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

Info

Publication number
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
Authority
ES
Spain
Prior art keywords
benzo
yloxy
thiazol
cyclohexanol
lamino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
ES07797244.6T
Other languages
English (en)
Inventor
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
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis AG
Original Assignee
Novartis AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novartis AG filed Critical Novartis AG
Application granted granted Critical
Publication of ES2654847T3 publication Critical patent/ES2654847T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—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
    • C07D417/02—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
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Vascular Medicine (AREA)
  • Immunology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicinal Preparation (AREA)

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
imagen2
imagen3
imagen4
imagen5
imagen6
imagen7
imagen8
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
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
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
imagen36
imagen37
imagen38
imagen39
imagen40
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
imagen68
imagen69
imagen70

Claims (1)

  1. imagen1
    imagen2
    imagen3
    imagen4
    imagen5
    imagen6
    imagen7
    imagen8
    imagen9
    imagen10
    imagen11
    imagen12
    imagen13
    imagen14
ES07797244.6T 2006-04-19 2007-04-18 Compuestos de benzoxazol y benzotiazol sustituidos en 6-O y métodos para inhibir la señalización CSF-1R Active ES2654847T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US79351706P 2006-04-19 2006-04-19
US793517P 2006-04-19
US89385707P 2007-03-08 2007-03-08
US893857P 2007-03-08
PCT/US2007/066898 WO2007121484A2 (en) 2006-04-19 2007-04-18 6-o-substituted benzoxazole and benzothiazole compounds and methods of inhibiting csf-1r signaling

Publications (1)

Publication Number Publication Date
ES2654847T3 true ES2654847T3 (es) 2018-02-15

Family

ID=38610468

Family Applications (1)

Application Number Title Priority Date Filing Date
ES07797244.6T Active ES2654847T3 (es) 2006-04-19 2007-04-18 Compuestos de benzoxazol y benzotiazol sustituidos en 6-O y métodos para inhibir la señalización CSF-1R

Country Status (30)

Country Link
US (3) US7553854B2 (es)
EP (1) EP2010528B1 (es)
JP (1) JP5328640B2 (es)
KR (1) KR101464385B1 (es)
AR (1) AR060545A1 (es)
AU (1) AU2007237904B2 (es)
BR (1) BRPI0710540B1 (es)
CA (1) CA2649288C (es)
CR (1) CR10365A (es)
CY (1) CY1119679T1 (es)
DK (1) DK2010528T3 (es)
EA (1) EA018917B1 (es)
EC (1) ECSP088830A (es)
ES (1) ES2654847T3 (es)
HR (1) HRP20171924T1 (es)
HU (1) HUE035654T2 (es)
IL (1) IL194662A0 (es)
LT (1) LT2010528T (es)
MA (1) MA30407B1 (es)
MX (1) MX2008013427A (es)
NO (1) NO20084800L (es)
PE (1) PE20080359A1 (es)
PL (1) PL2010528T3 (es)
PT (1) PT2010528T (es)
RS (1) RS56600B1 (es)
SI (1) SI2010528T1 (es)
SM (1) SMP200800063B (es)
TN (1) TNSN08406A1 (es)
TW (1) TW200813039A (es)
WO (1) WO2007121484A2 (es)

Families Citing this family (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003082272A1 (en) * 2002-03-29 2003-10-09 Chiron Corporation Substituted benzazoles and use thereof as raf kinase inhibitors
CA2649288C (en) * 2006-04-19 2015-11-24 Novartis Ag 6-o-substituted benzoxazole and benzothiazole compounds and methods of inhibiting csf-1r signaling
DK2120958T3 (da) * 2006-12-06 2013-07-01 Univ Central Florida Res Found Stat3-inhibitor med anticancer-aktivitet og associerede fremgangsmåder
AU2008254425A1 (en) 2007-05-21 2008-11-27 Novartis Ag CSF-1R inhibitors, compositions, and methods of use
CL2008001626A1 (es) 2007-06-05 2009-06-05 Takeda Pharmaceuticals Co Compuestos derivados de heterociclos fusionados, agente farmaceutico que los comprende y su uso en la profilaxis y tratamiento del cancer.
EP2181987B9 (en) 2007-08-23 2014-09-03 Takeda Pharmaceutical Company Limited 2-Carbonylaminobenzothiazoles and their use for the prophylaxis and treatment of cancer
BRPI0818003A2 (pt) * 2007-10-18 2019-09-24 Novartis Ag inibidores de csf-1r, composições e métodos de uso
WO2009107391A1 (ja) * 2008-02-27 2009-09-03 武田薬品工業株式会社 ６員芳香環含有化合物
US8697874B2 (en) 2008-12-01 2014-04-15 Takeda Pharmaceutical Company Limited Heterocyclic compound and use thereof
JO3101B1 (ar) 2008-12-02 2017-09-20 Takeda Pharmaceuticals Co مشتقات بنزوثيازول كعوامل مضادة للسرطان
WO2011133661A2 (en) * 2010-04-21 2011-10-27 Research Development Foundation Methods and compositions related to dopaminergic neuronal cells
AR081331A1 (es) 2010-04-23 2012-08-08 Cytokinetics Inc Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos
AR081626A1 (es) 2010-04-23 2012-10-10 Cytokinetics Inc Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos
US9133123B2 (en) 2010-04-23 2015-09-15 Cytokinetics, Inc. Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use
EP2661434A4 (en) * 2011-01-06 2014-07-09 Beta Pharma Canada Inc NEW UREAS FOR THE TREATMENT AND PREVENTION OF CANCER
US8759380B2 (en) 2011-04-22 2014-06-24 Cytokinetics, Inc. Certain heterocycles, compositions thereof, and methods for their use
WO2012151541A1 (en) * 2011-05-05 2012-11-08 Novartis Ag Csf-1r inhibitors for treatment of brain tumors
KR101938431B1 (ko) 2011-05-05 2019-01-14 노파르티스 아게 뇌 종양의 치료를 위한 csf-1r 억제제
MA41044A (fr) 2014-10-08 2017-08-15 Novartis Ag Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer
EP4245376A3 (en) 2014-10-14 2023-12-13 Novartis AG Antibody molecules to pd-l1 and uses thereof
HK1243931A1 (zh) * 2014-12-03 2018-07-27 F. Hoffmann-La Roche Ag 抗金黄色葡萄球菌抗体利福霉素缀合物及其用途
MX2017008218A (es) 2014-12-22 2017-10-18 Five Prime Therapeutics Inc Anticuerpos anti-csf1r para tratar pvns.
WO2016161952A1 (zh) * 2015-04-07 2016-10-13 广东众生药业股份有限公司 酪氨酸激酶抑制剂及包含该酪氨酸激酶抑制剂的药物组合物
US10722517B2 (en) 2015-05-08 2020-07-28 Memorial Sloan Kettering Cancer Center Compositions and methods for treatment of glioma
EP3878465A1 (en) 2015-07-29 2021-09-15 Novartis AG Combination therapies comprising antibody molecules to tim-3
HRP20211058T8 (hr) 2015-07-29 2021-11-26 Novartis Ag Kombinirane terapije koje sadrže molekule antitijela protiv lag-3
EP3328418A1 (en) 2015-07-29 2018-06-06 Novartis AG Combination therapies comprising antibody molecules to pd-1
ES2986067T3 (es) 2015-12-17 2024-11-08 Novartis Ag Moléculas de anticuerpos frente a PD-1 y usos de las mismas
CA3014269A1 (en) 2016-02-11 2017-08-17 Invictus Oncology Pvt. Ltd. Cellular signalling inhibitors, their formulations and methods thereof
KR102483020B1 (ko) 2016-03-28 2023-01-04 인사이트 코포레이션 Tam 저해제로서의 피롤로트리아진 화합물
US10689362B2 (en) * 2016-10-10 2020-06-23 Development Center For Biotechnology Quinoxaline compounds as type III receptor tyrosine kinase inhibitors
US10934273B2 (en) * 2016-10-14 2021-03-02 Novartis Ag Crystalline forms of 4-(2-((1R,2R)-2-hydroxycyclohexylamino)benzothiazol-6-yloxy)-N-methylpicolinamide
RU2019114205A (ru) 2016-10-14 2020-11-16 Новартис Аг Способы лечения глазного заболевания с применением ингибиторов csf-1r
CN110139852A (zh) 2016-11-04 2019-08-16 奥克兰联合服务有限公司 三环杂环衍生物及其用途
WO2018119387A1 (en) * 2016-12-23 2018-06-28 Tesaro, Inc. Small molecule inhibitors of colony stimulating factor-1 receptor (csf-1r) and uses thereof
WO2018146641A1 (en) * 2017-02-11 2018-08-16 Invictus Oncology Pvt. Ltd. Novel inhibitors of cellular signalling
MX394840B (es) 2017-03-28 2025-03-24 Novartis Ag Nuevos metodos para el tratamiento de la esclerosis multiple.
UY37695A (es) 2017-04-28 2018-11-30 Novartis Ag Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo
MY204117A (en) 2017-06-22 2024-08-08 Novartis Ag Antibody molecules to cd73 and uses thereof
EP3642240A1 (en) 2017-06-22 2020-04-29 Novartis AG Antibody molecules to cd73 and uses thereof
MA50655B1 (fr) 2017-09-27 2021-11-30 Incyte Corp Sels de dérivés de pyrrolotriazine utiles en tant qu'inhibiteurs de tam
CN111655288A (zh) 2017-11-16 2020-09-11 诺华股份有限公司 组合疗法
CN112040947A (zh) 2017-12-07 2020-12-04 密歇根大学董事会 Nsd家族抑制剂及用其进行治疗的方法
TWI869346B (zh) 2018-05-30 2025-01-11 瑞士商諾華公司 Ｅｎｔｐｄ２抗體、組合療法、及使用該等抗體和組合療法之方法
WO2019232244A2 (en) 2018-05-31 2019-12-05 Novartis Ag Antibody molecules to cd73 and uses thereof
AR117600A1 (es) 2018-06-29 2021-08-18 Incyte Corp Formulaciones de un inhibidor de axl / mer
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
EP3876939A4 (en) 2018-11-07 2022-08-10 Dana-Farber Cancer Institute, Inc. Benzothiazole derivatives and 7-aza-benzothiazole derivatives as janus kinase 2 inhibitors and uses thereof
US12522583B2 (en) 2018-11-07 2026-01-13 Dana-Farber Cancer Institute, Inc. Benzimidazole derivatives and aza-benzimidazole derivatives as Janus kinase 2 inhibitors and uses thereof
EP3877371A4 (en) 2018-11-07 2022-07-27 Dana-Farber Cancer Institute, Inc. IMIDAZOPYRIDINE DERIVATIVES AND AZA-IMIDAZOPYRIDINE DERIVATIVES AS JANUS KINASE 2 INHIBITORS AND USES THEREOF
KR20210106437A (ko) 2018-12-20 2021-08-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물
WO2020128637A1 (en) 2018-12-21 2020-06-25 Novartis Ag Use of il-1 binding antibodies in the treatment of a msi-h cancer
JP2022514087A (ja) 2018-12-21 2022-02-09 ノバルティス アーゲー ＩＬ－１β結合抗体の使用
US20220025036A1 (en) 2018-12-21 2022-01-27 Novartis Ag Use of il-1beta binding antibodies
US20220040324A1 (en) 2018-12-21 2022-02-10 Daiichi Sankyo Company, Limited Combination of antibody-drug conjugate and kinase inhibitor
BR112021012812A2 (pt) 2018-12-28 2021-12-07 Deciphera Pharmaceuticals Llc Csf1r inhibitors para uso e tratamento de câncer
CN113490528B (zh) 2019-02-15 2024-12-03 诺华股份有限公司 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
CA3123519A1 (en) 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
US20220213064A1 (en) * 2019-04-12 2022-07-07 National Health Research Institutes Heterocyclic compounds as kinase inhibitors for therapeutic uses
CN114502590A (zh) 2019-09-18 2022-05-13 诺华股份有限公司 Entpd2抗体、组合疗法、以及使用这些抗体和组合疗法的方法
BR112022011902A2 (pt) 2019-12-20 2022-09-06 Novartis Ag Terapias de combinação
WO2021178779A1 (en) 2020-03-06 2021-09-10 Incyte Corporation Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors
IL296226A (en) 2020-04-21 2022-11-01 Novartis Ag Dosing regimen for treating a disease modulated by csf-1r
US11691963B2 (en) 2020-05-06 2023-07-04 Ajax Therapeutics, Inc. 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors
KR20230027056A (ko) 2020-06-23 2023-02-27 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법
JP7819176B2 (ja) 2020-08-03 2026-02-24 ノバルティス アーゲー ヘテロアリール置換３－（１－オキソイソインドリン－２－イル）ピペリジン－２，６－ジオン誘導体及びその使用
US12043632B2 (en) 2020-12-23 2024-07-23 Ajax Therapeutics, Inc. 6-heteroaryloxy benzimidazoles and azabenzimidazoles as JAK2 inhibitors
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
WO2023009712A1 (en) * 2021-07-29 2023-02-02 Ajax Therapeutics, Inc. Heteroaryloxy thiazolo azines as jak2 inhibitors
US12162881B2 (en) 2021-11-09 2024-12-10 Ajax Therapeutics, Inc. Forms and compositions of inhibitors of JAK2
WO2023086319A1 (en) 2021-11-09 2023-05-19 Ajax Therapeutics, Inc. 6-he tero aryloxy benzimidazoles and azabenzimidazoles as jak2 inhibitors
TW202440100A (zh) 2022-10-31 2024-10-16 瑞士商諾華公司 用於治療由csf-1r調節的疾病的給藥方案
TW202535870A (zh) * 2023-10-26 2025-09-16 日商大塚製藥股份有限公司 作為csf1r抑制劑之化合物
WO2025103436A2 (en) * 2023-11-17 2025-05-22 Fujian Haixi Pharmaceuticals Co., Ltd. Sarcoma treatments using csf-1r/pdgfr multi-target inhibitors
WO2025122952A1 (en) 2023-12-08 2025-06-12 Deciphera Pharmaceuticals, Llc Formulations of vimseltinib
WO2025194063A1 (en) * 2024-03-15 2025-09-18 Board Of Trustees Of Northern Illinois University Benzothiazole derivatives for treating diseases
WO2025219395A1 (en) 2024-04-16 2025-10-23 Chu D'angers Treatment of cancers

Family Cites Families (155)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4107288A (en) 1974-09-18 1978-08-15 Pharmaceutical Society Of Victoria Injectable compositions, nanoparticles useful therein, and process of manufacturing same
US4294926A (en) 1979-06-15 1981-10-13 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4319039A (en) 1979-06-15 1982-03-09 Merck & Co., Inc. Preparation of ammonium salt of hypocholesteremic fermentation product
US4231938A (en) 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
DK149080C (da) 1980-06-06 1986-07-28 Sankyo Co Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre
JPS5889191A (ja) 1981-11-20 1983-05-27 Sankyo Co Ltd ３−ヒドロキシ−ｍｌ−２３６ｂ誘導体の製造法
HU204253B (en) 1982-11-22 1991-12-30 Sandoz Ag Process for producing mevalonolactone analogues and derivatives and pharmaceutical compositions containing them
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
US4911165A (en) 1983-01-12 1990-03-27 Ethicon, Inc. Pliabilized polypropylene surgical filaments
US4873346A (en) 1985-09-20 1989-10-10 The Upjohn Company Substituted benzothiazoles, benzimidazoles, and benzoxazoles
US4681893A (en) 1986-05-30 1987-07-21 Warner-Lambert Company Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
EP0261459A3 (de) 1986-09-09 1988-05-11 Nihon Tokushu Noyaku Seizo K.K. Neue N-Benzothiazolylamide
US4782084A (en) 1987-06-29 1988-11-01 Merck & Co., Inc. HMG-COA reductase inhibitors
US4885314A (en) 1987-06-29 1989-12-05 Merck & Co., Inc. Novel HMG-CoA reductase inhibitors
US4820850A (en) 1987-07-10 1989-04-11 Merck & Co., Inc. Process for α-C-alkylation of the 8-acyl group on mevinolin and analogs thereof
US5030447A (en) 1988-03-31 1991-07-09 E. R. Squibb & Sons, Inc. Pharmaceutical compositions having good stability
US5180589A (en) 1988-03-31 1993-01-19 E. R. Squibb & Sons, Inc. Pravastatin pharmaceuatical compositions having good stability
US4916239A (en) 1988-07-19 1990-04-10 Merck & Co., Inc. Process for the lactonization of mevinic acids and analogs thereof
US5118853A (en) 1988-10-13 1992-06-02 Sandoz Ltd. Processes for the synthesis of 3-disubstituted aminoacroleins
US5290946A (en) 1988-10-13 1994-03-01 Sandoz Ltd. Processes for the synthesis of 3-(substituted indolyl-2-yl)propenaldehydes
US4929437A (en) 1989-02-02 1990-05-29 Merck & Co., Inc. Coenzyme Q10 with HMG-CoA reductase inhibitors
US5189164A (en) 1989-05-22 1993-02-23 Sandoz Ltd. Processes for the synthesis of syn-(E)-3,5-dihydroxy-7-substituted hept-6-enoic and heptanoic acids and derivatives and intermediates thereof
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
PH27357A (en) 1989-09-22 1993-06-21 Fujisawa Pharmaceutical Co Pyrazole derivatives and pharmaceutical compositions comprising the same
US5420245A (en) 1990-04-18 1995-05-30 Board Of Regents, The University Of Texas Tetrapeptide-based inhibitors of farnesyl transferase
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
HU9203780D0 (en) 1991-12-12 1993-03-29 Sandoz Ag Stabilized pharmaceutical products of hmg-coa reductase inhibitor and method for producing them
EP0679088B1 (en) 1992-09-29 2002-07-10 Inhale Therapeutic Systems Pulmonary delivery of active fragments of parathyroid hormone
US5604260A (en) 1992-12-11 1997-02-18 Merck Frosst Canada Inc. 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
CA2111902A1 (en) 1992-12-21 1994-06-22 Jack Beuford Campbell Antitumor compositions and methods of treatment
EP0679157B1 (en) 1993-01-15 1997-11-19 G.D. Searle & Co. Novel 3,4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents
WO1994019357A1 (en) 1993-02-23 1994-09-01 Merrell Dow Pharmaceuticals Inc. Farnesyl:protein transferase inhibitors as anticancer agents
US5298627A (en) 1993-03-03 1994-03-29 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
US5409944A (en) 1993-03-12 1995-04-25 Merck Frosst Canada, Inc. Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase
CA2118985A1 (en) 1993-04-02 1994-10-03 Dinesh V. Patel Heterocyclic inhibitors of farnesyl protein transferase
AU6909194A (en) 1993-05-14 1994-12-12 Board Of Regents, The University Of Texas System Preparation of n-cyanodithioimino-carbonates and 3-mercapto-5-amino-1h-1,2,4-triazole
US5602098A (en) 1993-05-18 1997-02-11 University Of Pittsburgh Inhibition of farnesyltransferase
US5380738A (en) 1993-05-21 1995-01-10 Monsanto Company 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents
GB9602877D0 (en) 1996-02-13 1996-04-10 Merck Frosst Canada Inc 3,4-Diaryl-2-hydroxy-2,5- dihydrofurans as prodrugs to cox-2 inhibitors
US5474995A (en) 1993-06-24 1995-12-12 Merck Frosst Canada, Inc. Phenyl heterocycles as cox-2 inhibitors
US5436265A (en) 1993-11-12 1995-07-25 Merck Frosst Canada, Inc. 1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents
US5728830A (en) 1993-09-22 1998-03-17 Kyowa Hakko Kogyo Co., Ltd. Farnesyltransferase inhibitor
IL111235A (en) 1993-10-15 2001-03-19 Schering Plough Corp Medicinal preparations for inhibiting protein G activity and for the treatment of malignant diseases, containing tricyclic compounds, some such new compounds and a process for the preparation of some of them
US5661152A (en) 1993-10-15 1997-08-26 Schering Corporation Tricyclic sulfonamide compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5721236A (en) 1993-10-15 1998-02-24 Schering Corporation Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
US5719148A (en) 1993-10-15 1998-02-17 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
CA2174105C (en) 1993-10-15 2002-02-12 W. Robert Bishop Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
IL111257A0 (en) 1993-10-15 1994-12-29 Schering Corp Tricyclic sulfonamide compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
KR100378615B1 (ko) 1993-10-25 2003-10-10 파크데이비스앤드캄파니 단백질:파르네실트랜스퍼라제의치환된테트라및펜타펩티드억제제
US5344991A (en) 1993-10-29 1994-09-06 G.D. Searle & Co. 1,2 diarylcyclopentenyl compounds for the treatment of inflammation
CA2152822A1 (en) 1993-11-04 1995-05-11 William R. Baker Cyclobutane derivatives as inhibitors of squalene synthetase and protein farnesyltransferase
US5783593A (en) 1993-11-04 1998-07-21 Abbott Laboratories Inhibitors of squalene synthetase and protein farnesyltransferase
CA2170766A1 (en) 1993-11-05 1995-05-11 Gary Louis Bolton Substituted di- and tripeptide inhibitors of protein:farnesyl transferase
US5466823A (en) 1993-11-30 1995-11-14 G.D. Searle & Co. Substituted pyrazolyl benzenesulfonamides
US5484799A (en) 1993-12-09 1996-01-16 Abbott Laboratories Antifungal dorrigocin derivatives
US5393790A (en) 1994-02-10 1995-02-28 G.D. Searle & Co. Substituted spiro compounds for the treatment of inflammation
WO1995024612A1 (de) 1994-03-07 1995-09-14 International Business Machines Corporation Verfahren und vorrichtung zur schnellen interpolation von zwischenwerten aus periodischen phasenverschobenen signalen und zur erkennung von defekten in einem drehkörper
HUT77406A (hu) 1994-03-15 1998-04-28 Eisai Co., Ltd., 1-(4-Amino-5-tio-pent-2-en)-il oldalláncot tartalmazó peptidomimetikumok és az ezeket tartalmazó gyógyszerkészítmények
AU1615895A (en) 1994-03-31 1995-10-12 Bristol-Myers Squibb Company Imidazole-containing inhibitors of farnesyl protein transferase
US5523430A (en) 1994-04-14 1996-06-04 Bristol-Myers Squibb Company Protein farnesyl transferase inhibitors
US5510510A (en) 1994-05-10 1996-04-23 Bristol-Meyers Squibb Company Inhibitors of farnesyl protein transferase
US5563255A (en) 1994-05-31 1996-10-08 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of raf gene expression
DE69507476D1 (de) 1994-06-10 1999-03-04 Rhone Poulenc Rorer Sa Farnesyl-transferase-inhibitoren, ihre herstellung und sie enthaltende pharmazeutische zusammensetzungen
US5571792A (en) 1994-06-30 1996-11-05 Warner-Lambert Company Histidine and homohistidine derivatives as inhibitors of protein farnesyltransferase
WO1996005529A1 (en) 1994-08-09 1996-02-22 Micron Optics, Inc. Temperature compensated fiber fabry-perot filters
CA2155448A1 (en) 1994-08-11 1996-02-12 Katerina Leftheris Inhibitors of farnesyl protein transferase
EP0776884B1 (en) 1994-08-11 2000-01-05 Banyu Pharmaceutical Co., Ltd. Substituted amide derivative
EP0805154A1 (en) 1994-08-12 1997-11-05 Banyu Pharmaceutical Co., Ltd. N,n-disubstituted amic acid derivative
DE4429506B4 (de) 1994-08-19 2007-09-13 Degussa Gmbh Verfahren zur Extraktion natürlicher Carotinoid-Farbstoffe
DE4429653C2 (de) 1994-08-20 1997-04-03 Anton Dr More Konverter und Verfahren zum Frischen von Metallschmelzen insbesondere von Roheisen zu Stahl
JP4319251B2 (ja) 1994-11-22 2009-08-26 エヌエックスピー ビー ヴィ 半導体素子を有し導体トラックが形成されている基板が接着層により結合されている支持本体を有する半導体装置
CA2204144A1 (en) 1994-12-09 1996-06-13 Francis J. Tinney Substituted tetra- and pentapeptide inhibitors of protein:farnesyl transferase
WO1996021701A2 (en) 1995-01-09 1996-07-18 Magla International Ltd. Wear resistant image printing on latex surfaces
AU4915796A (en) 1995-01-12 1996-07-31 University Of Pittsburgh Inhibitors of prenyl transferases
FR2729390A1 (fr) 1995-01-18 1996-07-19 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
FR2730491B1 (fr) 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
FR2730492B1 (fr) 1995-02-09 1997-03-14 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
US5633272A (en) 1995-02-13 1997-05-27 Talley; John J. Substituted isoxazoles for the treatment of inflammation
US5684013A (en) 1995-03-24 1997-11-04 Schering Corporation Tricyclic compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
US5700806A (en) 1995-03-24 1997-12-23 Schering Corporation Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
US5712280A (en) 1995-04-07 1998-01-27 Schering Corporation Tricyclic compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
IL117798A (en) 1995-04-07 2001-11-25 Schering Plough Corp Tricyclic compounds useful for inhibiting the function of protein - G and for the treatment of malignant diseases, and pharmaceutical preparations containing them
US5891872A (en) 1995-04-07 1999-04-06 Schering Corporation Tricyclic compounds
DE69628559T2 (de) 1995-04-07 2004-04-29 Schering Corp. Carbonyl-piperaznyl und piperidinyl derivate zur hemmung farnesyl protein transferase
US5831115A (en) 1995-04-21 1998-11-03 Abbott Laboratories Inhibitors of squalene synthase and protein farnesyltransferase
IL118101A0 (en) 1995-05-03 1996-09-12 Abbott Lab Inhibitors of farnesyltransferase
AU6034296A (en) 1995-06-16 1997-01-15 Warner-Lambert Company Tricyclic inhibitors of protein farnesyltransferase
FR2736641B1 (fr) 1995-07-10 1997-08-22 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
AT402617B (de) 1995-07-11 1997-07-25 Datacon Schweitzer & Zeindl Gm Anlage zum automatisierten, hermetischen anlage zum automatisierten, hermetischen verschliessen von gehäusen verschliessen von gehäusen
FR2736638B1 (fr) 1995-07-12 1997-08-22 Rhone Poulenc Rorer Sa Nouveaux inhibiteurs de farnesyl transferase, leur preparation et les compositions pharmaceutiques qui les contiennent
CH690163A5 (fr) 1995-07-28 2000-05-31 Symphar Sa Dérivés gem-diphosphonates substitués utiles en tant qu'agents anti-cancers.
US6020343A (en) 1995-10-13 2000-02-01 Merck Frosst Canada, Inc. (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors
EP0873123B1 (en) 1995-11-06 2003-04-09 University Of Pittsburgh Inhibitors of protein isoprenyl transferases
JP4183099B2 (ja) 1995-11-17 2008-11-19 ゲゼルシャフト・フュア・ビオテヒノロジッシェ・フォルシュング・ミット・ベシュレンクテル・ハフツング（ゲー・ベー・エフ） エポチロンｃおよびｄ、製造法ならびに組成物
JP2000500502A (ja) 1995-11-22 2000-01-18 メルク エンド カンパニー インコーポレーテッド ファルネシル―タンパク質トランスフェラーゼ阻害剤
SK283335B6 (sk) 1995-12-08 2003-06-03 Janssen Pharmaceutica N. V. (Imidazol-5-yl)metyl-2-chinolinónové deriváty, spôsob a medziprodukty na ich prípravu, ich použitie a farmaceutické kompozície na ich báze
IL125062A (en) 1995-12-22 2003-11-23 Schering Corp Tricyclic amides and pharmaceutical compositions containing them for inhibition of g-protein function and for treatment of proliferative diseases
AU1529997A (en) 1996-01-16 1997-08-11 Warner-Lambert Company Substituted histidine inhibitors of protein farnesyltransferase
US6673927B2 (en) 1996-02-16 2004-01-06 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Farnesyl transferase inhibitors
EP0944388A4 (en) 1996-04-03 2001-08-16 Merck & Co Inc INHIBITORS OF FARNESYL PROTEIN TRANSFERASE
ATE233743T1 (de) 1996-04-12 2003-03-15 Searle & Co N-((4-(5-methyl-3-phenylisoxazol-4- yl)phenyl)sulphonylpropylamid und sein natriumsalz als pro-pharmakon von cox-2 inhibitoren
WO1997044350A1 (en) 1996-05-22 1997-11-27 Warner-Lambert Company Inhibitors of protein farnesyl transferase
WO1998002436A1 (en) 1996-07-15 1998-01-22 Bristol-Myers Squibb Company Thiadioxobenzodiazepine inhibitors of farnesyl protein transferase
US5861419A (en) 1996-07-18 1999-01-19 Merck Frosst Canad, Inc. Substituted pyridines as selective cyclooxygenase-2 inhibitors
CA2273083C (en) 1996-12-03 2012-09-18 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
EP0951285A1 (en) 1996-12-30 1999-10-27 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
CA2276081A1 (en) 1996-12-30 1998-07-09 Lekhanh O. Tran Inhibitors of farnesyl-protein transferase
TW475931B (en) 1997-10-08 2002-02-11 Sankyo Co A substituted condensed heterocyclic compound
DE69831013T2 (de) 1997-12-22 2006-04-20 Bayer Pharmaceuticals Corp., West Haven Inhibierung der raf-kinase durch substituierte heterocyclische harnstoffverbindungen
JP2002536968A (ja) 1999-01-29 2002-11-05 イムクローン システムズ インコーポレイティド Ｋｄｒに特異的な抗体およびその使用
GB9904387D0 (en) 1999-02-25 1999-04-21 Pharmacia & Upjohn Spa Antitumour synergistic composition
JP4169450B2 (ja) 1999-04-07 2008-10-22 第一三共株式会社 インスリン抵抗性改善剤
EP1187633A4 (en) 1999-04-08 2005-05-11 Arch Dev Corp USE OF ANTI-VEGF ANTIBODIES TO ENHANCE RADIATION IN ANTICANCER THERAPY
ES2231179T3 (es) 1999-04-12 2005-05-16 Aventis Pharma Limited Compuestos de heteroarilo biciclicos sustituidos como antagonistas de la integrina.
ES2260033T3 (es) 1999-07-02 2006-11-01 Stuart A. Lipton Uso de los inhibidores p38 mapk en efermadades oftalmicas.
CZ20021428A3 (cs) 1999-10-27 2002-11-13 Cytokinetics, Inc. Způsoby a kompozice vyuľívající chinazoliny
US6545004B1 (en) 1999-10-27 2003-04-08 Cytokinetics, Inc. Methods and compositions utilizing quinazolinones
JP2004517080A (ja) 2000-11-29 2004-06-10 グラクソ グループ リミテッド Ｔｉｅ−２および／またはｖｅｇｆｒ−２の阻害剤として有用なベンゾイミダゾール誘導体
AUPR213700A0 (en) 2000-12-18 2001-01-25 Biota Scientific Management Pty Ltd Antiviral agents
WO2002083139A1 (en) 2001-04-10 2002-10-24 Merck & Co., Inc. Inhibitors of akt activity
US20040106540A1 (en) 2001-04-10 2004-06-03 Barnett Stanley F Method of treating cancer
US7034026B2 (en) 2001-04-10 2006-04-25 Merck & Co., Inc. Inhibitors of Akt activity
US6958334B2 (en) 2001-04-10 2005-10-25 Merck & Co., Inc. Inhibitors of Akt activity
CZ20032829A3 (cs) 2001-04-16 2005-03-16 Tanabe Seiyaku Co., Ltd. Heterocyklické sloučeniny
US7642278B2 (en) 2001-07-03 2010-01-05 Novartis Vaccines And Diagnostics, Inc. Indazole benzimidazole compounds
WO2003013526A1 (en) 2001-08-08 2003-02-20 Merck & Co. Inc. Anticoagulant compounds
JP2005511581A (ja) 2001-11-07 2005-04-28 メルク　エンド　カムパニー　インコーポレーテッド 有糸分裂キネシン阻害剤
WO2003049527A2 (en) 2001-12-06 2003-06-19 Merck & Co., Inc. Mitotic kinesin inhibitors
CA2467722A1 (en) 2001-12-06 2003-06-19 Merck & Co., Inc. Thienopyrimidinone derivatives as mitotic kinesin inhibitors
JP2005515208A (ja) 2001-12-06 2005-05-26 メルク　エンド　カムパニー　インコーポレーテッド 有糸分裂性キネシン阻害剤
CA2468156A1 (en) 2001-12-06 2003-06-19 Merck & Co., Inc. Azolopyrimidinone compounds and their use
US20050107404A1 (en) 2001-12-06 2005-05-19 Fraley Mark E. Mitotic kinesin inhibitors
AU2003249597B2 (en) 2002-03-08 2007-06-28 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
WO2003082272A1 (en) 2002-03-29 2003-10-09 Chiron Corporation Substituted benzazoles and use thereof as raf kinase inhibitors
US8299108B2 (en) 2002-03-29 2012-10-30 Novartis Ag Substituted benzazoles and methods of their use as inhibitors of raf kinase
JPWO2003093238A1 (ja) * 2002-05-01 2005-09-08 麒麟麦酒株式会社 マクロファージコロニー刺激因子受容体自己リン酸化を阻害するキノリン誘導体およびキナゾリン誘導体
EP1517904A4 (en) 2002-05-23 2007-02-21 Merck & Co Inc INHIBITORS OF MITOTIC KINESINE
EP1509507A4 (en) 2002-05-23 2006-09-13 Merck & Co Inc INHIBITORS OF MITOTIC KINESINE
EP1515724B1 (en) 2002-06-14 2009-10-21 Merck & Co., Inc. Mitotic kinesin inhibitors
ATE356804T1 (de) 2002-06-14 2007-04-15 Merck & Co Inc Inhibitoren von mitotischem kinesin
AR041191A1 (es) 2002-08-08 2005-05-04 Amgen Inc Ligandos del receptor vanilloide y su uso en tratamientos
AU2003291403A1 (en) 2002-11-08 2004-06-03 Neurogen Corporation 3-substituted-6-aryl pyridined as ligands of c5a receptors
DE10306250A1 (de) 2003-02-14 2004-09-09 Aventis Pharma Deutschland Gmbh Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
US7531553B2 (en) 2003-03-21 2009-05-12 Amgen Inc. Heterocyclic compounds and methods of use
EP2210607B1 (en) 2003-09-26 2011-08-17 Exelixis Inc. N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer
KR20060118472A (ko) 2003-10-16 2006-11-23 카이론 코포레이션 치환 벤자졸 및 ｒａｆ 키나아제의 저해제로서 그것의 사용
BRPI0418212A (pt) 2003-12-29 2007-04-27 Banyu Pharma Co Ltd composto ou um sal deste farmaceuticamente aceitável, ativador da glicocinase, e, medicamentos para a terapia e/ou prevenção da diabete, e da obesidade
JP2007518823A (ja) * 2004-01-23 2007-07-12 アムゲン インコーポレイテッド キノリン、キナゾリン、ピリジン、及びピリミジン化合物と炎症、血管新生、及び癌に対する治療におけるそれら化合物の用途
EP2295426A1 (en) 2004-04-30 2011-03-16 Bayer HealthCare, LLC Substituted pyrazolyl urea derivatives useful in the treatment of cancer
WO2005110410A2 (en) 2004-05-14 2005-11-24 Abbott Laboratories Kinase inhibitors as therapeutic agents
BRPI0511741A (pt) 2004-06-04 2008-01-02 Astrazeneca Ab derivado de quinazolina ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, processo para a preparação de um derivado de quinazolina ou de um sal farmaceuticamente aceitável do mesmo
BRPI0510929A (pt) 2004-06-18 2007-07-17 Chiron Corp derivados de n-(1-(1-benzil-4-fenil-1h-imidazol-2-il)-2,2-dimetilpropil) benzamida e compostos relacionados como inibidores de proteìna de eixo de kinesin (ksp) para o tratamento de cáncer
CA2649288C (en) * 2006-04-19 2015-11-24 Novartis Ag 6-o-substituted benzoxazole and benzothiazole compounds and methods of inhibiting csf-1r signaling

Also Published As

Publication number Publication date
TNSN08406A1 (en) 2010-04-14
PE20080359A1 (es) 2008-06-06
EA018917B1 (ru) 2013-11-29
JP2009534410A (ja) 2009-09-24
CR10365A (es) 2009-01-07
US20100280006A1 (en) 2010-11-04
US8173689B2 (en) 2012-05-08
HRP20171924T1 (hr) 2018-02-09
KR20080112388A (ko) 2008-12-24
SMP200800063B (it) 2009-11-06
CY1119679T1 (el) 2018-04-04
BRPI0710540B1 (pt) 2022-04-12
WO2007121484A2 (en) 2007-10-25
AU2007237904B2 (en) 2011-03-03
DK2010528T3 (en) 2018-01-15
NO20084800L (no) 2008-11-17
WO2007121484A3 (en) 2008-02-07
EP2010528A2 (en) 2009-01-07
MA30407B1 (fr) 2009-05-04
JP5328640B2 (ja) 2013-10-30
US8710048B2 (en) 2014-04-29
AU2007237904A1 (en) 2007-10-25
US20080045528A1 (en) 2008-02-21
US20120225861A1 (en) 2012-09-06
IL194662A0 (en) 2009-08-03
CA2649288A1 (en) 2007-10-25
SMAP200800063A (it) 2008-11-19
EA200802129A1 (ru) 2009-04-28
EP2010528B1 (en) 2017-10-04
PL2010528T3 (pl) 2018-03-30
US7553854B2 (en) 2009-06-30
LT2010528T (lt) 2017-12-27
HUE035654T2 (en) 2018-05-28
TW200813039A (en) 2008-03-16
MX2008013427A (es) 2008-11-04
SI2010528T1 (en) 2018-02-28
AR060545A1 (es) 2008-06-25
CA2649288C (en) 2015-11-24
ECSP088830A (es) 2008-11-27
KR101464385B1 (ko) 2014-11-21
PT2010528T (pt) 2017-12-21
BRPI0710540A2 (pt) 2012-01-31
RS56600B1 (sr) 2018-02-28

Similar Documents

Publication Publication Date Title
ES2654847T3 (es) Compuestos de benzoxazol y benzotiazol sustituidos en 6-O y métodos para inhibir la señalización CSF-1R
CN102933564B (zh) 用作β-分泌酶(BACE)抑制剂的5,6-二氢-2H-[1,4]噁嗪-3-基-胺衍生物
DK2417120T3 (en) Substituted piperidines AS CCR3 ANTAGONISTS
BR112012017713A2 (pt) Aminopiridina, formulação farmacêutica, processo para a preparação de um derivado de aminopiridina, intermediário, e, uso de uma aminopiridina ou de uma formulação farmacêutica
RU2012126989A (ru) 2-амино-5,5-дифтор-5,6-дигидро-4н-оксазины в качестве ингибиторов васе 1 и(или) васе 2
RU2014131390A (ru) ПРОИЗВОДНЫЕ ТИЕНО[3,2-d]ПИРИМИДИНА, ОБЛАДАЮЩИЕ ИНГИБИРУЮЩЕЙ АКТИВНОСТЬЮ В ОТНОШЕНИИ ПРОТЕИНКИНАЗ
RU2007100136A (ru) Соединения и композиции в качестве ингибиторов протеинкиназы
RU2012134306A (ru) Азотосодержащие производные гетероарилов
AU2016284638B2 (en) Pyrazolo[1,5-a]triazin-4-amine derivatives useful in therapy
ME00681B (me) Jedinjenje indola
HRP20151435T1 (hr) Diamino heterociklički karboksamidni spoj
WO2004087153A2 (en) Use of organic compounds for immunopotentiation
JP2013539777A5 (es)
RU2011116226A (ru) Пиразолопиридиновые производные как ингибиторы надфн-оксидазы
CN105188694A (zh) 用于治疗疼痛的钠通道调节剂
RU2013143028A (ru) Тиазолилфенилбензолсульфонамидопроизводные в качестве ингибиторов киназ
AU2017222962A1 (en) Acid addition salts of piperazine derivatives
RU2005102098A (ru) Амидное производное
RU2013138834A (ru) N-[3-(5-амино-3,3а,7,7а-тетрагидро-1н-2,4-диокса-6-аза-инден-7-ил)-фенил]-амиды в качестве ингибиторов васе1 и(или) васе2
JP2010540462A5 (es)
JP2023551110A5 (es)
JP2020512401A5 (es)
HRP20140588T1 (hr) Spojevi kondenziranog prstena i njihova uporaba
JP7779953B2 (ja) 慢性前立腺炎／慢性骨盤痛症候群の予防及び／又は治療剤
RU2417223C2 (ru) Оксазолидиноновые производные, способ их получения (варианты) и фармацевтическая композиция на их основе