ES2651690T3 - Compuesto de glicina - Google Patents

Compuesto de glicina Download PDF

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Publication number
ES2651690T3
ES2651690T3 ES10817191.9T ES10817191T ES2651690T3 ES 2651690 T3 ES2651690 T3 ES 2651690T3 ES 10817191 T ES10817191 T ES 10817191T ES 2651690 T3 ES2651690 T3 ES 2651690T3
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ien
structure acid
bar
acid
2hci
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Kousei Yoshihara
Daisuke Suzuki
Susumu Yamaki
Yuji Koga
Norio Seki
Jiro Fujiyasu
Masahiro Neya
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Astellas Pharma Inc
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Astellas Pharma Inc
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
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    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
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Abstract

Un compuesto representado por la fórmula (I) o una sal del mismo:**Fórmula** (en la que R1 es H o alquilo C1-6 que puede estar sustituido con halógeno, R2 es halógeno, R3 y R4 son iguales o diferentes entre sí, y son H o halógeno, m es 0, 1, 2, 3 o 4, Y1 e Y2 son N, X es Z-(CR11R12)n-, n es 0, Z es**Fórmula** R21, R22, R23, R24, R25 y R26 son H, Y4 es N o CRY41, Y5 es N o CRY51, RY41, RY51 y RG32 son H, halógeno, -OH, -Oalquilo C1-6 (en el que el alquilo C1-6 puede estar sustituido con 1 a 3 grupos OH, halógeno, -O-alquilo C1-6 (en el que el alquilo C1-6 puede estar sustituido con uno o más grupos -COOH) o arilo), -CHO, -CO-alquilo C1-6 (en el que el alquilo C1-6 puede estar sustituido con 1 a 3 átomos de halógeno), -CO-cicloalquilo (en el que cicloalquilo puede estar sustituido con uno o más grupos -O-alquilo C1-6), -CO-arilo, un grupo de hetero anillo saturado -CO monocíclico, ciano, -COOH, -COO-alquilo C1-6 (en el que el alquilo C1-6 puede estar sustituido con 1 a 3 átomos de halógeno), alquilo C1-6 que puede estar sustituido con -COOH o -O-alquilo C1-6 o alquenilo C2-6 que puede estar sustituido con -COOH o -O-alquilo C1-6, y s es 0, 1, 2 o 3).

Description

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mismos, seguido de agitación como estaba durante 1 hora. A la mezcla de reacción se le añadieron agua y ácido clorhídrico 1 M y el pH de la capa acuosa se ajustó a aproximadamente 5,0. La capa acuosa se extrajo con EtOAc, la capa orgánica se separó y después la capa acuosa se extrajo con CHCl3 de nuevo. Estas capas orgánicas se combinaron y se secaron sobre Na2SO4, y el disolvente se concentró a presión reducida. El residuo obtenido se
5 purificó mediante cromatografía en columna de gel de sílice (CHCl3/MeOH) para obtener ácido 6-[4-(tercbutoxicarbonil)piperazin-1-il]-5-metilnicotínico (169 mg).
Ejemplo de Preparación 336
10 Se disolvió 4-fenilpiperazina-1-carboxilato de bencilo (2,1 g) en DMF (80 ml) y se añadió N-bromosuccinimida (1,4 g) a los mismos, seguido de agitación a temperatura ambiente durante 2 horas. La mezcla de reacción se concentró a presión reducida y se sometió a separación de líquidos mediante la adición de CHCl3 y una solución saturada acuosa de hidrógeno carbonato de sodio. La capa orgánica se separó y se secó sobre Na2SO4, y después el disolvente se evaporó a presión reducida. El residuo obtenido se purificó mediante cromatografía en columna de gel
15 de sílice (hexano/EtOAc) para obtener 4-(4-bromofenil)piperazina-1-carboxilato de bencilo (2,3 g).
Ejemplo de Preparación 338
Se disolvió 4-[3'-({[N-(terc-butoxicarbonil)glicil](metil)amino}metil)bifenil-4-il]piperazina-1-carboxilato de bencilo (1,5 g)
20 en una solución mixta de MeOH (15 ml) y THF (15 ml). Se añadió Pd al 10 %-C (150 mg) a los mismos, seguido de agitación a temperatura ambiente durante 1 día en una atmósfera de hidrógeno. La mezcla de reacción se filtró usando Celite como adyuvante de filtración y el filtrado se concentró a presión reducida. El residuo obtenido se purificó mediante cromatografía en columna de gel de sílice para obtener (2-{metil[(4'-piperazin-1-ilbifenilo-3il)metil]amino}-2-oxoetil)carbamato de terc-butilo (860 mg).
25 La Compuestos de Ejemplo de Preparación como se muestran en las Tablas a continuación se prepararon de la misma manera que en los métodos de los Ejemplos de Preparación anteriores, usando cada uno de los materiales de partida correspondientes. Las estructuras, los métodos de preparación y los datos fisicoquímicos de los Compuestos de Ejemplo de Preparación se muestran en las Tablas a continuación.
30 [Tabla 3]
Rf
Sín Estructura Ácido
1
R1 -
2
R2 -
3
R2 imagen29 -
4
R2 -
5
R2 -
6
R2 -
7
R7 -
[Tabla 4]
Rf
Sín Estructura Ácido
8
R7 imagen30 -
9
R7 imagen31 -
10
R10 imagen32 -
11
R10 imagen33 -
12
R10 imagen34 -
[Tabla 5]
Rf
Sín Estructura Ácido
13
R10 -
14
R10 -
15
R10 imagen35 -
16
R16 -
17
R17 -
Rf
Sín Estructura Ácido
18
R17 -
19
R17 -
20
R17 -
21
R17 -
22
R17 imagen36 -
Rf
Sín Estructura Ácido
23
R17 -
24
R17 -
25
R17 -
26
R17 -
27
R17 imagen37 -
[Tabla 8]
Rf
Sín Estructura Ácido
28
R17 -
29
R17 -
30
R17 -
31
R17 -
32
R17 imagen38 -
[Tabla 9]
Rf
Sín Estructura Ácido
33
R17 -
34
R17 -
35
R17 -
36
R17 -
37
R17 -
[Tabla 10]
Rf
Sín Estructura Ácido
38
R17 imagen39 -
39
R17 -
40
R17 -
41
R17 -
42
R17 -
[Tabla 11]
Rf
Sín Estructura Ácido
43
R17 imagen40 -
44
R17 -
45
R17 -
46
R17 -
47
R17 -
[Tabla 12]
Rf
Sín Estructura Ácido
48
R17 -
49
R17 imagen41 -
50
R17 -
51
R17 -
Rf
Sín Estructura Ácido
52
R17 imagen42 -
53
R17 imagen43 -
54
R17 imagen44 -
55
R17 imagen45 -
56
R17 imagen46 -
Rf
Sín Estructura Ácido
57
R17 imagen47 -
58
R17 imagen48 -
59
R17 imagen49 -
60
R17 imagen50 -
61
R17 imagen51 -
62
R17 imagen52 -
Rf
Sín Estructura Ácido
63
R17 imagen53 -
64
R17 imagen54 -
65
R17 imagen55 -
66
R17 imagen56 -
Rf
Sín Estructura Ácido
67
R17 imagen57 -
68
R17 imagen58 -
69
R17 imagen59 -
70
R17 imagen60 -
Rf
Sín Estructura Ácido
71
R17 imagen61 -
72
R17 imagen62 -
73
R17 imagen63 -
74
R17 imagen64 -
Rf
Sín Estructura Ácido
75
R17 imagen65 -
76
R17 imagen66 -
77
R17 imagen67 -
78
R17 imagen68 -
79
R17 imagen69 -
Rf
Sín Estructura Ácido
80
R17 imagen70 -
81
R17 imagen71 -
82
R17 imagen72 -
83
R17 imagen73 -
[Tabla 20]
Rf
Sín Estructura Ácido
84
R17 -
85
R17 -
86
R17 -
87
R17 imagen74 -
[Tabla 21]
Rf
Sín Estructura Ácido
88
R17 -
89
R17 -
90
R17 -
91
R91 2HCl
92
R92 imagen75 -
[Tabla 22]
Rf
Sín Estructura Ácido
93
R92 -
94
R92 -
95
R92 -
96
R92 -
97
R92 -
98
R92 -
[Tabla 23]
Rf
Sín Estructura Ácido
99
R92 -
100
R92 imagen76 -
101
R92 -
102
R92 -
103
R92 -
104
R92 -
[Tabla 24]
Rf
Sín Estructura Ácido
105
R92 imagen77 -
106
R92 -
107
R107 2HCI
108
R108 imagen78 -
109
R108 -
110
R108 -
111
R108 -
[Tabla 25]
Rf
Sín Estructura Ácido
112
R112 2HCI
113
R112 -
114
R112 -
115
R115 -
116
R115 imagen79 3HCI
117
R115 3HCI
[Tabla 26]
Rf
Sín Estructura Ácido
118
R115 2HCI
119
R115 2HCI
120
R115 2HCI
121
R115 2HCI
122
R115 2HCI
[Tabla 27]
Rf
Sín Estructura Ácido
123
R115 imagen80 2HCI
124
R124 -
125
R124 -
126
R124 -
127
R124 -
[Tabla 28]
Rf
Sín Estructura Ácido
128
R124 -
129
R124 imagen81 -
130
R124 -
131
R124 -
Rf
Sín Estructura Ácido
132
R124 -
133
R124 -
134
R124 -
135
R124 -
136
R124 imagen82 -
[Tabla 30]
Rf
Sín Estructura Ácido
137
R124 -
138
R124 -
139
R124 -
140
R124 imagen83 -
141
R124 -
[Tabla 31]
Rf
Sín Estructura Ácido
142
R124 -
143
R124 -
144
R144 -
145
R144 -
[Tabla 32]
Rf
Sín Estructura Ácido
146
R146 imagen84 -
147
R147 -
148
R148 -
149
R148 -
150
R148 -
151
R148 -
[Tabla 33]
Rf
Sín Estructura Ácido
152
R148 imagen85 -
153
R148 imagen86 -
154
R148 imagen87 -
155
R148 imagen88 -
156
R148 imagen89 -
Rf
Sín Estructura Ácido
157
R148 imagen90 -
158
R148 imagen91 -
159
R148 imagen92 -
160
R160 imagen93 -
161
R161 imagen94 -
162
R161 imagen95 -
Rf
Sín Estructura Ácido
163
R161 imagen96 -
164
R161 imagen97 -
165
R161 imagen98 -
166
R161 imagen99 -
167
R161 imagen100 -
168
R161 imagen101 -
Rf
Sín Estructura Ácio
169
R161 imagen102 -
170
R161 imagen103 -
171
R171 imagen104 -
172
R171 imagen105 -
173
R171 imagen106 -
174
R171 imagen107 -
Rf
Sín Estructura Ácido
175
R171 imagen108 -
176
R171 imagen109 -
177
R171 imagen110 -
178
R171 imagen111 -
179
R171 imagen112 -
180
R171 imagen113 -
Rf
Sín Estructura Ácido
181
R171 imagen114 -
182
R171 imagen115 -
183
R171 imagen116 -
184
R171 imagen117 -
185
R171 imagen118 -
Rf
Sín Estructura Ácido
186
R171 imagen119 -
187
R171 imagen120 -
188
R171 imagen121 -
189
R171 imagen122 -
190
R171 imagen123 -
191
R171 imagen124 -
Rf
Sín Estructura Ácido
192
R171 imagen125 -
193
R171 imagen126 -
194
R171 imagen127 -
195
R171 imagen128 -
196
R171 imagen129 -
Rf
Sín Estructura Ácido
197
R171 imagen130 -
198
R171 imagen131 -
199
R171 imagen132 -
200
R200 imagen133 -
201
R201 imagen134 -
Rf
Sín Estructura Ácido
202
R201 imagen135 -
203
R201 imagen136 -
204
R201 imagen137 -
205
R201 imagen138 -
206
R201 imagen139 -
Rf
Sín Estructura Ácido
207
R201 imagen140 -
208
R201 imagen141 -
209
R201 imagen142 -
210
R201 imagen143 -
211
R201 imagen144 -
212
R201 imagen145 -
Rf
Sín Estructura Ácido
213
R201 imagen146 -
214
R201 imagen147 -
215
R201 imagen148 -
216
R201 imagen149 -
217
R201 imagen150 -
Rf
Sín Estructura Ácido
218
R201 imagen151 -
219
R201 imagen152 -
220
R201 imagen153 -
221
R201 imagen154 -
222
R222 imagen155 -
[Tabla 46] [Tabla 47] [Tabla 48] [Tabla 49]
Rf
Sín Estructura Ácido
223
R222 -
224
R222 -
225
R222 -
226
R222 imagen156 -
227
R222 -
Rf
Sín Estructura Ácido
228
R222 -
229
R222 -
230
R230 -
231
R230 -
232
R230 -
233
R230 imagen157 -
Rf
Sín Estructura Ácido
234
R234 -
235
R234 -
236
R234 -
237
R237 -
238
R237 -
Rf
Sín Estructura Ácido
239
R237 -
240
R237 imagen158 -
241
R237 -
242
R237 -
Rf
Sín Estructura Ácido
243
R237 imagen159 -
Rf
Sín Estructura Ácido
244
R237 imagen160 -
245
R245 imagen161 -
246
R245 imagen162 -
Rf
Sín Estructura Ácido
247
R245 imagen163 -
248
R245 imagen164 -
249
R245 imagen165 -
250
R245 imagen166 -
251
R245 imagen167 -
Rf
Sín Estructura Ácido
252
R245 imagen168 -
253
R245 imagen169 -
254
R245 imagen170 -
255
R255 imagen171 -
256
R255 imagen172 -
Rf
Sín Estructura Ácido
257
R257 imagen173 -
258
R258 imagen174 -
259
R259 imagen175 -
260
R260 imagen176 -
261
R261 imagen177 -
[Tabla 54] [Tabla 55] [Tabla 56] [Tabla 57] [Tabla 58] [Tabla 59] [Tabla 60] [Tabla 61] [Tabla 63] [Tabla 64] [Tabla 65] [Tabla 66]
Rf
Sín Estructura Ácido
262
R261 -
263
R261 -
264
R261 -
265
R261 imagen178 -
Rf
Sín Estructura Ácido
266
R266 imagen179 -
267
R266 imagen180 -
268
R266 imagen181 -
269
R266 imagen182 -
270
R270 imagen183 Hel
Rf
Sín Estructura Ácido
271
R271 imagen184 -
272
R272 imagen185 -
273
R273 imagen186 -
274
R274 imagen187 -
275
R274 imagen188 -
Rf
Sín Estructura Ácido
276
R276 imagen189 -
277
R277 imagen190 -
278
R278 imagen191 -
279
R278 imagen192 -
280
R278 imagen193 -
281
R278 imagen194 -
Rf
Sín Estructura Ácido
282
R278 imagen195 -
283
R278 imagen196 -
284
R278 imagen197 -
285
R285 imagen198 -
286
R286 imagen199 -
Rf
Sín Estructura Ácido
287
R287 imagen200 -
288
R288 imagen201 -
289
R288 imagen202 -
290
R288 imagen203 -
291
R288 imagen204 -
292
R288 imagen205 -
Rf
Sín Estructura Ácido
293
R288 imagen206 -
294
R288 imagen207 -
295
R288 imagen208 -
296
R296 imagen209 -
297
R297 imagen210 -
298
R297 imagen211 -
Rf
Sín Estructura Ácido
299
R297 imagen212 -
300
R297 imagen213 -
301
R297 imagen214 -
302
R302 imagen215 2HCI
303
R303 imagen216 -
304
R304 imagen217 -
Rf
Sín Estructura Ácido
305
R304 imagen218 -
306
R306 imagen219 -
307
R306 imagen220 -
308
R306 imagen221 -
309
R309 imagen222 -
310
R309 imagen223 -
311
R309 imagen224 -
Rf
Sín Estructura Ácido
312
R309 imagen225 -
313
R313 imagen226 HBr
314
R314 imagen227 -
315
R315 imagen228 -
316
R316 imagen229 -
317
R316 imagen230 -
318
R318 imagen231 -
319
R318 imagen232 -
Rf
Sín Estructura Ácido
320
R320 imagen233 -
321
R320 imagen234 -
322
R320 imagen235 -
323
R321 imagen236 -
324
R321 imagen237 -
Rf
Sín Estructura Ácido
325
R325 imagen238 -
326
R326 imagen239 -
328
R328 imagen240 -
329
R329 imagen241 -
330
R330 imagen242 -
Rf
Sín Estructura Ácido
331
R7 imagen243 -
332
R245 -
333
R92 -
334
R115 3HCI
imagen244
imagen245
83
IEN+: 483
84
IEN+: 512
85
IEN+: 498
86
IEN+: 554
87
IEN+: 616
88
IEN+: 589
89
IEN+: 477
90
IEN+: 536
91
IEN+: 133
92
IEN+: 336
93
IEN+: 278
94
IEN+: 278
95
IEN+: 322
96
IEN+: 298
97
IEN+: 292
98
IEN+: 292
99
IEN+: 282
100
IEN+: 282
101
IEN+: 294
102
IEN+: 306
[Tabla 71]
Rf
Datos
103
IEN+: 336
104
IEN+: 278
105
IEN+: 278
106
RMN-CDCI3: 1,45-1,55 (9H, m), 2,33 (3H, s), 3,32-3,42 (4H, m), 3,50-3,64 (4H, m), 7,82-7,87 (1H, m), 8,518,56 (1H, m), 9,91 (1H, s)
107
IEN+: 178
108
IEN+: 236 ([M-tBu+H]+)
109
IEN+: 308
110
IEN+: 313
111
IEN+: 342, 344
112
IQPA+: 232
113
IEN+: 199, 201
114
IEN+: 198, 200
115
IEN+: 236
116
IEN+: 178
117
IEN+: 178
118
IEN+: 178
119
IEN+: 222
120
IEN+: 198
121
IEN+: 177
122
IEN+: 262
123
IEN+: 208
124
IEN+: 546
125
IEN+: 546
126
IEN+: 548
127
IEN+: 536
128
IEN+: 561
129
IEN+: 548
130
IEN+: 533
131
IEN+: 568
132
IEN+: 534
133
IEN+: 567
134
IEN+: 620
[Tabla 72] [Tabla 73] [Tabla 75]
Rf
Datos
135
IEN+: 498
136
IEN+: 553
137
IEN+: 551
138
IEN+: 537
139
IEN+: 512
140
IEN+: 590
141
IEN+: 646
142
IEN+: 517
143
IEN+: 630
144
IEN+: 316, 318
145
IEN+: 316, 318
146
IEN+: 321
147
IQPA+: 203
148
IEN+: 245
149
IEN+: 271
150
IEN+: 274
151
IEN+: 279
152
IEN+: 271
153
IEN+: 320
154
IEN+: 321
155
IEN+: 319
156
IEN+: 319
157
IEN+: 333, 335
158
IEN+: 332, 334
159
IEN+: 293
160
IEN+: 389
161
IEN+: 412
162
IEN+: 440
163
IEN+: 441
164
IEN+: 412
165
IEN+: 370
166
BAR+: 383
167
BAR+: 380
168
IEN+: 427
Rf
Datos
169
IEN+: 261
170
IEN+: 275
171
IEN+: 470
172
IEN+: 472
173
IEN+: 469
174
IEN+: 444
175
IEN+: 470
176
IEN+: 456
177
IEN+: 518
178
IEN+: 519
179
IEN+: 405
180
IEN+: 377
181
IEN+: 518
182
IEN+: 518
183
IEN+: 517
184
IQPA+: 458
185
IEN+: 374 ([M-Boc]+)
186
IEN-: 399
187
IEN+: 497
188
IEN+: 391
189
IEN+: 497
190
IEN+: 498
191
IEN+: 358 ([M-Boc]+)
192
IEN+: 454
193
IEN+: 517
194
IEN+: 276
195
RMN-CDCI3: 1,44 (2,7H, s), 1,47 (6,3H, s), 2,79-2,87 (2H, m), 2,92 (2,1H, s), 3,02 (0,9H, s), 3,92-4,11 (4H, m), 4,24-4,31 (2H, m), 4,52 (0,6H, s), 4,66 (1,4H, s), 5,50-5,63 (1H, m), 6,73-6,82 (2H, m), 7,05-7,20 (2H, m), 7,22-7,31 (1H, m), 7,35-7,51 (3H, m), 7,64-7,76 (2H, m), 8,43-8,48 (1H, m), 8,57-8,62 (1H, m)
Rf
Datos
196
RMN-CDCI3: 1,44 (2,7H, s), 1,47 (6,3H, s), 2,66-2,73 (2H, m), 2,92 (2,1H, s), 3,02 (0,9H, s), 3,92-4,11 (4H, m), 4,18-4,27 (2H, m), 4,52 (0,6H, s), 4,66 (1,4H, s), 5,50-5,63 (1H, m), 6,24-6,32 (1H, m), 6,75 (1H, d, J = 8,8 Hz), 7,05-7,20 (1H, m), 7,23-7,32 (1H, m), 7,35-7,51 (3H, m), 7,67-7,78 (2H, m), 8,43-8,48 (1H, m), 8,498,54 (1H, m), 8,69-8,74 (1H, m)
197
IQPA-: 382
198
IEN+: 518
199
IEN-: 482
200
IEN+: 590
201
IEN+: 557
202
IEN+: 495
203
IEN+: 440
204
IEN+: 496
205
IEN+: 601
206
IEN+: 585
207
IEN+: 496
208
IEN+: 585
209
IEN+: 531
210
IEN+: 496
211
IEN+: 573
212
IEN+: 511
213
IEN+: 551
214
IEN+: 553
215
IEN+: 579
216
IEN+: 539
217
IEN-: 582
218
IQPA+: 496
219
IEN+: 511
220
IEN+: 468
221
IEN+: 496
222
BAR-: 440
223
IEN+: 458
224
IEN-: 494
225
BAR-: 450
Rf
Datos
226
IEN-: 436
227
BAR+: 475
228
IEN-: 473
229
IEN+: 495
230
IEN+: 456
231
IEN+: 440
232
IEN+: 535
233
RMN-CDCl3: 1,44 (3,6H, s), 1,46 (5,4H, s), 2,80 (1,2H, s), 2,90 (1,8H, s), 3,0-3,1 (6H, m), 3,99-4,09 (2H, m), 4,51 (0,8H, s), 4,66 (1,2H, s), 5,52-5,62 (1H, a), 7,05-7,55 (8H, m)
234
IEN+: 456
235
RMN-CDCI3: 1,44 (3,6H, s), 1,46 (5,4H, s), 2,27 (3H, s), 2,64 (2H, t, J = 6 Hz), 2,91 (1,8H, s), 3,02 (1,2H, s), 3,59-3,69 (4H, m), 3,99-4,09 (2H, m), 4,53 (0,8H, s), 4,67 (1,2H, s), 5,52-5,63 (1H, a), 7,10-7,23 (1H, m), 7,32-7,57 (7H, m)
236
IEN+: 557
237
IEN+: 527
238
IEN+: 499
239
IEN+: 527
240
IEN+: 527
241
IEN+: 541
242
IEN+: 554
243
IEN+: 540
244
IEN+: 552
245
IEN+: 588
246
IEN+: 616
247
IEN+: 512
imagen246
imagen247
imagen248
imagen249
imagen250
imagen251
imagen252
imagen253
Ejemplo Comparativo 418
Al oxalato de N-metil-N-{[4'-(morfolin-4-il)bifenil-3-il]metil}glicinamida (100 mg) se le añadieron CHCl3 (10 ml) y una solución saturada acuosa de hidrógeno carbonato de sodio (10 ml), seguido de agitación durante 10 minutos. La
5 capa acuosa se extrajo con cloroformo (10 ml). La capa orgánica combinada se secó sobre sulfato de sodio anhidro y después se concentró a presión reducida. El residuo se disolvió en EtOH (2 ml) y se añadió ácido succínico a los mismos, seguido de agitación durante 3 horas. El cristal resultante se filtró y se lavó con EtOH. El residuo producto se secó a presión reducida y se secó para obtener hemisuccinato de N-metil-N-{[4'-(morfolin-4-il)bifenil-3il]metil}glicinamida (85 mg) en forma de un cristal incoloro.
10 Los Compuestos de Ejemplo y de Ejemplo Comparativo que se muestran en las Tablas a continuación se prepararon de la misma manera que en los métodos de los Ejemplos y Ejemplos Comparativos anteriores, usando cada uno de los materiales de partida correspondientes. Las estructuras, los métodos de preparación y los datos fisicoquímicos de los Compuestos de Ejemplo y de Ejemplo Comparativo se muestran en las Tablas a continuación.
15 En las tablas a continuación, la "C" adyacente al Número de Ejemplo indica que el Ejemplo es un Ejemplo Comparativo.
[Tabla 79]
Ej
Sín Estructura Ácido
C1
1 L-TA
C2
2 2HCl
3
3
L-TA
C4
3 imagen254 3HCI
C5
3 L-TA
Ej
Sín Estructura Ácido
C6
3 3HCI
7
3 L-TA
8
3 L-TA
9
3 L-TA
C10
3 imagen255 L-TA
Ej
Sín Estructura Ácido
C11
3 L-TA
C12
3 L-TA
C13
3 L-TA
C14
3 L-TA
C15
3 imagen256 L-TA
C16
3 L-TA
[Tabla 82] [Tabla 83] [Tabla 84] [Tabla 85] [Tabla 86]
Ej
Sín Estructura Ácido
C17
3 L-TA
C18
3 HCI
19
19
2HCI
C20
19 imagen257 HCI
C21
19 HCI
C22
19 HCI
Ej
Sín Estructura Ácido
C23
19 HCI
C24
19 2HCI
C25
19 HCI
C26
19 HCI
C27
19 4HCI
C28
19 imagen258 4HCI
Ej
Sín Estructura Ácido
29
19 3HCI
30
19 I 2HCI
C31
19 2HCI
32
19 2HCI
33
19 2HCI
Ej
Sín Estructura Ácido
C34
19 imagen259 HCI
C35
19 HCI
C36
19 2HCI
C37
19 2HCI
C38
19 HCI
C39
19 HCI
Ej
Sín Estructura Ácido
C40
19 3HCI
C41
19 imagen260 2HCI
C42
19 2HCI
C43
19 2HCI
44
19 3HCI
Ej
Sín Estructura Ácido
C45
19 3HCI
46
19 3HCI
C47
19 3HCI
C48
19 3HCI
C49
19 imagen261 2HCI
C50
19 2HCI
Ej
Sín Estructura Ácido
C51
19 3HCI
C52
19 4HCI
C53
19 3HCI
C54
19 3HCI
C55
19 imagen262 3HCI
[Tabla 89] [Tabla 90] [Tabla 91] [Tabla 92] [Tabla 93] [Tabla 94]
Ej
Sín Estructura Ácido
C56
19 3HCl
C57
19 3HCl
C58
19 3HCI
C59
19 imagen263 3HCI
C60
19 2HCI
Ej
Sín Estructura Ácido
C61
19 2HCI
C62
19 2HCI
C63
19 2HCI
C64
19 2HCI
C65
19 imagen264 2HCI
66
19 2HCI
Ej
Sín Estructura Ácido
67
19 3HCl
68
19 2HCI
C69
69 L-TA
C70
69 OA
C71
69 imagen265 OA
C72
69 OA
Ej
Sín Estructura Ácido
C73
69 OA
C74
69 OA
C75
69 L-TA
C76
69 L-TA
C77
69 L-TA
C78
69 L-TA
Ej
Sín Estructura Ácido
C79
69 imagen266 L-TA
C80
69 L-TA
C81
69 L-TA
C82
69 L-TA
C83
69 L-TA
C84
69 L-TA
Ej
Sín Estructura Ácido
85
69 L-TA
C86
69 imagen267 L-TA
C87
69 L-TA
88
69 L-TA
89
69 L-TA
Ej
Sín Estructura Ácido
90
69 imagen268 L-TA
91
69 imagen269 L-TA
C92
69 imagen270 L-TA
C93
69 imagen271 L-TA
C94
69 imagen272 L-TA
Ej
Sín Estructura Ácido
C95
69 imagen273 3HCl
C96
69 imagen274 L-TA
C97
69 imagen275 L-TA
C98
69 imagen276 L-TA
C99
69 imagen277 L-TA
C100
69 imagen278 L-TA
Ej
Sín Estructura Ácido
C101
69 imagen279 L-TA
C102
69 imagen280 L-TA
C103
69 imagen281 L-TA
C104
69 imagen282 L-TA
C105
69 imagen283 L-TA
C106
69 imagen284 L-TA
C107
69 imagen285 L-TA
Ej
Sín Estructura Ácido
C108
69 imagen286 L-TA
C109
69 imagen287 L-TA
C110
69 imagen288 L-TA
C111
69 imagen289 L-TA
C112
69 imagen290 L-TA
C113
69 imagen291 L-TA
Ej
Sín Estructura Ácido
C114
69 imagen292 L-TA
C115
69 imagen293 L-TA
C116
69 imagen294 L-TA
C117
69 imagen295 L-TA
C118
69 imagen296 L-TA
C119
69 imagen297 L-TA
Ej
Sín Estructura Ácido
C120
69 imagen298 L-TA
121
69 imagen299 L-TA
122
69 imagen300 L-TA
123
69 imagen301 L-TA
C124
69 imagen302 L-TA
Ej
Sín Estructura Ácido
C125
69 imagen303 L-TA
C126
69 imagen304 L-TA
C127
69 imagen305 L-TA
C128
69 imagen306 L-TA
C129
69 imagen307 L-TA
C130
69 imagen308 L-TA
C131
69 imagen309 L-TA
Ej
Sín Estructura Ácido
C132
69 imagen310 L-TA
C133
69 imagen311 L-TA
134
69 imagen312 L-TA
135
69 imagen313 L-TA
C136
69 imagen314 L-TA
Ej
Sín Estructura Ácido
C137
69 imagen315 L-TA
C138
69 imagen316 L-TA
C139
69 imagen317 L-TA
C140
69 imagen318 L-TA
[Tabla 104] [Tabla 105] [Tabla 106] [Tabla 107] [Tabla 108]
Ej
Sín Estructura Ácido
C141
69 imagen319 L-TA
C142
69 L-TA
C143
69 L-TA
C144
69 imagen320 L-TA
C145
69 L-TA
Ej
Sín Estructura Ácido
146
69 L-TA
147
69 L-TA
C148
69 L-TA
C149
69 L-TA
C150
69 imagen321 L-TA
Ej
Sín Estructura Ácido
151
69 L-TA
152
69 L-TA
153
69 L-TA
154
69 L-TA
155
69 L-TA
Ej
Sín Estructura Ácido
156
69 imagen322 L-TA
157
69 L-TA
158
69 L-TA
C159
69 L-TA
C160
69 L-TA
Ej
Sín Estructura Ácido
161
69 L-TA
C162
69 imagen323 L-TA
C163
69 L-TA
C164
69 L-TA
C165
69 L-TA
Ej
Sín Estructura Ácido
C166
69 imagen324 L-TA
C167
69 imagen325 L-TA
C168
69 imagen326 L-TA
C169
69 imagen327 L-TA
C170
69 imagen328 L-TA
Ej
Sín Estructura Ácido
C171
69 imagen329 L-TA
C172
69 imagen330 L-TA
C173
69 imagen331 L-TA
C174
69 imagen332 L-TA
C175
69 imagen333 L-TA
Ej
Sín Estructura Ácido
C176
69 imagen334 L-TA
C177
69 imagen335 L-TA
C178
69 imagen336 L-TA
C179
69 imagen337 L-TA
C180
69 imagen338 L-TA
Ej
Sín Estructura Ácido
C181
69 imagen339 L-TA
C182
69 imagen340 L-TA
C183
69 imagen341 L-TA
C184
69 imagen342 L-TA
C185
69 imagen343 L-TA
Ej
Sín Estructura Ácido
C186
69 imagen344 L-TA
C187
69 imagen345 L-TA
C188
69 imagen346 L-TA
C189
69 imagen347 L-TA
C190
69 imagen348 L-TA
Ej
Sín Estructura Ácido
C191
69 imagen349 L-TA
C192
69 imagen350 L-TA
C193
69 imagen351 L-TA
C194
69 imagen352 L-TA
C195
69 imagen353 OA
Ej
Sín Estructura Ácido
C196
69 imagen354 HCI
C197
69 imagen355 OA
C198
69 imagen356 OA
C199
69 imagen357 3HCI
C200
69 imagen358 OA
C201
69 imagen359 OA
Ej
Sín Estructura Ácido
C202
69 imagen360 OA
C203
69 imagen361 L-TA
C204
69 imagen362 L-TA
C205
69 imagen363 L-TA
C206
69 imagen364 L-TA
207
69 imagen365 L-TA
Ej
Sín Estructura Ácido
208
208
imagen366 L-TA
209
209
imagen367 L-TA
210
209 imagen368 L-TA
C211
209 imagen369 L-TA
212
212
imagen370 2HCl
Ej
Sín Estructura Ácido
C213
213 imagen371 HCI
C214
213 imagen372 HCI
C215
215 imagen373 OA
C216
11 imagen374 2HCI
C217
217 imagen375 3HCI
[Tabla 119] [Tabla 120] [Tabla 121] [Tabla 123] [Tabla 124] [Tabla 125] [Tabla 126]
Ej
Sín Estructura Ácido
C219
219 OA
C220
219 OA
C221
219 HCI
C222
222 L-TA
C223
222 imagen376 L-TA
Ej
Sín Estructura Ácido
C224
222 OA
C225
222 OA
C226
226 HCI
C227
226 HCI
C228
228 OA
229
19 3HCI
Ej
Sín Estructura Ácido
C230
228 OA
C231
228 imagen377 OA
C232
228 OA
C233
228 L-TA
C234
228 L-TA
C235
228 L-TA
Ej
Sín Estructura Ácido
C236
228 imagen378 L-TA
C237
228 imagen379 L-TA
C238
228 imagen380 L-TA
C239
239 imagen381 3HCI
C240
239 imagen382 2HCI
C241
239 imagen383 2HCI
Ej
Sín Estructura Ácido
C242
239 3HCI
C243
239 4HCI
C244
244 L-TA
C245
244 imagen384 L-TA
C246
244 L-TA
C247
244 L-TA
C248
248 2HCI
Ej
Sín Estructura Ácido
249
248 2HCI
C250
248 2HCI
C251
248 2HCI
252
248 2HCI
253
248 imagen385 2HCI
Ej
Sín Estructura Ácido
C254
254 L-TA
C255
254 3HCI
C256
254 HCI
C257
254 L-TA
C258
254 L-TA
C259
254 L-TA
C260
254 L-TA
Ej
Sín Estructura Ácido
261
261
imagen386 L-TA
262
261 L-TA
263
263
2HCI
C264
264 3HCI
C265
265 L-TA
C266
265 L-TA
Ej
Sín Estructura Ácido
C267
265 imagen387 L-TA
C268
265 imagen388 L-TA
C269
265 imagen389 L-TA
C270
270 imagen390 L-TA
C271
270 imagen391 L-TA
C272
272 imagen392 L-TA
Ej
Sín Estructura Ácido
C273
272 imagen393 L-TA
C274
272 imagen394 L-TA
C275
272 imagen395 L-TA
C276
272 imagen396 L-TA
C277
272 imagen397 L-TA
Ej
Sín Estructura Ácido
C278
272 imagen398 L-TA
C279
272 imagen399 L-TA
C280
272 imagen400 L-TA
C281
281 imagen401 -
C282
281 imagen402 -
[Tabla 130] [Tabla 131] [Tabla 132] [Tabla 133]
Ej
Sín Estructura Ácido
C283
281 imagen403 -
C284
281 -
C285
281 -
C286
281 imagen404 -
C287
281 -
Ej
Sín Estructura Ácido
C288
281 -
C289
281 -
C290
281 -
C291
281 -
C292
281 -
Ej
Sín Estructura Ácido
C293
281 imagen405 -
C294
281 -
C295
281 -
C296
281 -
C297
281 -
Ej
Sín Estructura Ácido
C298
281 -
C299
281 imagen406 -
C300
281 -
C301
281 -
C302
281 -
C303
281 -
[Tabla 134] [Tabla 135] [Tabla 136] [Tabla 137] [Tabla 138] [Tabla 140] [Tabla 141] [Tabla 142] [Tabla 144] [Tabla 145] [Tabla 146] [Tabla 147]
Ej
Sín Estructura Ácido
C304
281 imagen407 -
C305
281 -
C306
281 -
C307
281 imagen408 -
C308
281 -
Ej
Sín Estructura Ácido
C309
281 -
C310
281 -
C311
281 -
C312
281 -
C313
281 -
C314
281 imagen409 -
Ej
Sín Estructura Ácido
C315
281 -
C316
281 -
C317
281 -
C318
281 -
C319
281 -
Ej
Sín Estructura Ácido
C320
281 -
C321
281 imagen410 -
C322
281 -
C323
281 -
C324
281 -
Ej
Sín Estructura Ácido
C325
281 -
C326
281 imagen411 -
C327
281 -
C328
281 -
C329
281 -
Ej
Sín Estructura Ácido
C330
281 imagen412 -
C331
281 imagen413 -
C332
281 imagen414 -
C333
281 imagen415 -
C334
281 imagen416 -
Ej
Sín Estructura Ácido
C335
281 -
C336
281 -
C337
281 -
C338
281 imagen417 -
C339
281 -
Ej
Sín Estructura Ácido
C340
281 -
C341
281 -
C342
281 -
C343
281 -
C344
281 -
C345
281 imagen418 -
Ej
Sín Estructura Ácido
C346
281 -
C347
281 -
C348
281 -
C349
281 -
C350
281 -
C351
281 imagen419 -
Ej
Sín Estructura Ácido
C352
281 imagen420 -
C353
281 imagen421 -
C354
281 imagen422 -
C355
281 imagen423 -
C356
281 imagen424 -
C357
281 imagen425 -
Ej
Sín Estructura Ácido
C358
281 -
C359
281 -
C360
281 -
C361
281 imagen426 -
C362
281 imagen427 -
C363
281 imagen428 -
Ej
Sín Estructura Ácido
C364
281 -
C365
281 imagen429 -
C366
281 -
C367
281 imagen430 -
C368
281 imagen431 -
C369
281 imagen432 -
Ej
Sín Estructura Ácido
C370
281 -
C371
281 imagen433 -
C372
281 -
C373
281 -
C374
374 -
C375
374 -
Ej
Sín Estructura Ácido
C376
374 -
C377
374 imagen434 -
C378
374 -
C379
374 -
C380
374 -
C381
374 imagen435 -
[Tabla 148]
Ej
Sín Estructura Ácido
C382
374 -
C383
374 -
C384
374 -
C385
374 -
C386
374 imagen436 -
C387
374 -
C388
374 -
C389
374 -
C390
374 -
C391
374 -
C392
374 imagen437 -
C393
374 -
[Tabla 150]
Ej
Sín Estructura Ácido
C394
374 -
C395
374 imagen438 -
C396
374 -
C397
374 -
C398
374 -
C399
374 -
[Tabla 151]
Ej
Sín Estructura Ácido
C400
374 imagen439 -
C401
374 -
imagen440
C411
374 -
[Tabla 153]
Ej
Sín Estructura Ácido
C412
374 -
C413
374 imagen441 -
C414
374 -
C415
374 -
C416
374 -
[Tabla 154]
Ej
Datos
C1
IEN+: 313
C2
BAR+: 312
3
IEN+: 432
C4
IEN+: 431
C5
IEN+: 486
C6
IEN+: 430
7
IEN+: 453
8
IEN+: 457
9
IEN+: 452
C10
IEN+: 413
C11
IEN+: 406 RMN-DMSO-d6: 1,78-1,93 (2H, m), 2,01-2,14 (2H, m), 2,90 (0,9H, s), 2,96 (2,1H, s), 3,06-3,20 (2H, m),3,824,20 (4H, m), 4,47-4,68 (3H, m), 4,74-4,87 (2H, m), 6,18-6,26 (1H, m), 7,17-7,26 (1H, m), 7,37-7,52(3H, m), 7,53-7,65 (1H, m), 7,75-7,83 (1H, m), 8,72 (1,4H, s), 8,75 (0,6H, s)
C12
IEN+: 423
C13
IEN+: 409
C14
BAR+: 340 RMN-DMSO-d6: 1,22 (3H, d, J = 6,8 Hz), 1,63-1,75 (1H, m), 1,84-2,12 (3H, m), 2,88 (0,9H, s), 2,93 (2,1H, s), 3,39-3,69 (4H, m), 3,70-3,79 (2H, m), 4,18-4,30 (1H, m), 4,58 (0,6H, s), 4,6 (1,4H, s), 7,13-7,22 (1H, m),7,357,49 (2H, m), 7,49-7,60 (1H, m), 8,67 (1,4H, s), 8,69 (0,6H, s)
C15
BAR+: 344 RMN-DMSO-d6: 2,08-2,36 (2H, m), 2,88 (0,9H, s), 2,93 (2,1H, s), 3,38-3,94 (8H, m), 4,56 (0,6H, s), 4,60 (1,4H, s), 5,34-5,56 (1H, m), 7,13-7,24 (1H, m), 7,34-7,50 (2H, m), 7,50-7,62 (1H, m), 8,63-8,78 (2H, m)
imagen442
Ej
Datos
C43
IEN+: 370 RMN-DMSO-d6: 1,87-2,10 (4H, m), 2,89 (0,9H, s), 2,95 (2,1H, s), 3,28 (3H, s), 3,31-3,37 (1H, m), 3,41-3,52 (1H, m) 3,54-3,61 (2H, m), 3,88-4,02 (2H, m), 4,23-4,31 (1H, m), 4,60 (0,6H, s), 4,62 (1,4H, s), 7,20-7,25 (1H, m), 7,39-7,51 (2H, m), 7,53-7,65 (1H, m), 8,07-8,35 (3H, a), 8,72 (1,4H, s), 8,74 (0,6H, s)
44
IEN+: 417 RMN-DMSO-d6: 2,90 (0,9H, s), 2,98 (2,1H, s), 3,35-3,56 (4H, m), 3,87-4,01 (2H, m), 4,06-4,32 (4H, m), 4,61 (0,6H, s), 4,63 (1,4H, s), 7,10-7,29 (2H, m), 7,34-7,69 (7H, m), 8,15-8,35 (3H, a), 8,79 (1,4H, s), 8,81 (0,6H, s)
C45
IEN+: 461
46
IEN+: 447
C47
IEN+: 377
C48
IEN+: 391
C49
IEN+: 383
C50
IEN+: 354
C51
IEN+: 425
C52
IEN+: 438
C53
IEN+: 363
C54
IEN+: 377
C55
IEN+: 446
C56
IEN+: 432
C57
IEN+: 460
C58
IEN+: 433
C59
IEN+: 467
C60
IEN+: 397
C61
IEN+: 506 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,25-3,36 (4H, m), 3,87-4,05 (6H, m), 4,19 (2H, s), 4,57-4,66 (4H, m), 7,09-7,16 (1H, m), 7,21-7,26 (1H, m), 7,41-7,52 (2H, m), 7,55-7,65 (1H, m), 7,87-7,94 (1H, m), 8,058,19 (3H, a), 8,21-8,26 (1H, m), 8,75 (1,4H, s), 8,77 (0,6H, s)
C62
BAR+: 386
C63
IEN+: 454
C64
BAR+: 452
[Tabla 158] [Tabla 160] [Tabla 161]
Ej
Datos
C65
IEN+: 441
66
BAR+: 504 RMN-DMSO-d6: 2,41 (3H, s), 2,57-2,64 (2H, m), 2,78-2,87 (2H, m), 2,90 (0,9H, s), 2,97 (2,1H, s), 3,40-3,53 (4H, m), 3,86-4,03 (6H, m), 4,58-4,66 (2H, m), 7,20-7,28 (1H, m), 7,41-7,53 (2H, m), 7,55-7,66 (1H, m), 7,978,07 (2H, m), 8,13-8,30 (3H, m), 8,77 (1,4H, s), 8,80 (0,6H, s)
67
IEN+: 462 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,79-3,87 (4H, m), 3,89-4,02 (6H, m), 4,55-4,68 (2H, m), 7,04 (1H, d, J = 9,2 Hz), 7,24 (1H, d, J = 7,7 Hz), 7,39-7,53 (2H, m), 7,54-7,66 (1H, m), 7,98-8,07 (1H, m), 8,088,27 (3H, m), 8,62 (1H, d, J = 2,3 Hz), 8,76 (1,4H, s), 8,78 (0,6H, s)
68
IEN+: 461 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,40-3,50 (4H, m), 3,89-4,03 (6H, m), 4,60 (0,6H, s), 4,63 (1,4H, s), 7,03 (2H, d, J = 9,1 Hz), 7,24 (1H, d, J = 7,5 Hz), 7,39-7,53 (2H, m), 7,53-7,65 (1H, m), 7,81 (2H, d, J = 9,0 Hz), 8,10-8,31 (3H, m), 8,75 (1,4H, s), 8,77 (0,6H, s)
C69
IEN+: 342 RMN-DMSO-d6: 2,88 (1,2H, s), 2,93 (1,8H, s), 3,66-3,70 (4H, m), 3,73-3,77 (4H, m), 4,56 (0,8H, s), 4,60 (1,2H, s), 7,18-7,22 (1H, m), 7,40-7,61 (3H, m), 8,72 (1,2H, s), 8,74 (0,8H, s)
C70
IEN+: 485
C71
IEN+: 485
C72
IEN+: 501,3
C73
IEN+: 341
C74
IEN+: 486
C75
IEN+: 326 RMN-DMSO-d6: 1,85-2,04 (4H, m), 2,89 (1,2H, s), 2,96 (1,8H, s), 3,47-3,60 (4H, m), 3,88 (2H, s), 3,91 (0,8H, s), 3,96 (1,2H, s), 4,58 (0,8H, s), 4,62 (1,2H, s), 7,20 (1H, d, J = 8 Hz), 7,40-7,62 (3H, m), 8,68 (1,2H, s), 8,70 (0,8H, s)
C76
IEN+: 341
Ej
Datos
C77
IEN+: 368
C78
RMN-DMSO-d6: 1,16 (3H, s), 1,17 (3H, s), 2,54-2,62 (2H, m), 2,89 (1,2H, s), 2,96 (1,8H, s), 3,51-3,61 (2H, m), 3,83 (2H, s), 3,88 (0,8H, s), 3,94 (1,2H, s), 4,55 (2H, d, J = 13 Hz), 4,58 (0,8H, s), 4,62 (1,2H, s), 7,22 (1H, d, J = 8 Hz), 7,39-7,66 (3H, m), 8,70 (1,2H, s), 8,73 (0,8H, s)
C79
IEN+: 372
C80
IEN+: 369
C81
IEN+: 344
C82
IEN+: 353
C83
IEN+: 370
C84
IEN+: 356
85
IEN+: 418 RMN-DMSO-d6: 2,88 (1,2H, s), 2,93 (1,8H, s), 3,58-3,65 (4H, m), 3,70-3,75 (2H, m), 3,87-3,94 (4H, m), 4,56 (0,8H, s), 4,61 (1,2H, s), 6,64-6,70 (1H, m), 6,89 (1H, d, J = 9 Hz), 7,17-7,24 (1H, m), 7,40-7,63 (4H, m), 8,13-8,16 (1H, m), 8,73 (1,2H, s), 8,75 (0,8H, s)
C86
RMN-DMSO-d6: 2,21 (3H, s), 2,30-2,36 (4H, m), 2,90 (0,8H, s), 2,94 (1,2H, s), 3,43-3,48 (4H, m), 3,80 (2H, s), 3,83 (0,8H, s), 3,89 (1,2H, s), 4,59 (0,8H, s), 4,62 (1,2H, s), 7,16-7,21 (1H, m), 7,37-7,60 (7H, m), 8,60 (0,6H, s), 8,61 (0,4H, s)
C87
IEN+: 415
88
BAR+: 432
89
IEN+: 490
90
BAR+: 432 RMN-DMSO-d6: 2,90 (1,2H, s), 2,96 (1,8H, s), 2,26-2,32 (4H, m), 3,84-3,98 (8H, m), 4,59 (0,8H, s), 4,63 (1,2H, s), 7,20-7,25 (2H, m), 7,41-7,64 (3H, m), 7,88 (1H, s), 8,17 (1H, d, J = 3 Hz), 8,74 (1,2H, s), 8,76 (0,8H, s)
91
IEN+: 432 RMN-DMSO-d6: 2,90 (1,2H, s), 2,97 (1,8H, s), 2,92-2,99 (4H, m), 3,90-4,00 (6H, m), 4,09 (3H, s), 4,59 (0,8H, s), 4,63 (1,2H, s), 7,16-7,26 (2H, m), 7,40-7,65 (4H, m), 8,16 (1H, dd, J = 2, 5 Hz), 8,74 (1,2H, s), 8,77 (0,8H, s)
C92
IEN+: 424
Ej
Datos
C93
IEN+: 384
C94
BAR+: 412
C95
IEN+: 375 RMN-DMSO-d6: 2,91 (1,2H, s), 2,98 (1,8H, s), 3,89-4,04 (2H, m), 4,62 (0,8H, s), 4,64 (1,2H, s), 4,94-5,03 (4H, m), 7,23 (1H, d, J = 8 Hz), 7,46 (1H, t, J = 8 Hz), 7,49-7,68 (3H, m), 8,15-8,32 (4H, m), 8,68 (1H, d, J = 5 Hz), 8,84 (1,2H, s), 8,87 (0,8H, s)
C96
BAR+: 433 RMN-DMSO-d6: 1,90-1,98 (2H, m), 2,88 (1,2H, s), 2,93 (1,8H, s), 3,64-4,03 (10H, m), 4,56 (0,8H, s), 4,60 (1,2H, s), 7,17-7,22 (1H, m), 7,37-7,58 (3H, m), 7,73 (1H, d, J = 3 Hz), 7,99-8,02 (1H, m), 8,19 (1H, d, J = 2 Hz), 8,66 (1,2H, s), 8,68 (0,8H, s)
C97
IEN+: 384
C98
BAR+: 402
C99
IEN+: 370 RMN-DMSO-d6: 1,69-1,79 (1H, m), 2,02-2,12 (1H, m), 2,53-2,61 (1H, m), 2,89 (1,2H, s), 2,96 (1,8H, s), 3,24-3,54 (7H, m), 3,61-3,71 (2H, m), 3,84 (2H, s), 3,88 (0,8H, s), 3,95 (1,2H, s), 4,58 (0,8H, s), 4,62 (1,2H, s), 7,20 (1H, d, J = 8 Hz), 7,38-7,61 (3H, m), 8,68 (1,2H, s), 8,70 (0,8H, s)
C100
IEN+: 427
C101
BAR+: 397
C102
IEN+: 409
C103
BAR+: 447
C104
IEN+: 343
C105
IEN+: 398
C106
IEN+: 342
C107
IEN+: 358
C108
IEN+: 352
C109
IEN+: 396
C110
IEN+: 396
C111
IEN+: 384
C112
IEN+: 354
C113
BAR+: 395
C114
BAR+: 358
Ej
Datos
C115
IEN+: 358
C116
IEN+: 374
C117
IEN+: 397
C118
IEN+: 370 RMN-DMSO-d6: 1,87-2,09 (4H, m), 2,89 (0,9H, s), 2,95 (2,1H, s), 3,28 (3H, s), 3,30-3,37 (1H, m), 3,42-3,51 (1H, m), 3,52-3,61 (2H, m), 3,80 (2H, s), 3,85 (0,6H, s), 3,92 (1,4H, s), 4,23-4,28 (1H, m), 4,58 (0,6H, s), 4,61 (1,4H, s), 7,18-7,24 (1H, m), 7,39-7,50 (2H, m), 7,52-7,61 (1H, m), 8,70 (1,4H, s), 8,72 (0,6H, s)
C119
BAR+: 473
C120
IEN+: 419 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,68-3,73 (4H, m), 3,89-4,03 (8H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 7,21-7,26 (1H, m), 7,41-7,52 (2H, m), 7,55-7,65 (1H, m), 7,86-7,89 (1H, m), 8,10-8,13 (1H, m), 8,37-8,40 (1H, m), 8,75 (1,4H, s), 8,77 (0,6H, s)
121
BAR+: 431
122
BAR+: 435
123
IEN+: 451
C124
IEN+: 432
C125
IEN+: 454
C126
IEN+: 385
C127
IEN+: 413
C128
IEN+: 433
C129
IEN+: 364
C130
IEN+: 377
C131
IEN+: 369
C132
IEN+: 387
C133
IEN+: 432
134
IEN+: 490
135
IEN+: 443
[Tabla 162] [Tabla 164] [Tabla 165]
Ej
Datos
C136
IEN+: 446 RMN-DMSO-d6: 0,96-1,01 (3H, m), 1,22-1,29 (3H, m), 2,90 (0,9H, s), 2,97 (2,1H, s), 3,26-3,32 (1H, m), 3,41-3,56 (2H, m), 3,89-3,99 (4H, m), 4,20-4,31 (1H, m), 4,47-4,54 (1H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 4,98-5,08 (1H, m), 7,20-7,25 (2H, m), 7,30-7,35 (1H, m), 7,41-7,51 (2H, m), 7,54-7,64 (1H, m), 7,94-7,98 (1H, m), 8,29-8,33 (1H, m), 8,73 (1,4H, s), 8,75 (0,6H, s)
C137
IEN+: 476
C138
IEN+: 452
C139
IEN+: 432
C140
IEN+: 446
C141
IEN+: 446
C142
IEN+: 417
C143
BAR+: 417
C144
IEN+: 416
C145
BAR+: 418 RMN-DMSO-d6: 1,66-1,79 (2H, m), 1,98-2,08 (2H, m), 2,90 (0,9H, s), 2,96 (2,1H, s), 3,09-3,24 (3H, m), 3,80 (2H, s), 3,85 (0,6H, s), 3,92 (1,4H, s), 4,58 (0,6H, s), 4,62 (1,4H, s), 4,74-4,83 (2H, m), 7,19-7,24 (1H, m), 7,34-7,37 (1H, m), 7,40-7,51 (1H, m), 7,53-7,63 (1H, m), 8,70 (1,4H, s), 8,73 (0,6H, s), 8,75 (2H, d, J = 4,9 Hz)
146
IEN+: 443
147
IEN+: 452
C148
IEN+: 486
C149
IEN+: 417
C150
IEN+: 417 RMN-DMSO-d6: 1,52-1,66 (2H, m), 1,86-1,94 (2H, m), 2,85-3,08 (6H, m), 3,82 (2H, s), 3,87 (0,6H, s), 3,94 (1,4H, s), 4,58 (0,6H, s), 4,62 (1,4H, s), 4,84-4,92 (2H, m), 7,19-7,24 (1H, m), 7,28-7,32 (2H, m), 7,40-7,51 (2H, m), 7,54-7,63 (1H, m), 8,46-8,49 (2H, m), 8,71 (1,4H, s), 8,73 (0,6H, s)
151
IEN+: 436
152
IEN+: 431
153
IEN+: 435
154
IEN+: 453
Ej
Datos
155
IEN+: 436
156
IEN+: 452
157
IEN+: 496, 498
158
IEN+: 448
C159
IEN+: 448
C160
IEN+: 432
161
IEN+: 419 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,70-3,76 (4H, m), 3,88-3,99 (8H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 7,20-7,25 (1H, m), 7,29-7,34 (1H, m), 7,39-7,52 (3H, m), 7,55-7,65 (1H, m), 8,57-8,60 (1H, m), 8,75 (1,4H, s), 8,77 (0,6H, s)
C162
IEN+: 467
C163
IEN+: 383
C164
IEN+: 423
C165
IEN+: 382
C166
IEN+: 411
C167
IEN+: 356 RMN-DMSO-d6: 2,00-2,14 (2H, m), 2,89 (0,9H, s), 2,96 (2,1H, s), 3,27 (3H, s), 3,45-3,53 (1H, m), 3,55-3,70 (3H, m), 3,85 (2H, s), 3,90 (0,6H, s), 3,96 (1,4H, s), 4,05-4,11 (1H, m), 4,58 (0,6H, s), 4,62 (1,4H, s), 7,177,24 (1H, m), 7,38-7,50 (2H, m), 7,51-7,62 (1H, m), 8,69 (1,4H, s), 8,71 (0,6H, s)
C168
IEN+: 356 RMN-DMSO-d6: 2,00-2,14 (2H, m), 2,89 (0,9H, s), 2,96 (2,1H, s), 3,24 (3H, s), 3,44-3,54 (1H, m), 3,55-3,71 (3H, m), 3,83 (2H, s), 3,88 (0,6H, s), 3,95 (1,4H, s), 4,06-4,11 (1H, m), 4,58 (0,6H, s), 4,62 (1,4H, s), 7,187,24 (1H, m), 7,39-7,50 (2H, m), 7,51-7,62 (1H, m), 8,69 (1,4H, s), 8,71 (0,6H, s)
C169
IEN+: 398
C170
BAR+: 383
C171
IEN+: 405
C172
IEN+: 399
C173
IEN+: 427
C174
IEN+: 427
C175
IEN+: 441
Ej
Datos
C176
IEN+: 439
C177
IEN+: 451
C178
IEN+: 453
C179
IEN+: 479
C180
IEN+: 412
C181
BAR+: 453
C182
BAR+: 451
C183
BAR+: 437
C184
BAR+: 440
C185
IEN+: 412
C186
BAR+: 398
C187
IEN+: 381
C188
IEN+: 395
C189
BAR+: 367
C190
IEN+: 417 RMN-DMSO-d6: 1,52-1,72 (2H, m), 1,82-1,95 (2H, m), 2,85-3,09 (6H, m), 3,88-4,03 (4H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 4,83-4,95 (2H, m), 7,17-7,25 (1H, m), 7,29-7,35 (1H, m), 7,38-7,52 (2H, m), 7,53-7,64 (1H, m), 7,66-7,72 (1H, m), 8,38-8,46 (1H, m), 8,47-8,55 (1H, m), 8,71 (1,4H, s), 8,73 (0,6H, s)
C191
IEN+: 415
C192
IEN+: 414
C193
IEN+: 414
C194
IEN+: 377
C195
IEN+: 340
C196
IEN+: 340
C197
IEN+: 356
C198
IEN+: 342
C199
IEN+: 457
C200
IEN+: 457
C201
IEN+: 395
C202
IEN+: 396
C203
BAR+: 438
C204
BAR+: 396
C205
IEN+ 368
Ej
Datos
C206
IEN+: 411
207
IEN+: 452, 454
208
BAR+: 418 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,26-3,35 (4H, m), 3,90-4,04 (8H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 7,20-7,28 (2H, m), 7,36-7,52 (3H, m), 7,55-7,65 (1H, m), 8,00-8,05 (1H, m), 8,34-8,39 (1H, m), 8,74 (1,4H, s), 8,77 (0,6H, s)
209
IEN+: 432
210
IEN+: 432
C211
IEN+: 417 RMN-DMSO-d6: 1,59-1,76 (2H, m), 1,84-1,97 (2H, m), 2,85-3,12 (6H, m), 3,81-3,99 (4H, m), 4,59 (0,6H, s), 4,63 (1,4H, s), 4,78-4,91 (2H, m), 7,16-7,25 (2H, m), 7,27-7,33 (1H, m), 7,38-7,51 (2H, m), 7,53-7,64 (1H, m), 7,67-7,76 (1H, m), 8,42-8,52 (1H, m), 8,71 (1,4H, s), 8,73 (0,6H, s)
212
IEN+: 476
C213
BAR+: 288
C214
BAR+: 298
C215
IEN+: 326
C216
IEN+: 390
C217
BAR+: 431
218
IEN+: 432
C219
IEN+: 471
C220
BAR+: 354
C221
IEN+: 326
C222
IEN+: 441
C223
IEN+: 410
C224
IEN+: 471
C225
IEN+: 354
C226
IEN+: 366
C227
IEN+: 326
C228
BAR+: 354
229
IEN+: 418
C230
IEN+: 356
C231
IEN+: 383
[Tabla 166] [Tabla 167]
Ej
Datos
C232
BAR+: 354
C233
IEN+: 397
C234
IEN+: 411
C235
IEN+: 451
C236
BAR+: 411
C237
BAR+: 445
C238
IEN+: 425
C239
BAR+: 369
C240
IEN+: 352
C241
IEN+: 354
C242
BAR+: 403
C243
BAR+: 368
C244
IEN+: 432
C245
IEN+: 431
C246
IEN+: 355
C247
IEN+: 369
C248
IEN+: 520 RMN-DMSO-d6: 2,55-2,62 (2H, m), 2,82-2,87 (2H, m), 2,90 (0,9H, s), 2,97 (2,1H, s), 3,32-3,45 (4H, m), 3,87-4,02 (6H, m), 4,57 (2H, s), 4,60 (0,6H, s), 4,63 (1,4H, s), 7,21-7,28 (1H, m), 7,40-7,52 (2H, m), 7,557,65 (1H, m), 8,00-8,07 (2H, m), 8,08-8,22 (3H, a), 8,75 (1,4H, s), 8,78 (0,6H, s)
249
IEN+: 462
C250
IEN+: 518
C251
IEN+: 443
252
IEN+: 488
253
IEN+: 490
C254
IEN+: 381
C255
IEN+ 367
C256
IEN+: 402
C257
IEN+: 366
C258
IEN+: 368
C259
IEN+: 368
C260
IEN+: 431
261
IEN+: 443
Ej
Datos
262
IEN+: 443
263
IEN+: 495, 497 RMN-DMSO-d6: 2,90 (0,9H, s), 2,97 (2,1H, s), 3,11-3,22 (4H, m), 3,88-4,02 (6H, m), 4,60 (0,6H, s), 4,63 (1,4H, s), 7,19-7,30 (2H, m), 7,40-7,53 (2H, m), 7,54-7,65 (1H, m), 7,83-8,89 (1H, m), 7,89-7,93 (1H, m), 8,05-8,25 (3H, m), 8,75 (1,4H, s), 8,77 (0,6H, s)
C264
BAR+: 395
C265
IEN+: 382
C266
BAR+: 382
C267
BAR+: 368
C268
BAR+: 354
C269
BAR+: 381
C270
IEN+: 416
C271
IEN+: 416 RMN-DMSO-d6: 1,58-1,74 (2H, m), 1,80-1,93 (2H, m), 2,80-3,00 (6H, m), 3,60-3,82 (4H, m), 4,44-4,65 (4H, m), 6,92-7,20 (1H, m), 7,11-7,21 (1H, m), 7,27-7,35 (1H, m), 7,36-7,49 (2H, m), 7,49-7,60 (1H, m), 7,647,72 (1H, m), 7,78-7,89 (1H, m), 8,36-8,48 (2H, m), 8,48-8,54 (1H, m)
C272
IEN+: 457
C273
BAR+: 457
C274
BAR+: 455
C275
BAR+: 443
C276
BAR+: 469
C277
BAR+: 469
C278
IEN+: 471
C279
IEN+: 443
C280
IEN+: 455
C281
IEN+: 326
C282
IEN+: 368
C283
IEN+: 356
C284
IEN+: 398
C285
IEN+: 370
C286
IEN+: 398
[Tabla 168]
Ej
Datos
C287
IEN+: 342
C288
IEN+: 356
C289
IEN+: 356
C290
IEN+: 370
C291
IEN+: 384
C292
IEN+: 369
C293
IEN+: 383
C294
IEN+: 383
imagen443
imagen444
C393
IEN+: 366
C394
IEN+: 368
C395
IEN+: 348
C396
IEN+: 359
C397
IEN+: 274
C398
IEN+: 286
C399
IEN+: 290
C400
IEN+: 286
C401
IEN+: 299
C402
IEN+: 340
C403
IEN+: 354
C404
IEN+: 288
C405
IEN+: 292
C406
IEN+: 287
C407
IEN+: 300
C408
IEN+: 342
C409
IEN+: 326
C410
IEN+: 341
C411
IEN+: 359
C412
IEN+: 334
C413
IEN+: 424
C414
IEN+: 340
C415
IEN+: 362
C416
IEN+: 313
[Tabla 172]
Ej
Sín Estructura Ácido
417
417
1/2 FA
C418
418 1/2 SA
C419
418 1/2 FA
C420
418 imagen445 L-TA
imagen446

Claims (1)

  1. imagen1
    imagen2
    imagen3
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Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011143365A1 (en) 2010-05-13 2011-11-17 Amgen Inc. Nitrogen heterocyclic compounds useful as pde10 inhibitors
LT3002278T (lt) 2011-03-15 2017-06-26 Astellas Pharma Inc. Guanidino junginys
CN103626722B (zh) * 2012-08-27 2016-06-01 天津药物研究院 一氧化氮供体型降血糖化合物、其制备方法和用途
EP2906249B1 (en) * 2012-10-12 2018-06-27 MedImmune Limited Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation
US20160113893A1 (en) 2013-06-12 2016-04-28 Proximagen Limited New therapeutic uses of enzyme inhibitors
WO2015189534A1 (en) 2014-06-12 2015-12-17 Proximagen Limited Vap-1 inhibitors for treating muscular dystrophy
AU2016301745B2 (en) 2015-08-06 2020-07-16 Ube Industries, Ltd. Substituted guanidine derivative
WO2017098236A1 (en) 2015-12-07 2017-06-15 Proximagen Limited Vap-1 inhibitors for treating pain
EP3455216B1 (en) * 2016-05-12 2020-11-04 Boehringer Ingelheim International GmbH Pyridinyl derivatives, pharmaceutical compositions and uses thereof as aoc3 inhibitors
CN106008362B (zh) * 2016-05-24 2018-08-10 杰达维（上海）医药科技发展有限公司 一种嘧啶衍生物的制备方法
LT3564230T (lt) 2016-12-28 2022-04-11 Ube Industries, Ltd. Pakeistas guanidino junginys
WO2018148856A1 (en) * 2017-02-14 2018-08-23 Eli Lilly And Company Diazaspirodecanyl-pyrimidine compounds useful as ssao inhibitors
CN107082828B (zh) * 2017-05-19 2019-09-17 暨南大学 一种活性氧响应性高分子载体及其制备方法
US12213970B2 (en) 2018-10-29 2025-02-04 Boehringer Ingelheim International Gmbh Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1181871B (it) 1985-04-01 1987-09-30 Consiglio Nazionale Ricerche Inibitori selettivi delle benzilamminossidasi rispetto ad altre amminossidasi
WO1993023023A1 (en) 1992-05-15 1993-11-25 University Of Saskatchewan Method for preventing endothelium damage in mammals and for alleviating pain associated with gout and arthritis
PH11998001072B1 (en) 1997-05-07 2006-11-21 Univ Pittsburgh Inhibitors of protein isoprenyl transferases
AU2076299A (en) 1998-01-30 1999-08-16 Meiji Seika Kaisha Ltd. Phenylpiperazine derivatives as integrin alphavbeta3 antagonists
JP2000178243A (ja) * 1998-12-14 2000-06-27 Teijin Ltd ビフェニルアミジン誘導体
JP2002080439A (ja) * 2000-06-28 2002-03-19 Takeda Chem Ind Ltd ビフェニル化合物
AU2001266346A1 (en) 2000-06-28 2002-01-08 Takeda Chemical Industries Ltd. Biphenyl compound
JP2004502682A (ja) 2000-07-05 2004-01-29 バイオティ　セラピーズ　コーポレイション 銅含有アミン・オキシダーゼの阻害剤
ES2168084B1 (es) 2000-11-07 2003-11-16 Univ Barcelona Combinacion de aminas y compuestos de vanadio (iv) (v) para el tratatamiento y/o la prevencion de la diabetes mellitus.
AU2002214505A1 (en) 2000-11-09 2002-05-21 Biovitrum Ab New use of 4, 5, 6, 7-tetrahydroimidazo-(4,5-c)pyridine derivatives
US7507753B2 (en) 2001-12-28 2009-03-24 Takeda Chemical Industries Ltd. Biaryl compound and use thereof
AR042941A1 (es) 2003-01-27 2005-07-06 Fujisawa Pharmaceutical Co Derivados de tiazol, su preparacion, composiciones farmaceuticas que los contienen y su uso en la fabricacion de medicamentos inhibidores de la proteina-1 de adhesion vascular (vap-1)
EP1656370B1 (en) 2003-06-03 2012-08-15 Rib-X Pharmaceuticals, Inc. Biaryl heterocyclic compounds and methods of making and using the same
JP2007500707A (ja) * 2003-07-29 2007-01-18 リブ−エックス ファーマシューティカルズ，インコーポレイテッド ビアリールヘテロ環状のアミン、アミドおよび硫黄−含有化合物、並びに該化合物の製造方法および使用方法
SI1708711T1 (sl) 2004-01-30 2010-07-30 Biotie Therapies Oyj Spojine uporabne posebno za zdravljenje ali prepreäśevanje metaboliäśnega sindroma
CN1921841A (zh) 2004-02-25 2007-02-28 拉卓拉药物公司 用于治疗疾病的胺和酰胺类化合物
AU2005216955A1 (en) 2004-02-25 2005-09-09 La Jolla Pharmaceutical Company Amines and amides for the treatment of diseases
JP2007217282A (ja) * 2004-03-04 2007-08-30 Astellas Pharma Inc 置換ピリミジン誘導体
WO2005087236A1 (en) 2004-03-11 2005-09-22 Glaxo Group Limited Novel m3 muscarinic acetylcholine receptor antagonists
JP2008508348A (ja) 2004-08-02 2008-03-21 ジェンメディカ・セラピューティックス・ソシエダッド・リミターダ 銅含有アミンオキシダーゼを阻害するための化合物およびその使用
MX2007015675A (es) * 2005-07-04 2008-02-20 Novo Nordisk As Antagonistas del receptor de histamina h3.
US20070066646A1 (en) * 2005-08-02 2007-03-22 Genmedica Therapeutics Sl Compounds for Inhibiting Copper-Containing Amine Oxidases and Uses Thereof
JPWO2007018319A1 (ja) * 2005-08-11 2009-02-19 武田薬品工業株式会社 ピリジルフェノール化合物およびその用途
TW200813015A (en) 2006-03-15 2008-03-16 Mitsubishi Pharma Corp 2-(cyclic amino)-pyrimidone derivatives
EP2137158A4 (en) 2007-02-28 2012-04-18 Methylgene Inc LOW-MOLECULAR INHIBITORS OF PROTEINARGININE METHYLTRANSFERASES (PRMTS)
WO2009055002A1 (en) * 2007-10-24 2009-04-30 La Jolla Pharmaceutical Company Combined inhibitors of cyclooxygenase and semicarbazide-sensitive amine oxidase (ssao) (vascular adhesion protein, vap-1)

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