ES2654847T3 - Compuestos de benzoxazol y benzotiazol sustituidos en 6-O y métodos para inhibir la señalización CSF-1R - Google Patents

Compuestos de benzoxazol y benzotiazol sustituidos en 6-O y métodos para inhibir la señalización CSF-1R Download PDF

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ES2654847T3
ES2654847T3 ES07797244.6T ES07797244T ES2654847T3 ES 2654847 T3 ES2654847 T3 ES 2654847T3 ES 07797244 T ES07797244 T ES 07797244T ES 2654847 T3 ES2654847 T3 ES 2654847T3
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benzo
yloxy
thiazol
cyclohexanol
lamino
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James C. Sutton
Marion Wiesmann
Weibo Wang
Mika K. Lindvall
Jiong Lan
Savithri Ramurthy
Anu Sharma
Elizabeth J. Mieuli
Liana M. Klivansky
William P. Lenahan
Susan Kaufman
Hong Yang
Simon C. Ng
Keith Pfister
Allan Wagman
Victoria Sung
Martin Sendzik
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    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

Un compuesto seleccionado de entre el grupo que consiste en**Tabla** o un estereoisómero, tautómero, solvato, u óxido, o sal derivada del mismo farmacéuticamente aceptable.

Description

imagen1
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Esquema 4 de referencia
imagen17
En el esquema 4 de referencia, 3-(2-piperidin-1-il-etil)-fenilamina es un ejemplo de una amina que puede ser usada para formar un compuesto de los Ejemplos o Ejemplos de referencia. 3-(2-piperidin-1-il-etil)-fenilamina es formada por la sulfonación de 2-(3-nitrofenil)-etanol, luego introducción de amina en el 2-(3-nitrofenil)etil éster de ácido metanosulfónico resultante, y a continuación reducción de la 1-[2-(3-nitrofenil)-etil]-piperidina resultante.
Esquema 5 de referencia
imagen18
En el esquema 5 de referencia, con ciclohexilmetanamina se introduce amina en 4-(2-(metilsulfinil)benzo[d]oxazol
10 6-iloxi)-N-metilpiridin-2-carboxamida. La 4-(2-(ciclohexilmetilamino)benzo[d]oxazol-6-iloxi)-N-metilpiridin-2carboxamida resultante es entonces hidrolizada para formar ácido 4-[2-(ciclohexilmetil-amino)-benzooxazol-6-iloxi]piridin-2-carboxílico. El ácido 4-[2-(ciclohexilmetil-amino)-benzooxazol-6-iloxi]-piridin-2-carboxílico reacciona entonces con hexafluorofosfato de benzotriazol-1-iloxitris(dimetilamino)-fosfonio, tert-butil carbazato, y trietil amina para formar 4-(2-(ciclohexilmetilamino) benzo[d]oxazol-6-iloxi)piridin-2-carbohidrazida. La 4-(2
15 (ciclohexilmetilamino)benzo[d]oxazol-6-iloxi)piridin-2-carbohidrazida reacciona entonces con trimetil ortoformiato para formar un compuesto de los Ejemplos o Ejemplos de referencia.
Esquema 6 de referencia
imagen19
18
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Tabla 3
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
7
201 imagen41 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]oxazol6-iloxi)-N-metilpicolinamida 383, 1.96
10
171 imagen42 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N,Ndimetilpicolinamida 413.1, 1.87
11
171 N-ciclopropil-4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)picolinamida 425.2, 2.13
12
171 imagen43 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N-(tetrahidro-2H-piran-4il)picolinamida 469.2, 2.09
13
171 imagen44 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N-(1-metilpiperidin-4il)picolinamida 482.2, 1.85
14
171 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N-(1-metilpiperidin-3il)picolinamida 482.2, 1.87
15
171 imagen45 N-(2-acetamidoetil)-4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)picolinamida 470.2, 1.86
16
171 imagen46 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-(2-(pirrolidin-1il)etil)picolinamida 482.2, 1.84
17
171 imagen47 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-((tetrahidrofuran-2il)metil)picolinamida 469.2, 2.16
18
171 imagen48 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-((tetrahidro-2H-piran-4il)metil)picolinamida 483.2, 2.12
40
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
19
171 imagen49 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-((1-metilpiperidin-4il)metil)picolinamida 496.2, 1.84
20
171 imagen50 N-(((S)-1-etilpirrolidin-2-il)metil)-4-(2((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)picolinamida 496.2, 1.88
47
171 imagen51 N-etil-4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)picolinamida 413.2, 2.09
48
171 imagen52 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-(2,2,2trifluoroetil)picolinamida 467.1, 2.37
49
171 imagen53 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-propilpicolinamida 427.1, 2.25
50
171 imagen54 N-(ciclopropilmetil)-4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)picolinamida 439.2, 2.32
51
171 imagen55 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-isopropilpicolinamida 427.2, 2.24
125
162 imagen56 4-(2-((1r,4r)-4hidroxiciclohexilamino)benzo[d]tiazol6-iloxi)-N-metilpicolinamida 399.1, 1.83
155
175 imagen57 (1R,2R)-2-(6-(2-(1-metil-1H-imidazol2-il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.83
41
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
156
175 imagen58 (1R,2R)-2-(6-(2-(pirazin-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 420.1, 1.91
157
175 imagen59 (1R,2R)-2-(6-(2-(tiazol-5-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 425.0, 2.05
158
175 imagen60 (1R,2R)-2-(6-(2-(1-metil-1H-imidazol5-il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.84
159
175 imagen61 (1R,2R)-2-(6-(2-(tiazol-4-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 425.0, 1.85
160
175 imagen62 (1R,2R)-2-(6-(2-(tiazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 425.0, 2.28
161
188 imagen63 (1R,2R)-2-(6-(2-(1,2,3,6tetrahidropiridin-4-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 423.1, 1.38
162
177 (1R,2R)-2-(6-(2-(5-etil-4-metil-1Himidazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 450.1, 1.82
164
174 (1R,2R)-2-(6-(6’-(4-metilpiperazin-1-il)2,3’-bipiridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 517.2, 1.75
42
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
165
174 (1R,2R)-2-(6-(6’-morfolino-2,3’-bipiridin4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 504.1, 1.93
166
174 (1R,2R)-2-(6-(2-(3(morfolinometil)fenil)piridina-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 517.1, 1.78
167
174 (1R,2R)-2-(6-(2-ciclohexenilpiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 2.07
168
174 (1R,2R)-2-(6-(2-(4(morfolinometil)fenil)p yridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 517.2, 1.76
169
174 (1R,2R)-2-(6-(2-ciclopropilpiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 382.1, 1.84
170
174 (1R,2R)-2-(6-(6’-metoxi-2,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 449.1, 1.98
171
174 (1R,2R)-2-(6-(2’-fluoro-2,4’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 437.1, 2.22
172
174 (1R,2R)-2-(6-(3’-fluoro-2’-morfolino-2,4’bipiridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 522.2, 2.17
173
174 (1R,2R)-2-(6-(6’-fluoro-2,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 437.1, 2.04
43
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
174
183 (1R,2R)-2-(6-(2-(piperidin-1-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 425.1, 1.98
175
183 (1R,2R)-2-(6-(2-morfolinopiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 427.1, 1.80
176
183 (1R,2R)-2-(6-(2-(4-metilpiperazin-1il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 440.1, 1.66
177
183 N-((R)-1-(4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)piridin-2-il)pirrolidin-3-il)acetamida 468.1, 1.78
178
183 N-((S)-1-(4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)piridin-2-il)pirrolidin-3-il)acetamida 468.1, 1.77
179
183 4-(4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)piridin-2-il)piperazin-2-one 440.1, 1.70
180
175 (1R,2R)-2-(6-(2,2’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 419.0, 1.87
181
175 (1R,2R)-2-(6-(2-(1-metil-3(trifluorometil)-1H-pirazol-5-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 490.1, 2.60
44
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
182
174 (1R,2R)-2-(6-(2-(1-(2-morfolinoetil)-1Hpirazol-4-il)piridin-4-iloxi)benzo[d]tiazol2-ilamino)ciclohexanol 521.1, 1.71
184
192 (1R,2R)-2-(6-(6,7-dimetoxiquinolin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 452.1, 2.00
185
176 (1R,2R)-2-(6-(2-(1-etil-1H-pirazol-4il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 436.0, 1.89
186
176 (1R,2R)-2-(6-(2-(1-(2-(dietilamino)etil)1H-pirazol-4-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 507.1, 1.75
187
176 (1R,2R)-2-(6-(2-(1-(2,2-difluoroetil)-1Hpirazol-4-il)piridin-4-iloxi)benzo[d]tiazol2-ilamino)ciclohexanol 472.0, 1.90
188
179 (1R,2R)-2-(6-(3-(1H-pirazol-4-il)piridin4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 408.1, 1.70
189
179 (1R,2R)-2-(6-(3-(1-metil-1H-pirazol-4il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.79
45
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
190
179 (1R,2R)-2-(6-(3,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 419.1, 1.66
191
179 (1R,2R)-2-(6-(3-(1-metil-1H-pirazol-5il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.83
192
179 (1R,2R)-2-(6-(3,4’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 419.1, 1.61
193
179 (1R,2R)-2-(6-(6’-amino-3,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 434.1, 1.60
194
179 (1R,2R)-2-(6-(6’-(4-metilpiperazin-1-il)3,3’-bipiridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 517.2, 1.64
195
179 (1R,2R)-2-(6-(3-ciclopropilpiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 382.1, 1.97
196
174 (1R,2R)-2-(6-(2-(2-morfolinopirimidin-5il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 505.1, 2.03
46
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
197
174 (1R,2R)-2-(6-(2-(4-(4-metilpiperazin-1il)fenil)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 516.2, 1.85
200
177 (1R,2R)-2-(6-(2-(4-(trifluorometil)-1Himidazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 476.1, 2.35
203
192 (1R,2R)-2-(6-(2-metilpiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 356.1, 1.73
209
192 (1R,2R)-2-(6-(3-fluoropiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 360.1, 1.83
224
178 (1R,2R)-2-(6-(3-bromopiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 420.1/42 2.0, 1.81
225
173 (1R,2R)-2-(6-(2-chloropiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 376.1, 2.13
226
173 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)picolinonitrile 367.1, 2.03
231
177 (1R,2R)-2-(6-(2-(4-metil-1H-imidazol-2il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.88
47
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
232
177 (1R,2R)-2-(6-(2-(4,5-dimetil-1Himidazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 436.1, 1.93
258
177 (1R,2R)-2-(6-(2-(4,5,6,7-tetrahidro-1Hbenzo[d]imidazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 462.2, 2.03
259
176 (1R,2R)-2-(6-(2-(1-(2-fluoroetil)-1Hpirazol-4-il)piridin-4-iloxi)benzo[d]tiazol2-ilamino)ciclohexanol 454.2, 1.89
260
176 (1R,2R)-2-(6-(2-(1-(2-metoxietil)-1Hpirazol-4-il)piridin-4-iloxi)benzo[d]tiazol2-ilamino)ciclohexanol 466.2, 1.89
261
174 (1R,2R)-2-(6-(6’-amino-2,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 434.2, 1.78
262
187 (1R,2R)-2-(6-(2-(1H-imidazol-1-il)piridin4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 408.2, 1.85
265
174 (1R,2R)-2-(6-(2-(1-metil-1H-pirazol-5il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.1, 1.93
266
177 (1R,2R)-2-(6-(2-(4,5-dietil-1H-imidazol2-il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 464.2, 2.10
48
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
267
177 (1R,2R)-2-(6-(2-(5-metil-4-propil-1Himidazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 464.2, 2.10
280
174 (1R,2R)-2-(6-(2,4’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 419.0, 1.68
281
174 (1R,2R)-2-(6-(2-(1-propil-1H-pirazol-4il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 450.0, 2.02
282
174 (1R,2R)-2-(6-(6’-amino-5’(trifluorometil)-2,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 502.0, 2.02
283
174 (1R,2R)-2-(6-(2-(1,3,5-trimetil-1Hpirazol-4-il)piridin-4-iloxi)benzo[d]tiazol2-ilamino)ciclohexanol 450.0, 1.86
284
174 (1R,2R)-2-(6-(2-(1H-pirrolo[2,3-b]piridin5-il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 458.0, 1.91
285
174 (1R,2R)-2-(6-(2-(pirimidin-5-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 420.1, 1.90
286
174 (1R,2R)-2-(6-(2-(2(dimetilamino)pirimidin-5-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 463.1, 1.96
49
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
287
174 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-2,3’-bipiridine-6’-carbonitrile 444.0, 2.18
288
174 (1R,2R)-2-(6-(2-(4-fluorofenil)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 436.0, 2.06
291
195 4-(2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N-metilnicotinamida 399.1, 1.72
293
162 4-(2-(3hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-N-metilpicolinamida 399.1, 1.76
320
162 4-(2-((1S,2S)-2hidroxiciclopentilamino)benzo[d]tiazol6-iloxi)-N-metilpicolinamida 385.1, 1.74
322
162 4-(2-((1S,2R)-2hidroxiciclopentilamino)benzo[d]tiazol6-iloxi)-N-metilpicolinamida 385.1, 1.75
324
162 4-(2-((1R,2R)-2hidroxiciclopentilamino)benzo[d]tiazol6-iloxi)-N-metilpicolinamida 385.1, 1.75
344
174 (1R,2R)-2-(6-(2-(1-metil-1H-pirazol-4il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 422.2, 1.68
345
174 (1R,2R)-2-(6-(2,3’-bipiridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 419.1, 1.69
50
(cont.)
Comp.
Prep Ej. Estructura Nombre (M+H)+, Tr (min.)
346
174 (1R,2R)-2-(6-(2-(2-aminopirimidin-5il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 435.2, 1.61
359
174 (1R,2R)-2-(6-(2-(1-isobutil-1H-pirazol-4il)piridin-4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 464.4, 1.95
360
174 (1R,2R)-2-(6-(2-(1H-pirazol-4-il)piridin4-iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 408.1, 1.63
368
170 (1R,2R)-2-(6-(2-(metilamino)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 371.1, 1.79
369
170 (1R,2R)-2-(6-(2-(etilamino)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 385.1, 1.74
371
175 (1R,2R)-2-(6-(2-(furan-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 408.1, 1.94
372
175 (1R,2R)-2-(6-(2-(oxazol-2-il)piridin-4iloxi)benzo[d]tiazol-2ilamino)ciclohexanol 409.1, 1.98
376
195 4-(7-bromo-2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-Nmetilpicolinamida 479, 2.37
377
196 4-(2-((1R,2R)-2-hidroxiciclohexilamino)7-metilbenzo[d]tiazol-6-iloxi)-Nmetilpicolinamida 413, 2.09
378
197 4-(7-chloro-2-((1R,2R)-2hidroxiciclohexilamino)benzo[d]tiazol-6iloxi)-Nmetilpicolinamida 433, 2.33
51
imagen64
imagen65
imagen66
imagen67
muestras desconocidas a partir de la curva estándar y expresarse en U/L de Trap5b. La sensibilidad analítica del ensayo es 0.1 U/L y la variación dentro del ensayo y entre los ensayos está por debajo de 10%. Se encontró que los niveles de Trap5b tenían buena correlación con el promedio de puntaje osteolítico (evaluado por rayos x).
Mientras se han descrito en detalle varias realizaciones preferidas de la invención y variaciones de las mismas,
5 otras modificaciones y métodos de uso serán fácilmente evidentes para aquellos expertos en la técnica. De acuerdo con ello, debería entenderse que pueden hacerse diferentes aplicaciones, modificaciones y sustituciones de equivalentes, sin apartarse del espíritu de la invención o del alcance las reivindicaciones.
Las actividades de inhibición porcentuales de los compuestos de las tablas 2 y 3, cuando se prueban a aproximadamente 1µM en el ensayo indicado, como se describe en los Ejemplos biológicos, son mostrados
10 respectivamente en las tablas 5, 6, y 7. Se contempla que los compuestos que tienen una inhibición de 0 % a 1µM exhibirán actividades inhibitorias a una concentración mayor. Un "N/D" indica que el compuesto no fue probado en el ensayo particular.
Tabla 5. Actividades de los compuestos de la tabla 2
Comp.
PDGFRβ CSF-1R cKit M-NFS-60 CP pCSF1R
52
50 100 12 56 71
137
98 100 45 100 98
157
20 100 20 100 99
15 Tabla 6. Actividades de los compuestos de la tabla 3
Comp.
PDGFRβ CSF-1R cKit M-NFS-60 CP pCSF1R
7
9 100 12 35 N/D
10
9 67 0 N/D N/D
11
60 100 0 69 92
12
1 95 0 N/D N/D
13
0 93 9 N/D N/D
14
0 96 3 N/D N/D
15
7 99 15 4 N/D
16
9 99 12 30 N/D
17
12 99 19 23 N/D
18
23 99 80 22 N/D
19
0 96 8 23 N/D
20
0 76 0 N/D N/D
47
4 100 0 55 83
48
16 99 14 26
49
12 100 21 33 77
50
14 99 13 18 N/D
51
0 95 10 N/D N/D
125
9 99 2 17 N/D
155
18 99 34 0 N/D
156
3 100 36 33 N/D
157
17 100 43 42 N/D
56
Cont.
Comp.
PDGFRβ CSF-1R cKit M-NFS-60 CP pCSF1R
158
1 99 27 0 N/D
159
23 100 29 98 96
160
19 100 95 30 N/D
161
26 54 20 N/D N/D
162
30 100 20 100 99
164
87 100 79 100 100
165
83 100 83 100 98
166
0 100 13 49 78
167
0 100 16 24 N/D
168
43 100 40 100 99
169
0 75 12 N/D N/D
170
23 100 28 100 96
171
18 100 25 96 95
172
18 100 22 100 97
173
8 100 18 52 81
174
3 86 18 N/D N/D
175
1 100 11 17 N/D
176
0 63 12 N/D N/D
177
0 67 15 N/D N/D
178
-3 82 17 N/D N/D
179
16 98 10 27 N/D
180
12 100 23 96 93
181
17 72 27 N/D N/D
182
4 100 16 100 98
184
84 100 45 100 95
185
29 100 32 100 94
186
14 100 13 100 99
187
25 100 32 100 98
188
35 100 55 38 N/D
189
23 100 31 26 N/D
190
19 98 22 5 N/D
191
15 45 19 N/D N/D
192
22 99 56 14 N/D
193
15 95 27 0 N/D
194
16 77 20 N/D N/D
195
25 81 90 N/D N/D
196
23 100 29 100 98
57
Cont.
Comp.
PDGFRβ CSF-1R cKit M-NFS-60 CP pCSF1R
197
89 100 93 100 98
200
19 100 29 69 83
203
15 98 22 20 N/D
209
1 100 17 36 N/D
224
0 100 26 33 N/D
225
0 90 21 N/D N/D
226
0 80 20 N/D N/D
231
49 100 9 100 99
232
64 100 34 100 99
258
62 100 44 100 99
259
6 100 24 100 98
260
0 100 25 100 98
261
30 100 25 100 98
262
3 100 20 46 48
265
12 100 9 32 N/D
266
21 100 18 100 94
267
26 100 16 100 96
280
22 100 11 100 65
281
36 100 22 100 96
282
7 99 23 22 N/D
283
20 99 38 0 N/D
284
53 100 61 100 N/D
285
8 99 33 0 N/D
286
0 100 23 71 94
287
20 100 57 35 N/D
288
24 100 78 70 N/D
291
0 48 4 N/D N/D
293
0 100 22 67 82
320
20 100 16 25 N/D
322
11 99 18 21 N/D
324
19 99 21 15 N/D
344
65 100 45 100 95
345
13 100 19 97 93
346
0 100 13 67 84
359
19 100 31 95 93
360
16 100 29 100 98
368
8 100 24 12 N/D
58
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