclyl or cycloalkyl ring; or
alternatively, wherein J, together with both R17 and R18, forms a 5-8 membered aryl, cycloalkyl, heterocyclyl or heteroaryl ring; and
wherein each of R17 and R18 is of hydrido, halo, hydroxyl, alkoxy, amino, thio, sulfinyl, sulfonyl or
wherein R17 and R18 taken together can form a ketal, thioketal,
wherein each of R22 and R23 is independently hydrido or alkyl.

### Claim 3 (depends on 1, 2)

The compound according to either of claims 1 or 2, wherein R is
wherein each of R3, R4 R5, and R6 is independently hydrido, alkyl, aryl, heterocyclyl or heteroaryl, and wherein R44 alkyl, aryl, heterocyclyl or heteroaryl.

### Claim 4 (depends on 3)

The compound according to claim 3, wherein R is
wherein R4 is alkyl, aryl-substituted alkyl, substituted phenyl, heteroaryl, heterocyclyl, optionally substituted (C8-C14)-straight chain alkyl or
wherein R7 is an alkyl group.

### Claim 5 (depends on 4)

The compound according to claim 4, wherein R is
wherein X3 is chloro or trifluoromethyl and wherein q is 0 or 1.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein R1 is:
wherein R8 is a natural amino acid side chain or an amino acid side chain that is not naturally occurring;
wherein R9 is hydrido, alkyl, aryl, heterocyclyl or heteroaryl;
wherein R12 is heterocyclyl, heteroaryl, aryl, or alkyl
provided that R12 is other than C3-C13 unsubstituted alkyl; and
wherein R13 is (C1-C3-alkyl) wherein one or more hydrogen atoms is replaced by a substituent group selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo guanidino, and formyl.

### Claim 7 (depends on 6)

The compound according to claim 6, wherein RJ is:
wherein R8 is tryptophan side chain or lysine side chain;
wherein R12 is imidazolyl, N-methylimidazolyl, indolyl, quinolinyl, benzyloxybenzyl, or benzylpiperidenylbenzyl.

### Claim 8 (depends on 1, 4)

The compound according to either of claims 1 or 4, wherein J is hydrido, amino, azido or
wherein R17 and R18 taken together form a ketal,
or wherein R17 is hydroxyl when R18 is hydrido;
or wherein J, together with R17, forms a heterocyclyl ring.

### Claim 9 (depends on 8)

The compound according to claim 8, wherein
wherein R17 and R18 taken together form a
wherein R22 is H or alkyl; and wherein R19 is hydrido, amino, azido or

### Claim 10 (depends on 9)

The compound according to claim 9, wherein R2 is

### Claim 11 (depends on 1)

The compound according to claim 1 wherein said compound is
Cpd #
R
R1
R2
37
NHCO(CH2)8CH3
38
NHCO(CH2)8CH3
39
NHCO(CH2)8CH3
40
NHCO(CH2)8CH3
41
NHCO(CH2)8CH3
42
NHCO(CH2)8CH3
43
NHCO(CH2)8CH3
44
NHCO(CH2)8CH3
45
NHCO(CH2)8CH3
46
NHCO(CH2)8CH3
47
NHCO(CH2)8CH3
48
NHCO(CH2)8CH3
49
NHCO(CH2)8CH3
50
NHCO(CH2)8CH3
51
NHCO(CH2)8CH3
52
NHCO(CH2)8CH3
54
NHCO(CH2)8CH3
55
NHCO(CH2)8CH3
56
NHCO(CH2)8CH3
58
NHCO(CH2)8CH3
60
NHCO(CH2)8CH3
61
NHCO(CH2)8CH3
62
NHCO(CH2)8CH3
63
NHCO(CH2)8CH3
64
NHCO(CH2)8CH3
65
NHCO(CH2)8CH3
66
NHCO(CH2)8CH3
67
NHCO(CH2)8CH3
68
NHCO(CH2)8CH3
69
NHCO(CH2)8CH3
72
NHCO(CH2)8CH3
73
NHCO(CH2)8CH3
74
NHCO(CH2)8CH3
75
NHCO(CH2)8CH3
76
NHCO(CH2)8CH3
77
NHCO(CH2)8CH3
NH(CH2)2OH
78
NHCO(CH2)8CH3
79
NHCO(CH2)8CH3
80
NHGO(CH2)8CH3
81
NHCO(CH2)8CH3
82
NHCO(CH2)8CH3
83
NHCO(CH2)8CH3
84
NHCO(CH2)8CH3
85
NHCO(CH2)8CH3
86
87
NHCO(CH2)8CH3
88
NHCO(CH2)8CH3
89
NHCO(CH2)8CH3
90
NHCO(CH2)8CH3
91
NHCO(CH2)8CH3
92
NHCO(CH2)8CH3
93
NHCO(CH2)8CH3
94
NHCO(CH2)8CH3
95
NHCO(CH2)8CH3
96
NHCO(CH2)8CH3
97
NHCO(CH2)8CH3
98
NHCO(CH2)8CH3
99
NHCO(CH2)8CH3
100
NHCO(CH2)8CH3
101
102
NHCO(CH2)11CH3
103
NHCO(CH2)8CH3
104
NHCO(CH2)8CH3
105
NHCO(CH2)8CH3
106
NHCO(CH2)8CH3
107
NHCO(CH2)8CH3
108
NHCO(CH2)8CH3
109
NHCO(CH2)8CH3
110
NHCO(CH2)8CH3
111
NHCO(CH2)8CH3
112
NHCO(CH2)8CH3
113
NHCO(CH2)8CH3
114
NHCO(CH2)8CH3
115
NHCO(CH2)8CH3
116
NHCO(CH2)8CH3
117
NHCO(CH2)8CH3
118
NHCO(CH2)8CH3
119
NHCO(CH2)8CH3
120
NHCO(CH2)8CH3
121
NHCO(CH2)8CH3
122
NHCO(CH2)8CH3
123
NHCO(CH2)8CH3
124
NHCO(CH2)8CH3
125
NHCO(CH2)8CH3
126
NHCO(CH2)8CH3
127
NHCO(CH2)8CH3
128
NHCO(CH2)8CH3
129
NHCO(CH2)8CH3
130
NHCO(CH2)8CH3
131
NHCO(CH2)8CH3
132
NHCO(CH2)8CH3
133
NHCO(CH2)8CH3
134
NHCO(CH2)8CH3
135
NHCO(CH2)8CH3
136
NHCO(CH2)8CH3
137
NHCO(CH2)8CH3
138
NHCO(CH2)8CH3
139
NHCO(CH2)8CH3
140
NHCO(CH2)8CH3
141
NHCO(CH2)8CH3
142
NHCO(CH2)8CH3
143
NHCO(CH2)8CH3
144
NHCO(CH2)8CH3
145
NHCO(CH2)8CH3
146
NHCO(CH2)8CH3
147
NHCO(CH2)8CH3
148
NHCO(CH2)8CH3
149
NHCO(CH2)8CH3
150
NHCO(CH2)8CH3
151
NHCO(CH2)8CH3
152
NHCO(CH2)8CH3
153
NHCO(CH2)8CH3
154
NHCO(CH2)8CH3
155
NHCO(CH2)8CH3
156
NHCO(CH2)8CH3
157
NHCO(CH2)8CH3
158
NHCO(CH2)8CH3
159
NHCO(CH2)8CH3
160
NHCO(CH2)8CH3
161
NHCO(CH2)8CH3
162
NHCO(CH2)8CH3
163
NHCO(CH2)8CH3
164
NHCO(CH2)8CH3
165
NHCO(CH2)8CH3
166
NHCO(CH2)8CH3
167
NHCO(CH2)8CH3
168
NHCO(CH2)8CH3
169
NHCO(CH2)8CH3
171
NHCO(CH2)8CH3
172
NHCO(CH2)8CH3
173
NHCO(CH2)8CH3
174
NHCO(CH2)8CH3
175
NHCO(CH2)8CH3
176
NHCO(CH2)8CH3
177
NH2
178
NHCO(CH2)8CH3
179
NHCO(CH2)8CH3
180
NHCO(CH2)8CH3
181
NHCONH(CH2)10CH3
182
NHCO(CH2)8CH3
183
NHCO(CH2)8CH3
184
NHCO(CH2)8CH3
185
NHCO(CH2)8CH3
186
NHCO(CH2)8CH3
187
NHCO(CH2)8CH3
192
NHCO(CH2)8CH3
193
NHCO(CH2)8CH3
194
NHCO(CH2)8CH3
195
NHCO(CH2)8CH3
196
NHCO(CH2)8CH3
197
NHCO(CH2)8CH3
198
NHCO(CH2)8CH3
199
NHCO(CH2)8CH3
200
NHCO(CH2)8CH3
201
NHCO(CH2)8CH3
202
NHCO(CH2)8CH3
203
NHCO(CH2)8CH3
204
NHCO(CH2)8CH3
205
NH(CH2)8CH3
206
NHCO(CH2)8CO2Me
207
NHCO(CH2)6CO2Me
208
NHCO(CH2)8CH3
209
NHCO(CH2)8CH3
210
NHCO(CH2)8CH3
211
NHCO(CH2)8CH3
212
NHCO(CH2)8CH3
213
NHCO(CH2)6NHBoc
214
NHCO(CH2)7NHBoc
215
NHCO(CH2)10NHBoc
216
NHCO(CH2)11NHBoc
217
NHCO(CH2)10NH2
218
NHCO(CH2)11NH2
219
NHCO(CH2)6CH(CH3)2
220
NHCONH(CH2)11CH3
221
NHCO(CH2)8CH3
222
NHCO(CH2)8CH3
223
NHCO(CH2)8CH3
224
NHCO(CH2)8CH3
225
NHCO(CH2)8CH3
226
NHCO(CH2)8CH3
227
NHCO(CH2)8CH3
228
NHCO(CH2)8CH3
229
NHCO(CH2)8CH3
230
NHCO(CH2)8CH3
231
NHCO(CH2)8CH3
232
NHCO(CH2)8CH3
233
NHCO(CH2)8CH3
234
NHCO(CH2)8CH3
235
NHCO(CH2)8CH3
236
NHCO(CH2)8CH3
237
NHCO(CH2)8CH3
238
NHCO(CH2)8CH3
239
NHCO(CH2)8CH3
240
NHCO(CH2)8CH3
241
NHCO(CH2)8CH3
242
NHCO(CH2)8CH3
243
NHCO(CH2)8CH3
244
NHCO(CH2)8CH3
245
NHCO(CH2)8CH3
246
247
248
249
250
251
252
NHCO(CH2)8CH3
253
NHCO(CH2)8CH3
264
265
NHCO(CH2)8CH3
266
NHCO(CH2)8CH3
267
NHCO(CH2)8CH3
268
NHCO(CH2)8CH3
269
270
NHCO(CH2)8CH3
271
NHCO(CH2)8CH3
272
NHCO(CH2)8CH3
273
NHCO(CH2)8CH3
274
NHCO(CH2)8CH3
275
NHCO(CH2)8CH3
276
NHCO(CH2)8CH3
277
NHCO(CH2)8CH3
278
NHCO(CH2)8CH3
279
NHCO(CH2)8CH3
280
NHCO(CH2)8CH3
281
NHCO(CH2)8CH3
282
NHCO(CH2)8CH3
283
NHCO(CH2)8CH3
284
NHCO(CH2)8CH3
285
NHCO(CH2)8CH3
286
NHCO(CH2)8CH3
287
NHCO(CH2)8CH3
288
NHCO(CH2)8CH3
289
NHCO(CH2)8CH3
290
NHCO(CH2)8CH3
291
NHCO(CH2)8CH3
295
NHCO(CH2)11CH3
296
NHCO(CH2)10CH3
297
NHCO(CH2)9CH3
298
NHCONH(CH2)7CH3
299
NHCONH(CH2)10CH3
300
NHCONH(CH2)11CH3
301
NHCO(CH2)11CH3
302
NHCO(CH2)10CH3
303
NHCO(CH2)9CH3
304
NHCONH(CH2)7CH3
305
NHCONH(CH2)10CH3
306
NHCONH(CH2)11CH3
307
NHCO(CH2)9CH3
308
NHCO(CH2)10CH3
309
NHCO(CH2)10CH3
310
NHCO(CH2)9CH3
311
NHCONH(CH2)7CH3
315
NHCONH(CH2)7CH3
316
NHCONH(CH2)7CH3
317
NHCONH(CH2)7CH3
318
NHCO(CH2)9CH3
319
NHCO(CH2)9CH3
320
NHCO(CH2)11CH3
321
NHCO(CH2)11CH3
322
NHCO(CH2)11CH3
323
NHCO(CH2)8CH3
324
NHCO(CH2)8CH3
325
NHCO(CH2)8CH3
326
NHCO(CH2)8CH3
327
NHCO(CH2)8CH3
328
NHCO(CH2)8CH3
329
NHCO(CH2)8CH3
330
NHCO(CH2)8CH3
331
NHCO(CH2)8CH3
332
NHCO(CH2)10CH3
333
NHCO(CH2)10CH3
334
NHCO(CH2)10CH3
335
NHCONH(CH2)11CH3
336
NHCONH(CH2)11CH3
337
NHCONH(CH2)11CH3
338
NHCO(CH2)12CH3
339
NHCO(CH2)12CH3
340
NHCO(CH2)12CH3
341
NHCO(CH2)12CH3
345
NHCO(CH2)12CH3
346
NHCO(CH2)12CH3
347
NHCO(CH2)7CH3
348
NHCO(CH2)7CH3
349
NHCO(CH2)7CH3
350
351
NHCO(CH2)11CH3
352
NHCONH(CH2)10CH3
355
NHCONH(CH2)10CH3
356
NHCONH(CH2)10CH3
358
NHCO(CH2)8CH3
359
NHCO(CH2)8CH3
360
NHCO(CH2)8CH3
361
NHCO(CH2)8CH3
362
NHCO(CH2)8CH3
363
NHCO(CH2)8CH3
364
NHCO(CH2)8CH3
365
NHCO(CH2)8CH3
366
NHCO(CH2)8CH3
367
NHCO(CH2)8CH3
368
NHCO(CH2)8CH3
369
NHCO(CH2)8CH3
370
NHCO(CH2)8CH3
371
NHCO(CH2)8CH3
372
NHCO(CH2)8CH3
373
NHCO(CH2)8CH3
374
NHCO(CH2)8CH3
375
NHCO(CH2)8CH3
376
NHCO(CH2)8CH3
377
NHCO(CH2)8CH3
378
NHCO(CH2)8CH3
379
NHCO(CH2)8CH3
380
NHCO(CH2)8CH3
381
NHCO(CH2)8CH3
382
NHCO(CH2)8CH3
383
NHCO(CH2)8CH3
384
NHCO(CH2)8CH3
385
NHCO(CH2)8CH3
386
NHCO(CH2)8CH3
387
NHCO(CH2)8CH3
388
NHCO(CH2)8CH3
389
NHCO(CH2)8CH3
390
NHCO(CH2)8CH3
391
NHCO(CH2)8CH3
392
NHCO(CH2)8CH3
393
NHCO(CH2)8CH3
394
NHCO(CH2)8CH3
395
NHCO(CH2)8CH3
398
NHCO(CH2)8CH3
399
NHCO(CH2)8CH3
400
NHCO(CH2)8CH3
401
NHCO(CH2)8CH3
402
NHCO(CH2)8CH3
403
NHCO(CH2)8CH3
404
NHCO(CH2)8CH3
405
NHCO(CH2)8CH3
406
NHCO(CH2)8CH3
407
NHCO(CH2)8CH3
408
NHCO(CH2)8CH3
409
NHCO(CH2)8CH3
410
NHCO(CH2)8CH3

### Claim 12 (depends on 11)

The compound according to claim 11 wherein the compound is
Cpd #
R
R1
R2
45
NHCO(CH2)8CH3
54
NHCO(CH2)8CH3
76
NHCO(CH2)8CH3
81
NHCO(CH2)8CH3
85
NHCO(CH2)8CH3
102
NHCO(CH2)11CH3
209
NHCO(CH2)8CH3
212
NHCO(CH2)8CH3
253
NHCO(CH2)8CH3
282
NHCO(CH2)8CH3
285
NHCO(CH2)8CH3
319
NHCO(CH2)9CH3
322
NHCO(CH2)11CH3
333
NHCO(CH2)10CH3
334
NHCO(CH2)10CH3
335
NHCOKH(CH2)11CH3
336
NHCONH(CH2)11CH3
355
NHCOKH(CH2)10CH3

### Claim 13 (depends on 1)

A compound of formula (I) according to claim 1, wherein R is NHCO-[(C6-C14)-alkyl]-CH3, and R1 and R2 are selected from:
R1
R2
NH(CH2)2OH

### Claim 14 (depends on 13)

The compound according to claim 13, wherein R is NHCO-[(CH2)6-14]-CH3.

### Claim 15 (depends on 1, 2)

A pharmaceutical composition comprising the compound according to either-one of claims 1 or 2 and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 15)

A method of treating a bacterial infection in a subject, comprising the step of administering the pharmaceutical composition according to claim 15 to a subject in need thereof for a time and under conditions effective to ameliorate said bacterial infection.

### Claim 17 (depends on 16)

The method according to claim 16, wherein said subject is a human, an animal, a cell culture or a plant.

### Claim 18 (depends on 16)

The method according to claim 16, wherein said bacterial infection is caused by a gram-positive bacteria.

### Claim 19 (depends on 18)

The method according to claim 18, wherein said bacterial is an antibiotic-resistant bacteria that is resistant to an antibiotic that is not included within the scope of Formula (I).

### Claim 20 (depends on 19)

The method according to claim 19, wherein said antibiotic-resistant bacteria are resistant to vancomycin, methicillin, glycopeptide antibiotics, penicillin or daptomycin.

### Claim 21 (depends on 3, 4, 16)

The method according to claim 16, further comprising the step of co-administering more than one compound of Formula (I) according to either of claims 3 or 4 to a subject in need thereof.

### Claim 22 (depends on 16)

The method according to claim 16, further comprising the step of co-administering a second antimicrobial agent wherein said second antimicrobial agent is not included within the scope of Formula (I).

### Claim 23 (depends on 22)

The method according to claim 22, wherein said antimicrobial agent is penicillins, carbapenems, cephalosporins, aminoglycosides, bacitracin, gramicidin, mupirocin, chloramphenicol, thiamphenicol, fusidate sodium, lincomycin, clindamycin, macrolides, novobiocin, polymyxins, rifamycins, spectinomycin, tetracyclines, vancomycin, teicoplanin, streptogramins, anti-folate agents, trimethoprim, pyrimethamine, nitroimidazoles, quinolones, fluoroquinolones, isoniazid, ethambutol, pyrazinamide, para-aminosalicylic acid (PAS), cycloserine, capreomycin, ethionamide, prothionamide, thiacetazone, viomycin, everninomicin, glycopeptide, glycylcycline, ketolides, -oxazolidinones, imipenen, amikacin, netilmicin, fosfonycin, gentamicin, ceftriaxone, ZIRACIN (56-deacetyl-57-demethyl-45-O-de(2-methyl-1-oxopropyl)-12-O-(2,3,6-trideoxy-3-C-methyl-4-O-methyl-3-nitro-alpha-L-arabino-hexopyranosyl)flambamycin), LY333328 (oritavancin), linezolid (N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl) phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide), SYNERCID (dalfopristin-quinupristin), aztreonam (2-[[(Z)-[1-(2-amino-4-thiazolyl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2-methyl-propanoic acid), metonidazole (2-methyl-5-nitro-1H-imidazole-1-ethanol), epiroprim (5-[[3,5-diethoxy-4-(1H-pyrrol-1-yl)phenyl]methyl]-2,4-pyrimidinediamine), OCA-983 (1-[[(2S)-2-amino-3-methyl-1-oxobutyl]amino]-2,5-anhydro-3-S-[(4R,5S,6S)-2-carboxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3,2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol), GV-143253 (trinem), sanfetrinem ((1S, 5S,8aS, 8bR)-1, 2, 5, 6, 7, 8, 8a, 8b-octahydro-1-[(1R)-1-hydroxyethyl]-5-methoxy-2-oxo-azeto[2,1-a]isoindole-4-carboxylic acid), CS-83 ((4R,5S, 6S)-6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3R)-5-oxo-3-pyrrolidinyl]thio]-1-azabicyclo [3.2.0]hept-2-ene-2-carboxylic acid (2,2-dimethyl-1-oxopropoxy)methyl ester), biapenem (6[[(4R,5S,6S)-2-carboxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]thio]-6, 7-dihydro-5H-pyrazolo[1,2-a][1,2,4]triazol-4-ium inner salt), KA 159 (stipiamide), dynemicin A ((1S,4R,4aR, 14S,14aS,18Z)-1,4,7,12,13 14-hexahydro-6,8,11-trihydroxy-3-methoxy-1-methyl-7,12-dioxo-4a,14a-epoxy-4,14-[3]hexene[1,5]diynonaphtho[2,3-c]phenanthridine-2-carboxylic acid), DX8739 ((4R,5S,6S)-3-[[(3S,5S)-5-[[4-[(2S)-5-amino-2-hydroxy-1-oxopentyl]-1-piperazinyl]carbonyl]-3-pyrrolidinyl]thio]-6-[(1R)1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid), DU 6681 ((4R,5S,6S)-3-[[(6S)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-6-yl]thio]-6-(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylic acid), cefluprenam ((2E)-N-(2-amino-2-oxoethyl)-3-[[(6R,7R)-7-[[(2Z)-(5-amino-1,2,4-thiadiazol-3-yl)[(fluoro methoxy)imino]acetyl] amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]-N-ethyl-N-methyl-2-propen-1-aminium inner salt), ER 35786 ((4R, 5S,6S)-6[(1R)-1-hydroxyethyl]-3-[[(3S,5S)-5-[(R)-hydroxy(3R)-3-pyrrolidinylmethy]-3-pyrrolidinyl]thio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid monohydrochloride), cefoselis ((6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxy imino)acetyl]amino]-3-[[2,3-dihydro-2-(2-hydroxyethyl)-3-imino-1H-pyrazol-1-yl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid), sanfetrinem celexetil ((1S5S,8aS,8bR)-1,2,5,6,7,8,8a,8b-octahydro-1-[(1R)-1-hydroxyethyl]-5-methoxy-2-oxo-azeto[2,1-a]isoindole-4-carboxylic acid 1-[(cyclohexyloxy)carbonyl] oxy]ethyl ester), cefpirome (1-[[(6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-cyclopenta[b]pyridinium inner salt), HMR-3647 (3-de[(2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribo-hexopyranosyl)oxy]-11,12-dideoxy-6-O-methyl-3-oxo-12,11-[oxycarbonyl[[4-[4-(3-pyridinyl)-1H-imidazol-1-yl]butyl]imino]]-erythromycin), RU-59863 (C-7 catechol substituted cephalosporin), KP 736 ((6R,7R)-7-[[2Z)-(2-amino-4-thiazolyl)[[(1,4-dihydro-1,5-dihyroxy-4-oxo-2-pyridinyl)methoxy] imino]acetyl]amino]-8-oxo-3[(1,2,3-thiadiazol-5-ylthio)methyl]-5-this-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid disodium slat), Rifalazil (1′,4-didehydro-1-deoxy-1,4-dihydro-3′-hydroxy-5′-[4-(2-methylpropyl)-1-piperazinyl]-1-oxo-rifamycin VII, MEN 10700 ((5R,6S)-3-[[2-amino-2-oxoethyl)methylamino]methyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid), lenapenem ((4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[[3S,5S)-5-[(1R)-1-hydroxy-3-(methylamino)propyl]-3-pyrrolidinyl]thio]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid), BO 2502A ((4R,5S,6S)-3-[(2S,3′S,4S)-[2,3′-bipyrrolidin[-4-ylthio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid), NE-1530 (3+-sialyl]acto-N-neotetraose), K130 (5-[[4-[3-[[4-[(4-aminophenyl)sulfonyl]phenyl]amino]propoxy]-3,5-dimethoxyphenyl] methyl]-2,4-pyrimidinediarnine), PD 138312 ((R)-7-[3-(1-amino-1-methylethyl)-1-pyrrolidinyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid), PD 140248 (7-[(3R)-3-[(1S)-1-aminoethyl]-1-pyrrolidinyl]-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid), CP 111905 (5-deoxy-5-[[(2E)-3-[3-hydroxy-4-(2-propenyloxy)phenyl]-2-methyl-1-oxo-2-propenyl]amino]-1,2-O-methylene-D-neo-inositol), sulopenem ((5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[[(1R,3S)-tetrahydro-1-oxido-3-thienyl]thio]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid), ritipenam acoxyl ((5R,6R)-3-[]aminocarbonyl)oxy]methyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (acetyloxy)methyl ester), RO-65-5788 ((6R,7R)-7-[[(2Z)-(5-amino-1,2,4-thiadianol-3-yl)(hydroxyimino)acetyl]amino]-3-[(E)-[(3′R)-1′-[[(5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)carbonyl]-2-oxo[1,3′-bipyrrolidinyl]-3-ylidene]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monosoidum salt), Sch-40832 (N-[[48-[1-[[2,6-dideoxy-3-O-(2,6-dideoxy-D-arabino-hexopyranosyl)-D-arabino-hexopyranosyl]oxy]ethyl]-15-ethylidene-1,3a,4,510,11,12, 13,14,15,19,20,21,22,28,29,41,42-octadecahydro-41-hydroxy-12,45-bis(1-hydroxyethyl)-1-(hydroxymethyl)-22-(1-hydroxy-1-methylpropyl)-36-methyl-51,54,57-tris(methylene)-3-(methylthio)-10,13,20,27,38,49,52,55,58-nonaoxo-18H,27H-5a,29-(iminoethaniminoethanimino ethaniminoethanimino[7,2]quinolinomethanoxy methano)-9,6:19,16:26,23:33,30-tetranitrilo-16H,33aH-imidazo(1′,5′:1,6 pyrido [3,2-m][1,11,17,24,4,7,20,27]tetrathiatetraazacyclotriacontin-1-yl]carbonyl]-2,3-didehydroalanyl-2,3-didehydro-alanine methyl ester stereoisomer), micacocidin A((OC-6-26-A)-[(4S)-2-[(2S)-2-[(2R,4R)-2-[(4R)-4,5-dihydro-2-[2-(hydroxy-.kappa.O)-6-pentylphenyl]-4-thiazolyl-.kappa.N3]-3-methyl-4-thiaolidinyl-.kappa.N3]-2-(hydroxy-.kappa.N3, .kappa.O4]-Zinc), SR-15402 ((1S,5S,8aS,8bR)-1,2,5,6,7,8,8a,8b-octahydro-1-[(1R)-1-hydroxyethyl]-2-oxo-5-[(3S)-3-pyrrolidinylthio]-azeto[2,1-a]isoindole-4-carboxylic acid), TOC 39 (1-(2-amino-2-oxoethyl)-4-[[(1E)-2-[(6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl) (hydroxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]ethenyl]thio]-pyridinium inner salt), carurnonam ([[(Z)-[2-[[(2S,3S)-2-[[(aminocarbonyl)oxy]methyl]-4-oxo-1-sulfo-3-azetidinyl]amino]-1-(2-amino-4-thiazolyl)-2-oxoethylidene]amino]oxy]-acetic acid), cefozopran (1-[[(6R,7R)-7-[[(2Z)-(5-amino-1,2,4-thiadiazol-3-yl)(methoxy imino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-imidazo[1,2-b]pyridazinium inner salt), cefetamet pivoxil ((6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxy imino)acetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (2,2-dimethyl-1-oxopropoxy)methyl ester), and T 3811 (des-F(6)-quinolone).

### Claim 24 (depends on 22)

The method according to claim 22, wherein said antimicrobial agent is selected from the group consisting of imipenen, amikacin, netilmicin, fosfomycin, gentamicin, ceftriaxone, teicoplanin, ZIRACIN, LY333348, CL331022, HMR3647, linezolid, SYNERCID, aztreonam and metronidazole.

### Claim 25 (depends on 17)

The method according to claim 17, wherein said subject is selected from a human or an animal.

### Claim 26 (depends on 25)

The method according to claim 25, wherein said subject is a human.

### Claim 27 (depends on 1)

The compound of claim 1 having the formula (III):
wherein R15 is hydrido or a carbamate amino protecting group; wherein R16 is
and, wherein, R20 is an amino acid side chain.

### Claim 28 (depends on 27)

The compound according to claim 27 selected from:
Com-
pound
#
R16
45
54
79
80
81
82
84
139
158
146
212
85
174
78
150
130
138
168
274
317
280
275
283
285
50
38
115
105
76
147
164
210
107
111
103
253
227
372
386

### Claim 29 (depends on 2)

The compound according to claim 2 wherein said compound is
Cpd
#
R
R1
R2
189
NHCO(CH2)8CH3

### Claim 30 (depends on 2)

A compound of formula (I) according to claim 2, wherein R is NHCO-[(C6-C14)-alkyl]-CH3, and R1 and R2 are:
R1
R2