RU2472791C2 - Соединения, модулирующие внутриклеточный кальций - Google Patents

Соединения, модулирующие внутриклеточный кальций Download PDF

Info

Publication number
RU2472791C2
RU2472791C2 RU2011108969/04A RU2011108969A RU2472791C2 RU 2472791 C2 RU2472791 C2 RU 2472791C2 RU 2011108969/04 A RU2011108969/04 A RU 2011108969/04A RU 2011108969 A RU2011108969 A RU 2011108969A RU 2472791 C2 RU2472791 C2 RU 2472791C2
Authority
RU
Russia
Prior art keywords
compound according
disease
alkyl
phenyl
compound
Prior art date
Application number
RU2011108969/04A
Other languages
English (en)
Other versions
RU2011108969A (ru
Inventor
Гонул ВЕЛИСЕЛЕБИ
Кеннет А. СТОДЕРМАН
Джеффри П. УИТТЕН
Яжонг ПЕЙ
Цзяньгуо ЦАО
Чжицзунь ВАНГ
Эван РОДЖЕРС
Брайан Дик
Джонатан ГРЕЙ
Original Assignee
КалсиМедика Инк.
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 КалсиМедика Инк. filed Critical КалсиМедика Инк.
Publication of RU2011108969A publication Critical patent/RU2011108969A/ru
Application granted granted Critical
Publication of RU2472791C2 publication Critical patent/RU2472791C2/ru

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/14—Decongestants or antiallergics
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06—Antianaemics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Abstract

Изобретение относится к соединениям формулы (I):
Figure 00000466
где: A, J, R1, R4, X, Z представлены в п.1 формулы изобретения, а также к фармацевтической композиции, содержащей такие соединения, модулирующие активность депо-управляемых кальциевых (SOC) каналов. Кроме того, в данном изобретении описаны способы применения таких модуляторов SOC-каналов для лечения заболеваний или состояний, при которых может быть полезно ингибирование активности SOC-каналов. 4 н. и 13 з.п. ф-лы, 5 табл., 2 ил., 8 пр.

Description

Текст описания приведен в факсимильном виде.
Figure 00000001
Figure 00000002
Figure 00000003
Figure 00000004
Figure 00000005
Figure 00000006
Figure 00000007
Figure 00000008
Figure 00000009
Figure 00000010
Figure 00000011
Figure 00000012
Figure 00000013
Figure 00000014
Figure 00000015
Figure 00000016
Figure 00000017
Figure 00000018
Figure 00000019
Figure 00000020
Figure 00000021
Figure 00000022
Figure 00000023
Figure 00000024
Figure 00000025
Figure 00000026
Figure 00000027
Figure 00000028
Figure 00000029
Figure 00000030
Figure 00000032
Figure 00000033
Figure 00000034
Figure 00000035
Figure 00000036
Figure 00000037
Figure 00000038
Figure 00000039
Figure 00000040
Figure 00000041
Figure 00000042
Figure 00000043
Figure 00000044
Figure 00000045
Figure 00000046
Figure 00000047
Figure 00000048
Figure 00000049
Figure 00000050
Figure 00000051
Figure 00000052
Figure 00000053
Figure 00000054
Figure 00000055
Figure 00000056
Figure 00000057
Figure 00000058
Figure 00000059
Figure 00000060
Figure 00000061
Figure 00000062
Figure 00000063
Figure 00000064
Figure 00000065
Figure 00000066
Figure 00000067
Figure 00000068
Figure 00000069
Figure 00000070
Figure 00000071
Figure 00000072
Figure 00000073
Figure 00000074
Figure 00000075
Figure 00000076
Figure 00000077
Figure 00000078
Figure 00000079
Figure 00000080
Figure 00000081
Figure 00000082
Figure 00000083
Figure 00000084
Figure 00000085
Figure 00000086
Figure 00000087
Figure 00000088
Figure 00000089
Figure 00000090
Figure 00000091
Figure 00000092
Figure 00000093
Figure 00000094
Figure 00000095
Figure 00000096
Figure 00000097
Figure 00000098
Figure 00000099
Figure 00000100
Figure 00000101
Figure 00000102
Figure 00000103
Figure 00000104
Figure 00000105
Figure 00000106
Figure 00000107
Figure 00000108
Figure 00000109
Figure 00000110
Figure 00000111
Figure 00000112
Figure 00000113
Figure 00000114
Figure 00000115
Figure 00000116
Figure 00000117
Figure 00000118
Figure 00000119
Figure 00000120
Figure 00000121
Figure 00000122
Figure 00000123
Figure 00000124
Figure 00000125
Figure 00000126
Figure 00000127
Figure 00000128
Figure 00000129
Figure 00000130
Figure 00000131
Figure 00000132
Figure 00000133
Figure 00000134
Figure 00000135
Figure 00000136
Figure 00000137
Figure 00000138
Figure 00000139
Figure 00000140
Figure 00000141
Figure 00000142
Figure 00000143
Figure 00000144
Figure 00000145
Figure 00000146
Figure 00000147
Figure 00000148
Figure 00000149
Figure 00000150
Figure 00000151
Figure 00000152
Figure 00000153
Figure 00000154
Figure 00000155
Figure 00000156
Figure 00000157
Figure 00000158
Figure 00000159
Figure 00000160
Figure 00000161
Figure 00000162
Figure 00000163
Figure 00000164
Figure 00000165
Figure 00000166
Figure 00000167
Figure 00000168
Figure 00000169
Figure 00000170
Figure 00000171
Figure 00000172
Figure 00000173
Figure 00000174
Figure 00000175
Figure 00000176
Figure 00000177
Figure 00000178
Figure 00000179
Figure 00000180
Figure 00000181
Figure 00000182
Figure 00000183
Figure 00000184
Figure 00000185
Figure 00000186
Figure 00000187
Figure 00000188
Figure 00000189
Figure 00000190
Figure 00000191
Figure 00000192
Figure 00000193
Figure 00000194
Figure 00000196
Figure 00000197
Figure 00000198
Figure 00000199
Figure 00000200
Figure 00000201
Figure 00000202
Figure 00000203
Figure 00000204
Figure 00000205
Figure 00000206
Figure 00000207
Figure 00000208
Figure 00000209
Figure 00000210
Figure 00000211
Figure 00000212
Figure 00000213
Figure 00000214
Figure 00000215
Figure 00000216
Figure 00000217
Figure 00000218
Figure 00000219
Figure 00000220
Figure 00000221
Figure 00000222
Figure 00000223
Figure 00000224
Figure 00000225
Figure 00000226
Figure 00000227
Figure 00000228
Figure 00000229
Figure 00000230
Figure 00000231
Figure 00000232
Figure 00000233
Figure 00000234
Figure 00000235
Figure 00000236
Figure 00000237
Figure 00000238
Figure 00000239
Figure 00000240
Figure 00000241
Figure 00000242
Figure 00000243
Figure 00000244
Figure 00000245
Figure 00000246
Figure 00000247
Figure 00000248
Figure 00000249
Figure 00000250
Figure 00000251
Figure 00000252
Figure 00000253
Figure 00000254
Figure 00000255
Figure 00000256
Figure 00000257
Figure 00000258
Figure 00000259
Figure 00000260
Figure 00000261
Figure 00000262
Figure 00000264
Figure 00000265
Figure 00000266
Figure 00000268
Figure 00000269
Figure 00000270
Figure 00000271
Figure 00000272
Figure 00000273
Figure 00000274
Figure 00000275
Figure 00000276
Figure 00000277
Figure 00000278
Figure 00000279
Figure 00000280
Figure 00000281
Figure 00000282
Figure 00000283
Figure 00000284
Figure 00000285
Figure 00000286
Figure 00000287
Figure 00000288
Figure 00000289
Figure 00000290
Figure 00000291
Figure 00000292
Figure 00000293
Figure 00000294

Claims (17)

1. Соединение формулы (I):
Figure 00000295

где А представляет собой фенил или бензофуран, каждый из которых возможно замещен по меньшей мере одним R;
R выбран из F, Cl, Br, I, -CN, -NO2, -CF3, -ОН, -OR3, -OCF3, С1-С6алкила, С3-С6циклоалкила, C1-С6галогеноалкила и фенила;
J представляет собой связь;
R1 представляет собой CO2R2, где R2 представляет собой водород;
Z представляет собой О, S или NH;
X представляет собой W-L-B или В, где В возможно замещен по меньшей мере одним R;
W представляет собой NR2, О или связь;
L представляет собой метилен, этилен, замещенный по меньшей мере одним R, С3-С6алкилен, С2-С6алкенилен или С2-С6алкинилен, где метилен, С3-С6алкилен, С2-С6алкенилен или С2-С6алкинилен возможно замещен по меньшей мере одним R;
В выбран из фурана, тиофена, пиррола, пиридина, оксазола, тиазола, имидазола, тиадиазола, бензоксазола, бензотиазола, бензимидазола, бензоксадиазола, бензотиадиазола, пиразолопиридина, индолизина, фуропиридина, тиенотиофена, хинолина и изохинолина;
каждый R3 независимо выбран из С1-С6алкила;
каждый R4 независимо выбран из водорода или С1-С6алкила; или его фармацевтически приемлемые соль, сольват или N-оксид.
2. Соединение по п.1, где R4 представляет собой водород.
3. Соединение по п.2, где Z представляет собой О.
4. Соединение по п.3, где А представляет собой фенил.
5. Соединение по п.4, где фенил замещен по меньшей мере одним R.
6. Соединение по п.5, где фенил замещен тремя R.
7. Соединение по п.6, где R выбран из F, Cl, Br, I или С1-С6алкила.
8. Соединение по п.7, где С1-С6алкил представляет собой метил, этил, н-пропил, изопропил, н-бутил, изобутил или трет-бутил.
9. Соединение по п.8, где X представляет собой В.
10. Соединение по п.9, где В выбран из бензоксазола, бензотиазола, бензимидазола, пиразолопиридина, бензоксадиазола и бензотиадиазола.
11. Соединение, выбранное из:
Figure 00000296
,
Figure 00000297
,
Figure 00000298
,
Figure 00000299
,
Figure 00000300
,
Figure 00000301
,
Figure 00000302
,
Figure 00000303
,
Figure 00000304
,
Figure 00000305
,
Figure 00000306
,
Figure 00000307
,
Figure 00000308
,
Figure 00000309
,
Figure 00000310
,
Figure 00000311
,
Figure 00000312
,
Figure 00000313
,
Figure 00000314
,
Figure 00000315
,
Figure 00000316
,
Figure 00000317
,
Figure 00000318
,
Figure 00000319
,
Figure 00000320
,
Figure 00000321
,
Figure 00000322
,
Figure 00000323
,
Figure 00000324
,
Figure 00000325
,
Figure 00000326
,
Figure 00000327
,
Figure 00000328
,
Figure 00000329
,
Figure 00000330
,
Figure 00000331
,
Figure 00000332
,
Figure 00000333
,
Figure 00000334
,
Figure 00000335
,
Figure 00000336
,
Figure 00000337
,
Figure 00000338
,
Figure 00000339
,
Figure 00000340
,
Figure 00000341
,
Figure 00000342
,
Figure 00000343
,
Figure 00000344
,
Figure 00000345
,
Figure 00000346
,
Figure 00000347
,
Figure 00000348
,
Figure 00000349
,
Figure 00000350
,
Figure 00000351
,
Figure 00000352
,
Figure 00000353
,
Figure 00000354
,
Figure 00000355
,
Figure 00000356
,
Figure 00000357
,
Figure 00000358
,
Figure 00000359
,
Figure 00000360
,
Figure 00000361
,
Figure 00000362
,
Figure 00000363
,
Figure 00000364
,
Figure 00000365
,
Figure 00000366
,
Figure 00000367
,
Figure 00000368
,
Figure 00000369
,
Figure 00000370
,
Figure 00000371
,
Figure 00000372
,
Figure 00000373
,
Figure 00000374
и
Figure 00000375
,
Figure 00000376
,
Figure 00000377
,
Figure 00000378
,
Figure 00000379
,
Figure 00000380
,
Figure 00000381
,
Figure 00000382
,
Figure 00000383
,
Figure 00000384
,
Figure 00000385
,
Figure 00000386
,
Figure 00000387
,
Figure 00000388
,
Figure 00000389
,
Figure 00000390

Figure 00000391
,
Figure 00000392
,
Figure 00000393

и
Figure 00000394
,
Figure 00000395
,
Figure 00000396
,
Figure 00000397
,
Figure 00000398
,
Figure 00000399
,
Figure 00000400
,
Figure 00000401
и
Figure 00000402
;
Figure 00000403
,
Figure 00000404
,
Figure 00000405
,
Figure 00000406
,
Figure 00000407
,
Figure 00000408
,
Figure 00000409
,
Figure 00000410
,
Figure 00000411
,
Figure 00000412
,
Figure 00000413
,
Figure 00000414

и
Figure 00000415
,
Figure 00000416
,
Figure 00000417
,
Figure 00000418
,
Figure 00000419
,
Figure 00000420
,
Figure 00000421
,
Figure 00000422
,
Figure 00000423
,
Figure 00000424
,
Figure 00000425
,
Figure 00000426
,
Figure 00000427
,
Figure 00000428
,
Figure 00000429
,
Figure 00000430
,
Figure 00000431
,
Figure 00000432
,
Figure 00000433
,
Figure 00000434
,
Figure 00000435
,
Figure 00000436
,
Figure 00000437
,
Figure 00000438
,
Figure 00000439
,
Figure 00000440
,
Figure 00000441
,
Figure 00000442
,
Figure 00000443
,
Figure 00000444
,
Figure 00000445
,
Figure 00000446
,
Figure 00000447
,
Figure 00000448
,
Figure 00000449
,
Figure 00000450
,
Figure 00000451
,
Figure 00000452
,
Figure 00000453
,
Figure 00000454
,
Figure 00000455
,
Figure 00000456
,
Figure 00000457
,
Figure 00000458
,
Figure 00000459
,
Figure 00000460
,
Figure 00000461
,
Figure 00000462
,
Figure 00000463
,
Figure 00000464
и
Figure 00000465

или его фармацевтически приемлемые соль или сольват.
12. Фармацевтическая композиция для лечения аутоиммунного заболевания, гетероиммунного заболевания или состояния либо воспалительного заболевания, содержащая соединение по п.1 и фармацевтически приемлемый разбавитель, эксципиент, носитель или связующее вещество для них.
13. Применение соединения по п.1 или его фармацевтически приемлемой соли в изготовлении лекарственного средства для лечения аутоиммунного заболевания, гетероиммунного заболевания или состояния либо воспалительного заболевания.
14. Применение по п.13, где аутоиммунное заболевание представляет собой ревматоидный артрит, рассеянный склероз, псориаз или остеоартрит.
15. Применение по п.14, где аутоиммунное заболевание представляет собой псориаз.
16. Применение по п.13, где гетероиммунное заболевание или состояние представляет собой отторжение трансплантата или отторжение органного трансплантата.
17. Применение по п.13, где воспалительное заболевание представляет собой колит.
RU2011108969/04A 2008-08-27 2009-08-26 Соединения, модулирующие внутриклеточный кальций RU2472791C2 (ru)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
US9236408P 2008-08-27 2008-08-27
US61/092,364 2008-08-27
US14284609P 2009-01-06 2009-01-06
US61/142,846 2009-01-06
US14373909P 2009-01-09 2009-01-09
US61/143,739 2009-01-09
US15727409P 2009-03-04 2009-03-04
US61/157,274 2009-03-04
US15871009P 2009-03-09 2009-03-09
US15870209P 2009-03-09 2009-03-09
US61/158,702 2009-03-09
US61/158,710 2009-03-09
PCT/US2009/055090 WO2010027875A2 (en) 2008-08-27 2009-08-26 Compounds that modulate intracellular calcium

Publications (2)

Publication Number Publication Date
RU2011108969A RU2011108969A (ru) 2012-10-10
RU2472791C2 true RU2472791C2 (ru) 2013-01-20

Family

ID=41722281

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2011108969/04A RU2472791C2 (ru) 2008-08-27 2009-08-26 Соединения, модулирующие внутриклеточный кальций

Country Status (15)

Country Link
US (7) US7981925B2 (ru)
EP (1) EP2321303B1 (ru)
JP (1) JP5782377B2 (ru)
KR (1) KR101724161B1 (ru)
CN (1) CN102256969A (ru)
AU (1) AU2009288245B2 (ru)
BR (1) BRPI0917719A2 (ru)
CA (1) CA2734500A1 (ru)
IL (1) IL211391B (ru)
MX (1) MX2011002149A (ru)
MY (1) MY157445A (ru)
RU (1) RU2472791C2 (ru)
TW (1) TWI392673B (ru)
WO (2) WO2010027875A2 (ru)
ZA (1) ZA201101335B (ru)

Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101854933A (zh) 2007-09-10 2010-10-06 钙医学公司 调节细胞内钙的化合物
MX2011002149A (es) * 2008-08-27 2011-04-05 Calcimedica Inc Compuestos que modulan el calcio intracelular.
US8524763B2 (en) * 2008-09-22 2013-09-03 Calcimedica, Inc. Inhibitors of store operated calcium release
WO2011034962A2 (en) * 2009-09-16 2011-03-24 Calcimedica Inc. Compounds that modulate intracellular calcium
US8993612B2 (en) 2009-10-08 2015-03-31 Rhizen Pharmaceuticals Sa Modulators of calcium release-activated calcium channel and methods for treatment of non-small cell lung cancer
US8377970B2 (en) 2009-10-08 2013-02-19 Rhizen Pharmaceuticals Sa Modulators of calcium release-activated calcium channel
CN102574843B (zh) 2009-10-22 2015-06-17 法博太科制药有限公司 抗纤维化剂的稠环类似物
US10703722B2 (en) 2010-04-27 2020-07-07 Calcimedica, Inc. Compounds that modulate intracellular calcium
TWI504404B (zh) * 2010-07-22 2015-10-21 Univ Kaohsiung Medical 用於抑制結腸直腸癌細胞及子宮上皮癌細胞生長轉移之醫藥組合物
WO2012027710A2 (en) 2010-08-27 2012-03-01 Calcimedica Inc. Compounds that modulate intracellular calcium
US20120071516A1 (en) * 2010-09-22 2012-03-22 Calcimedica, Inc. Compounds that modulate intracellular calcium
KR20130106410A (ko) 2010-10-30 2013-09-27 루핀 리미티드 Crac 조절제인 옥사졸린과 이소옥사졸린 유도체
CA2871270A1 (en) 2012-05-02 2013-11-07 Lupin Limited Substituted pyridine compounds as crac modulators
EP2844656A1 (en) 2012-05-02 2015-03-11 Lupin Limited Substituted pyrazole compounds as crac modulators
CN104395326B (zh) * 2012-08-20 2017-04-05 玛耐科股份有限公司 二取代硼酸衍生物的制造方法和新型二取代硼酸衍生物
US9512116B2 (en) 2012-10-12 2016-12-06 Calcimedica, Inc. Compounds that modulate intracellular calcium
GB201302927D0 (en) * 2013-02-20 2013-04-03 Cancer Therapeutics Crc Pty Ltd Compounds
WO2014203217A1 (en) 2013-06-21 2014-12-24 Lupin Limited Substituted heterocyclic compounds as crac modulators
CA2914415A1 (en) 2013-06-24 2014-12-31 Lupin Limited Chromane and chromene derivatives and their use as crac modulators
CN111978319B (zh) 2014-06-27 2023-08-11 诺格拉制药有限公司 芳基受体调制剂及其制备和使用方法
WO2016034673A1 (en) 2014-09-03 2016-03-10 Ctxt Pty Ltd Tetrahydroisoquinoline derived prmt5-inhibitors
GB201415573D0 (en) 2014-09-03 2014-10-15 Cancer Therapeutics Crc Pty Ltd Compounds
US10005792B2 (en) 2014-09-03 2018-06-26 Ctxt Pty. Ltd. Aminoindane-, aminotetrahydronaphthalene- and aminobenzocyclobutane-derived PRMT5-inhibitors
PT3203840T (pt) 2014-10-06 2020-10-27 Vertex Pharma Moduladores do regulador da condutância transmembranar da fibrose quística
US11311535B2 (en) 2015-02-27 2022-04-26 Calcimedica, Inc. Pancreatitis treatment
DK3331525T3 (da) 2015-08-07 2020-12-14 Calcimedica Inc Anvendelse af CRAC-kanal-inhibitorer til behandling af slagtilfælde og traumatisk hjerneskade
GB201604020D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
GB201604027D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
GB201604022D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
GB201604031D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
GB201604030D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
GB201604029D0 (en) 2016-03-09 2016-04-20 Ctxt Pty Ltd Compounds
CA3019380A1 (en) 2016-03-31 2017-10-05 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator
CA3037986C (en) 2016-09-30 2024-03-05 Vertex Pharmaceuticals Incorporated Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
KR102269492B1 (ko) 2016-12-09 2021-06-24 버텍스 파마슈티칼스 인코포레이티드 낭포성 섬유증 막관통 전도성 조절인자의 조절제, 약제학적 조성물, 치료 방법, 및 상기 조절제를 제조하는 방법
KR20190115451A (ko) 2017-02-03 2019-10-11 세르타 테라퓨틱스 피티와이 엘티디. 항-섬유성 화합물
MA54105A (fr) 2017-06-08 2021-09-15 Vertex Pharma Méthodes de traitement de la fibrose kystique
WO2019018395A1 (en) 2017-07-17 2019-01-24 Vertex Pharmaceuticals Incorporated METHODS OF TREATING CYSTIC FIBROSIS
CN111051280B (zh) 2017-08-02 2023-12-22 弗特克斯药品有限公司 制备吡咯烷化合物的方法
TWI719349B (zh) 2017-10-19 2021-02-21 美商維泰克斯製藥公司 Ｃｆｔｒ調節劑之結晶形式及組合物
US11465985B2 (en) 2017-12-08 2022-10-11 Vertex Pharmaceuticals Incorporated Processes for making modulators of cystic fibrosis transmembrane conductance regulator
TWI810243B (zh) 2018-02-05 2023-08-01 美商維泰克斯製藥公司 用於治療囊腫纖化症之醫藥組合物
BR112020015743A2 (pt) 2018-02-08 2020-12-15 Enyo Pharma Derivados de tiofeno não fundido e seus usos
EP3774825A1 (en) 2018-04-13 2021-02-17 Vertex Pharmaceuticals Incorporated Modulators of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator
WO2020053834A1 (en) 2018-09-14 2020-03-19 Rhizen Pharmaceuticals Sa Compositions comprising a crac inhibitor and a corticosteroid and methods of use thereof
MX2022004579A (es) * 2019-10-17 2022-05-10 Enyo Pharma Derivados tiofeno para usarse en el tratamiento de inflamacion portal y fibrosis.
KR20230048361A (ko) * 2020-08-05 2023-04-11 엔요 파마 만성 신장 질환의 치료 방법
EP4334298A1 (en) 2021-06-14 2024-03-13 Scorpion Therapeutics, Inc. Urea derivatives which can be used to treat cancer
CN114436945B (zh) * 2021-12-30 2023-12-22 山东师范大学 一种苯磺酰胺类化合物、制备方法及应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2184731C2 (ru) * 1996-10-15 2002-07-10 Мерк Патент Гмбх Амиды аминотиофенкарбоновой кислоты, способ их получения (варианты) и фармацевтическая композиция
WO2003013517A1 (en) * 2001-08-06 2003-02-20 Pharmacia Italia S.P.A. Aminoisoxazole derivatives active as kinase inhibitors
WO2005033102A2 (en) * 2003-10-03 2005-04-14 Amphora Discovery Corporation Thiophene-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof
EA007484B1 (ru) * 2001-06-11 2006-10-27 Вирокем Фарма Инк. Соединения и способы лечения или предупреждения инфекций flavivirus

Family Cites Families (142)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3993073A (en) 1969-04-01 1976-11-23 Alza Corporation Novel drug delivery device
US3598122A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3710795A (en) 1970-09-29 1973-01-16 Alza Corp Drug-delivery device with stretched, rate-controlling membrane
US4069307A (en) 1970-10-01 1978-01-17 Alza Corporation Drug-delivery device comprising certain polymeric materials for controlled release of drug
US3731683A (en) 1971-06-04 1973-05-08 Alza Corp Bandage for the controlled metering of topical drugs to the skin
US3742951A (en) 1971-08-09 1973-07-03 Alza Corp Bandage for controlled release of vasodilators
US3996934A (en) 1971-08-09 1976-12-14 Alza Corporation Medical bandage
BE795384A (fr) 1972-02-14 1973-08-13 Ici Ltd Pansements
GB1419074A (en) 1972-06-09 1975-12-24 Ici Ltd Process for manufacturing substituted thiophene compounds
US3921636A (en) 1973-01-15 1975-11-25 Alza Corp Novel drug delivery device
US3993072A (en) 1974-08-28 1976-11-23 Alza Corporation Microporous drug delivery device
US4151273A (en) 1974-10-31 1979-04-24 The Regents Of The University Of California Increasing the absorption rate of insoluble drugs
US3972995A (en) 1975-04-14 1976-08-03 American Home Products Corporation Dosage form
US4077407A (en) 1975-11-24 1978-03-07 Alza Corporation Osmotic devices having composite walls
US4031894A (en) 1975-12-08 1977-06-28 Alza Corporation Bandage for transdermally administering scopolamine to prevent nausea
US4060084A (en) 1976-09-07 1977-11-29 Alza Corporation Method and therapeutic system for providing chemotherapy transdermally
US4201211A (en) 1977-07-12 1980-05-06 Alza Corporation Therapeutic system for administering clonidine transdermally
JPS5562012A (en) 1978-11-06 1980-05-10 Teijin Ltd Slow-releasing preparation
US4230105A (en) 1978-11-13 1980-10-28 Merck & Co., Inc. Transdermal delivery of drugs
US4229447A (en) 1979-06-04 1980-10-21 American Home Products Corporation Intraoral methods of using benzodiazepines
CA1146866A (en) 1979-07-05 1983-05-24 Yamanouchi Pharmaceutical Co. Ltd. Process for the production of sustained release pharmaceutical composition of solid medical material
US4291015A (en) 1979-08-14 1981-09-22 Key Pharmaceuticals, Inc. Polymeric diffusion matrix containing a vasodilator
US4327725A (en) 1980-11-25 1982-05-04 Alza Corporation Osmotic device with hydrogel driving member
DD201306A1 (de) 1981-12-10 1983-07-13 Juergen Liebscher Verfahren zur herstellung von 5-acyl-3-aryl-2-dialkylaminothiophenen
US4476116A (en) 1982-12-10 1984-10-09 Syntex (U.S.A.) Inc. Polypeptides/chelating agent nasal compositions having enhanced peptide absorption
US5116817A (en) 1982-12-10 1992-05-26 Syntex (U.S.A.) Inc. LHRH preparations for intranasal administration
DD216237A1 (de) 1983-06-23 1984-12-05 Univ Halle Wittenberg Verfahren zur herstellung von substituierten 4-phenyl-thiophenen
US4596795A (en) 1984-04-25 1986-06-24 The United States Of America As Represented By The Secretary, Dept. Of Health & Human Services Administration of sex hormones in the form of hydrophilic cyclodextrin derivatives
US4624848A (en) 1984-05-10 1986-11-25 Ciba-Geigy Corporation Active agent containing hydrogel devices wherein the active agent concentration profile contains a sigmoidal concentration gradient for improved constant release, their manufacture and use
DD235873A1 (de) 1984-09-11 1986-05-21 Univ Leipzig Verfahren zur herstellung von substituierten thieno/2,3-d/1,3-thiazin-4-onen mit aminofunktionen in 2-stellung
DD240890A1 (de) 1985-04-26 1986-11-19 Univ Halle Wittenberg Verfahren zur herstellung von n-(thien-2-yl)-n'-(alkoxycarbonylaryl-bzw.-alkyl)-thioharnstoffen
DE3529247A1 (de) 1985-05-17 1986-11-20 Bayer Ag, 5090 Leverkusen Verwendung von thienylharnstoffen und -isoharnstoffen als leistungsfoerdernde mittel bei tieren, neue thienylharnstoffe und -isoharnstoffe und ihre herstellung
GB8518301D0 (en) 1985-07-19 1985-08-29 Fujisawa Pharmaceutical Co Hydrodynamically explosive systems
JPH0778017B2 (ja) 1985-12-28 1995-08-23 住友製薬株式会社 パルス的かつ持続放出性製剤
US4755386A (en) 1986-01-22 1988-07-05 Schering Corporation Buccal formulation
CA1284642C (en) 1986-03-31 1991-06-04 Hikozo Iwakura Prostacyclin (pgi ) analogues
US5312325A (en) 1987-05-28 1994-05-17 Drug Delivery Systems Inc Pulsating transdermal drug delivery system
US4968509A (en) 1987-07-27 1990-11-06 Mcneilab, Inc. Oral sustained release acetaminophen formulation and process
US5033252A (en) 1987-12-23 1991-07-23 Entravision, Inc. Method of packaging and sterilizing a pharmaceutical product
US5052558A (en) 1987-12-23 1991-10-01 Entravision, Inc. Packaged pharmaceutical product
IL92966A (en) 1989-01-12 1995-07-31 Pfizer Hydrogel-operated release devices
PH27357A (en) 1989-09-22 1993-06-21 Fujisawa Pharmaceutical Co Pyrazole derivatives and pharmaceutical compositions comprising the same
US5739136A (en) 1989-10-17 1998-04-14 Ellinwood, Jr.; Everett H. Intraoral dosing method of administering medicaments
US5017381A (en) 1990-05-02 1991-05-21 Alza Corporation Multi-unit pulsatile delivery system
US5633009A (en) 1990-11-28 1997-05-27 Sano Corporation Transdermal administration of azapirones
DK0580860T4 (da) 1991-04-16 2005-03-21 Nippon Shinyaku Co Ltd Fremgangsmåde til fremstilling af en fast dispersion
JPH07501073A (ja) 1991-11-22 1995-02-02 プロクター、エンド、ギャンブル、ファーマス−ティカルズ、インコーポレーテッド リゼドロネート遅延放出組成物
US5229135A (en) 1991-11-22 1993-07-20 Prographarm Laboratories Sustained release diltiazem formulation
US5340591A (en) 1992-01-24 1994-08-23 Fujisawa Pharmaceutical Co., Ltd. Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine
US5461140A (en) 1992-04-30 1995-10-24 Pharmaceutical Delivery Systems Bioerodible polymers for solid controlled release pharmaceutical compositions
US5260068A (en) 1992-05-04 1993-11-09 Anda Sr Pharmaceuticals Inc. Multiparticulate pulsatile drug delivery system
US5281420A (en) 1992-05-19 1994-01-25 The Procter & Gamble Company Solid dispersion compositions of tebufelone
US5323907A (en) 1992-06-23 1994-06-28 Multi-Comp, Inc. Child resistant package assembly for dispensing pharmaceutical medications
AU4198793A (en) 1992-07-24 1994-01-27 Takeda Chemical Industries Ltd. Microparticle preparation and production thereof
US5700485A (en) 1992-09-10 1997-12-23 Children's Medical Center Corporation Prolonged nerve blockade by the combination of local anesthetic and glucocorticoid
DE69332291T2 (de) 1992-10-16 2003-07-31 Nippon Shinyaku Co Ltd Verfahren zur herstellung von wachsmatrizes
AU670454B2 (en) 1992-11-23 1996-07-18 Pfizer Inc. Regioselective synthesis of 4-chloro-2-thiophenecarboxylic acid
US5260069A (en) 1992-11-27 1993-11-09 Anda Sr Pharmaceuticals Inc. Pulsatile particles drug delivery system
US5604260A (en) 1992-12-11 1997-02-18 Merck Frosst Canada Inc. 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
ATE160345T1 (de) 1993-01-15 1997-12-15 Searle & Co 3,4-diarylthiophene und analoga davon, sowie deren verwendung als entzündungshemmende mittel
US5686105A (en) 1993-10-19 1997-11-11 The Procter & Gamble Company Pharmaceutical dosage form with multiple enteric polymer coatings for colonic delivery
US5409944A (en) 1993-03-12 1995-04-25 Merck Frosst Canada, Inc. Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase
US5380738A (en) 1993-05-21 1995-01-10 Monsanto Company 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents
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
US5474995A (en) 1993-06-24 1995-12-12 Merck Frosst Canada, Inc. Phenyl heterocycles as cox-2 inhibitors
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
US5344991A (en) 1993-10-29 1994-09-06 G.D. Searle & Co. 1,2 diarylcyclopentenyl compounds for the treatment of inflammation
US5466823A (en) 1993-11-30 1995-11-14 G.D. Searle & Co. Substituted pyrazolyl benzenesulfonamides
US5393790A (en) 1994-02-10 1995-02-28 G.D. Searle & Co. Substituted spiro compounds for the treatment of inflammation
US5665378A (en) 1994-09-30 1997-09-09 Davis; Roosevelt Transdermal therapeutic formulation
US5633272A (en) 1995-02-13 1997-05-27 Talley; John J. Substituted isoxazoles for the treatment of inflammation
US5567441A (en) 1995-03-24 1996-10-22 Andrx Pharmaceuticals Inc. Diltiazem controlled release formulation
EP0827402A2 (en) 1995-05-17 1998-03-11 Cedars-Sinai Medical Center Compositions containing fatty acids for improving digestion and absorption in the small intestine
SE9502244D0 (sv) 1995-06-20 1995-06-20 Bioglan Ab A composition and a process for the preparation thereof
US6020343A (en) 1995-10-13 2000-02-01 Merck Frosst Canada, Inc. (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors
GB9523946D0 (en) 1995-11-23 1996-01-24 Bayer Ag Leukotriene antagonistic benzoic acid derivatives
US5837284A (en) 1995-12-04 1998-11-17 Mehta; Atul M. Delivery of multiple doses of medications
US6323227B1 (en) * 1996-01-02 2001-11-27 Aventis Pharmaceuticals Products Inc. Substituted N-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides
US5858401A (en) 1996-01-22 1999-01-12 Sidmak Laboratories, Inc. Pharmaceutical composition for cyclosporines
US6929801B2 (en) 1996-02-19 2005-08-16 Acrux Dds Pty Ltd Transdermal delivery of antiparkinson agents
US6923983B2 (en) 1996-02-19 2005-08-02 Acrux Dds Pty Ltd Transdermal delivery of hormones
CN1098256C (zh) 1996-04-12 2003-01-08 G·D·瑟尔公司 作为cox－2抑制剂前药的取代的苯磺酰胺衍生物
US5861419A (en) 1996-07-18 1999-01-19 Merck Frosst Canad, Inc. Substituted pyridines as selective cyclooxygenase-2 inhibitors
US6458373B1 (en) 1997-01-07 2002-10-01 Sonus Pharmaceuticals, Inc. Emulsion vehicle for poorly soluble drugs
US5840329A (en) 1997-05-15 1998-11-24 Bioadvances Llc Pulsatile drug delivery system
US6037340A (en) 1997-05-28 2000-03-14 Cadus Pharmaceutical Corporation Synthesis and use of thiophene- and pyrrole-based heteroaromatic compounds
US6391452B1 (en) 1997-07-18 2002-05-21 Bayer Corporation Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations
US5869090A (en) 1998-01-20 1999-02-09 Rosenbaum; Jerry Transdermal delivery of dehydroepiandrosterone
US6946144B1 (en) 1998-07-08 2005-09-20 Oryxe Transdermal delivery system
ES2307482T3 (es) 1999-02-10 2008-12-01 Pfizer Products Inc. Dispersiones farmaceuticas solidas.
US6395300B1 (en) 1999-05-27 2002-05-28 Acusphere, Inc. Porous drug matrices and methods of manufacture thereof
US6313138B1 (en) 2000-02-25 2001-11-06 Merck & Co., Inc. Tyrosine kinase inhibitors
EP1143013A1 (en) 2000-04-03 2001-10-10 Warner-Lambert Company Methods and compositions for screening Icrac modulators
AU2001293372A1 (en) 2000-04-18 2001-10-30 Cytovia, Inc. Substituted 1,4-thiazepine and analogs and their use as activators of caspases
WO2002030976A1 (en) 2000-10-11 2002-04-18 The University Of Melbourne Cell control nucleic acids and proteins
DE10061876A1 (de) 2000-12-12 2002-06-20 Aventis Pharma Gmbh Arylierte Furan- und Thiophencarbonsäureamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen
US6465014B1 (en) 2001-03-21 2002-10-15 Isp Investments Inc. pH-dependent sustained release, drug-delivery composition
US6599310B2 (en) 2001-06-29 2003-07-29 Quill Medical, Inc. Suture method
US6960563B2 (en) 2001-08-31 2005-11-01 Morton Grove Pharmaceuticals, Inc. Spontaneous emulsions containing cyclosporine
JP2005511613A (ja) 2001-11-08 2005-04-28 ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー 疾患治療用アザビシクロ置換ヘテロアリール化合物
AR040123A1 (es) * 2002-05-31 2005-03-16 Upjohn Co Compuestos tiofeno, antihelminticos e insecticidas
EP1532128A1 (en) * 2002-07-01 2005-05-25 Pharmacia & Upjohn Company LLC Inhibitors of hcv ns5b polymerase
WO2004035078A1 (en) 2002-10-16 2004-04-29 The University Of Queensland Treatment of inflammatory bowel disease
DE60332475D1 (de) * 2002-10-30 2010-06-17 Vertex Pharma Zusammensetzungen verwendbar für die hemmung von rock und anderen kinasen
US7645588B2 (en) 2003-03-04 2010-01-12 Calcimedica, Inc. Composition comprising a cell comprising a STIM1 protein and an agent that modulates intracellular calcium and methods of use
DK1638551T3 (da) 2003-05-19 2012-04-02 Irm Llc Immunosuppressive forbindelser og sammensætninger
AU2003902851A0 (en) 2003-06-06 2003-06-26 Australian Ballet School Ballet shoe insert
BRPI0412257A (pt) 2003-07-23 2006-10-03 Synta Pharmaceuticals Corp compostos para inflamação e usos imuno-relacionados
JP4054741B2 (ja) * 2003-09-26 2008-03-05 日本圧着端子製造株式会社 低背型ｆｐｃ用ｚｉｆコネクタ
US20050227929A1 (en) 2003-11-13 2005-10-13 Masferrer Jaime L Combination therapy comprising a Cox-2 inhibitor and an antineoplastic agent
WO2006093518A2 (en) * 2004-06-25 2006-09-08 Apath, Llc Thienyl compounds for treating virus-related conditions
WO2006007864A1 (en) 2004-07-17 2006-01-26 Max Planck Geselllschaft Zur Förderung Der Wissenschaft Treating neurodegenerative conditions
AU2005266890C1 (en) * 2004-07-30 2014-09-25 Exelixis, Inc. Pyrrole derivatives as pharmaceutical agents
KR20070057965A (ko) 2004-09-21 2007-06-07 신타 파마슈티칼스 코프. 염증 및 면역 관련 용도를 위한 화합물
KR20070107022A (ko) 2005-01-07 2007-11-06 신타 파마슈티칼스 코프. 염증 및 면역 관련 용도를 위한 화합물
CA2595000C (en) * 2005-01-25 2013-10-15 Synta Pharmaceuticals Corp. Thiophene compounds for inflammation and immune-related uses
WO2006081391A2 (en) 2005-01-25 2006-08-03 Synta Pharmaceuticals Corp. Compounds for inflammation and immune-related uses
SG164378A1 (en) 2005-02-17 2010-09-29 Synta Pharmaceuticals Corp Compounds for the treatment of proliferative disorders
US7563813B2 (en) * 2005-05-13 2009-07-21 Wyeth Iminothiazolidinone derivatives as SFRP-1 antagonists
GB0516379D0 (en) * 2005-08-09 2005-09-14 Glaxo Group Ltd Compounds
EP1754483A1 (en) * 2005-08-18 2007-02-21 Merck Sante Use of thienopyridone derivatives as AMPK activators and pharmaceutical compositions containing them
CA2636417C (en) 2006-01-05 2020-08-25 Immune Disease Institute, Inc. Regulators of nfat
JPWO2007083689A1 (ja) * 2006-01-19 2009-06-11 株式会社レナサイエンス プラスミノーゲンアクチベーターインヒビター−１阻害剤
CA2639913A1 (en) 2006-01-25 2007-08-02 Synta Pharmaceutical Corp. Phenyl and pyridyl compounds for inflammation and immune-related uses
TW200806292A (en) 2006-01-25 2008-02-01 Synta Pharmaceuticals Corp Vinyl-phenyl derivatives for inflammation and immune-related uses
TW200806290A (en) * 2006-01-25 2008-02-01 Synta Pharmaceuticals Corp Substituted biaryl compounds for inflammation and immune-related uses
AU2007208225B2 (en) 2006-01-25 2013-05-02 Synta Pharmaceuticals Corp. Thiazole and thiadiazole compounds for inflammation and immune-related uses
AU2007208239B2 (en) 2006-01-25 2013-04-18 Synta Pharmaceuticals Corp. Substituted aromatic compounds for inflammation and immune-related uses
JP5430944B2 (ja) 2006-01-31 2014-03-05 シンタ ファーマシューティカルズ コーポレーション 炎症および免疫関連用途のためのピリジルフェニル化合物
TW200812587A (en) 2006-03-20 2008-03-16 Synta Pharmaceuticals Corp Benzoimidazolyl-pyrazine compounds for inflammation and immune-related uses
AU2007230911A1 (en) * 2006-03-23 2007-10-04 Synta Pharmaceuticals Corp. Benzimidazolyl-pyridine compounds for inflammation and immune-related uses
WO2008063504A2 (en) 2006-11-13 2008-05-29 Synta Pharmaceuticals Corp. Cyclohexenyl-aryl compounds for inflammation and immune-related uses
JP5399262B2 (ja) * 2006-12-08 2014-01-29 エグゼリクシス パテント カンパニー エルエルシー Ｌｘｒおよびｆｘｒのモジュレーター
WO2008122038A1 (en) 2007-04-02 2008-10-09 President And Fellows Of Harvard College Regulating autophagy
CN101854933A (zh) 2007-09-10 2010-10-06 钙医学公司 调节细胞内钙的化合物
DE102007057905A1 (de) 2007-11-29 2009-06-10 Microtac Systems Ag Haftverschlussteil und Verfahren zur Herstellung eines Haftverschlussteils
US8389567B2 (en) * 2007-12-12 2013-03-05 Calcimedica, Inc. Compounds that modulate intracellular calcium
EP2219646A4 (en) * 2007-12-21 2010-12-22 Univ Rochester METHOD FOR MODIFYING THE LIFETIME OF EUKARYOTIC ORGANISMS
MX2011002149A (es) 2008-08-27 2011-04-05 Calcimedica Inc Compuestos que modulan el calcio intracelular.
JP4879240B2 (ja) 2008-09-16 2012-02-22 株式会社リコー 発振回路、ｄｃ−ｄｃコンバータ及び半導体装置
US8524763B2 (en) 2008-09-22 2013-09-03 Calcimedica, Inc. Inhibitors of store operated calcium release

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2184731C2 (ru) * 1996-10-15 2002-07-10 Мерк Патент Гмбх Амиды аминотиофенкарбоновой кислоты, способ их получения (варианты) и фармацевтическая композиция
EA007484B1 (ru) * 2001-06-11 2006-10-27 Вирокем Фарма Инк. Соединения и способы лечения или предупреждения инфекций flavivirus
WO2003013517A1 (en) * 2001-08-06 2003-02-20 Pharmacia Italia S.P.A. Aminoisoxazole derivatives active as kinase inhibitors
WO2005033102A2 (en) * 2003-10-03 2005-04-14 Amphora Discovery Corporation Thiophene-based compounds exhibiting atp-utilizing enzyme inhibitory activity, and compositions, and uses thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A.Schepetkin et al., "High-Throughput Screening for Smoll-Molecule Activators of Neutrophils: Identification of Novel N-Formyl Peptide Receptor Agonists", Molecular Pharmacology, 2007, vol.71, No.4, p.1061-1074. *
A.Schepetkin et al., "High-Throughput Screening for Smoll-Molecule Activators of Neutrophils: Identification of Novel N-Formyl Peptide Receptor Agonists", Molecular Pharmacology, 2007, vol.71, №4, p.1061-1074. *

Also Published As

Publication number Publication date
US20110166159A1 (en) 2011-07-07
AU2009288245B2 (en) 2012-12-20
AU2009288245A1 (en) 2010-03-11
MY157445A (en) 2016-06-15
US8372991B2 (en) 2013-02-12
EP2321303A2 (en) 2011-05-18
WO2010027875A3 (en) 2010-06-10
US8394848B2 (en) 2013-03-12
BRPI0917719A2 (pt) 2019-11-19
KR101724161B1 (ko) 2017-04-06
WO2010025295A2 (en) 2010-03-04
US20100056532A1 (en) 2010-03-04
IL211391B (en) 2018-10-31
CN102256969A (zh) 2011-11-23
EP2321303A4 (en) 2011-11-16
ZA201101335B (en) 2011-10-26
WO2010025295A3 (en) 2010-06-17
US7906553B2 (en) 2011-03-15
JP5782377B2 (ja) 2015-09-24
US20100261725A1 (en) 2010-10-14
US7981925B2 (en) 2011-07-19
TWI392673B (zh) 2013-04-11
US20110212970A1 (en) 2011-09-01
EP2321303B1 (en) 2019-11-27
TW201022256A (en) 2010-06-16
KR20110059723A (ko) 2011-06-03
US20130245025A1 (en) 2013-09-19
US8383670B2 (en) 2013-02-26
MX2011002149A (es) 2011-04-05
JP2012501337A (ja) 2012-01-19
RU2011108969A (ru) 2012-10-10
US20110136816A1 (en) 2011-06-09
WO2010027875A2 (en) 2010-03-11
CA2734500A1 (en) 2010-03-11
US20130231344A1 (en) 2013-09-05

Similar Documents

Publication Publication Date Title
RU2472791C2 (ru) Соединения, модулирующие внутриклеточный кальций
ES2865284T3 (es) Derivados de 3-tetrazolil-benceno-1,2-sulfonamida como inhibidores de metalo-beta-lactamasas
JP2013507425A5 (ru)
RU2017138972A (ru) Ингибиторы репликации вируса иммунодефицита человека
JP2019530649A (ja) 統合ストレス経路のモジュレーター
RU2013114771A (ru) Диамиды азетидинила как ингибиторы моноацилглицерол липазы
RU2009117642A (ru) Применение спирооксиндоловых соединений в качестве терапевтических средств
JP2014506599A5 (ru)
NZ630259A (en) Heterobicyclic compounds as beta-lactamase inhibitors
NZ613234A (en) Compositions and methods for modulating fxr
JP2012528166A5 (ru)
CA2565813A1 (en) Substituted methyl aryl or heteroaryl amide compounds
AR073548A1 (es) Compuestos derivados de diazol y triazol, composiciones y uso de los mismos para modular los niveles de acido urico
WO2005028445A3 (en) Derivatives of n-(1h-indazolyl)- and n-(1h-indolyl)-urea as well as related compounds as modulators of the vanilloid-1 receptor (vr1) for the treatment of pain
MX342806B (es) Compuestos y método para reducir el ácido úrico.
RU2014105169A (ru) 2-пиридилзамещенные имидазолы в качестве ингибиторов alk5 и/или alk4
RU2009142431A (ru) Производные триазолопиридинкарбоксамидов и триазолопиримидинкарбоксамидов, их получение и их применение в терапии
PE20080409A1 (es) Compuestos que modulan en el receptor cb2
RU2012136451A (ru) Композиции и способы улучшения активности протеасомы
RU2007131274A (ru) Замещенные пиразолопиридины, композиции, содержащие их, способ получения и применение
RU2010154502A (ru) Трициклические 2,4-диамино-l,3,5-триазиновые производные, пригодные для лечения злокачественного новообразования и миелопролиферативных нарушений
RU2013108641A (ru) Способ лечения офтальмологических заболеваний с использованием соединений ингибиторов киназы в пролекарственных формах
RU2009149210A (ru) Ингибиторы днк-зависимой протеинкиназы (днк-пк)
RU2016104044A (ru) Ингибиторы усилителя zeste гомолога 2
RU2013108348A (ru) Конденсированные гетероарилы и их применение

Legal Events

Date Code Title Description
TK4A Correction to the publication in the bulletin (patent)

Free format text: AMENDMENT TO CHAPTER -FG4A- IN JOURNAL: 2-2013 FOR TAG: (57)

MM4A The patent is invalid due to non-payment of fees

Effective date: 20160827